458 22.5% (41/182) had malaria plus urinary tract infection. Other causes particular towards Plasmodium falciparum malaria. For reasons that are of fever among the children include measles, acute respiratory infection, not entirely understood by modern science, P. falciparum never ceases diarrhea diseases and mumps. ASAQ cleared the malaria parasitemia to be one step in front of the research community, repeatedly disarming promptly and was well tolerated. 78.8% of 189 parasitemic children the forces that try to combat the disease. The current global malaria who completed D28 follow up had adequate clinical and parasitological situation situation involves P. falciparum parasites that are resistant response. Two children who tested positive and receive ASAQ were towards artemisinin-based combination therapies in Asia, as well as referred to hospital because of severe anemia. The results of this study did global resistance towards sulphadoxine-pyrimethamine and chloroquine. not reveal any severe consequence sequel to the use of RDT result as basis With very limited antimalarial drugs remaining to effectively prevent for treatment. malaria in children and pregnant women, as well as treat malaria-infected individuals, the local situation regarding antimalarial drug resistance needs 1499 to be monitored. With the help of molecular markers of resistance in terms of single nucleotide polymorphisms representative of tolerance or TERTIAN DURATION OF ARTEMISININS SELECTS FOR resistance of P. falciparum parasites towards specific antimalarial drugs, DELAYED PARASITE CLEARANCE WITH SINGLE 48 HOUR monitoring the antimalarial drug resistance situation becomes feasible. LIFECYCLE ARTEMISININ EXPOSURE Furthermore, by applying used malaria rapid diagnostic tests, the source of P. falciparum DNA is acquired at very low costs and in plentiful David J. Sullivan numbers. Also, by applying a next-generation sequencing technology, the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United cost of sequence analysis is brought down 20-50 fold in comparison to States commercial Sanger sequencing. Lastly, by applying indexing of the samples In the 1990s many artemisinin combination dosing trials ranged from analysed, sequences can be traced back to a specific sample and a specific 2-7 days in duration. The three day or 48 hour dosing duration was just place of origin, allowing action to be taken in terms of fine-tuning policy as effective as five or more days. The correct rationale at that time was guidance at the local level. This platform allows for real-time monitoring that greater compliance would be achieved with tertian dosing rather of antimalarial drug resistance in a cost-efficient and extremely high than five or more days. This three day regimen was effective until the throughput manner. prolonged parasite phenotype was noted in Palin Cambodia. The three day or ‘tertian’ dosing equates to a single 48 hour Plasmodium falciparum 1501 lifecycle. The consequence of dosing most of the artemisinin component EVALUATION OF THE IMPACT OF SEASONAL MALARIA of an ACT within a single P. falciparum 48 hour lifecycle is selection for parasites with Kelch-13 gene mutations. Ring-stages of parasites in the CHEMOPREVENTION ADMINISTERED BY MASS CAMPAIGN peripheral blood at drug initiation only receive a single effective dose IN SOUTHERN SENEGAL coincident with the sensitive trophozoite-stages, because two artemisinin Jean Louis A. Ndiaye1, Babacar Faye1, Magatte Ndiaye1, Daouda doses (at initiation and the last dose) target the naturally more resistant Ndiaye1, Medoune Ndiop2, Isaac A. Manga1, Roger Tine1, Julie ring-stages. Sequestered trophozoites in the tissues at drug initiation Thwing3, Mady Ba2, Paul Milligan4, Oumar Gaye1 receive two effective trophozoite-stage drug doses at 0 and 40-48 hours 1Service de Parasitologie, Dakar, Senegal, 2Ministry of Health and Social resulting in greater reduction of these trophozoites in contrast to the Action, Dakar, Senegal, 3PMI, Dakar, Senegal, 4London School of Hygiene rings. The parasite has been selected by the short pharmacodynamics of & Tropical Medicine, London, United Kingdom artemisinin behaviour within a single lifecycle to favour a mutant Kelch-13 gene to permit survival beyond a single cycle so that if the quinoline Seasonal Malaria Chemoprevention (SMC) is a new strategy for the control partner drug in an ACT is failing as well, then elimination of remaining of malaria in children involving monthly administration of sulfadoxine- parasites is compromised. Clinical drug failure measured at day 28 or 42 pyrimethamine plus amodiaquine (SPAQ) to prevent malaria. In Senegal, is failure for both ACT drugs, and should therefore be termed treatment the southern regions where malaria is highly seasonal, and transmission failure. Importantly the tertian ACT 48 hour dosing regimens including is intense are the most suited areas for SMC with 620,000 children under the 60 hour every 12 hour artemether/lumefantrine dosing is presently 10 years of age eligible for SMC. It is however important that scaling selecting for additional foci of mutations outside Southeast Asia. Effective up of SMC by national Malaria Control Programmes is evaluated to artemisinin combination therapy with present drugs now requires doubling document its coverage, the safety profile, the impact on malaria morbidity the duration to six days. This allows initial ring-stage populations to and drug resistance molecular markers. In 2014, to monitor malaria encounter artemisinin drug exposure at least three times at the more morbidity surveillance, 230 health structures were listed by district, with sensititive trophozoite-stage rather than once. Incremental increase of an their catchment populations, (a total pop about 2 million) based on the extra day of therapy is not sufficient. 2012 census. A survey sample of 32 health post, 16 districts hospitals were selected with probability proportional per size, by systematic random 1500 sampling, checked with respect to geographical coverage, malaria cases and malaria incidence rates to ensure the sample was representative. NEXT-GENERATION SEQUENCING PLATFORM BASED ON One month after the 3 SMC rounds with an administrative coverage MALARIA RAPID DIAGNOSTIC TESTS FOR SURVEILLANCE OF of more than 95%, 2000 children under 10 and 1750 adults into 45 ANTIMALARIAL DRUG RESISTANCE villages selected by PPS were surveyed to document SMC coverage and drug resistance markers. A case - control study has been conducted in 2 1 2 3 Sidsel Nag , Marlene Dalgaard , Magatte Ndiaye , Poul-Erik L. districts to measure the efficacy of SMC treatments. 225 malaria cases and 4 5 6 7 Kofoed , Amabelia Rodrigues , Johan Ursing , Reginald Kavishe , controls who do not have malaria have been recruited concurrently, and 1 2 2 Michael Alifrangis , Ole Lund , Frank M. Aarestrup the dates of the doses of SMC they received noted by trained fieldworkers. 1University of Copenhagen, Copenhagen, Denmark, 2Technical University The strengthened passive pharmacovigilance system detected only 80 of Denmark, Kgs Lyngby, Denmark, 3University Cheikh Anta Diop, Dakar, mild adverse events and 2 serious adverse events (1 Lyell and 1 Steven - Senegal, 4Kolding Hospital, Kolding, Denmark, 5Bandim Health Project, Johnson syndromes) after 1.843 million SMC treatments. The analysis is Bandim, Guinea-Bissau, 6Karolinska Institute, Stockholm, Sweden, on going and efficacy results, impact on malaria morbidity and on drug 7Tumaini University, Moshi, United Republic of Tanzania resistance markers will be presented. Antimalarial drug resistance is a constantly present threat towards one of the major tools necessary for rolling back malaria, namely efficient antimalarial drugs. It has occurred on several occasions and rendered the health systems close to helpless towards the malaria parasites, in astmh.org 459 1502 artemisinin susceptibility assays. This study investigates alternative methods of assaying artemisinin resistance by in vitro exposure to dihydroartemisin THERAPEUTIC EFFICACY OF ATOVAQUONE-PROGUANIL (DHA) - the major metabolite of all ACT. Artemisinins have short half lives AND ARTESUNATE ATOVAQUONE-PROGUANIL FOR (1-2h) in-vivo and so short drug pulses were applied to parasites in an THE TREATMENT OF UNCOMPLICATED PLASMODIUM effort to better mimic in-vivo conditions. A 6hr drug pulse assay and a FALCIPARUM MALARIA IN AREAS OF MULTIDRUG standard 48hr assay were used to observe any differences that may exist in IC values between field isolates from Kenya (HL1204), Ghana (HL1210) RESISTANCE IN CAMBODIA 50 and Nigeria (HL1212). In all three isolates tested, the mean DHA IC50 values Chanthap Lon1, Mali Ittiverakul2, Sok Somethy3, Soklyda Chann1, for the 6hr pulse assays were higher than that of the standard 48hr assays. Worachet Kuntawunginn2, Nareth Kong1, Jessica Manning2, This trend was seen as a shift to the right in the dose response curve. This 4 5 5 5 Jessica Lin , Dustin Harrison , Andrew Vaughn , Agus Ratchmat , approach revealed differences in IC50 values for DHA among the isolates. Satharath Prom3, Lek Dysoley6, David Saunders2 Field isolates from Ghana (6 fold higher than 3D7 lab strain) and Nigeria 1 Armed Forces Research Institute of Medical Sciences, Phnom Penh, (3.4 fold higher) showed elevated mean DHA IC50 value compared to that Cambodia, 2Armed Forces Research Institute of Medical Sciences, from Kenya (1.7 fold higher than 3D7). Results also showed that DHA 3 Bangkok, Thailand, Royal Cambodian Armed Forces, Phnom Penh, IC50 values varied among experimental replicates, reflecting the polyclonal Cambodia, 4University of North Carolina, Chapel Hill, NC, United States, nature of the isolates used in this study. There is an urgent need to 5Naval Medical Research Unit - 2, Phnom Penh, Cambodia, 6National develop in-vitro assays that correlate with parasite artemisinin response in Center for Parasitology, Entomology and Malaria Control, Phnom Penh, vivo, as this will be useful in elucidating the molecular basis of artemisinin Cambodia resistance. We recently reported a clinical failure rate of greater than 54% for 1504 dihydroartemisinin-piperaquine, the last currently available artemisinin combination therapy (ACT) for the treatment of Plasmodium falciparum CONTRIBUTION OF PLASMODIUM FALCIPARUM, P. VIVAX malaria in Cambodia. Few alternatives remain unfortunately. Atovaquone- AND P. MALARIAE TO CLINICAL MALARIA CASES IN NORTH proguanil (AP) is a safe, well-tolerated drug for the treatment of drug SUMATERA PROVINCE, INDONESIA resistant P. falciparum, and has recently been used in limited areas of Cambodia as part of public health interventions. There have been recent Inke Nadia D. Lubis1,2, Chairuddin P. Lubis1, Munar Lubis1, Hendri though unconfirmed reports of developing clinical AP resistance in Pailin Wijaya1 and Colin J. Sutherland2 province, as well as reports of mutations to the cytochrome bc-1 complex 1Medical Faculty, University of Sumatera Utara, Medan, Indonesia, associated with atovaquone resistance. We are currently comparing 2Department of Immunology and Infection, London School of Hygiene & two fixed-dose 3 day regimens of AP, with or without a 3 day course of Tropical Medicine, London, United Kingdom co-administered artesunate (ASAP) for the treatment of uncomplicated malaria. This randomized, open label clinical trial will be conducted in Indonesia, a country situated at the southeastern tip of Asia, has a total up to 200 patients with P. falciparum or mixed P. falciparum/P. vivax population of 245 million, of which 61% live in malaria endemic areas. infection at two sites in Cambodia. Enrollment began in Anlong Veng on Most of the endemic regions are in stable transmission zones although the Thai-Cambodian border in December 2014, and will start in Kratie, on with low transmission risk. In 2012, WHO reported 2,051,425 malaria the Vietnamese border in May 2015. A single 15mg dose of primaquine cases from Indonesia, comprising 22% of the malaria burden in Southeast is given on day 1, and subjects are followed for recurrence for 42 days. Asia. All species of Plasmodium have been reported in the country with To date, 40 volunteers have been screened, 23 randomized to AP and 17 Plasmodium falciparum and P. vivax the predominant species. In order randomized to ASAP. Preliminary results indicate only 1 of 31 evaluable to carry out studies of in vivo efficacy of antimalarial treatment in North subjects (3.2%) completing 42 day follow up to date have had P.f. Sumatera, we conducted passive and active case screening by RDT and recurrence, while 8 (25.8%) have had a P. vivax recurrence. One subject microscopy examination in Batubara regency, Langkat regency and South in the ASAP group suffered a serious adverse event with suspected drug- Nias regency. These semi-forested areas comprise dispersed small- to induced liver injury. An interim report, including both efficacy, and safety medium sized communities practising a mixture of permanent and shifting results pertaining to the use of single low dose primaquine in subjects with agriculture, as well as foraging in the forests. Two malaria parasite species, G6PD deficiency, will be presented. P. falciparum and P. vivax, have previously been reported in these sites. Among febrile patients, P. vivax was the most common cause of malaria, 1503 followed by P. falciparum. Demographic data and the features of clinical malaria in these communities will be presented, as well as the prevalence MEASURING DIFFERENCES IN THE IN VITRO SUSCEPTIBILITY of each parasite species in febrile adults and children. We also describe the OF AFRICAN PLASMODIUM FALCIPARUM ISOLATES TO first PCR-confirmed clinical cases of P. malariae infection from this part of DIHYDROARTEMISININ USING A FLUORESCENT-READOUT Indonesia. PULSING ASSAY 1505 Ifeyinwa Aniebo, Gisela Henriques, Colin Sutherland, Donelly van Schalkwyk THE PREVALENCE OF MALARIA PARASITAEMIA IN SEVERELY London School of Hygiene & Tropical Medicine, London, United Kingdom MALNOURISHED AND WELL NOURISHED CHILDREN Artemisinin-based combination therapy (ACT) is currently the most PRESENTED AT MULAGO HOSPITAL UGANDA effective treatment strategy against Plasmodium falciparum malaria. Moses Kiggundu1, Sarah Kiguli1, Ann Nanteza1, Florence There have been reports from Southeast Asia of parasite resistance to Nalubowa2, Esther Sempa2, Samuel Lubwama Nsobya2 artemisinin and its derivatives, and there are fears that resistance to this 1Infectious Diseases Research Collaboration/Makere University, Kampala, class of drugs will spread to Africa. Artemisinin resistance is recognised Uganda, 2Mulago Hospital, Kampala, Uganda by a relatively slow parasite clearance rate in patients receiving an ACT or artemisinin. In-vitro or ex-vivo methods are conventionally used to Malnutrition and malaria remain the major causes of morbidity and mortality in young children mostly in sub-Saharan Africa. We hypothesized determin the IC50 value - the drug concentration that inhibits parasite growth by 50%- for parasite lines in the laboratory. To date, there have that the prevalence of Plasmodium falciparum will be higher in been no consistent correlations between half lives of P. falciparum treated malnourished children compared to well nourished children. This study was case and control study whereby 100 samples of blood from severely with artemisinin in-vivo and in-vitro IC50 estimates from standard 48-hour

astmh.org 460 malnourished (cases) and 100 from well nourished (controls) children who case management (i.e. referral, treatment). The register facilitates tracking presented to Mulago Hospital were examined for P. falciparum using numbers of patients, number of treatments administered, outcome of light microscopy. The prevalence of Plamodium faciparum in malnourished treatment and the extent to which providers are providing correct case children was 6% with mean geometric parasite density of 88/µl of blood, management according to the treatment algorithm. Patient register while that of well nourished children was 17% with average geometric data were entered into a database for calculation of indicators across parasite density of 1755/µl of blood caused by a mono-infection of P. the project. Trends in provider behavior over time will be presented. falciparum. Stratifying both groups with malaria and associating them Implications for improving quality of care in the private sector, and with age, children between 2- 36 months had high prevalence of malaria approaches to effectively monitoring private providers will be discussed. in both the cases (66.8%) and control (88.2%). The findings showed that malnourished children are less likely to suffer from malaria as compared 1508 to well nourished ones (P- value = 0.0148). The low prevalence of P. falciparum in malnourished child may be due to lack of essential nutrients POTENTIAL IMPACT OF RAPID DIAGNOSTIC TEST needed by malaria parasites to thrive in the red blood cells. In addition, the DIAGNOSTIC ERROR ON INCREASED MALARIA MORTALITY presence of parasites in both cases and controls may due to the fact that Colin Ohrt1, Awalludin Sutamardja1, Maciej F. Boni2, Andrew A. partial immunity for malarial infection is just developing. Lover1 1506 1University of California, San Francisco, San Francisco, CA, United States, 2Nuffield Department of Medicine, University of Oxford, Oxford University MALARIA IN DONATED BLOOD IN CHIPATA DISTRICT Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi HOSPITAL, EASTERN ZAMBIA Minh, Vietnam Lungowe Sitali It is crucial to investigate whether increased adoption of rapid diagnostic tests (RDTs) could have adverse effects on malaria mortality due to the University of Zambia, Lusaka, Zambia high absolute number of initially untreated cases. Malaria rapid diagnostic Although malaria is preventable and treatable, it still claims 584,000 tests (RDTs) have been recommended by the World Health Organization lives every year globally with children aged under five years having the to obtain a specific malaria diagnosis before treatment of malaria. RDTs highest burden. Plasmodium falciparum the parasite that cause malaria are now being used widely in malaria-endemic regions, including use is one the most commonly encountered blood parasite. This parasite is by community health workers. Published estimates of RDT sensitivity for transmitted by a female Anopheline mosquito, but can also be transmitted Plasmodium falciparum malaria typically range from 85-95% ((check)). through blood transfusion and results in transfusion transmitted malaria In addition, real world sensitivity is often lower and treatment decisions (TTM). TTM poses a considerable risk of illness to the major recipients of may not be made correctly for both positive and negative RDT results blood. Unfortunately the blood collected is not routinely tested for malaria; due to limited education of many users, poor training for proper use and hence the aim of this study was to determine the prevalence of malaria limited quality assurance. Globally, a 5% false negative rate in an RDT parasites in donated blood. A cross-sectional study where 600 donated represents 25 million ((confirm)) untreated malaria cases. It is currently blood samples from Chipata District Blood bank in Eastern Zambia were unknown what happens to these untreated cases. The mortality for tested using rapid diagnostic tests (RDTs) for P.falciparum. Out the 600 delayed treatment in travelers is estimated to be ((confirm XX)), but is sample 74 were positive; hence the study showed 12.3% prevalence of unknown in the developing world setting. The rationale for the use of malaria in donated blood. The study revealed prevalence 12.3%, therefore, RDTs will be presented along with methods to reduce the risk for mortality. it is important that there are preventive measures for all potential routes of Such methods include serial testing for a negative result, instructing of transmission if the goal to eliminate it is to be achieved. Although the RDTs the patient about the possibility of a false negative result and for the used have a 14 day antigen lag, hence is need to conduct a large study patient to return promptly for persistent or worsening symptoms. In fact, were microscopy and molecular methods are employed to detect parasites. presumptive treatment should be reconsidered in some situations. The myth of increasing artemisinin-resistance will be addressed and well as the 1507 potential real risk for resistance-induction with long half-life antimalarials. Lastly, methods to conduct quality assurance for RDTs, as well as to detect TRENDS IN PROVIDER BEHAVIOR CAPTURED THROUGH clinical relevant problems with RDTs will be described. ROUTINE MONITORING OF CASE MANAGEMENT OF FEVER AMONG ACCREDITED PROVIDERS IN UGANDA 1509 Robert Mugerwa, John Baptist Bwanika, Tonny Kyagulanyi, COMPARISON OF BLOOD SMEAR WITH SERUM MOLECULAR Elizabeth Streat, Grace Nakanwagi TESTING FOR THE DIAGNOSIS OF MALARIA AMONG FEBRILE Malaria Consortium, Kampala, Uganda KENYAN CHILDREN Coverage of fever case management interventions remains low across Jesse J. Waggoner1, Julie Brichard1, Francis Mutuku2, Bryson sub-Saharan Africa, including Uganda. While many caregivers seek Ndenga3, John Vulule3, Dunstan Mukoko4, Benjamin A. Pinsky1, A. treatment for symptoms of fever in the private sector, private sector Desiree LaBeaud1 outlets may not have adequate diagnostics, training, waste management, 1Stanford University, Palo Alto, CA, United States, 2Technical University of and first line quality assured treatments to ensure appropriate case Mombasa, Mombasa, Kenya, 3Kenya Medical Research Institute, Nairobi, management. Malaria Consortium together with FIND, PSI and WHO are Kenya, 4Ministry of Health, Nairobi, Kenya implementing a project creating a private sector market for quality assured RDTs in malaria endemic countries from April 2013 to date targeting In endemic countries, accurate malaria diagnostics are needed to both private sector. Accredited outlet types including drug shops, pharmacies correctly identify cases and exclude this as the etiology of nonspecific and clinics have been established, and participating members received acute febrile illness in children. Molecular testing is the most sensitive training in integrated case management for febrile illnesses, supportive diagnostic test for malaria, but this is typically performed using whole supervision, quality assured malaria rapid diagnostic test kits, and waste blood. Serum may provide a useful alternative; however, few data have management services. Malaria Consortium UNITAID Private Sector RDT been published on the performance of malaria molecular diagnostics project implements a program monitoring system that collects routine using this specimen type. To compare the performance of blood smear data on a monthly basis. Data is captured by accredited private providers with malaria molecular testing on serum, we randomly selected samples in a client register on phones and or patient slips, and which includes from 194 children who were enrolled in an ongoing, acute febrile illness information on symptoms (e.g. fever), assessment (e.g. RDT results), and surveillance study in coastal and western Kenya. Patients presented astmh.org 461 within the first 3 days of fever. Blood smear was performed at the time of 1511 presentation. Serum samples were tested using a multiplex molecular test (referred to as the UFI assay), which detects all five Plasmodium species HIDDEN PREVALENCE OF SUB-MICROSCOPIC INFECTIONS: with the specific detection of Plasmodium falciparum. Malaria was THE ROLE FOR MOLECULAR DIAGNOSTICS IN MADAGASCAR detected in 37 (19.1%) patients by blood smear and 59 (30.4%) patients 1 2 using the UFI assay (p=0.01). Five patients with positive blood smears Rosalind E. Howes , Thierry Franchard , Tovonahary A. 2 3 3 were negative for malaria in the UFI assay, whereas 27 patients only had Rakotomanga , Julie Rosenjack , Melinda Zikursh , Tiana 2 2 2 malaria detected by molecular testing. Compared to the UFI assay, the Ramanatiaray , Brune Ramiranirina , Arsène Ratsimbasoa , Peter 3 sensitivity of blood smear was 54.2% and specificity was 96.3%. Among A. Zimmerman the 59 samples positive for malaria in the UFI assay, 48 were confirmed 1Department of Zoology, University of Oxford, Oxford, United Kingdom, as P. falciparum (81.4%), 6 (10.2%) demonstrated evidence of a mixed 2National Malaria Control Programme of Madagascar, Antananarivo, infection with P. falciparum and another species, and 5 (8.5%) were Madagascar, 3Center for Global Health and Diseases, Case Western positive only for non-falciparum malaria. Patients who tested positive Reserve University, Cleveland, OH, United States for malaria by either method were significantly older than patients who Community prevalence of infection is a widely used, standardized tested negative (mean 5.7 yo (range 1-15.75) versus 4.4 yo (range 1-17.5), metric for evaluating malaria endemicity status at the population level. respectively; p<0.01). Using archived serum, the UFI assay detected Conventional methods for measuring prevalence include light microscopy malaria in significantly more febrile Kenyan children than peripheral blood (LM) and rapid diagnostic tests (RDT), but their detection thresholds leave smear performed at presentation. This study demonstrates the utility of them inadequate for assessing low density parasitaemias. The significance serum for malaria molecular testing and suggests that malaria may be of sub-microscopic malaria infections is poorly understood in Madagascar, underdiagnosed if blood smear is relied upon. a country targeting pre-elimination status by 2017. The country’s distinct epidemiological zones experience different patterns of endemic/ 1510 epidemic transmission, and their underlying parasite reservoirs remain DEVELOPMENT OF A POINT OF CARE MOLECULAR TEST FOR poorly quantified. A population prevalence survey of 2141 individuals was conducted across 25 villages in the western highland fringe region PLASMODIUM VIVAX of Ampasimpotsy, Tsiroanomandidy district, in March 2014. LM and the Omar A. Saldarriaga1, Alejandro Castellanos1, Hayley Sparks1, SD Bioline Combo Pf/Pan RDT were used to screen for infection. PCR- Gerald C. Baldeviano2, Salomon Durand2, Andres G. Lescano2, based molecular evaluation by a ligase detection reaction-fluorescent Peter C. Melby1, Bruno L. Travi1 microsphere assay (LDR-FMA) was subsequently conducted from filter- 1University of Texas Medical Branch, Galveston, TX, United States, 2U.S. paper blood spots. Prevalence of Plasmodium infection diagnosed by Naval Medical Research Unit - 6, Lima, Peru LM, RDT, and PCR was 2%, 5% and 20%, respectively. This diagnostic discordance was greatest for Plasmodium vivax infection, which ranged Malaria is a major public health problem in tropical and subtropical from 0.2% prevalence by LM, to 11% by PCR. Diagnostic sensitivities countries with almost 200 million cases reported annually. In the American and prevalence of sub-microscopic infections are examined in relation continent Plasmodium vivax extends from Mexico to northern Argentina to patient age, fever, and history of fever. These observations of high and is responsible for the majority (>70%) of the ≈670,000 reported prevalence of sub-microscopic infections in western Madagascar strongly annual cases. In addition to its known high rate of post-treatment call for wider assessment of the parasite reservoir in other regions of the recurrence, recent reports indicated that P. vivax could be responsible country. The deadly epidemic during early 2015 highlights the threat for severe malaria cases. The elimination/eradication efforts include the that these reservoirs can present, particularly in apparently low endemic development and implementation of specific and sensitive diagnostic settings such as southern Madagascar. Pre-elimination will require a tests. Several antigen-based Rapid Diagnostic Tests are currently being shift in focus towards attacking the parasite reservoir, including these used in endemic areas with good results when parasite loads are high sub-microscopic infections. The diagnostic disparities observed from this (≥2,000 parasites/µL), yet the sensitivity is poor when parasitemia is <200 study corroborate calls globally for a transition towards higher-sensitivity parasites/µL. This is particularly evident with P. vivax. Consequently, our diagnostics for epidemiological monitoring and assessing intervention objective was to develop a sensitive field-applicable molecular test for P. impact. vivax capable of detecting low parasite burdens. We designed primers and probes targeting 18S rRNA of P. vivax for isothermal DNA amplification 1512 using Recombinase Polymerase Amplification coupled with a lateral flow immunochromatographic strip (RPA-LF). Blood DNA from infected patients CLINICAL IMPACT OF MALARIA RAPID DIAGNOSTIC TESTING from an endemic are in the Peruvian Amazon was extracted using the IN A NON-ENDEMIC SETTING Qiagen® kit. Preliminary results in a small number of clinical samples (n=10) (30 min, 40 °C) showed that these primers specifically amplified Leslie A. Enane, Kaede Ota-Sullivan, Kristen A. Feemster P. vivax. There was no cross reactivity with P. falciparum (n=6). We are The Children’s Hospital of Philadelphia, Philadelphia, PA, United States currently evaluating the sensitivity of RPA-LF with the goal of detecting Children who develop malaria after returning to non-endemic settings samples with low parasite burden. The utilization of lateral flow (LF) strips are at high risk for critical delays in diagnosis and initiation of appropriate allowed detecting P. vivax infections with the naked eye, which makes this antimalarial therapy. Laboratory diagnosis traditionally depends on thick diagnostic test potentially applicable at the point of care. and thin Giemsa smears, requiring highly trained lab personnel. Rapid diagnostic testing (RDT) shows excellent sensitivity and negative predictive value, superior to blood smears, and does not require specific expertise. Yet RDT has not been adopted by most US clinical laboratories. An FDA-approved immunochromatographic assay for the rapid detection of Plasmodium antigens was introduced at the Children’s Hospital of Philadelphia on August 1, 2007. RDT is performed on all samples tested for blood parasites, followed by routine blood smears. Use of RDT dramatically decreased time to report a positive result with any Plasmodium species (from 9.8 to 1.7 hours) and with P. falciparum (from 10.2 to 1.6 hours). The objective of this retrospective cohort study is to measure the impact of RDT on the management of children with malaria at an urban tertiary care children’s hospital serving a large immigrant astmh.org 462 population. Among 71 children admitted with laboratory-confirmed improve testing and adherence rates towards these targets, the malaria malaria from 2000 to 2014, we will compare clinical management and program organized a two-day malaria case management training for outcomes of malaria cases before and after RDT introduction while providers and laboratory technicians in public health facilities between adjusting for disease severity and patient age. Primary outcome variables February and June 2014. As confirmatory diagnosis and adherence derived from electronic medical record abstraction include time to positive to negative tests were not routinely collected we placed consultation malaria result report, time to initiation of antimalarial therapy, time to registers between October 2013 and September 2014 in 157 public clearance of parasitemia, need for exchange transfusion, ICU admission, health facilities across five of the ten regions in Cameroon. Patients and length of hospital stay. We hypothesize that implementation of RDT is of any age seeking care for any cause were recorded in the registers. associated with a significant reduction in time to initiation of antimalarial Information was collected on demographics (age, gender), symptoms, therapy, time to resolution of parasitemia, and length of hospital stay. The malaria testing (microscopy or rapid diagnosis test), and any treatment clinical impact of RDT has not previously been reported in a non-endemic received. A multivariable analysis was performed to assess whether setting. This research will emphasize the utility of RDT as a critical tool patient symptoms and healthcare worker participation in the training were for the optimal management of patients with malaria in non-endemic associated with test uptake and adherence to test results, adjusting for settings. We anticipate completion of this ongoing study by August 2015. patient demographics, month of consultation, and health facility. During the study period, 126,462 patients were recorded across the 72 facilities 1513 that filled the register, of which 28% had suspected malaria. Overall, 69% of suspected malaria patients consulting before the training received ASSESSING THE MARKET LANDSCAPE FOR AN INFECTION a malaria test versus 76% after (p<0.001). However after adjusting for DETECTION TEST AIMED AT MALARIA ELIMINATION potential confounders, patient consulting after the training had reduced odds of being tested (OR=0.88, 95% CI=0.82-0.95) compared to those Bhavya Gowda1, Katherine Imus Misiuda2, Paul LaBarre2 consulting before. Among patients who tested negative and reporting 1PATH, Washington, DC, United States, 2PATH, Seattle, WA, United States receiving a treatment, 22% received an anti-malarial before training PATH’s Diagnostics for Malaria Elimination toward Eradication (DIAMETER) compared to 17% after (p<0.01), consistent with increased adjusted team is focused on bridging the gap between the rapidly evolving set odds of adhering to test results after training (OR=1.44, 95% CI=1.12- of infection detection requirements that support elimination and the 1.84). Over the course of the study, test uptake and adherence increased, limitations of existing diagnostic tests. As the managing partner for however uptake remained below the national target. Further studies Infection Detection Test (IDT) Development Initiative, the DIAMETER should explore whether additional efforts, such as mentorship, would be team is working to create a high quality, low cost, easy to use, and sufficient to improve test uptake to national targets. highly sensitive Plasmodium falciparum (Pf)-specific HRP2 IDT capable of identifying low density Pf infections that current rapid diagnostic 1515 tests (RDTs) cannot detect. In Phase 1, we worked with experts to draft a preliminary target product profile, landscaped potential pipeline EVALUATION OF MALARIA RAPID DIAGNOSTIC TESTS technologies, and conducted field work to understand use scenarios AND GIEMSA LIGHT MICROSCOPY IN HIGHLY MALARIOUS for improved diagnostics. In Phase 2, we managed technical feasibility DISTRICTS, AMHARA REGION, ETHIOPIA, 2014 activities for next generation tests aimed at identifying individuals with Belay Bezabih Beyene1, Woyneshet Gelaye1, Ermias Demilew2, low-density malaria infections. As a subset of this work, we sought to Getnet Abie1, Tsehay Tewabe1, Peter Wassawa3, Rick Steketee4 understand how the market will respond when such a test is available 1Amhara Regional Health Bureau, Bahir Dar, Ethiopia, 2World Vision, Addis for use. Ultimately, the goal of our market research activities was to Ababa, Ethiopia, 3African Field Epidemiology Network, Kampala, Uganda, support the definition, commercialization, and implementation of the 4PATH, Seattle, WA, United States most promising, cost-effective, and impactful diagnostic technologies for malaria elimination while promoting investment and development Malaria remains a leading health challenge in Ethiopia. A confirmatory of a healthy IDT market. First, we had to define the factors that could diagnosis with a rapid diagnostic test (RDT) or microscopy is recommended influence supply and demand of the proposed IDT. We assessed early for all suspected malaria cases, and understanding factors affecting market demand for the IDT by developing various demand scenarios. the comparability of these diagnostics is important for good case For instance, the IDT’s intended use and whether the IDT would replace management. We assessed factors related to RDT (SD BIOLINE) and existing RDTs would impact product uptake by countries, donors, and microscopic diagnosis of malaria. A cross-sectional study was conducted implementing agencies as well as manufacturers’ volumes. We modeled in eight high malaria districts of Amhara Region from May 15 to June key factors, capturing project assumptions and develop these scenarios 15, 2014. All suspected cases presenting to health facilities were eligible by engaging with subject matter experts and Ministry of Health malaria for inclusion. With an estimated 9% malaria prevalence, sample size was staff. Additionally, we conducted a comprehensive review in several focal calculated at 892 using Buderer’s formula and 1,000 suspected cases were countries to understand elimination strategy impact on the supply and sought from ten health centers; 987 and 990 were tested for malaria demand issues associated with RDTs. We will present our methodology, by RDT and microscopy, respectively. The median age was 21 years old findings, and implications related to IDT development decision. (range 1-88 years); 53% were male; 669 (67%) were over 15 years old, 172 (17%) were under 5 years old. The malaria positivity rate by RDT and 1514 microscopy was 17.1 % (169) and 16.5% (163), respectively. Compared to the microscopy standard, RDTs showed a sensitivity of 83.9%, specificity INCREASING USE OF AND ADHERENCE TO MALARIA of 96.0%, positive predictive value (PV) of 80.4%, and negative PV of DIAGNOSTIC TESTS THROUGH ENHANCED NATIONAL CASE 96.8%. The level of agreement (Kappa value) between first and second MANAGEMENT TRAINING IN CAMEROON microscopy reader was 0.74 (p-value < 0.001). In a multivariate logistic regression model, factors associated with higher infection included: male Katelyn Woolheater, Kathleen Maloney, Justin Graves, sex (OR=1.49, 95% CI=1.06-2.12), recent reported fever (OR=1.57, 95% Divine Nzuobontane, Andrew Atabe, Annold Vishi, Lyudmila CI=1.06-2.33), and having received malaria health education (OR=1.61, Gorokhovich, Leslie Emebuonye, Lindsay Bryson, Justin M. Cohen, 95% CI=1.12-2.32). Children under 5 years old had a lower risk of Arnaud Le Menach malaria infection (OR=0.32, 95% CI=0.17-0.60). In this malarious area Clinton Health Access Initiative, Boston, MA, United States of Amhara Region, the specificity and negative-PV of the RDTs were The national malaria strategy of Cameroon calls for at least 80% of excellent; however, the sensitivity and positive-PV were lower (83.9% and suspected malaria patients (fever or history of fever) to receive a malaria 80.4%, respectively). As malaria control improves and prevalence declines, test, and less than 20% of negative tests to receive anti-malarials. To the PV of a negative-RDT will be excellent, but the PV of a positive astmh.org 463 test will become very low. Continued quality assurance and training of reading photographic slide images of malaria parasites; and prepared laboratory technicians on RDTs and microscopy will be critical to maintain slides. There was a significant improvement in the mean post-test scores comparability of these two important diagnostic methods. for the written test from 38±9% to 71±12%. Mean post-test score for computer based picture speciation test (63±16%) and picture detection 1516 test (89.2±10.0) were significantly higher than the mean post-test score for slide reading speciation test (38±20%) and slide reading detection test USE OF MALARIA RAPID DIAGNOSTIC TESTING AND (70.7±15.3). The mean counting post-test score improved significantly ACCEPTABILITY OF RESULTS: AN ASSESSMENT AMONG from 4.2±8.0% to 27.9±14.0%. Parasite detection and speciation using MEDICAL LABORATORY SCIENTISTS IN NIGERIA enhanced visual imaging was significantly improved compared with using direct microscopy. Regular in-service training and provision of functional 1 1 2 Adolor Aisiri , Abiodun Ojo , Bolatito Aiyenigba , Oluwole and high resolution microscopes are needed to ensure quality malaria 2 3 Adeusi , Halima Mwenesi microscopy. 1Malaria Consortium/Malaria Action Program for States, Abuja, Nigeria, 2FHI360/MAPS, Abuja, Nigeria, 3FHI 360, Washington, WA, United States 1518 Confirming suspected cases of malaria through Rapid Diagnostic Tests REAL-TIME QUANTITATIVE PCR AS THE GOLD STANDARD (mRDT) is expected in secondary and tertiary health facilities when malaria microscopy is not feasible. Unavailability of trained microscopists, non- FOR MALARIA DIAGNOSIS: EVIDENCE FROM THE PERUVIAN availability of functional microscope and quality reagents, and in some AMAZON, A MALARIA HYPOENDEMIC REGION cases, high client load are challenges to quality malaria microscopy. Roberson Ramirez1, Lindsay Prado1, Mitchel Guzman1, Freddy Medical laboratory personnel sometimes question the validity of mRDT Gutierrez1, Jorge Sangama1, Dionicia Gamboa2, Joseph Vinetz3, results leading to their low use and acceptance. This study assessed the Alejandro Llanos-Cuentas2 perception of medical laboratory scientists on the validity and acceptance 1Laboratorio Satelite Iquitos, Universidad Peruana Cayetano Heredia and of mRDT results in secondary and tertiary health facilities in Nigeria. This University of California San Diego, Iquitos, Peru, 2Instituto de Medicina cross sectional study purposively sampled 66 medical laboratory scientists Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, attending a professional meeting. A pre-validated self-administered Lima, Peru, 3University of California San Diego, San Diego, CA, United questionnaire was used to assess attitude towards validity and acceptability States of results obtained through the use of mRDTs. The mean age of respondents was 43±8 years. The majority (98%) had heard of mRDT The diagnosis of malaria requires the identification of malaria parasites or but only 67% use mRDT in their health facility. Sixty four percent (64%) Plasmodium antigens/products in patient samples. While conventional agreed that mRDT results are valid and should be accepted by all health microscopy remains the gold standard, quantitative real time PCR (qPCR) care providers, however only 49% agreed that mRDT has specificity and despite technological and cost challenges remains an important tool for sensitivity levels comparable to microscopy. Although 83% of respondents quantification and confirmation of low density parasitemia and mixed agreed that mRDT results are useful for clinical decisions, 60% disagreed infections. With the goal of finding potential human reservoirs of malaria that mRDTs should be used in secondary and tertiary health facilities where transmission asymptomatic, clinically immune, Plasmodium-parasitemic microscopy is not feasible. Fifty percent claimed to have had challenges individuals_we compared qPCR (Plasmodium 18S rDNA target) to light using mRDTs and 26% were related to the discordance with microscopy microscopy on blood samples obtained from a longitudinal cohort of six results. A large majority, 94% agreed that mRDT use skills should be communities in the Peruvian Amazon. Of 7,494 samples 868 (11.6%) incorporated in the school curriculum for medical laboratory scientists. were positive by qPCR; of these, 73% were P. vivax, 27% P. falciparum. Distrust of mRDT results persist among medical laboratory scientist and By microscopy, only 320 (4.3%) were positive; 95% were P. vivax, 5%. may exist among other health care professionals. Integration of mRDT P. falciparum. Sensitivity and specificity of microscopy were 24% and training into medical professional curriculum should be advocated for, 17%, respectively, compared to qPCR. No mixed infections were detected to increase use and acceptance of mRDT results. The current in-service by either method. The 526 asymptomatic infections had very low parasite training on mRDT for primary health care workers should be strengthened density (16/µl; SD ± 18.47) detected only by qPCR. Most asymptomatic in secondary and tertiary health facilities in Nigeria. subjects (40%) were 30-50 years old. Compared to the light microscopy, qPCR or any other molecular tool, with appropriate quality controls, 1517 should be implemented at the public health level for monitoring programs and control of malaria. Further work to determine if treatment of qPCR- ASSESSMENT OF A STANDARD MALARIA MICROSCOPY positive/light microscopy-negative individuals has an impact on malaria is TRAINING PROGRAM ON THE PERFORMANCE OF MEDICAL important to carry out. LABORATORY SCIENTIST IN NIGERIA Abiodun Ojo1, Bolatito Aiyenigba2, Adolor A. Aisiri1, Oluwole 1519 Adeusi2, Halima Mwenesi3 DIAGNOSTIC TESTING AND ADHERENCE TO ANTIMALARIAL 1Malaria Consortium/Malaria Action Program for States, Abuja, Nigeria, MEDICATION: EVIDENCE FROM A RANDOMIZED 2FHI360/MAPS, Abuja, Nigeria, 3FHI 360, Washington, WA, United States CONTROLLED TRIAL IN UGANDA Rapid and precise diagnosis of malaria is an essential element in the Jessica L. Cohen, Indrani Saran effective case management and control of malaria. Malaria microscopy is Harvard T.H. Chan School of Public Health, Boston, MA, United States used as the gold standard for malaria diagnosis, however results remain poor as positivity rate is consistently over 90%. The President’s Malaria Artemisinin-combination therapies (ACTs), currently the only effective Initiative (PMI) through the Malaria Action Program for States in Nigeria treatment for malaria, have contributed to large declines in the morbidity supports 9 states to build capacity for malaria microscopy. This study and mortality burden of the disease over the past decade. Though it is a demonstrates the effectiveness of in-service training on malaria microscopy short 3-day treatment for malaria, 34 percent of patients do not complete amongst medical laboratory scientists. The training was based on WHO the full course of ACTs. This is not only harmful for the individual, but basic microscopy training manual. The training utilized a series of didactic also increases the risk of widespread pathogen resistance to the drugs. lectures and examination of quality teaching slides using a CX 21 Olympus Adherence to ACTs is complicated by the fact that, historically, both health binocular microscope. Purposive sampling was used to enroll 109 medical workers and patients have relied primarily on the patients’ symptoms to laboratory scientists across 5 states in Nigeria. Evaluation of the training diagnose malaria. Since the symptoms of malaria overlap with several using a pre and post-test method was based on: written test questions; other common diseases, patients are likely to be uncertain about whether astmh.org 464 they are actually suffering from malaria, which reduces the expected 1521 benefit of completing the treatment. We conducted a randomized controlled trial in Central Uganda to examine whether patients who A SEMI-QUANTITATIVE PAPER-BASED TEST FOR PREDICTING received a confirmed diagnosis of malaria, using a rapid diagnostic test PROGRESSION TO SEVERE MALARIA (RDT), are more likely to finish their medications. Among a sample of 1 2 2 1,525 patients purchasing ACTs at private drug shops, we randomly Chelsey Smith , Karl Seydel , Terrie Taylor , Rebecca Richards- 1 offered 573 (37%) a free malaria rapid diagnostic test and then visited all Kortum patients at their households three days later to assess whether they had 1Rice University, Houston, TX, United States, 2Michigan State University, completed the treatment. Of those who were offered and consented to East Lansing, MI, United States testing, 68% tested positive for malaria while, overall, 66% of patients Severe malaria affects thousands of children in sub-Saharan Africa finished the full course of drugs. Compared to those who were not offered annually, with the majority of these children under the age of five. the test, a positive malaria test did not increase the odds of completing the Parasites sequester in microcapillaries and cause hypoxia that may lead treatment, not even among young children for whom the risk of malaria to dysfunction of vital organs. Unless treatment is given quickly, severe mortality is highest. However, patients who received a positive malaria test malaria can lead to mortality or permanent complications for the child. had 25% fewer tablets remaining at the follow-up survey than those not Retinopathy and other suitable methods to predict progression to offered the test, indicating that a confirmed diagnosis encouraged some severe malaria are not feasible for low-resource settings due to cost and patients to complete a few additional doses of the drug. We also show infrastructure requirements. Additionally, the gold standard for malaria that patients who still felt unwell on the second day of treatment had diagnosis, blood smear microscopy, is not indicative of disease progression. approximately twice the odds of completing the treatment which suggests Recent studies have shown that plasma concentration of Plasmodium that many people may stop taking the medicines because they feel better falciparum histidine-rich protein 2 (pHPR2), a protein secreted by parasite- and believe that they are cured of malaria. infected erythrocytes, can identify children with uncomplicated malaria that might progress to severe malaria. We have developed a low-cost 1520 2D paper network which semi-quantitatively reports the concentration STRUCTURAL CHARACTERIZATION OF PLASMODIUM of pHRP2. The device works with one drop of whole blood, costs about 1 USD, and has a limit of detection of 10 ng/mL, which is lower than FALCIPARUM HRP2: ANALYTICAL CHALLENGES current RDTs on the market. It involves minimal user input and runs within IN PLASMODIUM FALCIPARUM HRP2-BASED IDT 30 minutes. Pilot tests have assessed the ability of the device to semi- DEVELOPMENT quantitatively differentiate levels of pHRP2 using spiked human blood Ihn Kyung Jang1, David Sullivan2, Maria Kahn1, Robert Burton1, from various donors. Once validated, our device could potentially allow for Paul LaBarre1 simultaneous diagnosis of malaria and prediction of progression to severe malaria. Therefore, we believe the test could provide clinicians with a low- 1PATH, Seattle, WA, United States, 2Johns Hopkins Malaria Research cost tool to make informed decisions for parasitemic children. Institute, Baltimore, MD, United States With improved performance over rapid diagnostic tests (RDTs), infection 1522 detection tests (IDTs) currently under development will provide improved diagnostic support for global Plasmodium falciparum (Pf) elimination IMPACT OF MALARIA RAPID DIAGNOSTIC TESTS ON PATIENT campaigns. By targeting Pf-specific histidine rich protein 2 (PfHRP2), which CARE: RESULTS FROM THE ACT CONSORTIUM persists several weeks in peripheral blood, prototype IDTs are designed to Katia Bruxvoort, Baptiste Leurent, Heidi Hopkins, ACT detect low-level and episodic Pf infections. Commercially available PfHRP2- Consortium RDTs in Context Working Group based RDTs have a high degree of variability in their clinical and analytical sensitivity. The naturally-occurring sequence variations of PfHRP2, London School of Hygiene & Tropical Medicine, London, United Kingdom especially the frequency and types of tandem amino acid repeats found Malaria rapid diagnostic tests (RDTs) are intended to have a beneficial in various isolates, may affect the performance of these tests, especially impact on management of suspected malaria, including that patients with at low levels of parasitemia. As we begin to characterize the performance confirmed malaria receive artemisinin-based combination therapy (ACT) of IDT prototypes in the product development pipeline, we recognize that and patients without malaria receive non-antimalarial treatment. The ACT evaluation of these tests using available PfHRP2 reference standards that Consortium includes several studies designed to test operational strategies are not equivalent to endogenous PfHRP2 may provide a relative, but not for ACT and RDT implementation in various settings, providing an truly definitive, quantitative measure of PfHRP2 test performance. The opportunity to draw on data from multiple projects that have introduced aim of the present study is to investigate the effects of the sequence and RDTs across a range of clinical, social, and epidemiological contexts, and in repeat number variation of PfHRP2 proteins on the binding of PfHRP2- public, private retail, and community health service sectors. To assess the specific antibodies, and to examine potential shortcomings of current impact of RDTs on patient treatment and satisfaction at the consultation, reference standards used for IDT test development. Recombinant PfHRP2 data were examined from nine studies comparing scenarios where RDTs proteins that possess or lack an affinity purification tag were evaluated for were made available to control scenarios where RDTs were not made binding to PfHRP2-specific antibodies in an in-house developed sandwich available. Where RDTs were introduced, the proportion of patients tested enzyme linked immunosorbent assay. Our preliminary data show that the ranged from 39% to 99%; figures were similar for children under 5 years detection limit of PfHRP2 proteins lacking an affinity purification tag is and for older patients. Prescription of ACT was lower in nearly all RDT much lower than for those carrying an affinity purification tag, indicating scenarios (range 8-64% versus 15-99% in scenarios without RDTs), driven that the extra unnatural amino sequence might hinder the access of mostly by reduced prescription for RDT-negative patients (range 3-45% antibodies to their epitopes. Evaluating the effect of PfHRP2 sequence versus 18-98% for RDT-positive patients). An exception to this pattern was variations on the binding of PfHRP2-specific antibodies used for IDTs is seen in public facilities in a high-transmission setting where RDTs were currently ongoing. The present study will provide new evidence to enable irregularly available in the control arm. The impact of RDTs on prescription rationale selection of reference standards in support of IDT development of systemic antibiotics varied, ranging from 15-73% in scenarios without for detecting low level Pf infections. RDTs and 21-75% in scenarios with RDTs available, and was slightly higher for RDT-negative patients (range 29-78% versus 13-65% for RDT-positive patients). There was no clear pattern observed for prescription of other treatments, polypharmacy, or patient satisfaction. This ongoing analysis

astmh.org 465 aims to understand factors associated with variation in case management distributed by the private sector, the public sector provides the majority outcomes in order to offer more tailored guidance for RDT introduction in of testing. The price of an mRDT among private sector outlets is generally other areas. higher than the price of a pediatric pre-packaged quality-assured artemisinin combination therapy (QAACT). However, the private sector 1523 price of an mRDT is generally lower than the price for one QAACT adult equivalent treatment dose. Confirmatory testing prior to antimalarial MODELLING THE COST-EFFECTIVENESS OF INTRODUCING treatment is currently limited across high burden countries in SSA due to MALARIA RAPID DIAGNOSTIC TESTS IN THE PRIVATE FOR- limited availability at the private sector outlets where most antimalarials PROFIT SECTOR are distributed. Where mRDTs are available, financial incentive to test before treating with QAACT is apparent with respect to adult testing and David Bath, Catherine Goodman, Clare Chandler, Shunmay treatment. There is generally no such incentive to test young children Yeung before QAACT treatment. Implications for policies and strategies to London School of Hygiene & Tropical Medicine, London, United Kingdom implement WHO and national guidelines on confirmatory malaria testing During the last five to ten years, major changes have occurred in the will be discussed. diagnosis of malaria in primary level public health facilities in endemic countries, as malaria rapid diagnostic tests (mRDTs) have been widely 1525 deployed. There are now increasing calls for mRDTs to be made available SUSCEPTIBILITY OF DIFFERENT STRAINS OF MICE TO outside formal public health facilities - and in particular through the private for-profit sector, where a high proportion of people with suspected malaria LIVER-STAGE INFECTION WITH PLASMODIUM BERGHEI seek care. Private sector antimalarial providers include private hospitals and SPOROZOITES BY USING IN VIVO IMAGING SYSTEM clinics, though in most settings the majority of antimalarials are distributed Qigui Li, Lisa Xie, Diana Caridha, Qiang Zeng, Norma Roncal, Jing through drug retailers, primarily drug stores and small pharmacies, which Zhang, Ping Zhang, Lisa T. Read very rarely provide blood tests. It is common to find that a high proportion Walter Reed Army Institute of Research, Silver Spring, MD, United States of patients sold antimalarials at such outlets are not parasite positive, while many other clients who are parasite positive do not receive appropriate The liver stages of Plasmodium parasites are important targets for the antimalarial treatment. Private sector mRDT introduction on a large scale discovery and development of prophylactic drugs. A sensitive and useful has already begun in several African countries, though robust evidence mouse model with an in vivo imaging system (IVIS) to monitor the liver on the impact and value for money of these strategies is not yet available. stage was established. The transgenic P. berghei parasite expressing Fundamental questions remain as to where and how mRDTs should the bioluminescent reporter protein luciferase was utilized to visualize be introduced, and what the impact will be on costs, individual health and quantify parasite development in BALB/c, C57BL/6, C57BL/6 albino, outcomes and public health. We have developed a cost-effectiveness C3H, and ICR mice. These inbred strains of mice were tested to study the decision tree model of management of non-severe febrile illness, adapting differences in susceptibility to P. berghei hepatic infections previously and expanding previous models to cover the private sector, and updating monitored with the liver resection methods. As an additional endpoint, them by drawing on parameters from recent published and unpublished blood stage parasitemia was monitored by flow cytometry. A real-time data. The model documents care-seeking pathways, test accuracy, and IVIS instrument determined the exposure level of luminescence measured the effect of test results on treatment choice and adherence to treatment. from luciferase expressing of sporozoites through development in the Results will be presented on the impact on treatment outcomes, costs, hepatocyte and assessed through liver, peritoneum, skin, and hair and cost effectiveness of different mRDT roll-out packages, for those with coat. The luminescence values (photon counts/min) measured from malaria and those with other febrile illnesses. Cost-effectiveness will be the anatomical liver location in untreated mice infected with 10,000 P. reported in terms of cost per disability adjusted life year (DALY) averted berghei sporozoites at 24 hours post inoculation were 8.15 x 105 for and cost per death averted. The overall cost implications for implementing C57BL/6 albino, 2.12 x 105 for C3H, 0.91 x 105 for C57BL/6 WT, 0.58 x 105 agencies, across a range of malaria transmission and health system for BALB/c, and 0.08 x 105 for ICR. The high grow-up rate of sporozoites settings, will also be discussed. in hepatocytes was also found in C57BL/6 albino, C57BL/6 WT, and C3H mice, and low rate was shown in BALB/c and ICR mice. In addition, similar 1524 to previous studies, the susceptibility of female mice to liver-stage infection is higher than that of male mice. In summary, this data supported the MALARIA RAPID DIAGNOSTIC TEST MARKET TRENDS IN use of highly susceptible mouse strains (C57BL/6 albino, C57BL/6 WT, SUB-SAHARAN AFRICA, 2009-2014 and C3H) at the WRAIR to study Plasmodium hepatic infection by IVIS monitoring. The study indicates that by using IVIS, the C57BL/6 albino, Megan Littrell, The ACTwatch Group C57BL/6 WT, and C3H mice infected with P. berghei sporozoites are Population Services International, Washington, DC, United States preferable for investigating the discovery and development of prophylactic In 2012, the WHO launched the Test, Treat, Track initiative recommending antimalarial drugs. confirmatory testing prior to antimalarial treatment. National malaria control programs (NMCP) across sub-Saharan Africa (SSA) subsequently 1526 aligned national guidelines with this recommendation. Strategies to scale up testing using malaria rapid diagnostic tests (mRDT) were introduced NICOTINAMIDE ENHANCES ANTIMALARIAL EFFECTS OF by NMCPs. We use multi-country outlet survey data collected between CHLOROQUINE, PYRIMETHAMINE AND ARTEMISININ IN 2009-2014 by ACTwatch to describe mRDT markets in Benin, the DRC, VITRO Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia. A census of Sergey O. Tcherniuk*, Olga Chesnokov*, Irina V. Oleinikov, outlets with potential to distribute antimalarials was conducted among a Andrew V. Oleinikov representative sample of administrative units. In addition to an antimalarial Charles E. Schmidt College of Medicine, Department of Biomedical audit, information was captured for malaria microscopy and all mRDTs Science, Florida Atlantic University, Boca Raton, FL, United States in stock including retail price and amount distributed in the past week. The private sector distributes the majority of antimalarials in all project Malaria is a dangerous infectious disease of humans and other countries except Zambia. Although modest improvements in mRDT animals caused by protozoan microorganisms belonging to the genus availability have occurred, testing availability among antimalarial-stocking Plasmodium. The malarial parasite causes different symptoms including private sector outlets remains low, ranging from 4% in Madagascar fever, fatigue, vomiting, headaches, yellow skin, seizures and even death. to 25% in Uganda. Subsequently, while majority of antimalarials are Plasmodium falciparum represents the most virulent form of human astmh.org 466 malaria, causing about a half million deaths per year. Despite the attempts 1528 to develop various antimalarial vaccines, chemotherapy is still a major approach of malaria prevention and treatment. Systematic use of common DIFFERENTIAL KINETIC PROFILES AND METABOLISM OF antimalarial drugs together with the high genetic variability of the PRIMAQUINE ENANTIOMERS BY HUMAN HEPATOCYTES malaria parasite leads to the appearance of resistant Plasmodium strains. 1 1 2 Therefore, identification and development of new antimalarial compounds Pius S. Fasinu , Bharathi Avula , Babu L. Tekwani , Dhammika 1 1 1 and treatments remains an important problem of malarial parasitology. Nanayakkara , Yan-Hong Wang , Bandera Herath , Narayan 1 2 3 2 Nicotinamide (vitamin B3) is a water soluble amide derivative of nicotinic Chaurasiya , Ikhlas Khan , Mahmoud ElSohly , Shabana Khan , 2 acid, which has been used at high doses for a variety of therapeutic Larry Walker applications. It has been demonstrated earlier that nicotinamide inhibits P. 1National Center for Natural Products Research, School of Pharmacy, falciparum growth. However, its antimalarial effect, in combination with University of Mississippi, University, MS, United States, 2National Center other antimarial drugs, has not been described to our knowledge. In this for Natural Products Research; and Department of Biomolecular Sciences, work, we analysed the antimalarial effects of nicotinamide in combinations School of Pharmacy, University of Mississippi, University, MS, United with chloroquine, pyrimethamine and artemisinin on the blood stages of States, 3National Center for Natural Products Research; and Department of P. falciparum. Our results demonstrate that combinations of nicotinamide Pharmaceutical Sciences and Drug Delivery, School of Pharmacy, University with chloroquine, pyrimethamine or artemisinin lead to synergetic of Mississippi, University MS; and ElSohly Laboratories, Oxford, MS, United antimalarial effects in vitro and significantly enhance the anti-parasite States potential of these drugs. Moreover, treatment of uninfected red blood cells The clinical utility of primaquine (PQ), which is used as a racemic mixture with high dose of nicotinamide (20 mM) does not provoke LDH release, of two enantiomers, is limited due to metabolism-linked hemolytic toxicity demonstrating its non-toxicity for erythrocytes. These results suggest that in G6PD deficient individuals. The current study aimed to investigate nicotinamide might be useful not only as a vitamin supplement but also differential metabolism of the enantiomers in light of the suggestions that as a strong enhancer of the anti-parasitic effect of common antimalarial toxicity and efficacy might be largely enantioselective. Using cryopreserved drugs, including chloroquine, pyrimethamine and artemisinin. *Equal human hepatocytes, 13C-labeled (+)-, (-)- and (±)-PQ were separately contributions incubated. Substrate depletion and metabolite production were monitored via UHPLC-MS/MS. The initial half-life was 217 and 65 min for (+)- and (-)- 1527 PQ; with an elimination rate constants ( ) of 0.19 and 0.64 h-1 respectively. DEVELOPMENT OF ANTIMALARIALS WITH SERCAP PROFILE The in vitro intrinsic clearance was 2.55 and 8.49 (µL/min)/million cells which when upscaled in vivo yielded 6.49ʎ and 21.6 (mL/min)/kg body FROM DOS DERIVED COMPOUNDS mass respectively for (+)- and (-)-PQ. Extrapolation to in vivo human Eamon Comer1, Nobutaka Kato1, Jessica Bastien1, Timothy Lewis1, hepatic clearance was performed using the well-stirred liver model. The Morgane Sayes1, Tomoyo Sakata-Kato2, Amanda Lukens2, Sean rate of hepatic clearance of (+)-PQ was only 45% that of (-)-PQ. Two major Eckley3, Fabian Gusovsky3, Jeremy Duvall1, Marshall Morningstar1, primary routes of metabolism were observed as earlier reported: oxidative Dyann Wirth2, Christina Scherer1, Stuart Schreiber1 deamination of the side chain terminal amine; and hydroxylations on the 1The Broad Institute, Cambridge, MA, United States, 2Harvard School of quinoline moiety. The major deaminated metabolite, carboxyprimaquine Public Health, Boston, MA, United States, 3Eisai Inc., Andover, MA, United (cPQ), a putative PQ terminal alcohol (m/z 261), a cyclized side chain States derivative from the aldehyde (m/z 241), cyclized carboxylic acid derivative (m/z 257), a quinone-imine product of hydroxylated cPQ (m/z 289), cPQ Despite increased efforts in the last decade, the antimalarial drug glucuronide (m/z 451), and the glucuronide of PQ alcohol (m/z 437) were discovery and development pipeline still lacks compounds with non- preferentially generated from the (-)-PQ. The major quinoline oxidation erythrocyte stage activity and target diversity. We previously performed product (m/z 274) was preferentially generated from (+)-PQ. A prominent a high throughput screen (HTS) on approximately 100,000 diverse conjugate (m/z 422) (seemingly a glycosylated PQ, but still under small molecules from the Broad Institute’s Diversity Oriented Synthesis investigation) was preferentially generated by (+)-PQ. An accumulating compound collection which contains unique core structures more likely metabolite (m/z 480) thought to be a carbamoyl glucuronide of PQ was to have novel antimalarial mechanisms of action. The present study exclusively generated from (+)-PQ. In the light of the desire to establish describes the discovery and optimization of a novel series from our clinical differences in PQ enantiomers, these current findings may provide HTS study displaying potent activity against a panel of clinical strains important information that may lead to clearer understanding of PQ- harboring resistance to known antimalarial drugs as well as agents in induced hemolysis and possible enantioselective safety. clinical development. The compound series inhibits phenylalanine t-RNA synthetase activity, a novel molecular target, and shows robust in vivo 1529 efficacy in erythrocytic, hepatic and sexual stages with a single dose. We also present extensive pharmacokinetic and preclinical safety data that NITRIC OXIDE DONOR DIHYDROARTEMISININ DERIVATIVES supports the progression of this novel antimalarial agent towards clinical AS MULTITARGET AGENTS FOR THE TREATMENT OF development to treat malaria. CEREBRAL MALARIA Massimo Bertinaria1, Pamela Orjuela-Sanchez2, Elisabetta Marini1, Anthony Hofer2, Stefano Guglielmo1, Graziela M. Zanini3, John Frangos2, Roberta Fruttero1, Alberto Gasco1, Leonardo J. Carvalho3 1Universita di Torino, Torino, Italy, 2La Jolla Bioengineering Institute, La Jolla, CA, United States, 3Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil A series of hybrid products in which the dihydroartemisinin scaffold is combined with NO-donor furoxan and NONOate moieties were designed, synthesized and studied as potential tools for the treatment of experimental cerebral malaria (ECM) in C57BL/6 mice infected with Plasmodium berghei ANKA. Five synthesized products were able to dilate rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism. All hybrid compounds showed preserved antiplasmodial activity in vitro and in vivo against Plasmodium berghei ANKA, astmh.org 467 comparable to artesunate. Compound 8, selected for additional studies, protection of liver stage infection at comparable dosage with primaquine. was capable of increasing survival of mice with late-stage ECM from Details of the design, chemistry, structure-activity relationships (SAR), 33.3% to 63.6% compared with artemether. Artemisinin-NO-donor hybrid safety, metabolic studies, and mechanism of action will be presented. compounds show promise as potential new drugs for treating cerebral malaria. 1532 1530 PROVEBLUE (METHYLENE BLUE): A PROMISING ANTIMALARIAL DRUG DIFFERENTIAL DECAY OF ANTIMALARIAL ACTIVITY OF 1 1 1 ARTEMISININ AND ITS DERIVATIVES WHEN INCUBATED IN Bruno Pradines , Jérôme Dormoi , Marylin Madamet , Bécaye Fall2, Rémy Amalvict1 PHYSIOLOGICALLY RELEVANT CONDITIONS 1Institut de Recherche Biomédicale des Armées, Brétigny sur Orge, France, Silvia Parapini1, Donatella Taramelli1, Piero Olliaro2, Nicoletta 2Hôpital Principal de Dakar, Dakar, Senegal Basilico1 In 2011, the World Health Organization recommended artesunate as the 1University of Milan, Milan, Italy, 2UNICEF/UNDP/World Bank/World Health first-line treatment for severe malaria. In recent years, several studies have Organization Special Programme on Research and Training in Tropical reported clinical failures or at least extended parasite clearance times in Diseases, World Health Organization, Geneva, Switzerland Asia. There is an urgent need to discover partners for combination with Artemisinins are peroxidic antimalarial drugs which are known to be artemisinin derivatives. Proveblue (PVB) (international patent no. PCT/ very potent, yet chemically highly unstable: they degrade quickly in the FR/2007/001193), which is a methylene blue preparation that complies presence of ferrous iron, Fe(II)-heme or biological reductans. Less known with the European Pharmacopoeia and contains limited organic impurities is how their chemical decay relates to antimalarial activity. We incubated and heavy metals of recognized toxicity, was demonstrated to possess dihydroartemisinin (DHA) and artemisinin (ART) in a range of conditions in vitro antimalarial activity (at a geometric mean 50% inhibitory relevant to both treated patients and in-vitro assays (PBS, plasma or concentration [IC50] of 3.62 nM) against 23 Plasmodium falciparum erythrocytes lysate for different durations and pHs) and measured their strains that were resistant to various other antimalarials. The IC50 for PVB residual activity on P. falciparum in vitro using the pLDH method. ranged from 0.88 nM to 40.2 nM with a mean of 5.3 nM in Senegalese Chloroquine was also used to verify if drug instability was related to the isolates collected from November 2013 to January 2014 at the Hôpital presence of the endoperoxide. A significant reduction of the antimalarial Principal de Dakar. PVB exhibited noticeable in vitro synergistic effects activity of DHA was observed after incubation in plasma or serum, and in combination with mefloquine and quinine and high synergistic effects to a lesser extent in erythrocytes lysate or PBS. ART showed a different associated with dihydroartemisinin, the active metabolite of artemisinin behavior: its antimalarial activity was significantly reduced by incubation derivatives. Treatment with 1 to 10 mg/kg of weight of PVB for five with erythrocytes lysate but was minimally affected by PBS, plasma or days significantly reduced or prevented cerebral malaria in mice. PVB serum. Moreover, the serum-enriched medium (10% human serum or demonstrated high efficacy in cerebral malaria in comparison with 10% albumax) customarily used for in vitro cultures also affected DHA, dihydroartemisinin or quinine. These results confirm the therapeutic and to a lesser extent, ART efficacy. Decreasing pH from 7.6 to 7.2 led potential of Proveblue, which could be integrated into the pipeline of new to a decrease in artemisinins degradation and this increased activity. The antimalarial combination therapies. presence of reductans such as ascorbic acid or N-acetylcysteine in the erythrocytes lysate strongly reduced artemisinins activity and CO binding 1533 to Fe(II)-heme conferred partial protection. Adding ascorbic acid to plasma had no effect on artemisinins activity. Chloroquine was unaffected in any RESISTANCE SELECTION APPROACH TO IDENTIFY AND of the tested in vitro conditions. Biological results correlated well with VALIDATE TARGETS FOR ANTIMALARIAL DRUG DISCOVERY chemical degradation quantified as degradation rate constant. These Pamela Magistrado1, Tomoyo Sakata-Kato1, Amanda K. Lukens2, results suggest that instability is likely due to the endoperoxide, but C10 Victoria C. Corey3, Maria Linares Gomez4, Francisco-Javier Gamo4, substitutions can further modulate the stability of the molecules. Particular Elizabeth A. Winzeler3, Dyann F. Wirth1 care should to be taken in conducting and interpreting in vitro studies, 1 and in storing these compounds. Moreover, conditions such as hemolysis Harvard T. H. Chan School of Public Health, Boston, MA, United States, 2 3 or acidosis associated with malaria severity may contribute to artemisinins The Broad Institute, Cambridge, MA, United States, University of instability and reduce its effectiveness. California San Diego School of Medicine, La Jolla, CA, United States, 4GlaxoSmithKline, Tres Cantos, Spain 1531 The emergence and spread of drug resistance to current antimalarial therapies remains a pressing concern, escalating the need for compounds LEAD CANDIDATE SELECTION OF BROAD-SPECTRUM that demonstrate novel modes of action and prevent the development ANTIMALARIAL ACRIDONES of drug-resistance. As part of the Malaria Drug Target Identification Jane X. Kelly1, Rosie Dodean1, Christina Nolan2, Yuexin Li1, Qiqui Project efforts, we have adopted a chemogenomic approach to identify Li2, Sean Marcsisin2, Paul Olmeda2, Thulan Long2, Heather Gaona2, the targets of the most prominent compounds from chemically diverse Diana Caridha2, Lisa Xie2, Norma Roncal2, Brittney Potter2, Isaac libraries. Study compounds were selected based on availability, purity, Forquer1, Rolf Winter1, Dave Hinrichs1, Stephanie Huezo3, Roland potency in a multi-drug resistant isolate, and lack of known mechanism Cooper3, Mike Riscoe1, Lisa Read2 of action towards the mitochondrion or folate biosynthesis. To further eliminate overlap with known targets, we performed cross-resistance 1Portland Veterans Affairs Medical Center, Portland, OR, United States, testing against a panel of drug resistant parasite lines with well- 2Walter Reed Army Institute of Research, Silver Spring, MD, United States, characterized mutations in diverse targets. Here we present studies of two 3Dominican University of California, San Rafael, CA, United States molecules: a drug-like compound from the Malaria Box, MMV007564, We have previously reported the discovery of a novel antimalarial acridone and a probe-like molecule from a Diversity Oriented Synthesis library, chemotype that displays efficacy against sporozoite-induced Plasmodium BRD3842. In vitro resistant lines were generated by single-step selection infection in addition to efficacy against blood stage parasites. We have and whole genome sequencing employed to identify genetic variants been successful in producing extremely potent new lead candidates with contributing to the resistance phenotype. Novel variants were identified pico molar IC50 values against MDR resistant parasites, as well as full in the Pf cyclic-amine resistance locus (PfCARL) (MMV007564), and the phosphatidylinositol-4-OH kinase (PI(4)K) (BRD3842), both of which have been previously implicated in the mechanism of action for compounds astmh.org 468 chemically distinct from those in this study. These results demonstrate metabolites and glucuronide conjugates. This pathway determines that multiple chemical classes are able to inhibit common parasite targets characteristic pharmacokinetic and pharmacodynamic properties of PQ. and suggest that there are a limited number of pathways in the parasite Another pathway mediated through CYPs (predominantly CYP2D6) susceptible to inhibition and/or that contribute to drug-resistance. generates multiple mono hydroxylated metabolites. CYP2D6 mediated Drug-development strategies that counteract these common escape oxidation of PQ occurs at different positions on the quinoline ring. An mechanisms may therefore become invaluable in extending the usable orthoquinone product of a hydroxyl product 5-OH-PQ was identified as lifetime of future therapies. the major CYP2D6 metabolite, a likely marker for the 5-hydroxylation pathway. Pharmacological studies suggest 5-OHPQ as highly reactive 1534 and may be responsible for the efficacy/toxicity of PQ. Direct metabolism of PQ through phase II glucuronide conjugation and excretion in urine TARGETING FREP1 TO BLOCK MALARIA TRANSMISSION was also observed. Critical analyses of these pathways have helped in THROUGH SMALL MOLECULES understanding the mechanism of efficacy and toxicity of PQ Guodong Niu, Genwei Zhang, Jarrod B. King, Robert H. Cichewicz, Jun Li 1536 The University of Oklahoma, Norman, OK, United States A PROTOCOL TO EVALUATE THE EFFECTIVENESS Inhibiting Plasmodium development in mosquitoes will block malaria AND FEASIBILITY OF REACTIVE TARGETED PARASITE transmission. Fibrinogen-related protein 1 (FREP1) has been demonstrated ELIMINATION (TPE) TO REACTIVE CASE DETECTION (RACD) to be critical for parasite infection in mosquitoes. Here, we further AS A COMMUNITY LEVEL INTERVENTION IN SWAZILAND determined that FREP1 protein binds P. falciparum-infected red blood Bongani A. Dlamini1, Mi-suk Dufour2, Nomcebo Mkhonta3, cells (iRBCs) and ookinetes. We propose that small molecules disrupting Calisile Malambe3, Gugu Mphalala4, Nyasatu Ntshalintshali1, the interaction between FREP1 and Plasmodium will prevent parasites Danica Helb5, Bryan Greenhouse6, Kimberly Batzell7, Hugh from infecting mosquitoes. To test this hypothesis, we developed an Starrock5, Grant Dorsey7, Deepika Kandula8, Justine M. Cohen8, ELISA-based method to screen a fungal extract library, and obtained one Arnaud LeMenach8, Roly Gosling5, Simon Kunene3, Michelle candidate fungal extract (Chapel SA-3) that inhibited about 98% of the Hsiang5 FREP1-Plasmodium interaction. The inhibition was further confirmed by 1 2 indirect immunofluorescence assays (IFA). We also verified the inhibition Clinton Health Access Initiative, Mbabane, Swaziland, University of 3 specificity between FREP1 and Plasmodium. Notably, feeding Chapel SA-3 California San Francisco, San Francisco, CA, United States, National 4 to mosquitoes significantly inhibits P. falciparum infection in midgut. The Malaria Control Programme, Manzini, Swaziland, Swaziland National 5 candidate fungal extract does not affect the development of P. falciparum Clinical Laboratory Services, Mbabane, Swaziland, Malaria Elimination gametocytes or ookinetes. Therefore, we conclude that disruption of the Initiative, Global Health Group, University of California San Francisco, 6 interaction between FRPE1 and Plasmodium effectively reduces malaria San Francisco, CA, United States, Department of Medicine, University of 7 infection in mosquitoes. Targeting FREP1 with fungal small molecules is California San Francisco, San Francisco, CA, United States, Department thus an effective novel approach to block malaria transmission. of Family Health Care Nursing, University of California San Francisco, San Francisco, CA, United States, 8Clinton Health Access Initiative, Boston, MA, 1535 United States Reactive case detection (RACD), which is testing and treatment of HUMAN PATHWAYS FOR METABOLISM OF PRIMAQUINE: individuals residing near passively detected index cases, is recommended IMPLICATIONS IN TOXICITY AND EFFICACY OF for malaria elimination yet some available diagnostics have limited 8-AMINOQUINOLINE ANTIMALARIALS sensitivity and there are logistical challenges including cost. Treatment without testing or targeted parasite elimination (TPE) may be a more Babu L. Tekwani1, Bharathi Avula1, NP. Dhammika Nanayakkara1, effective and feasible approach for reducing and interrupting transmission. Narayan D. Chaurasiya1, Pius Fasinu1, HMT Bandara Herath1, As an operational research study embedded into malaria program Shabana I. Khan1, Ikhlas A. Khan1, Mahmoud A. ElSohly1, Brandon activities, we plan a cluster-randomised control study design trial to S. Pybus2, Jason C. Sousa2, Sean R. Marcsisin2, Gregory A. evaluate reactive-TPE in the low transmission setting of Swaziland. Reichard2, James D. McChesney3, Larry A. Walker1 The primary aim is to compare the impact of reactive TPE versus RACD 1 2 University of Mississippi, University, MS, United States, Walter Reed on malaria incidence, with a hypothesis that TPE will result in lower 3 Army Institute of Research, Silver Spring, MD, United States, Ironstone cumulative malaria incidence. A total of 58 high risk localities or clusters Separations, Inc, Eta, MS, United States will be included in the trial (population 124,737) and randomized to Primaquine (PQ), an 8-aminoquinoline, is the drug of choice for the radical either TPE or RACD. Over 2 years, individuals residing within a radius of cure of Plasmodium vivax malaria and utility for prevention of malaria 200 m from an index case will be targeted for either RACD or TPE within transmission. Efficacy and hemolytic toxicity of PQ have been attributed to 1 week of index case presentation. Incidence will be measured using the metabolites. Reactive nature and low quantities pose major challenge passive surveillance with subsequent household follow up to identify for identification and quantification of these metabolites in clinical and which cluster the index case resides in. The study is powered to detect experimental studies. We have recently addressed this challenge with a difference in cumulative incidence of 1.1/1000 in the TPE arm versus application of PQ labeled with 13C-stable isotope and analysis of the 2.2/1000 in the RACD arm observed in 3 previous malaria seasons in metabolites with UPLC integrated with QTOF-MS. Chemical synthesis of RACD study area. Secondary outcome measures of effectiveness will key metabolites have provided necessary standards for confirmation of include: seroprevalence and prevalence (in a cross sectional survey at the structures and quantification. Comprehensive experimental and clinical end of the study), proportion of imported incident cases, and transmission studies with primary human hepatocytes, the recombinant human potential (utilizing genotypes). Secondary outcome measures of feasibility enzymes (CYPs and amine oxidases) and healthy human volunteers along will include: coverage, adherence, serious adverse events, acceptability, with use of specific enzyme inhibitors have been useful in phenotyping and cost-effectiveness. Findings will inform malaria elimination strategies of key PQ metabolites and their relative quantification. The results have for Swaziland and other countries pursuing malaria elimination. been utilized for prediction of pathways for metabolism of PQ. Human metabolism of PQ follows two distinct pathways. The major pathway is initiated by oxidative deamination of PQ by monoamine oxidase B to carboxy PQ. Carboxy PQ is further metabolized through CYP mediated pathways and phase II metabolism generating reactive quinoneimine astmh.org 469 1537 review are: results from prototype IDT evaluation; an update on regulatory pathways; an assessment of HRP2 issues that impact standard selection; a SEASONAL VARIATION IN ACCESSING BIOMEDICAL revised market assessment; and an updated target product profile. HEALTHCARE FACILITIES IN AN AREA OF LOW MALARIA TRANSMISSION IN RURAL ZAMBIA: POTENTIAL IMPACT ON 1539 MALARIA ELIMINATION PROGRAMS THAT USE REACTIVE PRIVATE SECTOR SURVEILLANCE AND RESPONSE: LESSONS CASE FINDING FROM WESTERN CAMBODIA Lynne Lohfeld1, Jailos Lubinda2, Timothy Shields3, Southern Africa ICEMR Group Soy Ty Kheang 1McMaster University, Hamilton, ON, Canada, 2Macha Research Trust, University Research Co., LLC, Bethesda, MD, United States Macha, Zambia, 3Johns Hopkins University, Baltimore, MD, United States Tracking data on malaria cases treated by Cambodian public health Many malaria elimination programs use reactive case finding or diagnose facilities (HFs) and village malaria workers (VMWs) is part of routine and treat malaria in symptomatic patients presenting at a biomedical surveillance. However, patients who first present to private providers healthcare facility and then track asymptomatic cases living in the vicinity remain largely untracked and unreported, limiting effective planning of an index case. The premise behind these programs is they are less and monitoring of national malaria control efforts. Data from a national expensive than communitywide mass diagnosis and treatment campaigns. health survey suggests 75% of recipients prefer seeking treatment from However, if symptomatic patients are unwilling or unable to travel to a the private sector due to perceptions of prompter service and constant biomedical facility for the initial diagnosis, the program cannot effectively availability. The National Strategy for Public and Private Mix (PPM) directs cut transmission due to missed pockets of asymptomatic carriers. private providers in endemic areas where no drug resistance has been Anecdotal evidence indicates that in the low-transmission area of Macha, documented (zone 2) to provide early diagnosis and treatment. However, Choma District, Southern Province, Zambia, people are less able to reach private providers in areas where drug resistance has been documented a government health center or regional hospital during the heavy rainy (zone 1) can test, but must refer cases to a public HF or VMW. Private season, which coincides with the period of highest malaria transmission. providers must report all suspected malaria cases (diagnosed, treated or We tested this hypothesis through transforming interview data on all referred) to the national malaria information system. Private providers pathways and routes used in the dry and rainy seasons to reach local taking part in PPM gain access to supplies available at local HFs. The healthcare providers (biomedical and traditional) in four villages into GPS Control and Prevention of Malaria (CAP-Malaria) Project strengthens coordinates and maps. Additional information on the highest level of linkages between public and private providers and improves the quality of use (footpath, bicycle, motorcycle, oxcart or car/truck), and average time care provided by the private sector. The project works with 167 registered needed to reach providers was used to calculate signficant differences in private providers in 3 operational districts (ODs) in Western Cambodia, access to biomedical resources providing malaria diagnosis and treatment. engaging them in public sector response. In 2014, 114 suspected malaria Results can help identify communities where environmental factors serve patients in zone 1 were referred from 56 private providers to HFs and as barriers to accessing a government-run malaria elimination program in VMWs. 102, (89%) reached the designated service points; of those, 93 an area of very low transmission. patients (91%) were diagnosed with malaria. In Sampov Meas (zone 2), 2,733 suspected patients were tested and 1,574 were found malaria positive and treated by private providers while 2,852 were tested and 1538 1,112 found positive at public HFs. In comparison, 39%, 27% and 34% NEW INFECTION DETECTION TESTS TO ENABLE of malaria cases in Sampov Meas were managed by private providers, IDENTIFICATION OF LOW DENSITY INFECTIONS: THE ACCESS public HFs and VMWs, respectively. Recognizing the strong role of the FRAMEWORK private sector, CAP-Malaria, with the provincial health department and ODs, engaged private sector partners in a campaign for intensive health Jenny Richards1, Robert Burton1, Katherine Imus Misiuda1, education, net distribution, and active case detection. Kendall Magnuson1, Smita Das1, Ihn Kyung Jang1, Bhavya Gowda2, Rebecca Barney1, Paul LaBarre1 1540 1PATH, Seattle, WA, United States, 2PATH, Washington, DC, United States INCREASING ACCESSIBILITY OF MALARIA SERVICES AMONG As malaria prevalence declines due to successful malaria control programs, CROSS-BORDER POPULATIONS IN THE GREATER MEKONG more sensitive diagnostic tests are need to identify an increasing number SUB-REGION of low-density infections that contribute to the infectious reservoir. PATH’s Diagnostics for Malaria Elimination towards Eradication (DIAMETER) team Soy Ty Kheang is committed to enabling access to the most appropriate diagnostic tools University Research Co., LLC, Bethesda, MD, United States to support malaria elimination, bridging the gap between rapidly evolving elimination tactics and diagnostic capabilities. As the managing partner While malaria morbidity and mortality have declined significantly in the for the Bill & Melinda Gates Foundation-funded Infection Detection Test Greater Mekong Sub-region countries, the emergence and spread of (IDT) Development Initiative, the DIAMETER team is working to create artemisinin-resistant malaria (ARM) in border areas has raised alarm. A a high quality, low cost, easy to use, and highly sensitive Plasmodium potential source of transmission and a cause of the spread of resistant falciparum (Pf)-specific HRP2 IDT capable of identifying low density parasites in the region is population mobility. Cross-border workers often Pf infections that current rapid diagnostic test cannot detect. In this have limited knowledge of malaria risk, making them highly vulnerable poster, we will review progress on the IDT’s development and outline to malaria. Because many are unfamiliar with the local health services, next stages in the product development value chain, focusing on the they may not seek services and thus remain untreated and unknown by transition from technical feasibility phase to operational feasibility and health authorities, inadvertently carrying the parasite from one country product development. We will identify remaining questions and propose to another. To improve accessibility of malaria services by cross-border a plan to resolve these while advancing the IDT toward commercialization populations in the GMS countries, the Control and Prevention of Malaria and impact. Finally, we will review remaining challenges and outline key Project (CAP-Malaria) is engaging local authorities along the borders elements of the access framework including manufacturing, forecasting, between Cambodia, Thailand, and Myanmar through a Twin-Cities procurement, distribution, delivery, and governance. Included in this approach that aims to increase coordination of activities and contain the spread of ARM. With the project’s support, Twin-Cities working groups were established in four pairs of cities located across a border, engaging representatives from the district level, from health facilities, and from astmh.org 470 among community-based malaria workers. The working groups meet on reported by 294 of 298 municipalities between 2003 and 2013, were a quarterly basis to share data on malaria, discuss and develop joint work combined with social, demographic, and ecological variables in a Bayesian plans, and monitor implementation of activities. The groups also conduct hierarchical model to predict incidence by municipality and year. Incidence exchange visits and maintain a map of health service delivery points along was predicted because of the potential for underreporting. Predicted the border areas to facilitate access to services. Health providers in the incidence in 2013 was compared with reported incidence, used to estimate area take advantage of bilingual malaria control materials developed by the population at risk, and used to evaluate the spatial distribution of the CAP-Malaria Project. Preliminary observations suggest that the Twin- malaria interventions. Highest risk of malaria was concentrated in the cities approach improves awareness of malaria among mobile and migrant Northeast along the border with Nicaragua. In 2013, predicted incidence populations, facilitates their access to malaria services, and promotes a was highest in two of the 294 municipalities, Wampusirpi (32 cases/1000 supportive environment for quality services. It also holds the potential for persons) and Puerto Lempira (18 cases/1000 persons), in which predicted improved coordination at the local level, coordination that is critical should incidence was higher and lower than reported incidence, respectively. the spread of ARM be contained. These two municipalities were expected to account for a third of all malaria cases and 0.5% of the total population in Honduras. Higher 1541 incidence was associated with lower elevation, greater distance to roads and rivers, and distribution of long-lasting insecticide treated nets (LLINs). ENGAGING THE PRIVATE SECTOR IN MALARIA In 2013, LLINs were targeted to high-risk municipalities in the Northeast, SURVEILLANCE: A REVIEW OF STRATEGIES AND while indoor residual spraying was targeted to low and medium risk RECOMMENDATIONS FOR ELIMINATION SETTINGS municipalities in other regions of the country. Focusing interventions, improving case management, and implementing active surveillance in Anton Lorenzo Villacorte Avancena municipalities at highest risk, may help reduce the burden of malaria in University of California San Francisco, San Francisco, CA, United States Honduras. Predictions based on aggregate case data can be used to direct In malaria elimination settings, all malaria cases must be identified, malaria resources. However, these predictions are still coarse in resolution. documented, and investigated. To facilitate complete and timely reporting Georeferenced case reports from a strong passive surveillance system could of all malaria cases and effective case management, engagement be used to target malaria elimination activities even further. with private providers is essential, particularly in settings where the private sector is a major source of healthcare. Research on the role and 1543 performance of the private sector in malaria case management and PRELIMINARY RESULTS FROM THE BIOMARKERS FOR reporting is limited. Moreover, effective strategies for private sector engagement in malaria diagnosis, treatment, and reporting in elimination MALARIA ELIMINATION (BIOME) STUDY settings remain unclear. A purposive sample of 21 key informant experts Paul LaBarre, Smita Das, Robert Burton, Ihn Kyung Jang, in malaria elimination, surveillance, and private sector engagement were Katherine Imus Misiuda interviewed. An extensive review of grey and published literature on PATH, Seattle, WA, United States malaria surveillance and private sector engagement in malaria testing, treatment, and reporting was also conducted. Additional literature The Bill & Melinda Gates Foundation Accelerate to Zero strategy aims to research was conducted for six country case studies on eliminating eradicate malaria swiftly to minimize the negative effects and setbacks (Swaziland and Vietnam) and neighboring, non-eliminating settings caused by malaria resurgence and the spread of drug resistance. (Cambodia, Mozambique, Myanmar, and Zambia). The private sector is a Acceleration will require identifying individuals who harbor and transmit diverse and often unaffiliated group of providers that can be categorized low density infections. The proportion of low density infections varies based on their profit or business model (for-profit vs. nonprofit) and their inversely with transmission intensity; when a high transmission region regulation status within a country (formal vs. informal). Because the private has a rapid decrease in prevalence, it can become more difficult to detect sector varies from country to country, conducting a baseline assessment and treat infected individuals. Active infection detection (ID) tactics such of the private sector is critical to understanding its composition, size, as mass test and treat, focal test and treat, and reactive ID following an geographical distribution and quality of services provided. Facilitating index case aim to find and treat low density infections. However, existing reporting, referral, and training linkages between the public and tools used for detecting clinical malaria lack the sensitivity to detect low private sectors and making malaria a notifiable disease are effective density infections. Other tools lack the ease of use, affordability, rapid time strategies to improve private sector involvement in malaria surveillance. to results, and portability required for large scale field use. To improve The private sector can also be organized and better engaged through the efficiency of active ID tactics, new, low cost, portable tools with social franchising, effective regulation, professional organizations, and improved limits of detection (LOD) are being developed and are called government outreach. This review highlights the importance of engaging malaria infection detection tests (IDTs). Very limited data exist regarding private sector stakeholders early and often in the development of malaria the concentration of target biomarkers and their kinetics over the course elimination strategies. of a Plasmodium falciparum (Pf) infection. Thus, informed IDT product development requires a greater understanding of the fraction of PCR 1542 positives we can detect with a new IDT at 10x improved LOD, and of the relevance of the undetected population to transmission at this LOD. The PREDICTIVE MALARIA RISK MODELING USING AGGREGATE BIOME study is generating clinical data to better characterize the extent CASE DATA FOR IMPROVED INTERVENTION TARGETING IN and relevance of the human Pf reservoir stratified by individual biomarker HONDURAS concentrations. This study builds evidence for validation of key target product profile performance criteria for an HRP2-based IDT. The focus 1 1 1 Darlene Bhavnani , Bricia Trejo , Luis M. Perez , Justin M. of the study is to generate data to select a LOD for the IDT sufficient 1 1 2 Cohen , Arnaud Le Menach , Engels Banegas to interrupt transmission. The study is a comparative evaluation of the 1Clinton Health Access Initiative, Boston, MA, United States, 2National concentration of DNA, HRP2, total NA, and asexual stage parasites in Malaria Control Program Ministry of Health, Tegucigalpa, Honduras the peripheral blood of individuals with low density infections. Here, we present the preliminary results from our Thailand and Uganda cohorts. Countries in Central America recently committed to eliminate malaria by 2020. Honduras, a low endemic country in the region, plans to reach elimination by strengthening surveillance, improving case management, and targeting interventions. To help target elimination efforts in Honduras, we used national surveillance data reported in aggregate to predict spatial patterns of malaria transmission. The numbers of confirmed malaria cases, astmh.org 471 1544 health system professionals, and very few if any activities directed at the policy-level. Two examples of the role of effective communication at the ASSESSING READINESS TO ACCELERATE TOWARDS policy-level include Suriname, which made significant strides against MALARIA ELIMINATION: A COMPARATIVE ANALYSIS OF THE malaria from 1995-2015 and is now on the path to elimination with help DECISION-MAKING ENVIRONMENT IN KENYA, ETHIOPIA, from a National Malaria Board that brings together technical advisors, civil SENEGAL AND ZAMBIA society actors, and other government ministries to help guide the policy making process. In Brazil, new legislation was passed in 2014 to require Geoffrey Kirkwood1, Adem Agmas2, Ashley Bennett3, Jeff companies completing infrastructure projects in the Amazon region to Bernson1, Yakou Dieye4, Duncan Earle5, Asefaw Getachew2, engage in a series of activities, including social mobilization, to assess Philippe Guinot4, Angela Hartley1, Michael Hainsworth1, Todd the impact and mitigate the risk of greater malaria transmission in the Jennings5, John Miller5, Abdi Mohamed2, Kammerle Schneider1, surrounding area. As more countries in the Americas transition towards Kammerle Schneider1, Hailemariam Reda2, Sarah Hamm Rush6, elimination, malaria communication will have a sizable role to create a Melkamu Tiruneh2 shared understanding among key decision-makers and malaria partners 1PATH, Seattle, WA, United States, 2PATH, Addis Ababa, Ethiopia, 3PATH, of what it means for countries to be working towards elimination and Washington, DC, United States, 4PATH, Dakar, Senegal, 5PATH, Lusaka, beyond, in terms of funding levels, technical interventions, multi-sectoral Zambia, 6Independent Consultant, Seattle, WA, United States engagement, and sustained surveillance and reporting requirements. Channels and mechanisms that have worked in some countries should be Optimizing national malaria control activities and accelerating towards explored for use in others, especially at the policy-level to ensure long-term malaria elimination will require a unified critical pathway in which robust commitment. evidence generation and national policy guidance are complemented by appropriate financing, planning and operations, and governance. The opinions of national decision makers and implementers in four sub- 1546 Saharan African countries with varying malaria epidemiology, health MASS TESTING AND TREATMENT FOR MALARIA IN and regulatory systems, and national malaria targets were collected and MODERATE TRANSMISSION AREAS IN AMHARA REGION, analyzed in order to assess opportunities and barriers to accelerating ETHIOPIA progress along this critical pathway. Attitudes towards the feasibility and desirability of national malaria elimination targets were also assessed. Callie Scott1, Caterina Guinovart1, Belendia Serda2, Berhane In each country, Ethiopia, Kenya, Senegal and Zambia, interviewers Tesfay2, Asnakew Yeshiwondim2, Adem Agmas2, Melkamu Zeleke2, conducted on average 35 semi-structured interviews with stakeholders Girma Guesses2, Asmamaw Ayenew2, Worku Workie2, Elias including policymakers, regulators, donors, procurement officials, Zegeye2, Michael Kalnoky1, Ruben Conner1, Rick Steketee1, Belay academic researchers, NGO representatives, health care workers, and Bezabih3, Asefaw Getachew2 community advocates. Stakeholder responses were qualitatively coded 1PATH, Seattle, WA, United States, 2PATH, Addis Ababa, Ethiopia, 3PATH, and ranked using quantitative indicators including formal power, informal Amhara National Regional State Health Bureau, Ethiopia influence, knowledge of national malaria targets and support for malaria elimination as a national target. Thematic content analysis revealed new In moderate malaria transmission areas, strategies to clear parasites from information about what stakeholders in each country perceive to be the populations are a means to reduce infection and transmission. A malaria strengths and challenges of their national malaria control programs and mass testing and treatment (MTAT) intervention was implemented in six what adjustments are needed along the critical pathway to accelerate intervention villages in Amhara Region, Ethiopia, at the beginning of the towards malaria elimination. The need to address population mobility, 2014 malaria transmission season. Intervention villages were purposively increase private sector engagement and strengthen and expand human selected and matched with control villages based on the incidence of resources for case management emerged as major themes. Attitudes passively detected Plasmodium falciparum (Pf) and mixed malaria during towards the feasibility and desirability of national malaria elimination the 2013 malaria transmission season. All households in the intervention targets, and levels of knowledge and approval of new tools and villages were targeted. Participants received a rapid diagnostic test (RDT) approaches for elimination, varied by country and by organizational and and RDT-positive individuals received artemether-lumefantrine (Pf, mixed) individual perspective. In addition, interview responses yielded numerous or chloroquine (Plasmodium vivax [Pv]). Of 9,130 households in the proposals for improving malaria implementation efforts that may merit intervention villages, 7,974 households (87.3%) were visited by 93 field additional consideration by policymakers. teams over a period of three weeks. The average household had 4.4 individuals and the average number of households visited per day per 1545 team ranged from 3.7 to 8.5. Of the 35,389 individuals living in the households, 30,712 (86.8%) received an RDT. Of these, 47% were <20 SO YOU SAY YOU WANT ELIMINATION? USING years of age, 67% slept under a mosquito net last night, 52% resided COMMUNICATION AND ADVOCACY TO ADVANCE MALARIA in a household that received indoor residual spraying (IRS) in the last 12 ELIMINATION IN THE AMERICAS months, and 1% spent ≥1 night away from home in the last month. Among tested individuals, 421 (1.4%) were RDT-positive. The prevalence Marisabel Sanchez, Julie de Carvalho, Ricardo Echalar of Pf or mixed RDT-positivity was 1.0% (0.7% Pf, 0.3% mixed), ranging Links Media, Rockville, MD, United States from 0.1% to 4.6% by village; 58% of Pf or mixed infections had no fever or history of fever in the preceding 24 hours. Of individuals with a A qualitative assessment of the communication component of National Pf or mixed RDT result, 61% were <20 years of age, 64% slept under a Malaria Control Programs (NMCPs) in 11 countries in Latin America mosquito net last night, 44% resided in a household that had received and the Caribbean was conducted from 2013-2014. The assessment IRS in the last 12 months, and 8% spent ≥1 night away from home in surveyed the overall programmatic objectives, existing resources for the last month. Spatial clustering of RDT-positives varied by village. The communication, malaria stakeholders, target audiences, ongoing incidence of passively detected, RDT-confirmed malaria cases at the health communication activities, and gaps. Among the main findings of the post in each village will be compared before and after the intervention and assessment showed challenges in providing information to decision- between intervention and control villages to evaluate the impact of the makers to support and sustain efforts, expanding and strengthening MTAT intervention and implementation costs will be estimated. partnerships beyond the health sector, and reaching special populations that have a higher burden of disease including indigenous communities and migrant workers. Overall, communication activities were found to be focused at the community level with less attention paid to decentralized

astmh.org 472 1547 scales and in varied transmission settings, with interconnectivity through human movement and spatially heterogeneous baseline transmission. This EVALUATING THE ANNUAL COSTS OF IMPLEMENTING spatial simulation is then used to demonstrate the operational impact of CASE INVESTIGATION TO SUPPORT MALARIA ELIMINATION surveillance systems once a sub-region has at least temporarily achieved IN SOUTHERN PROVINCE, ZAMBIA: A MICRO-COSTING elimination. Areas with different baseline transmission rates, potential ANALYSIS for transmission following re-introduction, population densities, local mosquito populations and feeding behaviors, and primary health care Bruce Larson1, Thandiwe Ngoma2, Kafula Silumbe2, Marie-Reine coverage require different levels of investment in surveillance systems to Rutagwera2, Busiku Hamainza3, Anna Winters4, John Miller2, Callie ensure robust maintenance of elimination. Scott5 1Center for Global Health and Development, Boston University School 1549 of Public Health, Boston, MA, United States, 2PATH, Lusaka, Zambia, 3National Malaria Control Programme, Lusaka, Zambia, 4Akros, Lusaka, THE IMPACT OF CLIMATE VARIABILITY ON MALARIA Zambia, 5PATH, Seattle, WA, United States INCIDENCE RATES IN LORETO, PERU The Zambian Ministry of Health and partners are implementing a package Aneela Mousam1, Antonio M. Quispe2, Viviana Maggioni1 of interventions and surveillance systems in Southern Province to support 1George Mason University, Fairfax, VA, United States, 2Johns Hopkins the national malaria control and elimination agenda. Case investigation Bloomberg School of Public Health, Baltimore, MD, United States (CI) is part of this package. With CI, if a malaria case is detected at a health facility or in the community, a community health worker (CHW) then visits Despite a decade of reduction (2001-2010), data shows that during 2011- the household of the malaria case and other nearby households, tests all 2014, malaria has increased about 5 folds in Loreto. Past studies indicate individuals using a rapid diagnostic test (RDT), and treats all RDT-positives that climate variables can play a crucial role in malaria transmission. The with artemether-lumefantrine. We estimated the cost of implementing CI purpose of this work is to understand why certain populated centers in 173 health facility catchment areas (HFCAs) in ten districts in Southern report a higher parasite incidence rate compared to other ones, and which Province during the 2014 calendar year. Primary data on unit costs and specific climate variable is the most associated with a higher malaria quantities of various resources used during implementation (e.g. drugs, incidence. Annual parasite incidence (API) and weekly NASA climate data RDTs, other supplies, labor) and key programmatic outputs (number of the 2000-2014 period from the 315 populated centers that serve as tested, number testing positive, number treated) were obtained from surveillance reporting units within Peru were analyzed using a generalized programmatic records and the health management information system. linear model with a Poisson distribution and a link log. The analysis At the HFCA level, average annual costs were estimated at US$2,142. focused on comparing the top 10 percentile in terms of API from the Main cost categories include: labor at the HFCA (33%), mobile phone whole period as compared to the rest. During the years 2000-2014 Loreto talk time for CHWs (15%), equipment (15%), RDTs (13%), artemether- reported 539,315 malaria cases, which were mostly due to Plasmodium lumefantrine (5%), and other supplies (19%). On average, 6.7 CHWs vivax (81%). The average API at the district-level was 51 cases per 1,000 conducted CI activities in each HFCA (average population 7,432). On inhabitants (95% Confidence Interval [95% CI], 41-61). The reporting average, 127 households were visited per HFCA in 2014, 560 individuals units were located on average at -4.5 degrees of latitude from the Equator were tested, and 86 (15%) were RDT-positive and treated. The average (range, -8.4− -0.14). The average microclimate was significantly different cost per household visited was $46, per individual tested was $11, and per across reporting units (p<0.01) regarding surface temperature (range, individual testing positive and treated was $232. The estimates reported 294.9− 300.8 K), 2 meter above ground temperature (294.9- 300.8 K), here are preliminary and do not yet include additional costs associated specific humidity (range, 0.012− 0.019 kg vapor * kg^-1 air), and surface with training CHWs on CI implementation and supervision. Costs of pressure (range, 91965-100065 Pa). The API rates are the log odds of surveillance and interventions implemented to support malaria control ranking among the top 10th percentile malaria endemic populated centers and elimination are useful for budgeting, identifying opportunities to in Loreto during the years 2000-2014. The API increased with latitude (OR, improve program efficiency, and informing additional analyses on the 1.11; 95% CI 1.10-1.12) and decreased with surface pressure (OR, 0.99; cost-effectiveness and budget impact of different approaches to malaria 95% CI 0.99-0.99), 2 meter above ground humidity (OR, 2.59*10^-10; elimination. 95% CI, 2.51*10^-13-2.66*10^-7), surface temperature (OR, 0.98; 95% CI, 0.97-0.99), and soil moisture (OR, 0.77; 95% interval, 0.59-0.99). The 1548 observed and regression-estimated API were poorly correlated (Pseudo R^2: 5%, p<0.001). Further studies will be conducted on weekly malaria DESIGNING A SUFFICIENT SURVEILLANCE SYSTEM incidence rates at each populated center to understand the potential AGAINST RE-ESTABLISHMENT OF MALARIA IN A SPATIALLY impact of microclimate variability. CONNECTED MODEL 1550 Philip A. Eckhoff, Caitlin A. Bever, Jaline Gerardin, Milen Nikolov, Andre Lin Ouedraogo, Edward A. Wenger ACTIVE SURVEILLANCE THROUGH PEER REFERRAL TO Institute for Disease Modeling, Bellevue, WA, United States IDENTIFY POPULATIONS AT HIGHER RISK FOR MALARIA IN ZAMBEZI REGION, NAMIBIA Malaria transmission is spatially heterogeneous, and movement of individuals connects locations over local, regional, and global scales. Carmen Cueto, Jerry Jacobson, Jenny Smith, Davis Elimination planning must therefore account for this interconnectivity and Mumbengegwi, Hugh Sturrock, Roly Gosling, Adam Bennett its ability to reintroduce parasites to previously-cleared areas or to stall University of California San Francisco, San Francisco, CA, United States progress at low prevalence. One important component of elimination efforts is surveillance systems in areas of low-prevalence and sub-regions As malaria transmission declines, infection risk is increasingly clustered in which have at least temporarily achieved elimination. Robust and timely individuals or groups of individuals with specific occupations or behaviors. surveillance may allow sufficiently vigorous and rapid response to the Often these individuals will remain uncaptured through passive surveillance reintroduction of parasites to prevent re-establishment of malaria in due to poor health care access or asymptomatic infections. With the goal cleared areas. Options for this surveillance may include clinic-based to eliminate malaria by 2020, Namibia faces the challenge of identifying surveillance, active and passive case detection, mass screening, parasite these higher risk populations in order to better target interventions. genetics, and immune serology. We implement a spatial simulation model Motivated by the novel patient-initiated peer referral approach to identify for malaria transmission in the EMOD framework across varying spatial undiagnosed HIV cases, we designed a strategy to screen and interview individuals connected through their social networks to malaria cases astmh.org 473 from February to May of 2015. RDT positive index cases, which served as 1552 “seeds” to begin the peer referral recruitment chains, were identified at 6 randomly selected health facilities within Zambezi Region in northern SCALE-UP OF CASE INVESTIGATION AND REACTIVE CASE Namibia; recruitment was embedded within a concurrent case-control DETECTION EVALUATIONS IN THAILAND: RESULTS FROM study at these health facilities to identify and refine risk factors. All eligible FIVE PROVINCES cases (15 years and older) were randomly assigned to distribute referral coupons within either their social network or their household. Each referral Prayuth Sudathip1, Chris Cotter2, Alex Luo3, Adam Bennett2, Roly in the social network group had to fit the risk criteria of regularly sleeping D. Gosling2 or working outdoors during evening and morning mosquito biting hours. 1Bureau of Vector Borne Diseases, Ministry of Public Health, Nonthaburi, Individuals receiving coupons from either group were asked to visit the Thailand, 2Global Health Group, University of California San Francisco, health facility to participate in an interview- assisted survey and provide San Francisco, CA, United States, 3Global Health Sciences, University of a blood sample for malaria testing via RDT and DBS. Participation was California San Francisco, San Francisco, CA, United States tracked to assess the linkage to his or her recruiter. Recruitment and Case investigation and reactive case detection (RACD) activities are return were incentivized with LLINs, travel reimbursement, or mobile implemented in many low transmission settings and recommended by phone airtime. In this presentation, we discuss the feasibility of this study the World Health Organization as a key strategy for malaria elimination. design in a rural setting characterized by transportation barriers as well Determining the origin of infection, known as case investigation, and as the challenges of peer centered recruitment during a season with low screening household members and neighbors of passively detected malaria case numbers. We also evaluate the ability of active surveillance through cases for infection, known as RACD, requires substantial programmatic peer referral to identify individuals with specific high risk behaviors and and human resources. By evaluating the program performance of case current infections diagnosed by PCR, through comparison to a concurrent investigation and RACD activities, gaps in reporting completeness and household survey. timeliness can be identified to determine if improvements are required. Thailand is implementing case investigation and RACD and aims to 1551 eliminate malaria by 2024. Based on the findings from a pilot evaluation MODELING THE OPTIMAL INTERVENTION MIX FOR MALARIA conducted, the Thailand Bureau of Vector-Borne Diseases (BVBD) scaled- ELIMINATION IN DIFFERENT SPATIALLY CONNECTED up the use of a standardized monitoring and evaluation (M&E) tool to identify best practices and gaps in case investigation and RACD to inform TOPOLOGIES active screening efforts in Thailand. Data will be presented on the five Caitlin A. Bever, Jaline Gerardin, Milen Nikolov, André Lin evaluation provinces covering a range of transmission endemicities. Ouédraogo, Philip A. Eckhoff, Edward A. Wenger Routine surveillance data on case investigation and RACD reporting Institute for Disease Modeling, Bellevue, WA, United States completeness, timeliness and coverage from 2013 and 2014 are analyzed from the national malaria information system as well as from district-level Elimination of malaria is not complicated, in principle, if we have unlimited malaria clinics, malaria posts and border malaria posts. Questionnaires resources at our disposal. In practice, logistical, political, and financial were administered to surveillance program personnel regarding RACD constraints couple with the complex etiology of the disease to cloud the operations and procedures to understand their knowledge, practices path forward. While there are many means at our disposal to address the and the challenges to conduct RACD. Costing data for personnel, issue, it is not clear how to combine them for optimal efficacy, especially commodities, and other services related to case investigation and RACD when we account for the fact that local variation in the characteristics of expenditures were collected and analyzed to determine the primary endemic settings may significantly impact the best choice of intervention cost drivers and operating costs for RACD. Preliminary findings from mix. To address this question, we used the EMOD malaria model as the evaluation provinces have informed the BVBD on where program the basis for a prioritization tool that recommends intervention mixes efficiencies can be achieved, including the need for additional RACD- as a function of a region’s current attributes. The results are based on specific trainings. M&E of case investigation and RACD will assist the BVBD simulations of the impact of combining interventions, such as vaccines, in improving RACD program effectiveness and help Thailand achieve its insecticide treated nets, drug campaigns, and case management, analyzed goal of malaria elimination. through a context of feasibility: grounded by data and experience, what are achievable levels of coverage, what does administration 1553 cost, and are there implementation synergies that could favor certain combinations? Spatial heterogeneity is another important factor in DEVELOPMENT OF A PREGNANCY-SPECIFIC SEROLOGY TEST: planning for elimination, particularly in environments that are susceptible A PATH TOWARDS A NEW TOOL TO MEASURE MALARIA to reimportation, and was accounted for by running the simulations across TRANSMISSION IN THE CONTEXT OF ELIMINATION spatially connected regions, each of which may be distinct in terms of transmission intensity and access to care. While the primary results were Ana Maria Fonseca1, Eusebio Macete2, Raquel González1, calculated using simulations of existing intervention standards, e.g., RTS,S Chenjerai Jairoce2, Chenjerai Jairoce2, Jennifer Hegewisch1, María in the case of vaccines, hypothetical scenarios provide insight into what Rupérez1, Llorenç Quintó1, Pau Cisteró1, Pau Cisteró1, Anifa Vala2, might be achievable if new products become available and suggest how Arsenio Nhacolo2, Chetan Chitnis3, Esperanza Sevene2, Clara elimination strategies might be adapted in response. Menéndez1, Alfredo Mayor1 1ISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain, Barcelona, Spain, 2Manhiça Health Research Center (CISM), Manhiça, Mozambique, 3International Center for Genetic Engineering and Biotechnology, New Delhi, India New metrics for malaria transmission are needed for malaria elimination. P. falciparum infection during pregnancy is associated with a strong antibody response against VAR2CSA (pregnancy-specific antigen expressed by the parasite on the erythrocyte membrane that binds to placental Chondroitin Sulphate A), suggesting that detection of these antibodies in pregnant women at antenatal clinics could be used for surveillance of malaria. To select antigens with the highest potential for a VAR2CSA-based serological test, we measured IgGs in Mozambican pregnant women, as

astmh.org 474 well as in non-exposed individuals, using a quantitative suspension array 1555 technology that included 46 peptides from both conserved and semi- conserved regions of VAR2CSA, 3 recombinant proteins (DBL3x, DBL5ε, THE PROBABILITY OF ACUTE ILLNESS FOLLOWING DBL6ε) and non-pregnancy specific antigens. Dynamics of antibody PLASMODIUM VIVAX PRIMARY INFECTION AND RELAPSE IN responses during pregnancy were also determined to assess acquisition A COHORT OF CHILDREN FROM PAPUA NEW GUINEA and longevity of antibody responses. We first excluded those antigens that were a) poorly recognized by plasmas from pregnant women with high Amanda Ross1, Cristian Koepfli2, Peter Siba3, Ingrid Felger1, Ivo antibody levels against a VAR2CSA-expressing parasite line (CS2) (n=106); Mueller2, Marcel Tanner1 b) recognized by Mozambican men (n=102) and Spanish individuals 1Swiss Tropical and Public Health Institute, Basel, Switzerland, 2Walter and (n=100) and c) not associated with antibody acquisition in women infected Eliza Hall Institute of Medical Research, Parkville, Australia, 3Papua New with P. falciparum during pregnancy (n=252, longitudinal cohort with Guinea Institute of Medical Research, Goroka, Papua New Guinea 3 time-points per women). Among the 25 antigens selected, antibodies The probabilities of clinical illness following Plasmodium vivax primary against 17 peptides, DBL3X and DBL5ε mirrored falls and rises in malaria infection and relapse are unclear in people living in endemic areas. A major prevalence in Manhiça during 2003-2012 (n=654). Finally, 9 out of the difficulty lies in the inability to distinguish primary infections and relapses. 17 peptides, DBL3X and DBL5ε were selected based on high boosting of We previously analysed genotyping data to show that the seasonal pattern antibody by malaria infection, low time to double the levels when infection of the incidence of primary infections and relapses differed in a cohort occur (rapid generation of antibodies) and short half-life (detectable during of children in Ilaita, Papua New Guinea. The differential seasonality can one pregnancy). We are currently exploring the value of VAR2CSA serology be used to gain leverage to estimate the probability of clinical illness to detect recent changes in P. falciparum exposure associated with the following primary infection and relapse in the same cohort. The children, use of intermittent preventive treatment with different antimalarials. This aged one to three years at enrolment, were followed up over 16 months. pregnancy-specific serological test could be placed into action to provide Illness was detected during active case detection every two weeks and information for malaria surveillance in elimination campaigns. carers were encouraged to visit the study clinic if the child was ill at other times. P. vivax illness was defined as fever or reported fever in the last 48 1554 hours with a parasite density of 500/µl or greater. We relate the number OVERVIEW OF MALARIA SURVEILLANCE SYSTEMS IN of observed P. vivax cases in each age-group and each two month time ELIMINATION SETTINGS: LESSONS FROM THE PAST, AND period to the expected numbers of primary infections and relapses, and use the expected cumulative number of lifetime genotypes seen as a ASSESSING CRITICAL PROGRAM NEEDS proxy for clinical immunity. The expected numbers of primary infections Christopher Lourenco1, Andrew J. Tatem2, Deepika Kandula1, and relapses are derived from a simulation model, parameterized by Justin M. Cohen1, Arnaud Le Menach1 previous analyses of the same cohort and including the seasonal pattern of 1Clinton Health Access Initiative, Boston, MA, United States, 2University of primary infections, differential biting by age by weighting by body surface Southampton, Southampton, United Kingdom area, the durations of blood-stage infections, the number and timing of relapses, and treatment. We assume relapses occurring when a blood- Achieving malaria elimination requires a well-designed surveillance system stage infection by the same genotype is present do not cause illness and which can guide targeted efforts and selection of impactful strategies. are not counted. The estimated probability of acute illness declined with However, challenges remain to design systems to fit countries’ needs and the cumulative number of genotypes seen. For the ages in this cohort, the constraints. A systematic literature review of surveillance systems from probability following primary infection ranged from 0.3 to 0.05, following countries that have eliminated malaria or have a national elimination the first relapse, 0.07 to 0.0006, and for the second or later relapse, the policy in place was conducted to build a stronger evidence-base on probability was low. These results can inform estimates of the burden of what technical elements are essential to efficiently support elimination. P. vivax disease and provide building blocks for mathematical models for The review evaluated the system structure and surveillance activities in predicting the impact of interventions against P. vivax. each country while focusing on what data were collected, what output was generated to direct programmatic response, and what technical 1556 components are required. We reviewed 10 countries worldwide that eliminated malaria between 1965 and 2014, and 9 countries that are in ABSENCE OF EFFECT OF HETEROZYGOUS HEMOGLOBIN S the process of eliminating. According to the review, every country that ON THE PREVALENCE OF PLACENTAL MALARIA AND LOW successfully eliminated malaria described a system that had strong passive BIRTH WEIGHT case detection as its backbone. The passive systems included individual case reporting and detailed investigations, parasitological confirmation of Jaymin C. Patel1, Victor Mwapasa2, Linda Kalilani2, Feiko O. ter cases, foci identification, staff at district or village level specifically assigned Kuile3, Carole Khairallah3, Kyaw L. Thwai1, Steven R. Meshnick1, to assist in surveillance activities, and entomological data collection. 7 out Steve M. Taylor4 of the 10 countries that have eliminated also described conducting reactive 1University of North Carolina, Chapel Hill, NC, United States, 2College case detection with responses varying depending on country context, and of Medicine, Blantyre, Malawi, 3Liverpool School of Tropical Medicine, 8 out of 10 had a response mechanism incorporated into their surveillance Liverpool, United Kingdom, 4Duke University Medical Center, Durham, NC, systems that triggered programs to target interventions based on current United States data (i.e. implementation of indoor residual spraying dependent on foci Heterozygous hemoglobin S (HbAS), or sickle trait, protects children from investigation). In comparison, not all of the 9 eliminating countries had life-threatening falciparum malaria. The mechanism of this protection individualized reporting or thorough case investigations directing their is unclear, and evidence suggests that HbAS reduces expression of, interventions. However, those countries have begun to adopt technologies Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) and such as web-based or mobile tools that might enable a quicker response. thereby attenuates adherence of infected erythrocytes (IEs) to extracellular As countries work to strengthen surveillance for elimination, lessons ligands. Such binding of IEs to ligands is central to the pathogenesis of learned from historical experience should be used to highlight and placental malaria, wherein the expression of the PfEMP1 variant VAR2CSA prioritize components critical for success. mediates IE binding to chondroitin sulfate in the placenta; thus, placental malaria serves as an in vivo model of PfEMP1-mediated sequestration of IEs. We hypothesized that HbAS would be associated with reduced risks of placental malaria and its sequelae, including low birth weight (LBW). We tested this hypothesis in a cross-sectional study of 850 delivering

astmh.org 475 women in Southern Malawi. Demographic, clinical, and antenatal records 1558 were collected from enrolled women along with infant birth weight. Placental histology was scored for markers of malaria, and parasites were ESTIMATING THE MALARIA ATTACK RATE IN TANZANIAN detected in peripheral and placental blood by real-time PCR. The overall MILITARY CAMP: RISK FACTORS ASSOCIATED WITH prevalence of HbAS was 3.7%. The prevalence of P. falciparum was MALARIA EPIDEMIOLOGY IN MILITARY CAMPS IN TANZANIA 8.5% in peripheral blood and 12.7% in placenta by PCR and 24.4% by any histological evidence. The prevalence of LBW (<2500g) was 11.2%. Charles E. Mwanziva1, Mercy Chiduo2, Lucky Temu3, Francis There were no significant associations between HbAS and placental P. Filbert2, Humphrey Mkali2, Sarah Chiduo3, David Schnabel4, falciparum (OR: 1.29, 95% CI: 0.48, 3.41) or any histological evidence of George Amoo5, Lalaine Anova6, Colin Ohrt4, Eyako Wurapa4, Akili placental malaria (OR: 0.98, 95% CI: 0.40, 2.34). P. falciparum densities, Kalinga7, Christopher Mswanya1, Deus Ishengoma2, Yadon M. as estimated by PCR, were also similar between groups. Furthermore, Kohi1, Dennis Janga1 mean (standard deviation) birth weights of infants born to HbAS (2947g 1Tanzania Peoples Defence Forces, Dar es Salaam, United Republic of [563g]) and HbAA (2991g [465g]) mothers were similar, as was prevalence Tanzania, 2National Institute for Medical Research, Tanga Research Centre, of LBW (OR: 0.82, 95% CI: 0.24, 2.73). Across a range of parasitologic, Tanga, United Republic of Tanzania, 3Walter Reed Malaria Programme- clinical, and histologic outcomes, HbAS did not confer protection Tanzania, Dar es Salaam, United Republic of Tanzania, 4Walter Reed from placental malaria or its adverse effects. Although HbAS reduces Army Institute of Research, Silver Spring, MD, United States, 5Amethyst cytoadherence of IEs to endothelium, the absence of protective effects Technologies LLC, Baltimore, MD, United States, 6ClinicalRM Inc., Hinckley, in this study suggest that HbAS does not attenuate the ability of IEs to OH, United States, 7National Institute for Medical Research, Tukuyu sequester in the placenta. Research Centre, Tukuyu, United Republic of Tanzania In Tanzania, malaria ranks number one cause of morbidity and mortality, 1557 accounts for over 32% of the National disease burden. There is high DISTRIBUTION AND PREVALENCE OF MALARIA IN CHILDREN heterogeneity of malaria transmission. Imported cases by travellers to UNDER THE AGE OF FIVE IN THE DEMOCRATIC REPUBLIC OF and from different areas in Tanzania poses a great challenge in malaria epidemiology. The aim of this study was to identify risk factors associated THE CONGO, 2013-2014 with malaria attack rate among individuals when entering a training camp Lauren Levitz1, Mark Janko2, Corinna Keeler2, Melchior in a highly endemic area. Tanzania People’s Defence Forces (TPDF) Recruits Kashamuka Mwandagalirwa3, Stephanie Doctor1, Olivia eligible to study in Mgambo National Service camp -Tanga, were randomly Anderson1, Amy Whitesell1, Kyaw Thwai1, Henry Ntuku3, Michael selected by multistage sampling; consented and followed for six months. Emch2, Joris Losimba Likwela4, Antoinette K. Tshefu3, Steven Fortnightly malaria smear was collected. Blood samples for serological Meshnick1 tests were collected. Microscopy was a gold standard method for malaria 1Department of Epidemiology, Gillings School of Global Public Health, diagnosis. Data was subjected to univariate and multivariate analysis, University of North Carolina, Chapel Hill, NC, United States, 2Department logistic regression model was used to identify the risk factors. Among of Geography, Carolina Population Center, University of North Carolina, 549 recruits who were involved in this study, 31.7% (174) were malaria Chapel Hill, NC, United States, 3Ecole de Santé Publique, Faculté de positive, of which 80.5% (442) were male recruits. Female recruits had Médecine, Université de Kinshasa, Kinshasa, Democratic Republic of the 54% significantly reduced chances of being malaria positive [OR: 0.46; Congo, 4Programme National de Lutte contre le Paludisme, Kinshasa, 95% CI: 0.28 - 0.77; P=0.003]. Among positive cases, those who didn’t Democratic Republic of the Congo sleep under treated net previous night were found to have significantly increased odds of being malaria positive [OR: 7.71; 95% CI: 1.01-58.61; The Democratic Republic of the Congo has one of the highest malaria P=0.048]. Travelling outside the camps in the past one month had burdens in the world. Over 8,000 children under the age of 5 in 540 increased odds of being malaria positive [OR: 1.25; 95% CI: 0.87-1.79; population-representative clusters were tested for malaria in the 2013-4 P=0.232]. There was significant difference between malaria positivity and Demographic and Health Survey. Infection was ascertained by microscopy, place of travel [X2=40.1; P=0.015]. This study revealed failure to use bed rapid diagnostic tests (RDT), and PCR for the Plasmodium falciparum nets and travel are major drivers of malaria. Identification of gaps in net lactate dehydrogenase gene. Weighting for populations, 34.1% of use, knowledge, relevant types of human movement and development of children were PCR-positive for P. falciparum malaria. In contrast, strategies addressing travel is highly recommended. Mgambo NS being 22.7% and 30.9% were positive by microscopy and RDT, respectively. a high malarial endemic area is ideal site for malaria drug prophylaxis or The prevalence of microscopic gametocytemia was 1.4%. Malaria vaccine studies, where TPDF recruits from various transmission intensity was common in all 26 national health divisions. PCR prevalence, like areas train under similar exposure environment. microscopy, increased with age and was higher in those living in rural areas compared to urban areas. PCR prevalences ranged from 10 to 68%. 1559 We estimate that prevalence of mono-infections with P. malaria or P. ovale was approximately 1%. Of the RDT-positive samples, 18% were both PCR- A COMPARISON OF HOUSEHOLD SURVEY SCREENING FOR and microscopy-negative, probably due to persistence of HRP-2 in the MALARIA AMONG OLDER CHILDREN (5-14YRS) AND ADULTS circulation. This high burden of malaria was found despite the fact that VERSUS YOUNG CHILDREN TO DETERMINE FINE-SCALE insecticide-treated net (ITN) ownership increased from 7% of households HETEROGENEITY IN AN AREA OF HIGH TRANSMISSION in 2007 to 70% in 2013. Mark Sherlock1, Emanuele Giorgi2, Arantxa Roca-Feltrer1, Clemens Masesa1, Kamija Phiri3, David Lalloo4, Peter Diggle2, Dianne Terlouw1 1Malawi-Liverpool Wellcome Trust Research Centre, Blantyre, Malawi, 2University of Lancaster, Lancaster, United Kingdom, 3College of Medicine, Blantyre, Malawi, 4Liverpool School of Tropical Medicine, Liverpool, United Kingdom There are increasing calls for more targeted malaria control interventions that take into account transmission heterogeneity. Capturing such heterogeneity and identifying hotspots accurately at the sub-district and district level however remains a challenge. Current parasitaemia indicators

astmh.org 476 for household surveys are based on children aged 6 to 59 months. artesunate due to misreported hyperparasitaemia. Overall P. knowlesi While there is an increasing interest to expand parasitaemia screening malaria predominantly affected adults, with AKI (16%) and severe malaria in household surveys to older children or adults, its added value remains (8.4%) commonly developing in this age-group. Although anaemia was unclear. We investigated whether screening older age groups in addition more common in children than adults with P. knowlesi, parasitemia was to young children within households could improve precision in mapping lower and severe anaemia, AKI or other severe disease was not seen. heterogeneity and malaria hotspots. We conducted a monthly continuous (‘rolling’) population based household-level malaria indicator survey (rMIS) 1561 in an area of ~400km2 in Chikwawa district, southern Malawi. Malaria parasitaemia screening was conducted in three age groups: 6-59 months, PROGRESS TOWARDS ACHIEVING MILLENNIUM 5-14 years, and ≥15 years, and based on a pLDH/HRP2 rapid diagnostic DEVELOPMENT GOAL AND ROLL BACK MALARIA TARGETS test (First Response® Malaria Ag. pLDH/HRP2 Combo Card Test, Premier IN GHANA Medical Corporation Ltd., India). Further collected household information included socioeconomic status, long-lasting insecticide-treated net Wahjib Mohammed, Keziah L. Malm, Constance Bart-Plange and indoor residual spraying coverage. A total of 1,197 children aged National Malaria Control Programme, Accra, Ghana 6-59 months, 1,506 aged 5-14 years, and 1,1881 aged ≥15 years were Ghana has been implementing the Roll Back Malaria Strategy since 2003, sampled. Parasite prevalence was 16.7% (95%CI 14.5, 19.2) in the and is currently operating with the 2008- 2015 strategic plan. The overall youngest age group, 11.8% (95%CI 10.1, 13.7) in the 5 to 14 years age goal of the 2008 - 2015 malaria strategic plan is to reduce both malaria group and 5.4% (95%CI 4.5, 6.3) in the ≥15 year group. This data was deaths and malaria burden by 75% by 2015 using 2000 as baseline. In line used to create geospatial maps of parasite prevalence for both individual with the MDG Goal 6, the programme is aimed at halting malaria deaths age groups and combined groups, using generalized linear geostatistical by 2015. This study aimed to assess progress towards attainment of 2015 models. Comparative analyses of these maps suggest that the older age MDG/RBM malaria targets in Ghana. This study employed desk review groups do not increase the accuracy or precision in mapping malaria of annual reports, policy and operational guidelines, reports of health hotspots. These findings thus suggest that in settings of high but varying facility and community based surveys including Multiple Indicator Survey malaria transmission the screening of older children and adults in addition (MICS), Demographic and Health Surveys (DHS) and Malaria Indicator to children under the age of 5 in household surveys will not contribute Surveys between 2000 -2014. All cause under-five years mortality rate to a more accurate picture of heterogeneity and identification of malaria was reduced from 111/1000 in 2003 to 60/1000 in 2014. Malaria case hotspots. fatality rate in under-five children reduced from 14.4% in 2001 to 0.51% in 2014. Ghana also achieved up to 50% reduction in parasite prevalence 1560 between 2002 and 2014 from a national average of over 50% to 26.7%. There was an increase in the use of ITNs among children under five and CLINICAL SPECTRUM OF DISEASE IN ADULTS AND CHILDREN pregnant women, from 3.5% and 2.7% in 2003 to 58.8% and 56.3% WITH PLASMODIUM KNOWLESI MALARIA IN A DISTRICT in 2014 respectively. Proportion of pregnant women receiving at least SETTING IN SABAH, MALAYSIA 2 doses of IPT was 64.4% in 2011 against the target of 80% by 2015. Matthew J. Grigg1, Timothy William2, Prabakaran Dhanaraj3, Proportion of malaria cases treated with Artemisinin-based Combination Jayaram Menon2, Giri Rajahram2, Bridget Barber1, Chris Wilkes1, Therapy (ACT) increase from 39% in 2011 to 82.5% in 2014. Ghana Arjun Chandna1, Kaajal Patel1, Jonathan Cox4, Chris Drakeley4, Tsin has made significant progress towards attainment of the MDGs goals of Yeo 1, Nicholas Anstey1 halting malaria deaths. There is however the need to sustain the gains and improve in areas such the coverage of IPTp and ITN use. 1Menzies School of Health Research, Darwin, Australia, 2Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia, 3Kudat District Hospital, Kudat, Sabah, Malaysia, 4London School of Hygiene & Tropical Medicine, London, 1562 United Kingdom ESTIMATING THE MOST RESOURCE-EFFICIENT MALARIA Plasmodium knowlesi is now the most common cause of malaria in INTERVENTION PACKAGES AND SPATIAL SCALES TO Malaysia, but prospective studies describing the clinical spectrum have ACHIEVE ELIMINATION ACROSS AFRICA only detailed adult disease. In our prospective study (2012-ongoing) at 3 district hospitals in Sabah, Malaysia, previously untreated, non-pregnant Patrick G. Walker, Jamie T. Griffin, Neil M. Ferguson, Azra C. patients of any age hospitalised with PCR-confirmed malaria includes: Ghani 368 P. knowlesi (32 [8.7%] children ≤ 12 yrs), 152 P. vivax (63 [41.5%] MRC Centre for Outbreak Analysis and Modelling, London, United children), 56 P. falciparum (11 [19.6%] children), 14 P. malariae, and Kingdom 1 mixed Pk/Pf. Preliminary data include a lower baseline parasite count Resource constraints mean that the elimination of malaria in much of for P. knowlesi malaria patients (median 2274/μL, IQR 537-9252) than Africa, if achievable, is likely to require available resources to be allocated P. falciparum (9762/μL, IQR 2030-24010, P<0.001), and P. vivax (4319/ carefully. Here we use a dynamical model of malaria transmission, μL, IQR 1588-9608, P=0.011). Parasite counts were higher in adults capturing the heterogeneity in transmission of malaria which exists with P. knowlesi compared to children (2427 vs. 890/μL, P=0.013). In P. across sub-Saharan Africa, to identify the most efficient combination of knowlesi (WHO criteria) anaemia was present in 37% of adults vs. 86% interventions and spatial scale of implementation to achieve different in children (P<0.001), however was less prevalent than in P. vivax overall elimination milestones. Our results demonstrate that, while bed-nets (60%, P<0.001). Acute kidney injury (AKIN criteria and/or creatinine are a cost-effective step towards any control target, the choice of >132mmol/L) was found in 42/285 (14.7%) with P. knowlesi including further interventions to deploy within a setting depends on the time 42/263 (16%) adults and 14/27 (52%) of those with severe disease, scale over which a given target is to be achieved and whether disease compared to P. vivax overall (12/140, 8.6%, P=0.073). In those with reduction or elimination of infection is the priority. We found that while P. knowlesi 28/366 (7.7%) had severe malaria (modified WHO 2010 chemoprevention within risk groups such as children are the most criteria): 28/334 (8.4%) in adults but none in children. In comparison, cost-effective means by which to achieve rapid reductions in malaria severe disease was seen in 5/152 (3.2%, P=0.062) with P. vivax and burden, the changing age-distribution of disease as transmission falls 4/56 (7.1%, P=0.839) with P. falciparum. 207/359 P. knowlesi patients and large asymptomatic reservoir means that sustaining low burden were treated with artemisinin combination therapy, including 39 with or other more ambitious elimination milestones requires interventions prior intravenous artesunate, and the remainder with oral chloroquine. which target the general population such as indoor residual spraying There were no treatment failures in knowlesi malaria patients seen at 28 or mass drug administration (MDA). At 90% population coverage, we days. There was one P. knowlesi malaria death, with delayed parenteral estimate that packages including one, two or three annual rounds of astmh.org 477 MDA would achieve pre-elimination levels of transmission (<0.001 case 1564 per person year) in 75%, 82% and 91% of the population at risk in mainland Africa respectively, with the latter achieving pre-elimination in COST-EFFECTIVE SCALE-UP OF CURRENT INTERVENTIONS 25 of the 42 countries with ongoing transmission. We then investigated AND RTS,S IN SUB-SAHARAN AFRICAN SETTINGS how the resources needed to achieve this target depend upon whether interventions are deployed at the country or provincial (first administrative Peter Winskill, Patrick G. Walker, Jamie T. Griffin, Azra C. Ghani unit) level. We found that on average provincial level policies reduced the Imperial College London, London, United Kingdom resources necessary to achieve pre-elimination by 40%, with countries Despite continuing progress in the control of malaria, in many countries, with high levels of heterogeneity in transmission such as Tanzania, especially in sub-Saharan Africa, the burden of disease remains high Senegal, and Angola benefiting most. In other countries such as Zambia, and the availability of interventions remains sub-optimal and subject to high within-province variation may suggest the need for even higher resource constraints. In light of this, the setting-specific cost-effectiveness resolution local-level policies. of new tools to control malaria, such as the RTS,S vaccine, must be evaluated alongside other control options, including investing more 1563 resources in further scaling-up existing interventions already in place. SPATIAL AND TEMPORAL DYNAMICS OF MALARIA We used an existing mathematical model of malaria to describe the effectiveness of LLINS, RTS,S and chemoprevention in children across the INCIDENCE FROM 2009-2013 IN BANDIAGARA, MALI highly heterogeneous range of transmission settings that exist across Drissa Coulibaly1, Mark A. Travassos2, Jean Gaudard3, Youssouf Africa. Costs were estimated using a production function framework for Tolo1, Abdoulaye K. Kone1, Matthew B. Laurens2, Karim Traore1, a range of interventions, including LLINs and the RTS,S vaccine. The most Issa Diarra1, Amadou Niangaly1, Modibou Daou1, Mody Cissoko1, efficient, step-wise approach to scaling up a combination of interventions Boureima Guindo1, Stanislas Rebaudet3, Bourema Kouriba1, was determined by comparing the incremental cost-effectiveness ratios Mahamadou A. Thera1, Renaud Piarroux3, Christopher V. Plowe4, (ICERs) associated with increasing the coverage of each intervention and Ogobara K. Doumbo1 choosing the most favourable option. This process was repeated until 1Malaria Research & Training Center, University of Science, Techniques the coverage or usage of all interventions was maximised. Outcomes & Technology, Faculty of Medicine and Dentistry, Bamako, Mali, 2Center considered include the reduction over ten years of clinical incidence in for Malaria Research, Institute for Global Health, University of Maryland infants (6 months to 5 years old) and clinical incidence in all age groups. School of Medicine, Baltimore, MD, United States, 3Aix-Marseille LLINs are generally considered the most cost-effective malaria control University, Marseille, France, 4Center for Malaria Research, Institute for method currently available. We found that, when including RTS,S with an Global Health, University of Maryland School of Medicine, Baltimore, MD, assumed unit cost of production of $5 per dose as an option, providing United States LLINs to the majority of the population remains the most cost-effective control strategy across a wide range of transmission settings. However, Despite recent progress in reducing malaria morbidity and mortality in under the realistic assumption that reaching individuals without a net many places, empirical and theoretical evidence suggests that the current becomes increasingly difficult as coverage increases, if there are sufficient suite of interventions will not be sufficient to eliminate malaria from remaining resources, strategies such as chemoprevention or RTS,S may many areas in sub-Saharan Africa with historically high levels of malaria be a more cost-effective alternative to achieving very high levels of LLIN transmission. Careful description of the micro-epidemiology of malaria is coverage. essential for an accurate assessment of local transmission risk and hotspot localization in order to support malaria control programs, particularly in 1565 countries with limited resources. Our study aimed to measure malaria incidence and to investigate spatial and temporal dynamics of malaria COMPARING THE EPIDEMIOLOGY OF MALARIA INFECTION in a single town in Mali from June 2009 to July 2013. Malaria incidence AND ILLNESS IN PNG CHILDREN BEFORE, DURING AND was measured in a cohort of 400 children through active and passive AFTER THE INTENSIFICATION OF CONTROL MEASURES surveillance. Households were georeferenced using a handheld Global Position System (Garmin: Personal Navigator) with an accuracy goal of Maria Ome-Kaius1, Johanna H. Kattenberg1, Matthew Siba1, <15m and assigned to blocks of houses. A GIS map of Bandiagara was Shadrach Jally1, Daisy Mantila1, Jason Ginny1, Peter M. Siba1, established from satellite photography and field surveys. Malaria cases Christopher L. King2, Ingrid Felger3, James W. Kazura2, Ivo were mapped using PHILCARTO (TM). SaTScan® software was used to Mueller4, Leanne J. Robinson4 look for intra-annual and inter-annual clusters of high or low risk. The 1Papua New Guinea Institute of Medical Research, Madang, Papua New incidence was stable from 2009-2013. The annual cumulative incidence Guinea, 2Case Western Reserve University, Cleveland, OH, United States, varied from 1.3 to 2.0 clinical episodes per child from 2009-2013. The 3Swiss Tropical and Public Health Institute, Basel, Switzerland, 4Walter and weekly clinical malaria episodes and rainfall were plotted. Three month Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia phase shifts were detected between the beginning of seasonal rains and In Papua New Guinea (PNG), children less than 5 years of age typically the peaks of clinical malaria episodes. During high malaria transmission experience high levels of clinical illness with Plasmodium falciparum and periods, hotspots were stable and localized to the southwest part of the P. vivax. Children appear to acquire clinical immunity to P. vivax rapidly town, as well as in the northeast section near the Yamé river. The central and clinical episodes are rare after 5 years of age, whilst clinical episodes and eastern parts of the town were relatively protected. No significant of P. falciparum remain common. Perennial exposure as well as the high clustering was found during the low transmission period. Overall, there rates of relapses and clinical disease due to P. vivax in early childhood may was a marked spatial heterogeneity of malaria cases with stable hotspots contribute to the rapid acquisition of clinical immunity early in life. The and stable incidence in Bandiagara from 2009 to 2013. This analysis incidence of clinical malaria with both species is comparable in children of malaria microepidemiology may inform local malaria control and less than 5 years. However, the prevalence and incidence of P. falciparum elimination strategies. infection and illness increases with age, with minimal signs of any acquisition of clinical immunity to P. falciparum in this age group. In the last decade, there has been a renewed focus on the implementation of an effective National Malaria Control Program and this is successfully reducing malaria transmission in the country. However, a detailed understanding of the impact on the burden of infection and clinical malaria, as well as the acquisition of clinical immunity in the most vulnerable age group, 1-5 year olds, is lacking. To assess this, a longitudinal cohort study of 1-5 year astmh.org 478 olds was conducted in the same area of East Sepik Province as previous has hyperendemic malaria, with greater than 50% parasite prevalence studies that were conducted prior to (Lin et al) and during (Betuela et al) by rapid diagnostic test (RDT). Malaria vectors in Nchelenge District are the introduction of sustained control measures. Preliminary analysis shows susceptibile to the organophosphate insecticide pirimiphos-methyl, and a marked reduction in the prevalence of P. vivax infection at enrolment (by this compound was used for the first time in Zambia in a large-scale IRS PCR) from 53.0% in 2006 to 14.0% in 2013 and P. falciparum infection campaign in Nchelenge District conducted by the Ministry of Health, the from 49.6% to 14.0%. Similarly, prevalence of clinical malarial episodes President’s Malaria Initiative (PMI), and NGO partners over 6 weeks in has significantly declined from 20.5% to 4.8%. Detailed analysis of the October-December 2014. Sub-district areas were targeted for spraying incidence and risk of malaria in the 10 month follow-up period will be based on population density and health center case reports. This is the first presented. In conclusion, preliminary data confirms a profound decline use of a targeted IRS strategy in Zambia. Approximately 30 months of data in the prevalence of malaria infection and episodes achieved through from 425 households in active surveillance cohorts was used to establish sustained control measures. baseline seasonal malaria prevalence in Nchelenge District. After the IRS campaign, six months of enhanced surveillance from 250 households will 1566 be used to evaluate the impact of this IRS strategy, both in targeted areas and district-wide. Parasite prevalence as measured by rapid tests and PCR EXPLORING THE RELATIONSHIP BETWEEN CLIMATIC in serial bimonthly cross-sectional data collections are compared pre- and FACTORS AND ITN USE IN 17 AFRICAN COUNTRIES post-intervention, and changes in time to reinfection in longitudinal cohorts and vector abundance using CDC light traps are quantified. Emily E. Ricotta1, Hannah Koenker1, Joshua Yukich2, Olivier Briët3 1Johns Hopkins Center for Communication Programs, Baltimore, MD, 1568 United States, 2Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States, 3Swiss Tropical and Public SHIFTING EPIDEMIOLOGICAL PATTERN OF MALARIA IN Health Institute, Basel, Switzerland NORTH CENTRAL AND SOUTHWESTERN NIGERIA While there is much anecdotal evidence of climatic factors such as rainfall Adeola Y. Olukosi, Chimere Agomo, Oluwagbemiga Aina, and temperature affecting insecticide-treated net (ITN) use, there is little Samuel Akindele, Hilary Okoh, Bartholomew Brai, Olusola actual data demonstrating this association. Qualitative research has Ajibaye, Bassey Orok, Bamidele Iwalokun, Adeniyi Adeneye, reported decreased ITN use during the dry season due to perceptions Adedapo Adeogun, Olajumoke Akinyele, Nkechi Oparaugo, Grace of being too hot, and increased use during the rains due to increases in Akintunde, Veronica Enya, Maureen Aniedobe, Olatoun Fesobi, perceived nuisance biting. This analysis uses data from national household Abiodun Olakiigbe, Samson Awolola surveys, as well as remotely-sensed climate data, to assess how factors Nigerian Institute of Medical Research, Lagos, Nigeria such as ITN use is influenced in different ecological environments at different times of the year. The most recent national survey with available Characterization of malariometric indices is a necessary precursor for geographic location data was obtained for 17 African countries. Monthly planning malaria control activities. Resulting baseline values of these rainfall estimates (mm) at a roughly 4 km resolution were acquired, and epidemiological parameters provide evidence basis for intervention the mean rainfall estimate at each survey cluster location for the month purposes. A survey of four villages in Borgu, Niger State representing a in which the survey was conducted was merged with the national survey Sudan savannah vegetation of North Central Nigeria and Ijede a semi dataset. Logistic regression was run to assess whether there was a urban town, in a forest vegetation belt of South West was conducted. significant relationship between estimated rainfall quantile and ITN use Consenting participants were screened for malaria using mRDT and in each of the study countries. Preliminary results suggest that in 10 of microscopy. Temperature, PCV, height and weight were measured. Of a the 17 countries surveyed in this analysis, there is a significant association total of 1648, 813 from Borgu and 835 from Ijede, malaria positivity by between estimated rainfall and ITN use. In some countries, higher RDT was 19.4%, 95% CI = 17.42-21.53 (Ijede 9.6% and Borgu 32.5%) quantiles of estimated rainfall increased the odds of net use significantly and 11.9 %, 95% CI = 10.33-13.67 by microscopy (Ijede 11.5% and (Benin – OR: 1.45, p=0.001). However, in a few countries, higher quantiles Borgu 17.1%). Fever was significantly associated with malaria positivity were associated with decreased odds of using an ITN when controlling for [OR = 2.1417 (1.3554-3.3842), P=0.001] overall but not at individual sites access to an ITN in the household (Senegal – OR: 0.75, p=0.024). Further [Ijede: OR=1.361 (0.4647 - 3.9865), P=0.573; Borgu: OR= 1.6869 (0.9812 studies are necessary in order to understand what additional climatic - 2.90), P=0.057]. Malaria positivity rate was significantly lower in under 5 factors, such as land surface temperature, nocturnal dew point, and year than in 5-15 year (P = 0.043) in both study sites. Children under five relative humidity, play a role in ITN use, as well as the reasoning behind years of age had significantly lower malaria positivity rate (16.3%) as well these associations and what they mean for in-country malaria prevention as a lower parasitemia level(382p/µl) when compared to 5-15 years age programs. group with 41.3% and 490p/µl corresponding values (P<0.001). Overall anemia rate was 21.6%; 95% CI 19.46%-23.74%. Anemia rate and 1567 distribution was similar at both sites with children under the age of 5years 17.7% recording lower rates, compared to the rest of the population THE EFFECTIVENESS OF A TARGETED INDOOR RESIDUAL 22.3 %(P<0.001). This preliminary investigation revealed a lower malaria SPRAY CAMPAIGN WITH PIRIMIPHOS-METHYL IN prevalence rate and parasitemia in under fives compared to children NCHELENGE DISTRICT, NORTHERN ZAMBIA 5-10years. There should be a high index of suspicion for alternative causes of fever, other than malaria in children under the age of 5years in Nigeria. Marisa A. Hast1, Mike Chaponda2, Daniel J. Bridges3, David Larsen3, Kelly M. Searle1, James Lupiya2, Tamaki Kobayashi1, Timothy M. Shields1, Modest Mulenga2, Frank C. Curriero1, William J. Moss1 1Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States, 2Tropical Disease Research Centre, Ndola, Zambia, 3Akros, Lusaka, Zambia The WHO has identified vector control as a key priority in reducing community malaria burden. In Nchelenge District, Luapula Province, Zambia, the main malaria vectors are An. gambiae s.s. and An. funestus, both of which are highly anthropophilic and endophilic, making indoor residual spraying (IRS) a potentially effective strategy. Nchelenge District astmh.org 479 1569 analysis; 27.2% of them were primigravidae and 29.3% were HIV- infected. A significant drop in peripheral parasitemia prevalence was MULTIPLICITY OF INFECTION AND DISEASE SEVERITY IN found between 1998 and 2010 (from 15.3 % to 0.5% p<0.001) with PLASMODIUM FALCIPARUM AND P. VIVAX IN AREAS WITH a slight but significant rebound in 2012 (to 3.5%, p=0.003). The mean SEASONAL TRANSMISSION OF COLOMBIA parasite density in peripheral blood was higher in 2010 compared with that in 1998 (66683 versus 4667.9 parasites/µL, p<0.001). The prevalence M. Andreina Pacheco1, Mary Lopez-Perez2, Andres Vallejo2, of placental infection also significantly drop during the study years (from Socrates Herrera2, Myriam Arevalo-Herrera3, Ananias A. Escalante1 50.7% in 2003 to 3.5% in 2012, p<0.001).Primigravidae had higher 1Temple University, iGEM, Philadelphia, PA, United States, 2Caucaseco prevalence of P. falciparum infection than multigravidae across all studied Scientific Research Center and Centro Internacional de Vacunas, Cali, periods (p<0.001). No significant differences were found in the prevalence Colombia, 3Faculty of Health, Universidad del Valle, Cali, Colombia of peripheral parasitemia between HIV- infected and uninfected pregnant women. Maternal anemia ranged between 57.4% and 37.4% with no A common observation in malaria endemic areas is that there could be specific pattern over the study years. The prevalence of low birth weight multiple lineages of the parasite concurrently infecting a patient; this is decreased during the study period (from 19.8% in 2003 to 6.1% in referred to as multiplicity of infection (MOI). MOI is the result of the co- 2012, p<0.001).A significant decrease in the malaria burden in pregnancy transmission of parasite variants (co-infections) or the overlap of variants was observed in this area of southern Mozambique over the period. due to multiple infectious contacts (superinfections). Distinguishing Importantly, the increase in P falciparum infection found at the end of the between the two processes is laborious so MOI usually refers to a sample period calls for the need of continuous monitoring and surveillance of with multiple parasite genotypes. Previous studies have postulated a link malaria transmission in pregnant women. between MOI and disease severity; association that has been tested in Plasmodium falciparum mostly in Africa with limited information on P. vivax. In this study, the association between MOI and disease severity is 1571 explored in seasonal malaria areas from Colombia where P. vivax and P. MALARIA EPIDEMIOLOGY IN LOW ENDEMICITY AREAS OF falciparum can be compared. Overall 422 P. vivax and 282 P. falciparum THE NORTHERN COAST OF ECUADOR samples were collected between 2011 and 2013 from three distinct malaria endemic areas of Colombia. A total of 41 P. vivax and 27 P. Fabián E. Sáenz1, Andrea Arévalo1, Andrés F. Vallejo2, Gabriela falciparum cases were classified as clinically complicated cases. Samples Valenzuela1, Andrea Poveda1, Angélica Castellanos2, Enrique were genotyped by using 8 microsatellite loci, any infection with two or Castro3, Julio Valencia4, Amanda Pereira5, Myriam Arévalo2, more alleles at any locus was considered a multiple infection. P. vivax Sócrates Herrera2 displayed more MOI (50.9%) than P. falciparum (21.6%). Uncomplicated 1Pontificia Universidad Católica del Ecuador, Quito, Ecuador, 2Centro de cases were sampled in an interval of 5 to 8 days around each complicated Investigación Científica Caucaseco, Cali, Colombia,3 Ministerio de Salud case so both complicated/uncomplicated cases where matched in time as Pública, Guayaquil, Ecuador, 4Ministerio de Salud Pública, Esmeraldas, closely as possible. An analysis using a Fisher exact test yield a significant Ecuador, 5Ministerio de Salud Pública, San Lorenzo, Ecuador association (p<<0.05) between MOI and disease severity in P. vivax. In contrast, no association was observed in P. falciparum. Similar analyses The recent scale up in malaria control measures in Latin America has were performed on all the samples regardless time of collection and the resulted in an impressive decrease in the number of reported cases in association observed in P. vivax remained whereas no association was most countries of the region. In Ecuador the incidence decreased from still observed in P. falciparum. We observed that multiple infections with more than 100 thousand cases in 2001 to 377 cases in 2013) with P. falciparum usually involved genetically related lineages whereas in P. occasional outbreaks of both falciparum and vivax malaria particularly in vivax there were distinct genotypes circulating. However, the low number the coastal and Amazonian regions. The success in control measures in of complicated malaria cases did not allow to proper exploring the effect recent years has led Ecuador to change its malaria policy from control to that this factor may have in the differences observed between the two elimination, nevertheless, there is no evidence that current interventions parasites species. alone particularly the passive case detection could lead to malaria elimination in the country as it has been reported that a large proportion 1570 of human malaria infections could be asymptomatic. We have studied the malaria prevalence in four communities of an endemic area in northwest DECLINE IN THE BURDEN OF MALARIA IN PREGNANCY IN Ecuador. A total of 650 blood samples were analyzed by microscopy, real SOUTHERN MOZAMBIQUE: EVIDENCE FROM A 14-YEAR time PCR as well as serology using ELISA and immunofluorescence. The PERIOD AND IMPLICATIONS FOR MALARIA ELIMINATION total prevalence of malaria infections in the study area was 8% (98% asymptomatics). This number is comparable to the reported prevalence Raquel Gonzalez1, Francisco Saúte2, Azucena Bardaji1, Sonia in a neighbor endemic area of Colombia (Tumaco) and it implies a much Maculuve2, María Rupérez1, Caterina Guinovart1, Anifa Vala2, Ruth higher prevalence of malaria in the area than expected according to Aguilar1, Esperança Sevene2, John Aponte1, Eusebio Macete2, the official records. Our results infer that the transition from control Pedro L. Alonso1, Clara Menendez1, Alfredo Mayor1 to elimination strategies in a country like Ecuador will demand an 1Barcelona Institute for Global Health, Barcelona, Spain, 2Manhiça Health improvement in malaria diagnostics to detect parasites in asymptomatic Research Center (CISM), Maputo, Mozambique carriers and in infections with low parasite densities as well as a change in the treatment policy. Knowledge of the trends in malaria transmission is essential to evaluate the impact of elimination campaigns. Pregnant women are especially vulnerable to malaria and have been suggested as a potential reservoir of Plasmodium falciparum parasites. The objective of this study was to describe changes in the burden of malaria in pregnancy and its maternal and infant adverse consequences over a 14-year period in southern Mozambique. The study was designed as a retrospective pooled analysis of data collected in five studies that enrolled pregnant women of all gravidities between 1998 and 2012. Temporal changes of maternal P. falciparum infection and pregnancy outcomes, as well as the effect of gravidity and HIV infection on the changes on malaria burden were assessed over the period. 4973 pregnant women contributed to this

astmh.org 480 1572 was 12.5%. With a mean parasitaemia of 356 trophozoites per microliterd with the highest parasitemia at 27300 trophozoites per microliter These CHANGING MALARIA EPIDEMIOLOGY IN UGANDA BETWEEN results show that the malaria profil in DRC is vaery varoius and the control 2011 AND 2014: RETROSPECTIVE ANALYSIS OF KEY effort must be considered differently. MALARIA INDICATORS AND SURVEILLANCE DATA 1574 Bosco B. Agaba1, Peter Okui1, Ann Gasasira2, Humprey Wanzira3, Henry Katamba1, Mathias Kasule1, Belay Kassahun4, Bryan HOW INFECTIOUS IS THE ASYMPTOMATIC RESERVOIR? Kapella4, Emmanuella Baguma5, Lucia Baguma1, Denis Rubahika1, 1 2 3 1 Denis Walusimbi5, Myers Lugemwa1, Anthony Nuwa6, Charles Hannah C. Slater , Chris Drakeley , Teun Bousema , Azra Ghani Katureebe7 1Imperial College, London, United Kingdom, 2Malaria Centre, London 1Department of Disease Control, Malaria Program, Kampala, Uganda, School of Tropical Medicine and Hygiene, London, United Kingdom, 3 2Uganda Malaria Surveillance Project, Kampala, Uganda, 3Department Radboud University, Medical Center, Nijmegen, Netherlands of Disease Control, Malaria Control, Kampala, Uganda, 4U.S. President’s In a malaria endemic population, many individuals will have asymptomatic Malaria Initiative, Kampala, Uganda, 5Clinton Health Access Initiative, infections. These individuals do not seek treatment, so continue to Kampala, Uganda, 6Malaria Consortium Uganda, Kampala, Uganda, infect mosquitoes and continue transmission. In a time where malaria 7World Health Organization, Kampala, Uganda elimination is back on the agenda, identifying and treating these The National Malaria Program has been implementing the malaria 2011- asymptomatic individuals is likely to be a key part of any elimination 2015 strategic plan (MSP) since January 2011. A mid-term review was strategy. An important question yet to be answered is: how infectious is conducted to examine progress against the targets outlined in the MSP, the asymptomatic reservoir, and how much of this reservoir do we need identify key challenges and provide evidence to inform the next 2016- to target to drive the reproductive number of malaria below one? In 2020 strategic planning period. This paper summarizes key findings from this study we use a range of data sources from the published literature the review and their implications on future malaria control plan. The to estimate how infectivity varies across different age groups, different Review was conducted between November 2013 and April 2014. Data to transmission settings, and across the transmission season. We also assess changes in intervention coverage, malaria burden and compliance consider how parasite densities of asymptomatic populations vary, and, to Uganda’s malaria “testing guidelines” were primarily from the HMIS for a given time, how many of these infections are detectable using a (DHIS2). Where available, sentinel surveillance data were used to validate diagnostic such as microscopy or RDT. A study from Burkina Faso estimates HMIS findings and additional data were got from surveys and program that 53% of infected individuals in a population have sub-microscopic reports. We used descriptive statistics to assess changes in intervention parasite densities, and that these individuals contribute 24% to the coverage and generate trends for key malaria indicators. To assess the infectious reservoir. We also find that in areas with high transmission, changes in malaria burden, we analyzed the difference between the Test children are more infectious to mosquitoes than adults, therefore Positivity Rate in the baseline year (2011) and 2014. The proportion of identifying and treating children could be a relatively more impactful way households with 1 LLIN per 2 persons increased from 28% in 2011 to 59.6 to reduce the infectious reservoir. Finally, we use the available information % by end of 2013 while outpatient visits attributed to malaria in under-5s to validate an existing mathematical model of malaria transmission and was recorded to have declined from 52% to 13.7% in the same period. to explore the implications of age- and location-specific infection and In ten districts where IRS has been consistently deployed for 5 years, the infectivity profiles on malaria control interventions. test positivity rate declined by 25%. Malaria Case fatality rate dropped from 2% in 2010 to 0.72% in 2013. Proportion of cases receiving a 1575 parasitological test before treatment improved from 25% in 2010 to 59% in 2013.The MTR was used as an opportunity to identify,collate and DECLINING PARASITE PREVALENCE AND IDENTIFICATION OF analyze data from different sources to evaluate progress in malaria control. NON-PLASMODIUM FALCIPARUM INFECTIONS IN MALARIA- Although our results should be interpreted with caution because of the ENDEMIC SOUTHWESTERN UGANDA inherent data quality problems of routine surveillance systems and low Michelle Roh1, Caesar Oyet2, Gertrude Kiwanuka2, Juliet malaria testing during the review period, the compilation of data from Mwanga-Amumpaire3, Sunil Parikh1, Yap Boum II3 different sources suggests that Uganda has made progress in malaria 1Yale School of Public Health, New Haven, CT, United States, 2Mbarara control and is on track to achieve most of its 2015 intervention targets. University of Science and Technology, Mbarara, Uganda, 3Epicentre Strategies contributing to these successes were evaluated and informed Mbarara Research Centre, Mbarara, Uganda the next strategic planning period Malaria transmission in Uganda is remarkably heterogeneous, and declines 1573 in prevalence have not been uniform. Previous surveys in southwestern Uganda have shown declines in parasite prevalence from 2004 to 2010. MALARIA PREVALENCE IN REPUBLIC DEMOCRATIC OF THE In order to assess the current status of malaria control, we conducted a CONGO: PRELIMINARY RESULTS IN 13 HEALTH ZONES multi-stage cluster sampling cross sectional survey for malaria infection using rapid diagnostic tests and microscopy. 631 children under five years Thierry L. Bobanga1, Dieudonné N. Mumba1, Solange E. of age were sampled from three districts, previously characterized as Umesumbu2, Zimbombe Vulu1, Celestin Manianga1, Celestin N. low (Mbarara), intermediate (Bushenyi), and high (Isingiro) transmission Nsibu1 intensities. Blood samples were collected to determine the presence of 1 University of Kinshasa, Kinshasa, Democratic Republic of the Congo, parasitemia using the following: (1) a combined Plasmodium HRP-2/LDH 2 National Malaria Control Program, Kinshasa, Democratic Republic of the rapid diagnostic test (RDT) (SD Bioline Malaria Ag P.f/Pan), (2) microscopy, Congo and (3) PCR testing for species confirmation. Prevalence of parasitemia was Malaria remains a health problem in the DRC despite interventions today higher by RDT compared to microscopy (6.2% (95% CI: 4.3-8.1) vs. 3.2% conducted a large scale. Few evaluations were conducted in the DRC on (95% CI: 1.8-4.5)). By district, parasitemia prevalence was 1.2% (3/242) in malaria, the country has very little information on the basic indices of Mbarara, 3.2% (5/157) in Bushenyi, and 5.2% (12/232) in Isingiro. All 20 malaria. This makes it difficult to evaluate the interventions and monitor microscopy positive cases were detected by RDT. Of the 19 cases detected their impact. A community survey was conducted in 13 health zones only by RDT, 7 (36.8%) reported having been treated for malaria within in different regions with different epidemiological characteristics The the past month. Notably, of the 20 microscopy positive children, 50% prevalence ranged from 0.4% to 42% respectively at Musienene in North (10/20) were infected with P. falciparum, 40% (8/20) with P. malariae, Kivu Province and Kapolowe in Katanga Province. The average prevalence and the remaining 2 children were P. vivax and P. ovale mono-infections. astmh.org 481 Knowledge, attitudes, and practice regarding malaria prevention were also 1577 assessed, revealing a high proportion of households reporting bednet use (91.6%), but only a small fraction of households participating in indoor EPIDEMIOLOGICAL AND ENTOMOLOGICAL residual spraying (0.8%). Our preliminary findings indicate continued CHARACTERIZATION OF URBAN MALARIA TRANSMISSION significant strides in malaria control over the past 10 years in southwestern IN QUIBDÓ-COLOMBIA Uganda. Combined HRP-2/LDH correctly identified all microscopy positive cases. Most notably, our survey reveals a striking shift in species prevalence Karen Molina-Gómez1, Julio Padilla2, Pablo Chaparro3, Martha L. in this region of Uganda, with nearly 50% of asymptomatic children Quiñones4, Martha Ahumada5, Myriam Arévalo-Herrera6, Sócrates infected with non-falciparum species. PCR confirmation of screening Herrera7 results is currently underway and will be presented. 1Malaria Vaccine on Drug Development Center, Cali, Colombia, 2Ministerio de Salud y Protección Social de Colombia de Colombia, Bogotá, Colombia, 1576 3Instituto Nacional de Salud de Colombia, Bogotá, Colombia, 4Universidad Nacional de Colombia, Bogotá, Colombia, 5Universidad Nacional de MALARIA INFECTION AND GAMETOCYTE CARRIAGE RATE, Colombia, Cali, Colombia, 6School of Health-Universidad del Valle, ASSESSED IN A COHORT OF ADULTS DURING MALARIA Asoclinic Inmunología LTDA, Cali, Colombia, 7Malaria Vaccine on Drug TRANSMISSION BLOCKING ASSAY DEVELOPMENT IN Development Center; Caucaseco Scientific Research Center, Cali, Colombia BANCOUMANA, MALI It is suspected that anarchical urbanization, presence of mosquito vector Issaka Sagara1, Mahamadoun H. Assadou1, Yimin Wu2, Merepen with high adaptability to urban environments, arrival of infected individuals A. Guindo1, Mamady Kone1, Kourane Sissoko1, Moussa L. Diakite1, to communities with low levels of immunity and deficiency of sanity and Sintry Sanogo1, M’Bouye Doucoure1, Sekouba Keita1, Ruth Ellis3, infrastructure contributes to establishment of malaria transmission in Erin Gabriel4, Sara A. Healy5, Patrick E. Duffy5, Ogobara Doumbo1 urban and peri-urban areas. A number of malaria endemic municipalities in Colombia (n=17) have been reported by the National Surveillance System 1University of Bamako, Bamako, Mali, 2Laboratory of Malaria Immunology as having urban malaria transmission, although there is poor evidence and Vaccinology/National Institute of Allergy and Infectious Diseases/ for the presence of autochthonous urban cases. A pilot study is being National Institutes of Health and MVI, Rockville, MD, United States, conducted in Quibdó the municipality with highest amount of reported 3Laboratory of Malaria Immunology and Vaccinology/National Institute cases in order to ascertain urban malaria transmission. The study includes of Allergy and Infectious Diseases/National Institutes of Health, Rockville, malaria active case detection (ACD) and passive case detection (PCD) both MD, United States, 4Biostatistical Research Branch, National Institute of followed by a reactive case detection (RCD), to assess epidemiological Allergy and Infectious Diseases, Bethesda, MD, United States, 5Laboratory and entomological dynamics in selected urban and peri-urban settings. of Malaria Immunology and Vaccinology, National Institute of Allergy and Adult Anopheles mosquitos collected by human landing catches and larval Infectious Diseases, Rockville, MD, United States habitats are being searched neighborhood of malaric houses in urban, For malaria elimination/eradication, transmission blocking tools are peri-urban settings. Preliminary data has been collected from a total of 68 key interventions to be integrated into existing control strategies. houses with 390 inhabitants in the peri-urban (Cabi and Casablanca) and Epidemiological characterization of the transmission reservoirs in endemic urban neighborhoods by ACD. Two positive cases were detected by thick countries are being evaluated in targeted populations prior to the start blood smear (1Pv, 1 Pf) whereas qPCR detected eight (3Pf 5Pv). So far only of phase 1 or 2 transmission blocking vaccine clinical trials in order 1 case (Pv) has been recorded among urban patients who reported not to support study designs and analysis plans. From 2011 to 2014, we having visited endemic areas. RCD of this urban case indicated that neither have followed a dynamic cohort of adults aged from 18 to 50 years, the family nor neighbors had malaria, in contrast, the RCD of the other in Bancoumana, Mali, in order to improve assays that support trials of seven positive cases confirmed by qPCR as index cases indicated that: In transmission blocking vaccines. After community permission, individual peri-urban areas, Casablanca none of the family members of one of the informed consent was obtained for each volunteer. Both National Institute cases was infected, whereas a neighbor of a second case was positive (Pf). of Allergy and Infectious Diseases/NIH in USA and FMPOS IRB in Mali In Cabi, a total of 13 additional cases were found in index case homes approved the study protocol and informed consent documents. Volunteers and 11 more in neighbors’ houses. Of 298 adult mosquitos collected 75% were screened monthly for malaria parasites and gametocytes carriage. were from rural area, 23% peri-urban area and only 1 specimen (0.3%) Passive surveillance and care were also provided to volunteers in cases of urban area where no larvae habitats were found. This data clearly indicate illness throughout the duration of the study. Malaria smears were stained that transmission in Quibdó is mainly peri-urban with so far no evidence using Giemsa and assessed by two different readers for the presence of for urban transmission. malaria parasites. In November, a peak month for parasite carriage, the Plasmodium falciparum infection rates were: 22.58 (14/62), 25.79 1578 (57/221), 32.94 (28/85), respectively in 2011, 2012 and 2014. Likewise, October, a peak month for gametocytes carriage, the gametocyte carriage MALARIA CASES TRENDS IN RWANDA 2001-2014 rates were: 8.57 (6/70), 10.07 (30/298), 6.82 (6/88), respectively in 2011, Corine K. Karema1, Alphonse Rukundo1, Allan Kabayiza1, Kaendi 2012 and 2014. There were no statistically significant differences seen, in Munguti2, Agnes Binagwaho3, Abdisalan M. Noor4 the Plasmodium falciparum infection rate or the gametocyte carriage 1 2 rate between the different years of the study during the peak months Malaria and Other Parasitic Diseases Division, Kigali, Rwanda, President’s of carriage. Malaria infection and gametocytes carriage are sufficiently Malaria Initiative-United States Agency for International Development, 3 4 prevalent in the adult population at the study area to conduct trials that Kigali, Rwanda, Ministry of Health, Kigali, Rwanda, INFORM, Spatial assess the activity of transmission blocking vaccines. Health Metrics Group, Department of Public Health Research, KEMRI/ University of Oxford-Wellcome Trust Research Programme, Nairobi, Kenya Rwanda has achieved signficant progress in scaling up malaria control interventions with reductions of more than 50% of malaria prevalence and incidence countrywide. Rwanda is now considered to be on target to achieve malaria pre-elimination by 2018. However, recently the NMCP Rwanda reported rise of malaria cases for the past 3 years which threatens to undermine these gains. The aim of our study was to investigate the trends in malaria over a 13-year period (2001-2014) and to evaluate the impact of malaria control interventions on malaria burden in Rwanda. Monthly health facility data on countrywide confirmed malaria cases from astmh.org 482 the Rwanda Health information system were assembled for the period 1580 2001-2014. Data were aggregated by district, province and national levels. Time series analaysis was undertaken to describe the trends in malaria THE ROLE OF MATERNALLY DERIVED ANTIBODIES TO cases, slide positivity rate, crude case incidence and the proportion of PLASMODIUM FALCIPARUM SCHIZONT EGRESS ANTIGEN-1 outpatients attendances that were due to malaria. These were matched (PFSEA-1) AND NATURAL EXPOSURE IN THE DEVELOPMENT with a timeline of changes in climate indices, policy and malaria control OF INFANTS’ ANTIBODIES TO PFSEA-1 interventions to contextualise the observed trends. From 2001 there was a generally declining trend in malaria slide positivity rate while cases Sangshin Park1, Sunthorn Pond-Tor1, Edward R. Kabyemela2, numbers were lower compared to the peak of 2005. However, compared Michal Fried3, Patrick E. Duffy3, Jonathan D. Kurtis1, Jennifer F. to 2011, when the lowest case numbers and slide positivity rates were Friedman1 recorded, there was an increase in the malaria burden. The highest 1Center for International Health Research, Rhode Island Hospital, Brown increase for the last 3 years was in the districts of Eastern and Southern University Medical School, Providence, RI, United States, 2Tumaini provinces located in high malaria transmission zones bordering the high University, Moshi, United Republic of Tanzania, 3Laboratory of Malaria transmission countries . Some of the peaks appear to correspond to Immunology and Vaccinology, National Institute of Allergy and Infectious lagged rainfall and temperature changes as well as low malaria control Diseases, National Institutes of Health, Rockville, MD, United States interventions effective coverage. In conclusion, malaria cases have steadily Recently, we demonstrated that antibodies (Abs) to a novel malarial increase in Rwanda in the last three years in Rwanda despite substantial vaccine candidate, Plasmodium falciparum schizont egress antigen-1 scale up in malaria control. The increase in malaria control interventions (PfSEA-1), are associated with protection from severe malaria in children. coverage appear to result in a declining trend as was observed between Few studies have evaluated the impact of passively transferred cord 2005-2008 and 2010-2011. A detailed empirical analysis is required to blood anti-malarial Abs on the development of antimalarial Abs following determine the key drivers of the rising trend. natural exposure in early childhood. The objectives of this study were to a) longitudinally assess the relationship between parasite densities and 1579 subsequent anti-PfSEA-1 Ab levels among young children and b) evaluate TOOLS FOR IDENTIFYING MALARIA HIGH RISK whether higher levels of maternal Abs modified the relationship between POPULATIONS: PILOT OF A CASE-CONTROL METHODOLOGY natural exposure and development of infant anti-PfSEA-1 Ab. A total of IN ZAMBEZI REGION, NAMIBIA 646 Tanzanian infants born between 2002 and 2005 were monitored every 6 months for anti-PfSEA-1 Ab levels until 30 months of age. We Jenny Smith1, Erastus Haindongo2, Carmen Cueto1, Roly used two-way repeated measures analysis of variance to evaluate the Gosling1, Adam Bennett1, Davis Mumbengegwi2, Hugh Sturrock1 changes in anti-PfSEA-1 Ab levels across three levels of both cord blood 1University of California San Francisco, San Francisco, CA, United States, anti-PfSEA-1 Ab and cumulative parasite density in the preceding six 2University of Namibia, Windhoek, Namibia months. Anti-PfSEA-1 Ab levels decreased up to 6 months of age and then began to increase until 24 months. Parasitemia within 6 months after Targeting interventions to populations at high-risk for malaria infection birth induced significantly higher anti-PfSEA-1 Abs at 6 and 12 months remains a challenge in meeting Namibia’s elimination target for 2020. compared to the group without parasitemia (P < 0.05). At 6, 12, and 24 To effectively target infections, it is crucial to better understand the months of age, infants with the highest tertile of average parasite densities demographic, occupational and geographic risk factors for malaria. A for 6 months prior had significantly higher anti-PfSEA-1 level than the case-control methodology, termed the Malaria Elimination Risk Factor non-parasitemic group (P < 0.05). Cord blood Ab level did not modify the Assessment Tool (MERFAT), was piloted between February and May 2015 relationship between parasite density in preceding six months and infant in Zambezi Region, in order to locally characterize high risk groups and anti-PfSEA-1 Ab level, (P < 0.05) suggesting cord blood Ab endowment inform intervention strategies. All malaria cases confirmed by RDT at six does not interfere with Ab development during natural exposure. Malaria randomly selected health facilities were included in the study. Controls exposure influenced anti-PfSEA-1 Ab levels in infants longitudinally, were age and gender-matched to cases using frequency matching within and cord blood anti-PfSEA-1 Ab levels did not dampen acquisition of broad categories and allocated to health facilities based on probability anti-PfSEA-1 Abs during natural exposure, suggesting that vaccinating proportional to size of the health facility catchment population. Following pregnant women is unlikely to interfere with naturally acquired immune an incident case, the first eligible patient who (i) tested negative for responses to PfSEA-1. malaria by RDT or microscopy and (ii) matched a site-specific control profile was recruited into the study, with an aim of matching all cases 1581 within a two-week period. Multivariate logistic regression was used to evaluate potential environmental, socio-demographic, intervention, HETEROGENEOUS PREVALENCE OF ASYMPTOMATIC behavioral and travel-related risk factors. Spatial patterns of malaria risk MALARIA AND LOW PREVALENCE OF HIV IN PREGNANT were also analyzed. We will present descriptive statistics of the case and WOMEN IN MYANMAR control study populations and evaluate spatial clustering of infection over the study area. We will also present results from the risk factor analysis, Kay Thwe Han1, Aung Thi2, Zaw Lin3, Myat Phone Kyaw1, Khin including assessment of environmental, sociodemographic, intervention, Thet Wai1, Kyin Hla Aye1, Poe Poe Aung4, Matthew Adams5, behavioral and travel-related risk factors. Implications for targeting local Shannon Takala Harrison5, Christopher V. Plowe5, Myaing M. intervention strategies by geographical location and to profiled high-risk Nyunt5 characteristics will be discussed, as well as the use of these methods as a 1Department of Medical Research (Lower Myanmar), Ministry of Health, programmatic tool in elimination settings. Yangon, Myanmar, 2National Malaria Control Program, Department of Health, Ministry of Health, Nay Pyi Taw, Myanmar, 3Department of Medical Research (Lower Myanmar), Yangon, Myanmar, 4Burnet Institute Myanmar, Yangon, Myanmar, 5University of Maryland School of Medicine, Baltimore, MD, United States As plans develop to eliminate malaria from Greater Mekong Subregion in hopes of stopping the dissemination of artemisinin-resistant Plasmodium falciparum, malaria infection without clinically recognizable illness is being targeted for drug treatment. It has long been recognized that asymptomatic malaria is common in semi-immune people in parts of sub-

astmh.org 483 Saharan Africa where malaria transmission is moderate or high, and that 1583 asymptomatic malaria during pregnancy in these regions is associated with adverse pregnancy outcomes. However, studies of asymptomatic malaria FOCAL TRANSMISSION OF MALARIA: PREVALENCE AND are very limited in areas of low malaria transmission such as Myanmar, INCIDENCE OF MALARIA IN DANGASSA VS. BAMOGOLA IN particularly in pregnant women. We conducted a prospective longitudinal MALI FROM 2012 TO 2014 cohort study of pregnant women in 12 villages in Shwe Kyin and Madaya, two rural townships in Bago and Mandalay Regions, respectively, in Mahamoudou Toure1, Sory I. Diawara1, Daouda Sanogo1, Myanmar, to estimate the prevalence of asymptomatic malaria over time. Nafomon Sogoba1, Sekou F. Traore1, Seydou Doumbia1, Donald J. Co-infections including HIV and intestinal helminths were also diagnosed. Krogstad2 A total of 699 pregnant women making their first antenatal visit to a rural 1University of Science, Technologies and Techniques, Bamako, Mali, health center were enrolled between August 2013 and October 2014, 2Tulane University, New Orleans, LA, United States and followed monthly for clinical and laboratory evaluations. Blood was During the past decade, the Government of Mali has launched a number collected for hemoglobin measurement, microscopic and PCR analysis of of interventions to improve the prevention and treatment of Plasmodium P. falciparum and P. vivax malaria, and rapid diagnostic testing of HIV. falciparum malaria among the most vulnerable subgroups within the Stool was collected for microscopic examination of ova and parasites and population. The purpose of this study was to examine the prevalence and speciation of intestinal helminths. In preliminary analyses, the prevalence incidence of P. falciparum malaria in Dangassa, a village located in an of falciparum malaria at enrollment ranged from 3-15% and the area of Mali with intense seasonal transmission. In 2011 we performed a prevalence of vivax malaria was less than 1%, and only one participant census to select a representative sample of 1412 persons from the general tested positive for HIV. Results from laboratory analyses, including the population. Because we used a household-based sampling approach, once sequence analysis of K13 molecular marker associated with artemisinin a household was selected, all the members of the household were invited resistance, and longitudinal dynamics of falciparum and vivax malaria will to participate in the study. We then performed five serial (longitudinal) be presented. Preliminary data suggest that the burden of asymptomatic surveys to estimate the prevalence of parasitemia (infection) in the study malaria in pregnancy in Myanmar is higher than expected at some sites, population at the beginning and the end of the transmission season and and heterogeneous across the study sites. during the dry season. A clinician based in Dangassa throughout the year was responsible for passive case detection (PCD) during those two and a 1582 half years in order to assess the incidence of malarial disease. Standard SEASONAL CHANGES IN THE EPIDEMIOLOGY OF MALARIA methods such as rapid diagnostic tests and positive thick smears were used IN THE GAMBIA to identify P. falciparum infection and thus to estimate the prevalence of infection and the incidence of disease (based on PCD). The prevalence of Abdullahi Ahmad, Serign J. Ceesay, Musa Jawara, Alfred parasitemia (infection) varied with the season from 10% in June (at the Ngwa, Muna Affara, Fatou Joof, Ismaela Abubakar, Umberto beginning of the transmission season) to 39% in October (at the peak of D’Alessandro, Davis Nwakanma the transmission season). A similarly low prevalence of 9% was observed Medical Research Council, The Gambia Unit, Banjul, Gambia during the dry season in February. These variations in the prevalence of infection are consistent with the PCD data which indicate that 55% of Recent reductions in the burden of malaria observed in many malaria malaria cases occurred during the four month period from August to endemic areas have mainly been due to improved coverage of malaria November. In addition, 60% of the severe malaria cases occurred during control interventions. To track the progress from these interventions October and November. Despite the use of multiple interventions such and assess their impact, changes in malaria transmission and in the as insecticide-treated bed nets for malaria prevention, the prevalence of disease and immunity patterns needs to be monitored regularly in areas infection (parasitemia) remains high in Dangassa among all age groups where these interventions are deployed. In a prospective cohort study, during the transmission season. Interventions such larviciding and seasonal we enrolled 1402 individuals of all ages and of both genders from malaria chemoprevention may be required to further reduce the burdens 168 households in Gambissara(GMB), Sare Bondo(SBND), Fula Morie of infection and disease in such communities. Boche(FMB) and Sare Jawbe(SJWB) villages located within distance of 3 to 11 kilometres from each other in the upper river region (URR) of The 1584 Gambia. Over malaria transmission seasons of 2012, 2013 and 2014, we followed up the cohort via cross sectional surveys at beginning and MALARIA IN GOLD-MINING AREAS IN COLOMBIA at the end of each transmission season to determine parasite prevalence 1 2 2 by microscopy. In addition, filter paper blood spots for later polymerase Angélica M. Castellanos , Cristhian Morales , Cindy Alegría , 3 4 5 chain reaction analysis and blood samples for later haemoglobin typing Pablo Chaparro , Julio Padilla , Myriam Arévalo-Herrera , Sócrates 2 and determination of prevalence of antibodies to selected malaria parasite Herrera antigens were collected at each survey. Results of 2012 surveys showed 1Malaria Vaccine and Drug Development Center, Cali, Colombia, malaria prevalence was 1.6%(19/1147),10.9%(7/65), 18.1%(21/116) 2Caucaseco Scientific Research Center, Cali, Colombia,3 National Institute and 29.4%(20/68) at the beginning of transmission season and of Health of Colombia, Bogotá, Colombia, 4Ministerio de Salud y 10.7%(97/907), 14.3%(8/56), 35.2%(38/108), and 60.3%(35/58) at the Protección Social, Bogotá, Colombia, 5Facultad de Salud, Universidad del end of the transmission season in GMB, SBND, FMB and SJWB villages Valle, Cali, Colombia respectively. In 2013, malaria prevalence was 2.6%(25/969), 8.1%(5/62), Despite significant decrease in recent years, malaria remains a major public 20.0%(19/95) and 26.2%(16/61) at the beginning of transmission season health problem in Colombia. Among the multiple factors contributing and 4.6%(42/896), 5.4%(3/55), 20.3%(21/103), and 40.0%(21/53) at to malaria maintenance, gold mining appears to play a major role. the end of the transmission season in GMB, SBND, FMB and SJWB villages During the last decades, gold mining mostly illegal and associated to respectively. In 2014, malaria prevalence was 3.4%(31/906), 6.4%(4/62), the military conflict, has significantly expanded in Colombia in areas 14.0%(14/102) and 42.2%(21/54) at the beginning of transmission season with limited health care and disease prevention for the National Malaria in GMB, SBND, FMB and SJWB villages respectively. The wide differences in Control Program, as well as their efficacy and generate a great negative malaria prevalence consistently observed between our study villages over impact on the socio-economic structure of the mining communities. In three transmission seasons suggests heterogeneity in malaria transmission order to set up the bases for more effective malaria control strategies a in the URR of The Gambia. descriptive study has been carried out to characterize the epidemiology and transmission of malaria in gold mining areas. The study focused on determining the prevalence of malaria cases in mining districts of Colombia. Approximately 31.6% of malaria cases from gold mining astmh.org 484 district were reported from Nordeste Antioqueño (Antioquia), Montelibano 1586 (Córdoba) and from Buenaventura (Valle del Cauca) in the Pacific Coast. In Itsmina mining district (Chocó), it was found that 58.5% of malaria GENOME-WIDE ANALYSIS AND DIVERSITY OF PLASMODIUM cases (165/282) displayed clinical symptoms some of them with (52/165) FALCIPARUM IN SOUTHWESTERN NIGERIA warning signs, and 52.8% in adolescents (< 18 years old). While on the 1 2 1 study in Buenaventura was detected that 33% (162/492) of the cases Muyiwa K. Oyebola , Emmanuel Idowu , Adeola Olukosi , 1 2 1 occurred in miner worker specifically from Zaragoza, a rural site near Olusola Ajibaye , Olubunmi Otubanjo , Samson Awolola , Alfred 3 the city which contributed 89% of total cases of the region; most of Amambua-Ngwa them (34%) asymptomatic only detectable by PCR. In conclusion, gold 1Nigerian Institute of Medical Research, Lagos, Nigeria, 2University of mining represents a specific epidemiological scenario of high risk for Lagos, Lagos, Nigeria, 3Medical Research Council, Banjul, Gambia malaria transmission in communities engaged in this activity. The constant The burden of malaria is especially high in sub-Saharan Africa. Varying generation of small and temporary mines creates mosquito breeding sites selection caused by differences in host immunity and antimalarial drug which make it difficult to establish a profile of the vector species involved pressure leads to evolutionary changes responsible for high level of genetic in transmission. Intervention strategies in the mining population have not variations in the parasite. Effective control methods require population- been evaluated but are potentially useful to reduce the disease burden. specific genetic studies to survey for genes under polymorphisms as a The impact on the socio-economic structure of the mining communities result of the influence of drug pressure or host immunity. We performed help to maintain or increase malaria when mining populations migrate a genome-wide analysis of Nigerian isolates of Plasmodium falciparum from or to malaria naïve communities. and used frequency based neutrality test (Tajima’s D) and integrated haplotype score (iHS) to identify genes under selection. Fourteen shared 1585 iHS regions that had at least 2 SNPs with a score > 2.5 were identified. PARALLEL DECLINES IN MALARIAL AND NON-MALARIAL These regions contained genes that were likely to have been under strong directional selection. Two of such genes were chloroquine resistance CHILDHOOD FEBRILE ILLNESS IN WESTERN KENYA transporter (CRT) located in chromosome 7 and multidrug resistance 1 Alastair I. Matheson1, Ondari Mogeni2, Allan Audi3, Godfrey (MDR1) located in chromosome 5. There was a weak signature of selection Bigogo3, Jennifer R. Verani4, Jon Wakefield1, Judd L. Walson1, Joel in dihydrofolate reductase (DHFR) in chromosome 4 and MDR5 genes M. Montgomery4 in chromosome 13 with only 2 and 3 SNPs respectively identified within 1University of Washington, Seattle, WA, United States, 2Kenya Medical the iHS window. Although there was no evidence of recent directional Research Institute/Centers for Disease Control and Prevention Public Health selection in dihydropteroate synthase (DHPS) gene in chromosome 8, and Research Collaboration, Nairobi, Kenya, 3Kenya Medical Research there exists strong selection pressure attributable to continued chloroquine Institute/Centers for Disease Control and Prevention Public Health and and sulfadoxine-pyrimethamine use despite the official proscription; Research Collaboration, Kisumu, Kenya, 4Centers for Disease Control and hence the re-introduction of the drug as was done in other endemic Prevention, Nairobi, Kenya countries after a period of withdrawal may yet be inappropriate. There was also a major selective sweep on chromosome 6 which had 32 SNPs Much of sub-Saharan Africa has recently seen substantial declines in within the shared iHS region. Tajimas’s D values were mostly negative malaria-related childhood morbidity due, in part, to effective control with a mean value of -0.86. One hundred and twelve genes (3.59%) interventions. This has implications both for the etiologies of acute febrile had positive values. Tajima’s D values of Circumsporozoite Protein (CSP), illness (AFI) and demand for healthcare services. Overall childhood AFI Erythrocyte-Binding Antigen (EBA-175), Merozoite Surface Proteins - MSP3 may decline in parallel with malaria or, alternatively, non-malarial AFI and MSP7, Merozoite Surface Protein Duffy Binding-Like (MSPDBL2) may increase due to a reduction in asymptomatic parasitemia that was and Serine Repeat Antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and previously misclassified as malarial AFI. Current research has only described 0.21 respectively. These positive values suggest their candidacy as target changes in rates of malaria rather than AFI overall. We used data from antigens of host immunity. an area of high malaria transmission to examine this issue. We included 11,560 records of visits of children (<5 years) to an outpatient clinic in 1587 western Kenya from Jan. 1, 2009-Dec. 31, 2014. AFI was defined as temperature of ≥38.0°C from any cause and malaria by a positive smear COMPLEXITY OF INFECTION, DIVERSITY AND DRUG result. We used quasi-Poisson regression to explore changes in counts RESISTANCE IN CAMBODIAN PLASMODIUM VIVAX of total, malarial, and non-malarial AFI, and quasi-binomial regression to 1 2 2 examine the change in proportion of AFI that was malaria positive. We Lindsey R. Friedrich , Jean Popovici , Didier Menard , David 1 compared outpatient data with rates of self-reported AFI during regular Serre household visits over the same period. There was marked seasonal 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic variation in numbers of clinic visits for both malarial and non-malarial AFI, Foundation, Cleveland, OH, United States, 2Institute Pasteur in Cambodia, with some commonality to the patterns. We found similar rates of decline Phnom Penh, Cambodia for numbers of total, malarial, and non-malarial AFI visits (0.76%, 0.79%, In Cambodia, malaria is one of the foremost public health problems, with and 0.72% per month, respectively, P<0.01 for all three rates). The 2.5 of the estimated 13 million inhabitants living at risk of contracting probability of a febrile child having malaria varied seasonally but remained the disease. Despite the implementation of extensive control efforts, the constant across each year (P<0.748). Self-reported AFI from household number of reported malaria cases attributed specifically to Plasmodium surveillance declined at a slightly greater rate (0.94% per month, vivax has significantly increased since 1997 and treatment failure to P<0.001). We found no evidence of change in the ratio of malarial to chloroquine (CQ) has been reported. In absence of reliable long-term non-malarial AFI; both decreased at similar rates and may reflect a general in vitro cultures, measures of genetic diversity by using neutral single improvement in the population’s health. Non-malarial AFI declines may nucleotide polymorphisms (SNPs) are useful to characterize P. vivax also stem from introduction of the pneumococcal conjugate vaccine or a population structure, assess impacts of control efforts, and identify link between malaria and risk of other AFI etiologies. Long-term reductions and track parasites lineages through space and time. We developed in outpatient AFI morbidity may be driven by factors other than malaria a genotyping technique to amplify and sequence 130 selected SNPs control programs. distributed throughout the P. vivax genome that are highly variable among Cambodian P. vivax isolates. We first applied this assay to 401 P. vivax-infected patients recruited from nine study sites throughout Cambodia between 2004 and 2013. Our analyses revealed that most P. vivax infections in Cambodia (92%) are polyclonal and confirmed the astmh.org 485 high genetic diversity of this population. Interestingly, our analyses showed South-East Asia. We identify loci under strong, recent, positive selection in that the proportion of monoclonal infections significantly increased these samples, including known drug resistance loci, and we recapture the between 2004 and 2013 suggesting that the control strategies against kelch locus underpinning artemisinin resistance. vivax malaria in Cambodia may be successfully affecting the parasite population. We then analyzed with the same method, blood samples from 1590 23 P. vivax infected patients collected before treatment and every eight hours after CQ treatment to evaluate the relative susceptibility of each PATTERNS OF PLASMODIUM FALCIPARUM GENOTYPES IN clone to CQ compared to the original infection. Combined with on-going AN AREA OF LOW MALARIA TRANSMISSION IN SOUTHERN whole genome sequencing of the parasites before treatment, these data ZAMBIA will enable us to conduct a genome wide association study to hopefully 1 2 1 identify polymorphisms underlying CQ susceptibility in P. vivax. Kelly M. Searle , Ben Katowa , Tamaki Kobayashi , Mwiche Siame2, Sungano Mharakurwa3, William J. Moss1 1588 1Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States, 2Macha Research Trust, Macha, Zambia, 3Biomedical Research A SPATIAL GENETIC-EPIDEMIOLOGICAL MODEL OF MALARIA Training Institute, Harare, Zimbabwe PARASITE TRANSMISSION Understanding the epidemiologic patterns of local malaria transmission Edward A. Wenger and importation is crucial to achieving elimination and preventing re- introduction. A 24 single nucleotide polymorphism (SNP) Plasmodium Institute for Disease Modeling, Bellevue, WA, United States falciparum molecular barcode has been used to identify and track A model of malaria transmission dynamics is presented that tracks the circulating parasite populations. This molecular barcode was used to full genomes of individual Plasmodium falciparum infections including determine the genetic diversity and complexity of the circulating parasite outcrossing of strains both within and between infections. We explore population among malaria infected participants enrolled in a population- quantitatively the relationship between transmission intensity and genetic based, serial cross-sectional cohort study in Choma District, southern observations, for example the repeated observations of identical and Zambia from 2008-2013. In this region the prevalence of malaria by rapid closely related strains and their persistence across successive transmission diagnostic test decreased from 8% in 2008 to <1% in 2013. Parasite DNA seasons. Extending to a spatially connected network of human and was extracted from dried blood spots from approximately 100 infected parasite populations, we model the sensitivity of genetic sequencing to participants using the Chelex method. DNA pre-amplification specific to identify the relative contributions of local hotspots versus re-importation the target sites of each of the 24 SNPs was performed because of the in sustaining transmission in pre-elimination settings. Finally, we model the low level of parasitemia. The molecular barcoding was performed using effects of local transmission intensity and anti-malarial drug pressure on TaqMan genotyping assays on the Applied Biosystems StepOne and the the population-level genetic signatures of emerging drug resistance. Roche Lightcycler. Genotype results were assigned using each system’s software. When the software was not able to identify the allele, the 1589 call was made manually. A subsample of duplicates was analyzed using both the Applied Biosystems and Roche platforms to validate the results. ROBUST SCORING OF MICROSATELLITE MARKERS FROM Analyses were conducted to determine the number of identical molecular NEXT GENERATION SEQUENCING IN PLASMODIUM barcodes within each year and persistent molecular barcodes between FALCIPARUM years. The proportions of mixed infections and polygenomic molecular barcodes were calculated for each year and compared across all years. No Ian H. Cheeseman1, Shalini Nair1, Standwell Nkhoma2, Marina identical barcodes were identified within any year or between years. The McDew-White1, Ashley M. Vaughn3, Richard Pinapati4, Aung P. proportion of samples with mixed infections was high for all years with an Phyo5, Kanlaya Sriprawat5, Francois Nosten5, Stefan H. Kappe3, increasing trend as prevalence declined (90% in 2008, 94% in 2009, and Mike T` Ferdig4, Timothy J. Anderson1 100% in years 2010-2013). The proportion of samples with polygenomic 1Texas Biomedical Research Institute, San Antonio, TX, United States, molecular barcodes decreased from 85% in 2008 to 73% in 2010, then 2Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, increased to 92% in 2011 and 100% in 2012 and 2013. The results Malawi, 3Seattle Biomedical Research Institute, Seattle, WA, United States, suggest that as malaria prevalence declined, local transmission ceased, and 4Notre Dame University, South Bend, IN, United States, 5Shoklo Malaria all infections were imported. Research Unit, Mae Sot, Thailand There are enormous numbers of microsatellites repeats (~1 microsatellite 1591 every 650bp) in the genome of the malaria parasite, Plasmodium falciparum. These markers are multiallelic and therefore more informative COMBINATION OF HEMOGLOBIN-Α2 PROMOTER VARIANTS 3.7 than SNPs for many research questions, yet they are problematic to score AND THALASSEMIA-Α DELETION IS ASSOCIATED WITH using next generation sequence data, and remain an untapped source PLASMODIUM FALCIPARUM ANEMIA of genetic variation for population genomic analyses. We used three Zachary S. Karim1, Prakasha Kempaiah1, Samuel B. Anyona2, approaches to validate scoring of microsatellite loci from next generation John M. Ong’echa3, Douglas J. Perkins1 sequence data: (1) we sequenced the progeny of a genetic cross (n=14), 1Center for Global Health, Department of Internal Medicine, University and examined microsatellite calling in genome regions inherited from of New Mexico Health Sciences Center, Albuquerque, NM, United each parent; (2) we sequenced (in duplicate) parasites from a mutation States, 2Maseno University, Maseno, Kenya, 3University of New Mexico accumulation experiment (n=38), and measured reproducibility and Laboratories of Parasitic and Viral Diseases, Kenya Medical Research accuracy of scoring in >36K microsatellite loci throughout the parasite Institute, Kisumu, Kenya genome. (3) We compared microsatellite genotypes in genome sequence data from 6 single clone patient samples that had previously been Alpha (α)+ thalassemia (α-thal) is a hemoglobinopathy induced by defective scored for 335 microsatellites using traditional capillary electrophoresis. α-globin production which can be characterized by deletions in either These analyses define the robustness with which microsatellites bearing or both hemoglobin (HBA1 and HBA2) genes. Amongst populations different sequence motifs can be scored, and provide a map of callable in sub-Saharan Africa, a 3.7kb (-α3.7) deletion of the region between microsatellites for large scale analysis of malaria parasite populations. To HBA1 and HBA2 results in phenotypes of heterozygous (-α3.7/αα) and examine the utility of these markers for population genomic analyses, we homozygous (-α3.7/-α3.7) carriers. Within sub-Saharan African populations, determined genome-wide patterns of microsatellite variation in sequence severe malarial anemia [SMA, hemoglobin (Hb)<5.0g/dL with Plasmodium data from 50 isolates obtained from a focus of emerging drug resistance in falciparum infection], is a leading cause of morbidity and mortality, astmh.org 486 particularly in children. In the present study, we utilized our findings from 1593 high-throughput genotyping [Human BeadChip’ (>2.45x106 markers)] and global gene expression arrays [HumanHT-12 v4 BeadChip (47,231 ASSOCIATION BETWEEN INTERFERON GAMMA (IFN-Γ) probes)] to identify novel genetic variants. Among the list of significant PROMOTER HAPLOTYPES AND ERYTHROPOIESIS IN KENYAN novel genes, HBA2 emerged as an important gene associated with CHILDREN WITH PLASMODIUM FALCIPARUM MALARIA susceptibility to severe malaria in Kenya children (3-36mos). To validate the whole genome findings, we genotyped two functional promoter SNPs Evans Raballah1, Prakasha Kempaiah2, Zachary S. Karim2, Elly (rs1203833 and rs2974771) in HBA2 (n=1,668 study participants). To Munde3, Douglas J. Perkins4, John M. Ong’echa3 examine the influence of the α3.7 deletion on SMA, this genotype was also 1Department of Medical Laboratory Sciences, Masinde Muliro University generated. Binary logistic regression analysis, controlling for covariates of Science and Technology, Kakamega, Kenya, 2Center for Global Health, (age, gender, G6PD, HIV-1, bacteremia, and HbAS status) revealed University of New Mexico Health Sciences Center, Albuquerque, NM, that carriage of the TA haplotype (-1789T/-4314A) together with the United States, 3Centre for Global Health Research, Kenya Medical Research homozygous α-thalassemia deletion (-α3.7/-α3.7) increased susceptibility to Institute, Kisumu, Kenya, 4Center for Global Health, University of New SMA (OR: 3.2, 95%CI: 1.2-8.4, P<0.05). These results demonstrate that Mexico, Albuquerque, NM, United States variation in HBA2 in combination with α-thalassemia variants influence Plasmodium falciparum malaria is among the leading causes of susceptibility to SMA. morbidity and mortality among African children. In P. falciparum holoendemic transmission areas of western Kenya, severe malaria 1592 commonly manifests as severe malarial anemia [SMA; hemoglobin (Hb) HAPLOTYPES WITHIN THE NFKB1 PROMOTER ARE <5.0 g/dL, any density parasitemia] in pediatric populations. Interferon- γ ASSOCIATED WITH RISK OF SEVERE MALARIAL ANEMIA gamma (IFN- ) is a pleotrophic cytokine associated susceptibility to severe malaria. Since the functional role of IFN-γ genetic variants in conditioning Elly O. Munde1, Zachary S. Karim2, Frank G. Onyambu3, Evans susceptibility to SMA remains largely unexplored, the association between O. Raballah3, John M. Ong’echa3, Collins Ouma4, Prakasha single nucleotide polymorphisms (IFN-γ; -183 G/T, rs2069709 and -1616 Kempaiah2, Douglas J. Perkins2 A/G, rs2069705), their haplotypic structures, and SMA were investigated 1Department of Biomedical Sciences and Technology, School of Public in parasitemic children (n=744, aged 3-36 mos.) presenting at a rural Health and Community Development, Maseno University, Maseno, hospital in Siaya, western Kenya. Bivariate logistic regression analysis, Kenya, 2University of New Mexico, Center for Global Health Research, controlling for age, gender, sickle-cell trait, bacteremia, and HIV-1 status, Albuquerque, NM, United States, 3Centre for Global Health Research, demonstrated that relative to homozygous -1616 A (wild-type) individuals, Kenya Medical Research Institute, Kisumu, Kenya, 4Health Challenges and carriage of GG genotype was associated with protection against reduced Systems Program, African Population and Health Research Center, Nairobi, erythropoiesis [reticulocyte production index (RPI)<2] (OR, 0.564; 95% CI, Kenya 0.323-0.983; P=0.043). Additionally, carriage of the GA haplotype was associated with protection against reduced erythropoiesis (OR, 0.500; 95% Understanding the molecular mechanisms involved in pathogenesis of CI, 0.393-0.637; P<0.001). Conversely, GG (OR, 1.910; 95% CI, 1.504- severe malaria anaemia [SMA, hemoglobin (Hb)<5.0g/dL and any density 2.427; P<0.001) and TG (OR, 6.551; 95% CI, 1.399-30.679; P=0.017) parasitemia)] in children is a crucial step in the design of therapeutics haplotypes were associated with increased risk of reduced erythropoiesis. interventions. Transcription factors are important in modulating cellular Taken together, these results suggest the association between variation in processes, such as immunity, since they are the primary regulators of gene IFNG and SMA may be mediated through the impact of the variants on expression. For example, nuclear factor of kappa light enhancer in B-cells erythropoiesis (NF-κB) plays an important role in infectious and autoimmune disease pathogenesis through regulation of molecular pathways that generate 1594 soluble immune modulators (e.g. cytokines). Imbalances in immune modulators, such as IL-17, are central to the pathogenesis of childhood AUTOMATED METHODS FOR HIGH-THROUGHPUT ANALYSIS SMA. As such, we examined if genetic variation within the NFKB1 OF PLASMODIUM MICROSATELLITE GENOTYPING DATA promoter affected susceptibility to SMA. Functional association between NFKB1 variants (-3297 T>C, rs980455 and -8079A>G, rs747559), SMA, Max Murphy1, Alanna Schwartz1, Yaobao Liu2, Jordan Kemere3, and production of IL-17 was, therefore, determined in children (n=1,065, Michelle Hsiang4, Bryan Greenhouse1 aged 6-36 months) presenting with P. falciparum malaria in Siaya County, 1University of California San Francisco, San Francisco, CA, United States, a holoendemic transmission area of Kenya. Bivariate regression analyses 2Jiangsu Institute of Parasitic Diseases, Jiangsu, China, 3Baylor College of controlling for covariates revealed that carriage of the NFKB1 -8079A/- Medicine, Houston, TX, United States, 4University of Texas Southwestern 3297C (AC) haplotype was associated with increased risk of SMA (OR Medical Center, Dallas, TX, United States 1.60, 95%CI 1.10-2.40, P=0.012). The AC haplotype was also associated Microsatellite genotyping of Plasmodium infections offers some with reduced Hb levels (P=0.001) and low circulating IL-17 levels (P=0.018) advantages, in particular the relatively large diversity present at each locus determined by the Human Cytokine 25-plex Array (Invitrogen). Spearman and the resultant ability to obtain information from mixed infections. correlation revealed that Hb and IL-17 levels were positively associated However, manual classification of electropherogram peaks as true alleles (ρ=0.151, P=0.027). Taken together, these results demonstrate that versus artifact can make this process subjective and time-consuming. variation in the promoter of NFKB1 is associated with susceptibility to To overcome these barriers, we have developed software to analyze pediatric SMA, potentially through altering the downstream expression of microsatellite data in a high throughput and automated manner. These inflammatory mediators, such as IL-17. processes include automated processing of raw data files to carry out basic quality control and identify spectral pull-up, storage of run data in a centralized database, robust automated peak detection, contextual algorithms exploiting patterns identified in artifactual peak stutter on a per microsatellite basis that allow for true peak classification, and a web- based interface for manual curation of data. Using lab-cultured strains of Plasmodium falciparum (Pf) with known genotypes, we quantified segmental linear relationships between allele length and surrounding artifactual “stutter” peaks. With these relationships, we classified peaks as true alleles or artifact. Using 9 lab-cultured strains of Pf in 16 distinct double strain mixtures with relative parasite concentrations ranging from astmh.org 487 2% to 98%, for a total 181 combinations, we identified true alleles 1596 for 9 microsatellite loci. Of these 9 loci, 2 were found to have complex artifact patterns, such as interactions between alleles, not well handled A NEW ASSESSMENT OF THE TRANSCRIPTOMES OF PFSPZ by a linear model and requiring manual curation. For the remaining 7, we AND THREE DAY LIVER STAGES identified true alleles with 94% specificity and 85% sensitivity. On a per 1 2 3 microsatellite basis, specificity ranged from 83% to 98% and sensitivity Malcolm J. Gardner , Liliana Losada , Yun Wu , Sumana 4 2 3 ranged from 76% to 97%. Automated peak classification shortens time Chakravarty , William Nierman , B. Kim Lee Sim , Stephen L. 4 from experiment to results and reduces bias incurred by manual analysis Hoffman and makes possible high-resolution genotyping. 1Global BioConsulting, Shoreline, WA, United States, 2J. Craig Venter Institute, Rockville, MD, United States, 3Protein Potential, Rockville, MD, 1595 United States, 4Sanaria, Rockville, MD, United States PRELIMINARY STUDY: DIFFERENT POPULATION STRUCTURE Over the last 20 years, genomics, transcriptomics, and proteomics have provided fascinating insights into Plasmodium biology and pathogenesis, OF PLASMODIUM VIVAX BETWEEN SYMPTOMATIC AND contributing to basic research and development of new diagnostics, ASYMPTOMATIC PATIENTS FROM PERUVIAN AMAZON drugs, and vaccines against malaria. The opportunity to understand the Henry Herrera1, Julio Miranda1, Paulo Manrique1, Oscar Nolasco1, biology of sporozoites and exoerythrocytic stages has arisen due to the Ananias Escalante2, Alejandro Llanos-Cuentas3, Joseph Vinetz4, ability to produce large quantities of these stages for analysis. We assessed Dionicia Gamboa1 aseptic, purified, and viable P. falciparum salivary gland sporozoites, and sporozoites that were axenically transformed, morphologically similar 1Departamento de Ciencias Celulares y Moleculares, FCF, Universidad to 3-day ‘liver stage’ parasites expressing new proteins. We used next Peruana Cayetano Heredia, Lima, Peru, 2Institute for Genomics and generation sequencing to profile transcripts expressed in sporozoites, Evolutionary Medicine, Temple University, Philadelphia, PA, United States, axenic 72-hr liver stages, and asexual stages in order to uncover the 3Instituto de Medicina Tropical Alexander von Humboldt, Universidad molecular, biochemical, and cell biological processes that occur across the Peruana Cayetano Heredia, Lima, Peru, 4University of California San Diego, parasite’s life cycle. San Diego, CA, United States Different diagnostic methods have revealed a high frequency of 1597 Plasmodium vivax infections that occur without clinical symptoms. Furthermore little is known about its implications in the transmission THE HUMAN PRENATAL ANTIBODY RESPONSES TO dynamics of these infections and their relationship with the parasite PLASMODIUM FALCIPARUM population structure. The aim of this study was to explore the parasite 1 1 population structure of symptomatic and asymptomatic patients from Samuel Tassi Yunga , Anna Babakhanyan , Livo Esemu 2 1 2 Cahuide, a rural community located 60 km away from Iquitos city. To Forju , Obadia Mfuh Kenji , Jean-Claude Djontu , Philomena 2 2 2 achieve our goal, 20 microsatellites were amplified (a new set of 11 Gwanmesia , Emile K. Yuosembom , Rose G. Leke , Diane W. 1 markers and 9 previously reported) in a selected group of samples. In Taylor this way, 113 P. vivax positive field samples were collected in March (55 1University of Hawaii, Honolulu, HI, United States, 2The Biotechnology samples) and June 2013 (58 samples) by active case detection. 25 Samples Center, University of Yaounde 1, Yaounde, Cameroon were excluded due to low parasitemia levels and the 88 remaining In malaria endemic areas, the fetus may be exposed to malarial antigens samples were used for microsatellite analysis. Microsatellite PCRs were in utero and produce sensitized B and T lymphocytes. Most of our performed and subsequently analyzed using an ABI PRISM 3100 avant knowledge of in utero responses to malaria comes from studies of full genetic analyzer. Out of 88 samples, 24 were polyclonal whereas 64 were term newborns. Little is known about the timing of malaria-specific monoclonal, but just 50 had an almost-complete allele profile (75% or immune responses in utero. This study investigated the timing of in utero higher). Our results showed an average genetic diversity of 0.47 and 39 antibody (Ab) responses to P. falciparum (Pf) antigens. Since B1-cells are haplotypes were found. Interestingly, the diversity found in June was functional during prenatal life, the possibility of innate B1-derived Ab to greater than in March (0.58 and 0.38 respectively). Using Structure ver2.3, Pf was also explored. Plasma samples from 600 Cameroonian neonates 2 sub-populations (A and B) were found arranging by month (March 2013 were studied: 373 full-term deliveries (FTD, ≥37weeks) and 227 pre-term and June 2013) and by symptomatology (symptomatic and asymptomatic deliveries (PTD, <28 weeks [n=33], 28-33 weeks [n=100] and 34-36 patients). In March sub-population A was mainly found in asymptomatic weeks [n=94]). Since IgM does not cross the placenta, fetal IgM in cord patients while sub-population B was predominant in the symptomatic plasma was quantified to a panel of 8 Pf antigens (PfAg) and to known ones. In contrast, in June sub-population A was predominant in the B1 antigens phosphorylcholine (PC) and pneumococcal polysaccharides symptomatic patients and both sub-populations were equally distributed in (PP). IgG to PfAg was also measured in culture supernatants of cord blood the asymptomatic ones. This data suggests that the asymptomatic patients mononuclear cells (CB-MNC) (n=70). Placental malaria (PM) was assessed carrying sub-population A might have served as a reservoir for further from placental impression smears. IgM to one or more PfAg was detected infections of the symptomatic patients. This study provides a first approach in 10.6% of the neonates, with similar prevalence and titers in PTD and of the role of asymptomatic patients in malaria transmission which should FTD. IgM to PfAg was detected at 22 weeks of gestation and throughout be considered within the malaria control strategies. the 2nd and 3rd trimesters. PfAg IgM was significantly associated with PM in PTD and FTD (p=0.01). The proportion of PC IgM responders was not influenced by PM (p=0.83) and 51% of PC IgM-positive newborns were Pf IgM negative, suggesting that in utero “innate” Ab were not directly induced by malaria. Overall, 65% of culture supernatants from 70 CB-MNC cultures had IgG to one or more PfAg. In summary, the data show that fetal B cells made Pf-specific IgM Ab from as early as 22weeks of pregnancy through birth. Many of the newborns also had Pf-specific IgG-producing cells at delivery. B1-derived Ab were not associated with malaria. Studies are in progress to determine if in utero exposure to Pf leads to the production of short-lived antibody secreting cells or memory B cells.

astmh.org 488 1598 2011-13 (FIS). We measured IgG levels detected by bead array recognizing 20 P. falciparum (Pf) antigens and 14 P. vivax (Pv) antigens. ICs were IMMUNE PROFILING OF PLASMODIUM FALCIPARUM measured using a C1q-based ELISA. Tetanus toxoid (TT) IgG levels served ENDEMIC SERA USING BESPOKE PROTEIN MICROARRAYS as controls. Placental malaria (PM) prevalence was 59%, MHG (≥1700mg/ dL) was 54%, and high IC (≥0.85 mg/ml) was 30% in the AXH cohort; 1 2 3 4 Kevin K. Tetteh , Danica Helb , Federica Verra , Teun Bousema , compared to 10%, 7% and 10% respectively in the FIS cohort. Differences 5 6 1 Luisa Nunziangeli , Andrea Crisanti , Eleanor Riley , Bryan were statistically significant with p values of <0.0001, 0.0034, and 0.0004. 2 1 Greenhouse , Chris Drakeley The cord to maternal transfer ratio (CMTR) was significantly lower in the 1London School of Hygiene & Tropical Medicine, London, United Kingdom, AXH cohort for almost all anti-malaria antibodies (Ab), compared to the 2University of California San Francisco, San Francisco, CA, United States, FIS cohort (P <0.001). Impaired transport of malaria-specific IgG (CMTR 3University of Rome “La Sapienza”, Rome, Italy, 4Radboud University <1) ranged from 66% to 92% in AXH compared to 48% to 84% in FIS. Nijmegen Medical Centre, Nijmegen, Netherlands, 5Universita Degli Studi By contrast, transplacental transport of TT-specific IgG was the same Di Perugia, Terni, Italy, 6Imperial College London, London, United Kingdom between the two cohorts and averaged of 35% impaired transport. A multivariate model showed a strong negative effect of MHG (P=0.0013), The complex nature of the Plasmodium falciparum life cycle coupled but no association of PM or IC, on transplacental transfer of TT Ab. By with the further complexities of antigenic polymorphism presents a contrast, impaired transplacental transfer of Pf and Pv antibodies was significant challenge for the design of an effective vaccine against malaria. associated with MHG, PM and IC with p values of <0.01, <0.001, and There is a strong body of evidence that supports antigens expressed by <0.001 respectively. There was an interaction between MHG, PM and IC P. falciparum merozoites as important targets of human immunity and for some antigens, but those factors were also independently associated therefore promising vaccine candidates. However, the specific targets with impaired transplacental transfer of malaria-specific IgG.The negative of protective immunity remain elusive. Therefore identifying candidate correlation of PM and IC only with Pf and Pv Ab but not with TT suggest antigens that correlate with a protective immune response remains a receptor saturation and/or trapping of Abs rather than impaired placental priority. We have developed an antigen production pipeline based on function are the primary factors reducing transplacental Ab transfer. E. coli for the expression of purified recombinant antigens. By applying a number of in silico tools intended to aid the design of each antigen construct, we have focused on key regions, where appropriate, of each 1600 target gene avoiding the wholesale expression of candidate open reading THE TIMING OF MALARIA INFECTION DURING PREGNANCY frames. Using this approach we have been able to avoid difficult to express INFLUENCES THE TYPE OF FETAL IMMUNE RESPONSE regions (e.g. transmembrane domains) and achieve expression of soluble constructs with a >90% success rate. Each antigen is then screened by Celia Dechavanne1, Roslyn Tobby2, Phantica Yambo2, Daisy ELISA and validated for reactivity to a subset of positive and negative Mantilla2, Alice Sato1, Maria Ome-Kaius2, Indu Malhotra1, Stephen control sera. Using protein microarrays we have screened approximately 94 Rogerson3, Peter Siba4, Leanne Robinson2, Christopher Lee King1 validated antigens, many of which represent new, previously undescribed 1Case Western Reserve University, Cleveland, OH, United States, 2Papua targets across a range of lifecycle stages. So far this panel largely focusses New Guinea Institute of Medical Research, Madang, Papua New Guinea, on the merozoite stage (81%) but also includes proteins associated with 3University of Melbourne, Parkville, Australia, 4Papua New Guinea Institute the infected erythrocyte (18%) and sporozoite (1%) stages. Work is of Medical Research, Goroka, Papua New Guinea currently ongoing to address this unintended bias. Comparison of data between the protein microarray and ELISA platforms using key validatory Epidemiological studies show that infants born to mothers with antigens, PfMSP1-19 and PfAMA, showed a strong correlation between Plasmodium falciparum (Pf) malaria during pregnancy have a higher risk the platforms (r2=0.78 and 0.73, respectively). Antibody reactivities from of malaria infection in early childhood. This increased risk is associated 350 individuals assayed at three time points (1050 sera total) from a region with whether the fetus has been exposed to malaria in utero and the of high endemicity in Northern Uganda were used to determine reactivity generation of an immunoregulatory phenotype characterized by high profiles for each antigen. Preliminary analysis has identified a number IL-10 and low IFNg/IL-13 production that persists into early childhood. of novel immune-reactive targets for prioritisation as putative vaccine Why some fetuses acquire this immunoregulatory phenotype and candidates. others do not may relate to when the fetus is exposed to malaria during gestation. To examine this hypothesis, mothers were randomly assigned to 1599 receive intensive or limited malaria chemoprophylaxis during pregnancy. Depending on the gestational age at the time of enrolment and study IMPACT OF MALARIA, HYPERGAMMAGLOBULINEMIA, AND arm, mothers were protected from malaria during defined times during IMMUNE COMPLEXES ON TRANSPLACENTAL TRANSFER pregnancy. Cytokine levels in cord plasma and/or cord blood mononuclear OF MALARIA-SPECIFIC AND ANTI-TETANUS TOXOID cells from 407 newborns defined the type of immune response. Cytokine ANTIBODIES IN PAPUA NEW GUINEA responses were measured in culture supernatants, by flow cytometry of lymphocyte subsets and transcript levels by quantitative PCR following Fernanda L. Alvarado1, Indu Malhotra1, Phantica Yambo2, stimulation with Pf schizont extract and/or recombinant PfMSP1. Jessica Atwell3, Célia Dechavanne1, Maria Ome-Kaius2, Peter Siba2, Preliminary results indicate malaria exposure during the second trimester Stephen Rogerson4, Leanne J. Robinson2, Christopher L. King1 compared to the third trimester is associated with elevated IFNg and low 1Case Western Reserve University and Veterans Affairs Medical Center, IL-10 levels. By contrast the offspring of women exposed to malaria during Cleveland, OH, United States, 2Papua New Guinea Institute of Medical the third trimester was associated with higher IL-10 levels relative to IFNg Research, Goroka, Papua New Guinea, 3Johns Hopkins School of levels. More complete results will be available by the time of the meeting. Public Health, Baltimore, MD, United States, 4University of Melbourne, These results suggest that the timing of malaria infection during pregnancy Melbourne, Australia differently affects the newborns’ lymphocyte responses and thus implications for the timing and frequency of malaria chemoprophylaxis Malaria in pregnancy (MIP) can induce placental alterations during pregnancy. (PM), malaria-specific immune complexes (IC), and/or maternal hypergammaglobulinemia (MHG) that may interfere with transplacental transfer of immunoglobulin G (IgG). To determine the relative roles of these factors in IgG transfer, 300 paired maternal and cord serum specimens were collected from two geographically similar cohorts in Papua New Guinea in 2005-08 (AXH) and after malaria control interventions

astmh.org 489 1601 1602 RELATING ANTIBODIES TO THE SURFACE OF PLASMODIUM MALAWIAN NEWBORNS SHARE A VARIANT SURFACE FALCIPARUM-INFECTED ERYTHROCYTE WITH CLINICAL ANTIGEN ANTIBODY REPERTOIRE WITH THEIR MOTHERS OUTCOMES THAT IS AFFECTED BY MATERNAL MALARIA INFECTION IN PREGNANCY Oumar Attaher1, Kadidia B. Cisse1, Almahamoudou Mahamar1, Moussa B. Kanoute1, Bakary S. Diarra1, Sekouba Keita1, Adama Mark Travassos1, Jenny A. Walldorf1, Jason A. Bailey1, Sarah Dembele1, Gaoussou Santara1, Djibrilla Issiaka1, Moussa Traore1, Boudova1, Titus Divala2, Randy Mungwira2, Patricia Mawindo2, Bruce Swihart2, Patrick E. Duffy3, Alassane Dicko1, Michal Fried3 Jozelyn Pablo3, Algis Jasinskas3, Rie Nakajima3, Matthew Adams1, 1Malaria Research & Training Center, Faculty of Medicine, Pharmacy and Terrie Taylor4, Philip L. Felgner5, Christopher V. Plowe6, Miriam K. Dentistry, University of Sciences Techniques and Technologies of Bamako, Laufer6 Bamako, Mali, 2BRB, National Institute of Allergy and Infectious Diseases, 1Center for Malaria Research, Institute for Global Health, University of National Institutes of Health, Rockville, MD, United States, 3Laboratory of Maryland School of Medicine, Baltimore, MD, United States, 2Blantyre Malaria Immunology and Vaccinology, National Institute of Allergy and Malaria Project, University of Malawi College of Medicine, Blantyre, Infectious Diseases, National Institutes of Health, Rockville, MD, United Malawi, 3Division of Infectious Diseases, Department of Medicine, States University of California Irvine, Irvine, CA, United States, 4Blantyre Malaria Project, University of Malawi College of Medicine and Department In areas of high malaria transmission, immunity to disease develops more of Osteopathic Medical Specialties, College of Osteopathic Medicine, rapidly than immunity to infection. Proteins expressed on the surface of Michigan State University, East Lansing, Michigan, Blantyre, Malawi, infected erythrocytes (IE) have been described as the targets of immunity 5Division of Infectious Diseases, Department of Medicine, University of to malaria. Chan et al 2012, reported that the presence of antibodies California Irvine and Antigen Discovery, Irvine, CA, United States, 6Center to 3D7 parasite line is associated with a reduced risk of developing for Malaria Research, Institute for Global Health, University of Maryland symptomatic malaria. Here, in the context of a longitudinal birth cohort School of Medicine, Baltimore, MD, Baltimore, MD, United States we examined prospectively the association between antibodies to surface IE of parasites circulating among the children and protection from clinical In malaria-endemic regions, severe malaria in infants is rare. Protection malaria and reduction in parasite density. The study was conducted in may be attributable to maternal antibody transfer during pregnancy. Ouelessebougou Mali, where malaria transmission is highly seasonal. Parasite antigens expressed on the surface of infected erythrocytes are Antibodies to IE surface proteins in plasma were measured by flow associated with severe malaria pathogenesis. We hypothesized that cytometry. The analysis included samples from 125 children at the end of the repertoire of antibodies to these variant surface antigens (VSAs), the transmission season and at the end of the dry season. Median (range) particularly Plasmodium falciparum erythrocyte membrane protein-1 age of the children at the two time points were 17.9 (6-32) and 21 (9.3- (PfEMP1) antigens, is transferred to newborns, potentially providing 39) months. IgG levels were defined as geometric MFI after subtracting protection against severe malaria. A protein microarray was printed with MFI with uninfected erythrocytes and reactivity with plasma from naïve 176 fragments of PfEMP1s based on the 3D7 reference genome, including donors. On average children included in this analysis experienced 2.2 both extracellular and intracellular fragments, along with three repetitive malaria infections (range 0-12) and 1.4 clinical malaria episodes (range interspersed family proteins (RIFINs), and six sub-telomeric variable open 0-5). The proportion of parasite isolates recognized by the plasma samples reading frame proteins (STEVORs). Seroreactivity to these fragments was and the level of reactivity did not predict protection from clinical malaria. measured in the second trimester for 36 Malawian mothers in their first or Similarly, antibody reactivity with surface IE proteins was not associated second pregnancy and compared to seroreactivity at delivery and in cord with reduced parasite burden. Here, the children were younger than blood samples of their newborns. Eleven mothers had evidence of malaria subjects included in previous studies that reported increased IE recognition infection in the placental or peripheral blood during pregnancy. Reactivity with age that could account for the different results. Alternatively, we to VSAs was higher in sera from women with evidence of malaria infection hypothesize that functional antibodies such as those that inhibit parasite versus women who did not have malaria during pregnancy at both adhesion may be more strongly associated with reduced risk of clinical enrollment and delivery and extended to the cord blood of newborns. malaria and parasite density, and these studies are ongoing. We will Overall, seroreactivity intensity to VSAs was similar in cord blood compared present data relating anti-adhesion antibodies with surface IE recognition, to mothers at delivery. However, for mothers who did not have malaria and the association between anti-adhesion antibodies to multiple during pregnancy, seroreactivity for several VSAs was higher in the infant receptors and the risk of malaria disease and parasite density. than in the mother. These findings indicate that malaria infection during pregnancy may interfere with antibody transfer and may lead to increased risk of malaria disease during infancy. Future work will examine malaria infection and disease vis-à-vis the rate of decline of VSA antibodies in this infant cohort over time. 1603 CYTOKINE PROFILE IN HELMINTH AND MALARIA INFECTIONS AMONG AFEBRILE AND FEBRILE CHILDREN IN IBADAN, SOUTHWEST NIGERIA George O. Ademowo, Ayokulehin M. Kosoko, Olawunmi R. Rabiu, Hannah A. Dada-Adegbola, Ganiyu O. Arinola, Catherine O. Falade College of Medicine, University of Ibadan, Ibadan, Nigeria Intestinal helminths and malaria are among the most prevalent infectious diseases in the tropics. The effect of coinfections on immune response is not clearly understood. We therefore investigated the immune response profile in children with and without symptoms. A total of 78 afebrile school children (20 helminth-malaria co-infected, 17 helminth infected, 19

astmh.org 490 malaria infected and 22 uninfected) and 75 febrile children (14 helminth- 1605 malaria co-infected, 16 helminth infected, 20 malaria infected and 25 uninfected) were recruited into the study. Helminths were screened using CHARACTERIZATION OF NATURALLY ACQUIRED BINDING- Kato Katz method while malaria parasite screening was done using INHIBITORY ANTIBODIES AGAINST PLASMODIUM VIVAX Giemsa-stained thick blood films. Circulating TNF-α, IFN-γ, IL-1, IL-10 DUFFY BINDING PROTEIN IN RURAL AMAZONIA and IL-6 concentrations were assessed by ELISA from serum samples. Data were analysed using analysis of variance. Among the afebrile school Sarah Frischmann1, Vanessa Nicolete2, Michael Razavi1, Marcelo children, IL-10 was significantly increased in helminth infected children Ferreira2, Christopher King1 compared with helminth-malaria co-infected, malaria infected and 1Case Western Reserve University, Cleveland, OH, United States, 2University uninfected groups (p<0.05). IFN-γ was significantly elevated in malaria of Sao Paulo, Sao Paulo, Brazil and malaria-helminth coinfection relative to helminth alone (p<0.05). IL-1 Plasmodium vivax (Pv) invades human reticulocytes requiring an level was significantly higher in single infection of helminth and malaria interaction of the parasite ligand, Duffy Binding Protein (PvDBPII), with relative to coinfection and the uninfected groups (p<0.05). An insignificant an erythrocyte membrane protein known as the Duffy antigen/receptor difference was observed for IL-6 and TNF-α concentrations across all the for chemokines or DARC. Some Pv exposed subjects acquire functional four groups while among febrile children, IL-6 was significantly increased antibodies that block binding of PvDBPII to DARC (Fy), partially inhibit Pv among helminth alone and helminth-malaria coinfection relative to malaria invasion of reticulocytes in vitro, and correlate with protection against infected group (p<0.05). IL-10 was significantly elevated in co-infected Pv malaria. PvDBPII is highly polymorphic and DARC has a polymorphism group compared with helminth or malaria infected group while TNF-α which influences PvDBPII binding to DARC. The frequency, persistence, and was significantly increased in helminth and helminth-malaria coinfection strain-specificity of these naturally acquired binding-inhibitory antibodies compared with uninfected or malaria infected group (p<0.05). IFN-γ level (BIAb) under changing malaria transmission conditions have been poorly was insignificant in the infection groups relative to uninfected group characterized. We measured BIAbs from 587 samples from 271 individuals (p<0.05). IL-1 level similar across the groups. Helminth infection seem seen 1-8 times in serial cross-sectional surveys, conducted in the Brazilian to upregulate Th2 immune response among children with symptomatic Amazon between 2010 and 2014, when malaria transmission dropped uncomplicated malaria while there was no significant changes in Th significantly. 82% of malaria infections were Pv. Binding inhibition was immune response among afebrile children. measured using an ELISA-based format to look at binding between DARC and multiple PvDBPII variants. Samples with greater than 80% binding 1604 inhibition relative to a North American control were defined as high BIOSIGNATURES OF NATURALLY ACQUIRED IMMUNITY blockers. We found 17% of unique individuals tested had high blocking UNDER CHANGING MALARIA TRANSMISSION IN MALARIA activity and the proportion of individuals with high blocking activity increased with age. Once high levels of BIAb were obtained, the majority ENDEMIC AREA OF PAPUA NEW GUINEA of individuals with repeated sampling retained high blocking activity even Gabriel Frato1, Leanne Robinson2, Maria Orme2, Robert Fort1, Ivo in the presence of declining Pv transmission. Some individuals retained Mueller3, James Kazura1, Peter Siba2, Christopher L. King1 high blocking activity with titers as high as 1:640. For most individuals, 1Case Western Reserve University, Cleveland, OH, United States, 2Papua blocking activity was strain-specific - apparent when samples were titered. New Guinea Institute of Medical Research, Madang, Papua New Guinea, The presence of DARC polymorphisms affected acquisition of high BIAbs; 3Walter and Eliza Hall Institute of Medical Research, Parkville, Australia 4% of the FyA/Fy- (reduced binding) compared to 16% of all other DARC phenotypes associated with higher binding (p=0.065). The presence of A simple blood test that assesses levels of naturally acquired immunity high BIAbs may represent a biomarker of naturally acquired immunity (NAI) would provide a critical tool to monitor the impact of interventions in some individuals and may suggest induction of high blocking activity to reduce malaria transmission and broaden our understanding of how following vaccination with rDBPII, predicting strain-specific protection NAI develops around the world as a function of age and exposure. against Pv. Since antibodies (Abs) are important in mediating malaria immunity, we postulate when an individual acquires a certain threshold of Abs to panel 1606 of malaria antigens (Ags), they become clinically immune to malaria. To examine this hypothesis, we measured immunoglobulin G (IgG) Abs to ANTIBODY SEROREACTIVITY TO PLASMODIUM FALCIPARUM a panel of 32 Plasmodium falciparum (Pf) and P. vivax (Pv) antigens, ERYTHROCYTE MEMBRANE PROTEIN 1 DOMAINS AND using a multiplex bead array assay. Samples were collected from two CLINICAL PRESENTATION OF MALARIA IN MALIAN CHILDREN geographically similar cohorts of children aged 5-14 years. The first cohort was completed before malaria control measures (Mugil I, 2004, N=206) Jason A. Bailey1, Amed Ouattara1, Drissa Coulibaly2, Matthew and the second cohort was completed following malaria control measures B. Laurens1, Matthew Adams1, Shannon T. Harrison1, Kirsten E. (Mugil II, 2012/13, N=433). Children who were treated with antimalarials Lyke1, Christopher G. Jacob1, Jozelyn Pablo3, Rie Nakajima3, Aldis at enrollment were observed prospectively for malaria reinfection. High Jasinskas3, Amadou Niangaly2, Mahamadou A. Thera2, Ogobara IgG levels to Pf microneme, rhoptry and EBA proteins, which are involved K. Doumbo2, Philip L. Felgner3, Christopher V. Plowe1, Mark A. in merozoite invasion of erythrocytes, were strongly associated with Travassos1 protection against clinical malaria, similar to previously published studies 1University of Maryland, Baltimore, Baltimore, MD, United States, from the same cohort. High IgG levels to Pv microneme, rhoptry and some 2University of Sciences, Techniques and Technologies of Bamako, Bamako, merozoite proteins were significantly associated with protection against Pv Mali, 3University of California Irvine, Irvine, CA, United States infection. IgG levels to almost all the proteins were significantly lower in A strong correlate for protection from malaria disease has been largely subjects from the Mugil II versus Mugil I cohorts although some individuals elusive. Plasmodium falciparum erythrocyte membrane protein-1 retained high malaria-specific IgG levels associated with protection in the (PfEMP1) is a parasite surface adhesion protein implicated in malaria Mugil I cohort. Analysis is currently underway to assess whether individuals pathogenesis, particularly for placental and cerebral malaria. We probed that sustained high Ab levels corresponding to the protective threshold a diversity-reflecting protein microarray with pre-rainy season sera found in the Mugil I cohort also confer protection in the Mugil II cohort. collected from 75 children one to six years of age enrolled in a malaria These analyses will be completed by the time of the meeting. This study vaccine trial in Bandiagara, Mali. The array was populated with protein identifies Ags that are possible targets of protective immunity and/or fragments representing coupled domains of all PfEMP1 proteins in the biosignatures of immunity in malaria surveillance and control. laboratory reference strain 3D7. Clinical malaria outcome was defined as parasitemia (>2500 parasites per ul) and presence of fever (>37.5C) during

astmh.org 491 unscheduled clinic visits during 240 days of follow up. Using a Kaplan- 1608 Meier survival analysis, children with above-mean PfEMP1 seroreactivity at baseline had a delayed time until first clinical malaria episode versus those LIVER STAGE MALARIA INDUCES INTERFERON-DEPENDENT with below-mean PfEMP1 seroreactivity. Lower pre-season seroreactivity to GENE EXPRESSION IN HEPATOCYTES PfEMP1 domains was associated with an increased odds of having at least one clinical malaria episode, controlling for covariates. Pre-season PfEMP1 Jessica Brownell, Alyse Douglass, Nadia Arang, Brandon Sack, seroreactivity was significantly associated with time to clinical malaria Alexis Kaushansky, Stefan Kappe episode in a multivariable Cox proportional hazards model; suggesting that Seattle BioMed, Seattle, WA, United States antibodies directed at PfEMP1 may have an association with protection Malaria is a serious global health problem that causes substantial morbidity distinct from other malaria antigens. In addition, pre-season seroreactivity and mortality in developing countries. Infection is caused by Plasmodium to CD36 binding PfEMP1 domains correlated with increased time until sporozoites, which are transmitted to a mammalian host through a bite clinical malaria episode compared to non-CD36 binding domains. These from an infected female Anopheles mosquito. Sporozoites then travel results suggest the importance of PfEMP1 antibodies in the prevention or from the skin to the liver, invade hepatocytes, and quickly replicate to delay in the progression of more severe instances of symptomatic malaria, produce tens of thousands of first generation infectious merozoites. particularly when compared to antibodies directed at other malaria These merozoites initiate the blood stage infection that is responsible for candidate vaccine antigens. Multivariable regression models are particularly symptomatic illness. Live-attenuated sporozoite vaccination can prevent powerful in using protein microarray results to identify antigens associated the onset of disease by inducing sterile, adaptive immunity against liver with natural protection against malaria. stage infection. However, few studies have explored whether parasite liver infection engenders localized innate immune responses as well. 1607 Recent studies in our laboratory have shown that Plasmodium induces INTERFERON GAMMA AND INTERLEUKIN-10 PROFILE IN type I interferon (IFN) responses in the liver, and that these responses can protect from a secondary liver stage infection. We show here that these PATIENTS WITH PLASMODIUM FALCIPARUM MALARIA type I IFNs are produced by infected hepatocytes and coincide with the INFECTION IN LAGOS, NIGERIA induction of pro-inflammatory Interferon Stimulated Genes (ISGs) such as Uche T. Igbasi, Wellington A. Oyibo the chemokine CXCL10 and the anti-viral protein Viperin. Furthermore, we demonstrate that Plasmodium infection of hepatocytes impacts ANDI Centre of Excellence for Malaria Diagnosis, College of Medicine expression of the JNK signaling pathway in a type I IFN-dependent University of Lagos, Idi-Araba, Lagos, Nigeria manner. Future work will help uncover how these initial responses impact Malaria is the world’s most prevalent parasitic disease and is a top public inflammatory gene expression, liver stage parasite growth, and the health concern although currently, its control and interventions has progression to blood stage infection. This knowledge will have significant been scaled up in Nigeria. Challenges encountered in the design of a impact on the selection and use of adjuvants in the future development of successful vaccine against Plasmodium are our dearth knowledge of vaccines targeting the liver stage of malaria infection. protective immunity and how it can be induced. The immune response to Plasmodium falciparum infection involves interplay between 1609 different cell types and cytokines. Therefore, a greater appreciation of the mechanisms of protective immunity and of immunopathology would ANALYSIS OF ANTIBODIES IN LYMPHOCYTE SECRETIONS provide crucial clues as to how manipulation of the immune system may (ALS) OF MALIAN CHILDREN WITH ACUTE MALARIA best be achieved. The study aimed to determine the plasma profile of REVEALS PLASMABLASTS AND MEMORY B-CELL SUB- IFN-γ and IL-10 in malaria patient drawn from a P. falciparum-endemic POPULATIONS OF DIVERSE ANTIGEN SPECIFICITY area in Ikorodu LGA of Lagos State, Nigeria. A cross sectional study of 1650 participants who assessed malaria diagnostic services at our study Emmanuel Y. Dotsey1, Silva Portugal2, Huw D. Davies1, sites (four health facilities at Ikorodu LGA, Lagos State) were screened Ogobara K. Doumbo3, Aissata Ongoiba3, Boubacar Traore3, Peter for malaria by microscopic method using Giemsa stained thick and thin Crompton2, Philip L. Felgner1 blood films. The plasma level of IL-10 and IFN- γ was assessed among 140 1University of California Irvine, Irvine, CA, United States, 2National Institute patients who were diagnosed as having P. falciparum infection and 8 of Allergy and Infectious Diseases, National Institutes of Health, Rockville, malaria negative subjects, using indirect enzyme-linked immunosorbent MD, United States, 3Mali International Center of Excellence in Research, assays (ELISA) (MABTECH AB, Sweden). The mean plasma concentration of University of Sciences, Techniques, and Technology of Bamako, Bamako, IL-10 was found to be elevated (6966.8 ±5028.2 pg/ml) in malaria infected Mali individuals compared to the aparasitemic control group 5747.6 ± 3861.7 During a primary response to an acute infection, naïve B cells are activated pg/ml and this was statistically significant (p<0.01). In contrast IFN-γ levels in the presence of Follicular Helper T cells within the follicles of secondary were found to be lower in malaria patients (17277.6 ± 12055.8 pg/ml) lymphoid tissue leading to clonal expansion and affinity maturation to compared to non-malaria patients tested (23362.4 ± 11341.3pg/ml). There produce antigen-specific memory B cells and plasma cells in the germinal was however a significant relationship between IL-10 and parasite density center (GC). Prior to homing into secondary lymphoid tissue, immature (r=0.213; p value= 0.009); negative correlation between age and parasite plasma cells (plasmablasts) circulate in the blood producing the initial density (r=-0.163; p=0.048). In conclusion, levels of IFN- γ and IL-10 and protective antibodies against invading pathogens. After several days, the relative balance between the pro- and anti-inflammatory cytokines plasmablasts die or differentiate into mature plasma cells which migrate response, illustrates how populations residing in areas of varying disease to the bone marrow to become long lived plasma cells. Affinity-matured endemicity may respond to P. falciparum-induced immune challenge. plasma cells and memory B cells provide the antibody response to subsequent infection by the same pathogen. To evaluate the plasmablast and memory B cell/plasma cell compartments generated after infection in the context of malaria, we employed the ALS assay and proteome microarray. PBMCs and serum samples were collected from Malian children with malaria at day 14 post infection and from malaria-naïve US adults. PBMCs were cultured in media containing stimulatory factors and after 3 days the culture media was removed and replaced with fresh media. PBMCs were then cultured for 3 additional days and final culture supernatants were collected at day 6. Sera and culture supernatants

astmh.org 492 containing lymphocyte secretions were probed on Pf1000 microarray 1611 containing 1000 proteins from Plasmodium falciparum strain 3D7. Our results show that the antibody profile of 3-day (plasmablast) cultures DEVELOPMENT OF A MICROSCALE INHIBITION OF is a subset of the 6-day (memory B cell/plasma cell) cultures and serum LIVER STAGE DEVELOPMENT ASSAY FOR PLASMODIUM antibody profiles. The results also reveal a sub-population of antibodies FALCIPARUM AND P. VIVAX present only in the memory B cell/plasma cell compartment and in serum. Our approach successfully illustrates how combining ALS assay Alison E. Roth1, Steven P. Maher1, Naresh Singh1, Jetsumon and proteome arrays can be used to rapidly profile serum antibody and Sattabongkot2, Dennis E. Kyle1, Wajeeh Saadi3, PATH Malaria antibodies in the plasmablast and memory B cell/plasma cell compartments Vaccine Initiative, John H. Adams1 after an acute infection. 1University of South Florida, Tampa, FL, United States, 2Mahidol Vivax Research Unit, Mahidol University, Bangkok, Thailand, 3Draper Laboratory, 1610 Tampa, FL, United States SERO-EPIDEMIOLOGICAL EVALUATION OF PLASMODIUM Vaccine development targeting sporozoite and pre-erythrocytic stages FALCIPARUM MALARIA IN SENEGAL of the Plasmodium parasite is one of most challenging areas in malaria research because biological complexities, such as inadequate methods Khadime Sylla1, Roger Clément Kouly Tine1, Magatte NDiaye1, for in vitro culture, result in the lack of a functional assay capable of Doudou Sow1, Aïssatou Sarr1, Marie Louise Tshibola Mbuyi2, visualizing and quantifying antibody inhibition. This study describes the Ibrahima Diouf1, Amy Colé Lô1, Annie Abiola1, Mame Cheikh development of a new type of Inhibition of Liver Stage Development Seck1, Mouhamadou NDiaye1, Aïda Sadikh Badiane1, Jean Louis Assay (ILSDA) utilizing cryopreserved sporozoites paired with an in vitro Abdourahim NDiaye1, Daouda NDiaye1, Oumar Faye1, Thérèse human liver model based on a microscale platform. Proof of concept is Dieng1, Yémou Dieng1, Oumar Ndir1, Oumar Gaye1, Babacar Faye1 demonstrated in experiments targeting the P. vivax and P. falciparum 1University Cheikh Anta Diop, Dakar, Senegal, 2Département de circumsporozoite (CSP) protein with inhibitory concentrations of species- Parasitologie-Mycologie, Université des Sciences de la Santé, Libreville, specific anti-CSP monoclonal antibodies. The bioassay was found to Gabon be sensitive and efficient, showing the blocking of pre-erythrocytic stages of both P. vivax and P. falciparum in a concentration dependent In Senegal, significance decrease of malaria transmission intensity has fashion. Additionally, the assay allows for further functional validation as been noted the last years. In such a context parasitaemia has become immunofluorescence imaging revealed a potential anti-CSP mechanism lower and therefore more difficult to be detected by microscopy. In involved in the post-invasion inhibition of sporozoite and liver stage the context of submicroscopic parasitaemia, it has become relevant to development. This study provides an improved ILSDA that can be used to rely on relevant malaria surveillance tools to better document malaria evaluate future drug and vaccine candidates targeting the pre-erythrocytic epidemiology in such settings. Serological markers have been proposed stages of P. falciparum and P. vivax. as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria 1612 in two sentinels sites in Senegal. Cross sectional surveys were carried out in Velingara (South of Senegal) and Keur Soce (Center of Senegal) IDENTIFYING CRITICAL BIOLOGICAL AND IMMUNOLOGICAL between September and October 2010. Children less than 10 years living ROLES OF GLYCOSAMINOGLYCANS IN THE DEVELOPMENT in these areas were enrolled using two level random sampling methods. OF PLACENTAL MALARIA P. falciparum infection was diagnosed using microscopy. Pf antibodies against Circum Sporozoït Protein (CSP), Apical Membrane Protein (AMA1) Louise Randall, Stephen Rogerson, Wina Hasang and Merozoït Surface Protein 1_19 (MSP1_42) were measured by ELISA Department of Medicine, Melbourne Academic Centre at the Doherty method. A stepwise logistic regression analysis was done to asses factors Institute, The University of Melbourne, Australia associated with Pf antibodies carriage. A total of 1865 children less than During pregnancy, the developing fetus must be protected from the 10 years were enrolled. The overall Pf malaria prevalence was 4.99% maternal immune system. The maternal immune system is considered with high prevalence in Velingara 10.03% compared to Keur Soce to be in an altered or compromised state during pregnancy and this is 0.03%. Symptomatic malaria cases (fever associated with parasitaemia) achieved by factors released by the placenta, including hormones and represented 17.37%. Sero-prevalence of anti-AMA1, anti-MSP1 and cytokines. Placental malaria is characterised by the accumulation of anti-CSP antibody was 38.12%, 41.55% and 40.38% respectively. The Plasmodium falciparum-infected erythrocytes (IE) in the placenta, and sero-prevalence was more important in Velingara and increased with age, results in poor outcomes for both the mother and the fetus, including active malaria infection and area of residence. Conclusion: The use of anaemia, low birth weight and miscarriage. Pregnancy-specific IE bind to serological markers can contribute to improve malaria surveillance in areas the glycosaminoglycan chondroitin sulphate A within the placenta. We with declining malaria transmission. This study provided useful baseline hypothesise that chondroitin sulphate containing proteoglycans act as information about the sero-epidemiological situation of malaria in Senegal immune system modulators during pregnancy and that the binding of and can contribute to the identification of malaria hot spots in order to IE to chondroitin sulphate A in the placenta allows the establishment of concentrate intervention efforts. the initial parasite niche. Here, we show that bovine-derived chondroitin sulphate A dampens the immune response of human peripheral blood mononuclear cells (PBMCs) to IE and bacterial products. In the presence of chondroitin sulphate A, monocytes produced less tumour necrosis factor, had differential expression of pattern recognition receptors and were skewed towards a classical phenotype. We show that proteoglycans derived from human placental tissue also modulate the monocyte response to pathogen products and discuss the implications of the parasite interacting with the placental barrier.

astmh.org 493 1613 1614 MEASURING ANTIBODY-MEDIATED PROTECTION AGAINST NOVEL SEROLOGIC BIOMARKERS PROVIDE ACCURATE PLASMODIUM FALCIPARUM CHALLENGE IN LIVER CHIMERIC- ESTIMATES OF RECENT PLASMODIUM FALCIPARUM HUMANIZED MICE EXPOSURE FOR INDIVIDUALS AND COMMUNITIES Brandon K. Sack1, Sebastian Mikolajczack1, Matthew Danica A. Helb1, Kevin K. Tetteh2, Philip L. Felgner3, Jeff Skinner4, Fishbaugher1, Ashley Vaughan1, Judith Epstein2, Bradley Hickey2, Alan E. Hubbard5, Emmanuel Arinaitwe6, Harriet Mayanja- Eileen Villasante2, Joanne Lumsden2, Sharina Reyes2, Robert Kizza7, Isaac Ssewanyana6, Moses R. Kamya7, James G. Beeson8, Sauerwein3, Robert Hermsen3, Stephen Hoffmann4, Robert Seder5, Jordan Tappero9, David L. Smith10, Peter D. Crompton4, Peter D. Andrew Ishizuka5, Stefan H. Kappe1 Crompton4, Philip J. Rosenthal11, Grant Dorsey11, Chris Drakeley2, 1Seattle Biomedical Research Institute, Seattle, WA, United States, 2Naval Bryan Greenhouse11 Medical Research Center, Silver Spring, MD, United States, 3Radboud 1University of California Berkeley/University of California San Francisco, University Medical Center, Nijmegan, Netherlands, 4Sanaria, Inc., Rockville, San Francisco, CA, United States, 2London School of Hygiene & Tropical MD, United States, 5National Institutes of Health, Bethesda, MD, United Medicine, London, United Kingdom, 3University of California Irvine, States Irvine, CA, United States, 4National Institute of Allergy and Infectious Diseases/National Institutes of Health, Bethesda, MD, United States, Immunization with live-attenuated sporozoites has proven to be the most 5University of California Berkeley, Berkeley, CA, United States, 6Infectious efficacious means of vaccination against malaria parasite infection, yielding Disease Research Collaboration, Kampala, Uganda, 7Makerere University, complete sterilizing protection in controlled human malaria challenge Kampala, Uganda, 8Burnet Institute for Medical Research and Public trials. These encouraging clinical results not only provide a strong rational Health, Melbourne, Australia, 9Centers for Disease Control and Prevention, for development of a live-attenuated parasite vaccine, but enable Atlanta, GA, United States, 10Sanaria Institute for Global Health and exploration of immune correlates of protection which further accelerate Tropical Medicine/University of Oxford, Rockville, MD, United States, malaria vaccine development and will inform the design of subunit 11University of California San Francisco, San Francisco, CA, United States malaria vaccine candidates. However, there are limited tools available to directly assess contribution of cellular and humoral immune responses to Tools to reliably measure Plasmodium falciparum (Pf) exposure protection. Currently, functional analysis of anti-Plasmodium falciparum in populations are needed to guide and evaluate malaria control sporozoite antibodies is largely limited to in vitro invasion assays using interventions. Serologic assays can potentially produce precise exposure hepatoma cells, an environment which does not accurately mimic the estimates at low cost; however current approaches, based on responses complex journey of sporozoites from the dermis to the liver parenchyma. to a few established antigens, are not designed to detect recent changes Here, we have optimized in vivo P. falciparum infection in a humanized or estimate exposure in individuals. Pf-specific antibody responses differ liver-chimeric mouse model where sporozoite challenge is delivered by by antigen, suggesting that selection of antigens with defined kinetic mosquito bite and liver stage parasite burden quantified by bioluminescent profiles will improve estimates of Pf exposure. We tested this hypothesis imaging. This model supports measurement of protection by passive by evaluating responses to 856 Pf antigens via protein microarray in 186 transfer of polyclonal antibodies from individuals immunized with whole Ugandan children, for whom detailed Pf exposure data in the prior year sporozoites as well as monoclonal antibodies to individual sporozoite were available. Using data-adaptive statistical methods, we identified proteins such as CSP. We found this method to be sensitive and reliable in combinations of antibody responses which maximized information on directly detecting varying degrees of antibody efficacy against sporozoite exposure. Considering individual exposure, responses to three novel Pf liver infection while allowing for animal survival and simultaneous analysis antigens accurately classified whether an individual had been infected of parasite progression to blood stage infection. We will present data within the last 30, 90, or 365 days (cross-validated AUC: 0.86-0.93), while on the inhibitory activity of serum and IgG elicited by different types of responses to another three antigens accurately estimated malaria incidence attenuated sporozoite immunizations as well as data for antibodies to in the prior year. Considering community exposure, cross-validated specific parasite proteins. The liver-chimeric humanized mouse/challenge incidence predictions provided accurate stratification of exposure between model thus constitutes the most physiologically relevant system for communities and suggest that precise estimates can be obtained from analysis of antibody-mediated protection against malaria infection. As analysis of a single plasma sample from a small subset of the population. such it will accelerate the identification of new antibody targets and the In addition, serologic incidence predictions accurately characterized establishment of immune-correlates of protection. heterogeneity within a community, performing nearly as well as one year of incidence data. Development of simple, ELISA-based assays derived from the successful selection strategy outlined here offers the potential to generate rich epidemiologic surveillance data that will be widely accessible to malaria control programs. 1615 HOUSE STRUCTURE AND SLEEPING ARRANGEMENT AFFECTS BED NET USE IN THE GAMBIA Susan Dierickx1, Charlotte Gryseels1, Julia Mwesigwa2, Fatou Jaiteh2, Sarah O’Neill1, Melanie Bannister-Tyrrell1, Julia Irani1, Maya Ronse1, Jane Achan2, Umberto D’Alessandro2, Koen G. Peeters1 1Institute of Tropical Medicine, Antwerp, Belgium, 2Medical Research Council Unit, Fajara, Gambia Although coverage of Long-Lasting Insecticide-treated Nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. In order to achieve universal coverage and use of LLIN, there is a need to identify those population sub-groups that are least protected. Certain types of housing structures and inside-outside sleeping arrangements may make the attempt to use bed nets difficult. This study aimed to identify risk groups by understanding the relationship between astmh.org 494 bed net use, housing structure and inside-outside sleeping patterns in the 1617 Gambia. An ethnographic study was carried out in the Gambia between April 2013 and November 2014 in two phases: a first explorative phase INSECTICIDE-TREATED NET DISTRIBUTIONS IN SUB- in 12 rural villages representing a variety of ethnic groups, and a second SAHARAN AFRICA: AN ASSESSMENT OF MASS CAMPAIGNS phase in which two villages with different traditional housing styles were FROM 2006-2014 selected as cases for in-depth analysis. In addition to net availability, net use is affected by housing structure and sleeping patterns inside Cristin A. Fergus1, Sadaf Milani2, Michael Lynch3, Richard and outside the house. Children, women and men often rest and sleep Cibulskis1, n. Global Malaria Programme, World Health unprotected outside their houses during the early evenings. Boys leave the Organization bed of their mother at a younger age compared to girls, and as such are 1World Health Organization, Grand-Saconnex, Switzerland, 2University of less likely to sleep under LLIN. Boys and adolescent men are particularly Florida, Gainesville, FL, United States, 3Centers for Disease Control and at risk because they are not prioritized when allocating nets, are more Prevention, Atlanta, GA, United States likely to rest and sleep outdoor in public spaces, and often move between Insecticide-treated mosquito nets (ITNs) are one of the most cost-effective different sleeping spaces. In addition, particular subgroups are unlikely malaria interventions. This aim of this project is to compile and analyze to use their bed nets due to late night activities such as the protection data from ITN distribution campaigns in Sub-Saharan Africa from 2006- of farms, the herding of cattle, charcoal burning, fishing and hunting. 2014. A database of ITN distribution campaigns occurring from 2006-2014 Malaria risk varies substantially between different regions in the Gambia, was assembled by extracting data from weekly conference calls organized which could partially be explained by the variable uptake of malaria by the Alliance for Malaria Prevention, and supplementing campaign data control interventions such as LLINs. Designing bed nets adapted to the through a systematic review of published literature. We identified 95 ITN local context and taking into account people’s net preference may increase campaigns occurring from 2006 to 2014. The defining characteristics of the uptake of LLINs in particular risk groups. ITN distribution campaigns were determined to be geographic location, length, targeting, integration, allocation, and delivery system. There were 1616 campaigns across all geographic regions of Africa, with the majority in SUPPLY CHAIN MANAGEMENT CONSIDERATIONS FOR LONG- West Africa. The lengths of campaigns were found to be highly varied LASTING INSECTICIDE-TREATED BED NETS CONTINUOUS from a couple days to a few years. Several other common characteristics were noted: campaigns tended to target the general population rather DISTRIBUTION SYSTEMS than solely focusing on pregnant women and children under five years Naomi Printz1, Hannah Koenker2 old; among campaigns aiming to achieve universal coverage, the most 1United States Agency for International Development | DELIVER PROJECT, commonly used net allocation formula was one net per two people, John Snow, Inc., Arlington, VA, United States, 2Johns Hopkins Bloomberg although there were several other formulas utilized; and the majority of School of Public Health, Bethesda, MD, United States campaigns directly delivered the ITNs, while few campaigns used voucher schemes. Of the campaigns that reported integrating the distribution Many countries, as part of their national malaria strategy, use a with other public health interventions, a majority were integrated with combination of mass distribution of free long-lasting insecticide-treated immunization campaigns. The most widely cited problems in planning and bed nets (LLINs) and continuous distribution of LLINs through health implementing campaigns were financial and availability of nets at the time facilities as a proven intervention to reduce malaria-related morbidity of the campaign. The results of this analysis have highlighted a number of and mortality. LLINs have unique supply chain characteristics that must needs pertaining to the surveillance and monitoring of insecticide-treated be considered when implementing continuous distribution systems. net distribution for the prevention of malaria. With such a large amount Generally, LLINs have long procurement lead times. Because they contain of resources being invested in ITNs as a malaria intervention, there is a pesticides, their logistics management is often outside malaria medicines need for systematic tracking of campaigns. Assessments of ITN distribution and tests. They are extremely bulky, which has implications for attendant mechanisms should continue, and the results should be incorporated into storage and inventory management. Expert coordination is required campaign planning processes. because they may be managed at different points within a facility, and by different cadres of staff. LLINs can be a target for theft, underscoring 1618 the need for accountability; as they need to be replaced periodically, their demand is ongoing. The demand for LLINs for campaigns may take DEVELOPING NOVEL IN VITRO MODELS OF HEME-INDUCED priority over LLINs earmarked for routine distribution. Program managers DISRUPTION OF BLOOD-BRAIN BARRIER should conduct a logistics system design activity by describing how commodities and information moves through the different levels of the Mingli Liu, Carmen Dickinson-Copeland, Hassana Salifu, health system. As part of this design, a logistics management information Jonathan K. Stiles system (LMIS) is included_managers should collect consumption data on Morehouse School of Medicine, Atlanta, GA, United States LLINs and days out of stock. Reporting and resupply should be linked. To Background: The blood-brain barrier (BBB) breakdown is the major calculate resupply, consumption data and stock on hand data should be pathological change of cerebral malaria. The BBB is an active interface used. Accountability of LLINs throughout the supply chain is critical, and which contains cerebral endothelial cells sealed together by tight junctions information detailing the movement and use of LLINs must be tracked (TJ), the basement membrane, and pericytes as well as astrocytes. In this and verified. To accommodate the bulkiness of LLINs, minimal buffer study, we tried to develop an in vitro BBB model based on the culture stock should be used to reduce the required storage space; if possible, of human brain endothelial cells (HBVEC) and C6 glioma cells to test smaller bale sizes should be procured. System designers should consider the effects of heme on the TJs.Methods: Co-culture (Trans-well): C6 the advantages and disadvantages of longer review periods; they must glioma cells were grown in the bottom of the lower chamber which also ensure sufficient and secure storage. The quantification of LLINs for possibly influence the other cells by secreted factors into the media. 24 continuous distribution and campaigns should be coordinated; program h later, HBVECs were grown on a filter insert coated with attachment managers should routinely compare LMIS data and health management factor for 24 h. After starvation with serum-free medium for 24 h, information systems data. HBVECs were then treated with 60μM heme for another 24 h. Staining by anti- occluding, claudin and ZO-1 antibodies were visualized using the Alexa-488 fluorescence system. Results: In mono-culture systems, phase contrast images show the spindle shaped morphology o HBVECs in culture. Proteins occludin, claudin-5 are located in the cell membrane, while ZO-1 is located in cytoplasmic region. However the cells are not astmh.org 495 capable of forming a continuous line of tight junctions at the cell borders 1620 as detected by staining with antibodies against the TJ proteins occludin, ZO-1 and claudin-5. In co-culture systems, transmembrane protein QUINAZOLINDIONE SERIES IDENTIFIED FROM TCAMS: occludin and cytoplasmic protein ZO-1 show a clear and continuous A NEW ANTIMALARIAL SERIES WITH POTENTIAL FOR membrane staining, which reveals a line of tight junctions at the cell BLOCKING TRANSMISSION OF THE DISEASE borders. However, the normal structure of tight junctions is significantly lost after heme treatment. In addition, heme also decreases expression Esther Fernandez-Velando, Malaria DPU, Diseases of the of occludin, ZO-1 and claudin-5, and induces an irregular cell border Developing World staining.Conclusions: Data regarding baseline expression of TJ proteins GlaxoSmithKline, Tres Cantos, Spain and changes in expression of these proteins in response to heme stimuli Nowadays, Malaria is still one of the major global health problems. can be obtained by using in vitro co-culture BBB models. These co-culture Plasmodium has been able to adapt to the different treatments conditions provide a BBB model that is easy to use to perform histological developed by humans along history. However there has not been such analysis and permeability test induced by heme. a wide knowledge of the illness as we currently have. This fact, joined to the urgent need for novel antimalarial drugs that can replace ACTs 1619 and the awareness of governments/health systems/funding agencies, COMPARISON OF MALARIA DIAGNOSTIC TESTING AND makes the current time a unique opportunity to change the course of TREATMENT OUTCOMES AT OUTLETS PARTICIPATING IN A this disease and achieve the control and finally the eradication. Using a Phenotypic screening approach, in 2010 GSK published the Tres Cantos PROJECT TO SUPPORT PRIVATE SECTOR RDT ADOPTION IN antimalarial set (TCAMS) which comprises over 13,533 hits derived from MBEYA, MOROGORO AND TANGA, TANZANIA: RESULTS whole cell screening of 2M compounds from the GSK corporate collection FROM CLIENT EXIT INTERVIEWS against P. falciparum. A clear strategy was required to rapidly identify Stephen Poyer1, Emily Gloekler2, Daniel Michael2, Stephanie those molecules that have both the best chance of being converted Dolan1, Nikki Charman1 into differentiated antimalarial drugs and that are also likely to have the lowest risk of attrition in development. Identification of a new class of 1Population Services International, Nairobi, Kenya, 2Population Services anti-malarial agents that possess dual activity and are able to inhibit the International, Dar es Salaam, United Republic of Tanzania asexual blood-stage (schizonticidal, responsible of disease symptoms) Tanzania’s malaria treatment guidelines state that all suspected cases as well as block transmission was initiated in our group. As a result, a should be confirmed prior to treatment. By late 2012 RDTs had been rolled new assay to screen compounds for their potential to inhibit late stage out to public facilities nationwide, supported by a comprehensive training gametocytes was developed and used successfully to screen the output plan. As part of an intervention to support increased RDT availability from TCAMS. Quinazolindione series was identified as a very promising and correct use in the private sector in Tanzania, we conducted client family with dual activity (both schizonticidal and gametocytocidal). Initial exit interviews at 26 project (intervention) and 26 matched non-project weaknesses of the series were modest in vitro and in vivo potency as well (control) facilities 8 months into the project. The aim was to describe as poor pharmacokinetic profile. After a Lead Optimisation program, Late differences in testing and treatment outcomes between the two groups. Leads have been identified having excellent in vitro and in vivo potency, Eligible outlets were those that offered any diagnostic testing services at a very good developability profile and potential for targeting two different the time of interview and eligible clients were adults seeking treatment TCPs (Target Compound Profiles). Medicinal Chemistry strategy followed for fever for themselves or on behalf of someone else. In total, 2,383 during the Lead Optimisation program was focused on improving the clients were screened and interviews were conducted with 1,118 eligible physicochemical and developability properties. clients. Clients at intervention clinics were slightly less likely to be tested than those at control clinics (89.4% compared to 94.8%, p=0.08), and 1621 intervention clinics presented greater clinic-level variation in testing levels (min: 45.1%, max: 100%) than did control clinics (min: 73.3%, “THERE IS NO FREE HERE, YOU HAVE TO PAY”: ACTUAL max: 100%). Overall, 46.1% of tested clients reported testing positive AND PERCEIVED COSTS AS BARRIERS TO INTERMITTENT for malaria, with no significant difference between the groups. 86.8% PREVENTIVE TREATMENT OF MALARIA IN PREGNANCY IN of test-positive clients received ACT at intervention clinics, compared MALI with 77.2% at control clinics (p=0.3), and less than 5% of test-negative clients received any antimalarial in both groups. The study provides some Meredith C. Klein, Emily Hurley, Namratha Rao, Steve Harvey evidence that when both microscopy and RDTs were available RDT use was Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United more common in intervention clinics (44.0%) than control clinics (25.4%, States p=0.09), while microscopy was more common in the control clinics “There is no free here,” the words of a Malian husband, illustrate how (65.4% compared to 41.5%, p=0.06). Preliminary modelling suggests perceptions of cost can deter uptake of intermittent preventive treatment clients tested by microscopy were twice as likely to receive a positive test of malaria in pregnancy (IPTp). Following WHO recommendations, the result, and that treatment outcomes depended on both test result and Malian Ministry of Health (MOH) recommends three doses of IPTp at type of test. Understanding variations between and within study groups is monthly intervals. However, despite a national policy that IPTp be provided important to ensure efficient and cost-effective performance improvement free of charge, only 35% of pregnant women receive at least one dose steps are taken to improve malaria case management in these private and less than 20% receive two or more doses. We explored perceptions facilities. and experiences of IPTp cost in Mali, and their impact on uptake, using qualitative interviews and focus groups with pregnant women, husbands and mothers-in-law. We also interviewed and observed health workers at four health centers two in Sikasso Region and two in Koulikoro. Despite national-level policies, actual IPTp costs varied widely at our study sites - between regions, facilities, and visits. Pregnant women may pay for IPTp, receive it free, or both at different times. Health centers often charge a lump sum for ANC visits that include both some free and some fee-based drugs and services. This makes it difficult for women and families to decipher which services are free and which require payments. As a result, some forego even free care that, because it is not itemized, appears not

astmh.org 496 to be free. Varying costs also complicate household budgeting for health of all household sleeping spaces and a net utilization rate of 80%. We care, particularly as women often rely on their husbands or husbands’ estimated the cost of this mass distribution of LLINs in 183 health facility families for money. While health facilities operating under the cost- catchment areas (HFCAs) in ten districts in Southern Province. Various recovery model strive to provide free IPTp, their own financial constraints partners were engaged at different stages of implementation, which often make this impossible. Preventing malaria in pregnancy depends upon included importing LLINs with delivery to Lusaka, delivery from Lusaka women receiving the recommended doses of IPTp. However, it is clear to multiple staging locations in Southern Province, delivery from staging that both actual and perceived costs are currently barriers to IPTp uptake. locations to specific HFCAs, and then delivery by community health Given the confusion around cost of services in the two study regions, more workers (CHWs) to households in their catchment area. Primary data on detailed national-level studies of both perceived and actual costs could unit costs of various resources used during implementation, quantities help inform policy and program decisions promoting IPTp. These studies of resources used, and key programmatic outputs were obtained from should evaluate both quantitatively and qualitatively the cost information programmatic records. The average implementation cost per HFCA in provided by health facilities and pharmacies to pregnant women and their 2014 was US$28,892. Procurement of LLINs and delivery to Lusaka families. accounted for 54% of the total cost. Other costs included storage, loading, offloading (43%), and labor for CHWs, health facility, and 1622 district-based staff (3%). On average, 1,800 households_representing approximately 5,300 sleeping spaces_received LLINs in each HFCA during BENEFICIARY SATISFACTION ASSESSMENT TO GUIDE the distribution. A coverage rate of 80% was achieved. The average cost HEALTH PROGRAM COMMUNICATION AND INCREASE per sleeping space reached was US$5.45 (US$15 per household reached). ACCEPTANCE OF INDOOR RESIDUAL SPRAYING These results are preliminary and do not yet include costs associated with training and supervision of implementation. Costs of LLIN distribution 1 2 3 Beth Brennan , Allison Belemvire , Shadreck Sande , Tendayi and other malaria interventions are useful for budgeting and planning, 3 1 Muchenje , Ben Johns identifying opportunities to improve program efficiency, and informing 1Abt Associates, Bethesda, MD, United States, 2United States Agency additional analyses on the cost-effectiveness and budget impact of for International Development, Washington, DC, United States, 3Abt different approaches to malaria elimination. Associates, Zimbabwe, Zimbabwe Indoor Residual Spraying (IRS) is considered effective when 85 percent 1624 of a community’s homes are sprayed. However, there are logistical and DETERMINING THE OPTIMAL MODE FOR DELIVERY OF educational barriers that affect residents’ decisions to accept IRS and a program’s ability to fully protect a targeted area from malaria infection. SEASONAL MALARIA CHEMOPREVENTION IN MALI Current behavioral change communication (BCC) efforts for an IRS Djirilla Issiaka1, Amadou Barry1, Moctar Tounkara1, Tiangoua campaign primarily require paying hundreds of mobilizers to walk long Traore1, Ibrahim Diarra1, Diakalia Kone2, Mohamed Keita2, Issaka distances to reach residents during work hours, when people are typically Sagara1, Ogobara Doumbo1, Erin Gabriel3, Patrick Duffy4, Michal not home. BCC efforts seek to highlight the dangers of malaria, the Fried4, Alassane Dicko1 benefits of IRS, and how and when people can prepare their homes for 1Malaria Research and Training Center, University of Bamako, Bamako, spraying; but, these messages are not universally received. After the 2014 Mali, 2National Malaria Control Program, Bamako, Mali, 3BRB/National IRS campaign in Zimbabwe, the President’s Malaria Initiative-supported Institute of Allergy and Infectious Diseases/National Institutes of Health, (PMI) Africa Indoor Residual Spraying (AIRS) project randomly surveyed 485 Rockville, MD, United States, 4Laboratory of Malaria Immunology and households in four IRS districts to assess beneficiary IRS knowledge and Vaccinology/National Institute of Allergy and Infectious Diseases/National satisfaction, and identify locally-preferred methods of IRS messaging. Two Institutes of Health, Rockville, MD, United States thirds of the respondents were females, roughly 43 years old, reporting a high level of IRS and malaria knowledge. However, preliminary findings Seasonal malaria chemoprevention (SMC), the administration of complete show that the BCC campaign did not reach all target areas or publicize therapeutic courses of antimalarials to children aged 3-59 months during clearly the IRS schedule. It is crucial to finish an IRS campaign in the the malaria transmission season, is a new strategy recommended by fewest number of days possible, since each additional day needed to WHO for malaria control in Sahelian countries with seasonal transmission revisit an unprepared village adds significant costs to the program budget. such as Mali. The strategy is a highly cost-effective approach to reduce AIRS Zimbabwe is using the beneficiary feedback to reshape their BCC malaria burden in these areas. Despite the huge benefit of SMC on malaria messaging and improve operational efficiency in 2015. I will present the infection and disease, the optimal approach to deliver SMC remains to be full findings of the assessment and explain how this activity, a first for the determined. While fixed-point delivery (FPD) combined with non-directly project, can also improve spray coverage in the other AIRS countries. observed treatment (NDOT) by community health workers is attractive for the SMC implementation, it needs to be evaluated and compared to other 1623 modes of delivery. To determine the optimal mode (fixed-point (FPD) vs door-to-door delivery (DDD); directly observed treatment (DOT) vs. non- THE MASS DISTRIBUTION OF LONG-LASTING INSECTICIDE- DOT (NDOT)), 32 villages in four health sub-districts were randomized to TREATED NETS IN SOUTHERN PROVINCE, ZAMBIA: HOW receive three rounds of SMC with SP+AQ at monthly intervals using one MUCH DOES IT COST? of the following methods: FPD+DOT; FPD+NDOT; DDD+DOT; DDD+NDOT. The primary endpoint was SMC coverage assessed by cross-sectional 1 1 1 Thandiwe Ngoma , Bruce Larson , Kafula Silumbe , Busiku survey in 2,132 children at the end of intervention period. Coverage 2 3 4 1 Hamainza , Ketty Ndhlovu , Mukumbuta Nawa , John Miller , was defined as the proportion of children who received all three days 5 Callie Scott of SMC treatment during the three monthly rounds (primary endpoint). 1PATH, Lusaka, Zambia, 2National Malaria Control Programme, Lusaka, Coverage was significantly higher in children who received SMC using Zambia, 3Zambia Ministry of Health, Lusaka, Zambia, 4United Nations DDD compared to FPD (76.1% versus 62.2%), p = 0.0028). It was similar Development Programme, Lusaka, Zambia, 5PATH, Seattle, WA, United in children who received SMC using DOT or NDOT (68.2% versus 68.6%; States p = 0.95). When the four arms are compared, coverage was highest in DDD+NDOT (77.7%), followed by DDD+DOT (74.5%), FPD+DOT (64.2%) The Zambian Ministry of Health and partners are implementing a package and FPD+NDOT (60.0%), p =0.038. In summary, door-to-door delivery of of interventions and surveillance systems in Southern Province in support SMC provides better coverage than FPD. Directly observed therapy, which of the national malaria control and elimination agenda. As part of this requires more time and resources, did not improve coverage with SMC. package, mass distribution of long-lasting, insecticide-treated nets (LLINs) was implemented in 2014 with the aim of achieving universal coverage astmh.org 497 1625 were targeted for an MTAT early in the 2014 malaria transmission season (September). All households were visited, all consenting individuals were MDA-A: AN ANDROID-BASED ODK TOOL TO SUPPORT FIELD tested with a rapid diagnostic test (RDT), and, if positive, treated with DATA COLLECTION AND MANAGEMENT FOR A MALARIA dihydroartemisinin-piperaquine. Following the MTAT, a weekly screening MASS DRUG ADMINISTRATION TRIAL IN ZAMBIA of fever cases, testing (only fever cases were tested), and treatment was conducted in all households throughout the transmission season until Chris Lungu1, Benjamin Kayungwa1, Timothy Finn2, Thom Eisele2, end of January 2015. To evaluate the impact of the interventions, the John M. Miller1 incidence of passively detected, RDT-confirmed malaria cases at the health 1PATH MACEPA, Lusaka, Zambia, 2Department of Global Health Systems posts will be compared before and after the intervention and between and Development, Tulane University School of Public Health and Tropical intervention and control villages. During the MTAT, 1954 (83%) of 2361 Medicine, New Orleans, LA, United States total households were visited, 16,583 (86%) out of 19,389 individuals were tested, and of those 1.5% had a positive RDT (ranging from 0.5% to Since 2011, the Zambia Ministry of Health (MoH) has developed time- 5.2% by health post). Overall, 44% of infections occurred in households limited antimalarial treatment campaigns conducted by trained community with at least one other infection and 94% of households did not have any health workers (CHWs) to reduce the malaria parasite reservoir in an RDT positives; 82% of RDT-positive individuals were younger than 20 years area of Southern Province with current high levels of malaria prevention old, 72% were asymptomatic (no fever or history of fever in the last 24 coverage. These operational research activities focused on mass drug hours), and 85% completed treatment. All reported adverse events (9.5% administration (MDA) or focal MDA (fMDA) targeting 60 health facility vomited, 3.5% had fever and 0.4% had itching) were mild and tolerable. catchment areas (HFCAs) randomized for participation. Key to monitoring Results of the impact evaluation, assessment of geographical clustering of uptake of treatment interventions is collection of intervention data on a infections, and estimates of implementation costs will be available in mid- large scale across all HFCAs. Data collection tools were developed and 2015. have been used by CHWs and enumerators that visit households as part of a cross-sectional campaign or longitudinal cohort study. An application, MDA-a, was developed on an Android platform using ODK survey 1627 software. It is used to document data of all eligible household participants REVIEW OF DATA STRENGTHENING PROCESS FOR MALARIA including their existing coverage and use of prevention interventions, travel SURVEILLANCE SYSTEM, ZAMBIA histories, and results from malaria parasite tests. Adherence monitoring to taking DHAp (anti-malaria drug dihydroartemisinin-piperaquine) for Marie-Reine Rutagwera1, John Miller1, Michael Hainsworth1, mass and focal treatment administration is also done by in-field data Chris Lungu1, Prudence Malama1, Kalenga Kakompe1, Mercy exchange among adherence officers accompanying testing pairs. The Mwanza2, Mulakwa Kamuliwo2 application monitors the campaign process by the CHW-enumerator 1PATH, Lusaka, Zambia, 2Ministry of Health, Lusaka, Zambia pair team and adherence to treatment administered by the testing pair team matched to individuals from a household. We will describe the A robust, high-quality surveillance system is crucial for the Zambia Ministry development of MDA-a, using android-based smart phones at catchment of Health to achieve its goal of at least five malaria free zones by 2015. level for large volume data handling, to effectively plan, implement, and Effective malaria control depends on timely acquisition of high-quality monitor MDA activities. The implementation of MDA-a, its functionality, data to efficiently deploy supplies, plan interventions, and focus attention and field use experience during the two rounds of the MDA trial in Zambia where most needed. To inform action and monitor progress towards this will be discussed. Results show that in the first round a total of 35,996 goal, MACEPA supported the Zambia National Malaria Control Program households were involved in the MDA and fMDA arms, with 81% of to establish a scalable Rapid Reporting system at health facility and household members tested for malaria in the fMDA arm, and 89% in the community levels in 2011. This system is currently active in 36 districts MDA arm. Malaria incidence in these areas was low to modest, with a and was designed to track malaria outpatient trends, malaria diagnostics, rapid diagnostic test prevalence of 8.3%. and treatment commodities at health facility and community levels using the DHIS2 mobile reporting platform with low cost mobile phones. Data 1626 quality standards to strengthen malaria surveillance are enforced at two levels. Within DHIS2, dashboard charts are used to identify outliers, MASS TESTING AND TREATMENT FOR MALARIA FOLLOWED data validation rules are checked to identify logical errors, and summary BY WEEKLY VISITS TO SCREEN FOR FEVER CASES IN LOW reports are run to review completeness and timeliness. At the facility and TRANSMISSION AREAS IN MATAM AND LOUGA REGIONS, community levels, routine data quality audits (RDQA) compare data in SENEGAL: A PILOT STUDY source documents with reported data on DHIS2. The RDQA approach includes monitoring and technical support (MTS) to discuss key findings, Farba Faye1, Caterina Guinovart2, Yakou Dieye1, Badara Cisse1, develop data quality improvement action plans, and provide necessary Adama Tall1, Michael Hainsworth2, Callie Scott2, Ruben Conner2, field-level support. The RDQA and MTS approach identifies data to be Mame Demba Sy3, Doudou Sene3, Souleymane Ba3, Elhadji corrected and reporting procedures to strengthen, provides feedback to Doucoure3, Tidiane Thiam3, Ritu Kumar2, Michael Kalnoky2, community and health facility staff, and promotes capacity building and Moustapha Cisse3, Fatou Ba Fall3, Mady Ba3, Duncan Earle4, collaboration across multiple levels of the health system. Factors identified Philippe Guinot1, Richard Steketee2 in 2015 that affect reporting completeness and timeliness include staff 1PATH, Dakar, Senegal, 2PATH, Seattle, WA, United States, 3Ministry of turnover with poor hand-over procedures, poor network coverage, and Health, Dakar, Senegal, 4PATH, Lusaka, Zambia damaged or lost phones. Sources of most data quality problems included entering data incorrectly on mobile phones and incomplete aggregation of Population-wide interventions using antimalarial drugs to decrease the data from registers. Thus, integration of monitoring and technical support reservoir of Plasmodium falciparum infection are malaria elimination with data audits can provide instant on-site capacity building and promote tools that need further evaluation in different transmission settings. A pilot collaboration between health facility staff and the local health teams. quasi-experimental study of a malaria mass testing and treatment (MTAT) followed by weekly screening of fever cases was conducted in six health post catchment areas in the districts of Kanel, Linguère, and Ranérou (Senegal). Seven adjacent health posts with similar characteristics and malaria incidences were selected as controls. Villages within the catchment areas were stratified according to the 2013 incidences of passively detected malaria cases, and those with an incidence ≥15 cases/1000/year

astmh.org 498 1628 Southern Province, Zambia, covering a population of nearly 2 million in Zambia. We used two methods for assessing data quality: applying data CASE INVESTIGATION WITH REACTIVE FOCAL TESTING AND validation rules on reported data elements directly in DHIS2 to check TREATMENT FOR MALARIA IN A LOW-TRANSMISSION AREA for logical inconsistencies and produce performance indicators around IN AMHARA REGION, ETHIOPIA reporting, completeness, timeliness, and validity; and applying a routine data quality assessment tool to describe the strengths and gaps in the data Asnakew Kebede Yeshiwondim1, Callie Scott2, Caterina management and reporting systems, comparing source data from health Guinovart2, Belendia Serda1, Berhane Tesfay1, Adem Agmas1, facility registries with data reported through the mobile phone-based Belay Bezabih3, Melkamu Zeleke1, Girma Guesses1, Asmamaw rapid reporting system. This multi-country approach has produced well Ayenew1, Worku Workie1, Elias Asefaw Zageye1, Pooja Bansil2, Rick documented, promising quality assessment practices and lessons learned Steketee2, Asefaw Getachew1 along with an opportunity to compare the quality of data from rapid 1PATH, Addis Ababa, Ethiopia, 2PATH, Seattle, WA, United States, 3Amhara reporting systems in different contexts: varying malaria incidence profiles, National Regional State Health Bureau, Bahir Dar, Ethiopia different mobile technology, role of data reporters, and levels of support by partners and national health systems, providing insights into factors to When malaria transmission is low, investigation of individual cases strengthen and normalize data quality. and neighboring households is a means of identifying and containing the source and spread of infections. Case investigation with testing and treatment for malaria in the case and neighboring households 1630 was implemented in ten intervention villages in Amhara Region, SAIMIRI BOLIVIENSIS AS A MODEL TO STUDY MOSQUITO Ethiopia during the 2014 transmission season. Intervention villages TRANSMISSION OF PLASMODIUM VIVAX were purposively selected and matched with control villages based on the incidence of passively detected Plasmodium falciparum (Pf) and Jennifer S. Armistead1, Juliana M. Sá2, Roberto R. Moraes mixed malaria cases during the 2013 malaria transmission season. In Barros2, Thomas E. Wellems2, John H. Adams1 intervention villages, a passively detected Pf or mixed index case triggered 1Department of Global Health, University of South Florida, Tampa, FL, an investigation that targeted the index case household and up to ten United States, 2Laboratory of Malaria and Vector Research, National neighboring households in a 100-meter radius. All available household Institute of Allergy and Infectious Diseases, National Institutes of Health, members received a rapid diagnostic test (RDT) and RDT-positive individuals Rockville, MD, United States received artemether-lumefantrine (Pf, mixed) or chloroquine (P. vivax [Pv]). From October to November, 2014, 353 Pf or mixed index cases Despite the global burden of malaria disease caused by Plasmodium were passively detected in the intervention villages. Of these, 209 (59.2%) vivax, little advancement has been made to enable the study of this were investigated; 88.9% were male; 63.5% were aged 20-39 years; parasite’s unique biology. Lack of an in vitro continuous culture system and 61.5% spent ≥1 night away from home in the last month, ranging has made non-human primates (NHPs) a critical model to study P. vivax from 0.0% to 96.6% by village. Among the 3,711 residents in the 838 asexual and sexual stages, and mosquito transmission. It has also become households investigated, 2,923 (78.8%) received an RDT and 121 (4.1%) the main source of intraerythrocytic stages and sporozoites to investigate were RDT-positive (2.4% Pf, 0.6% Pv, and 1.2% mixed). Comparisons drug efficacy, liver stage biology, dormant hypnozoite forms, and relapse. between intervention and control villages and estimates of implementation Despite the suitability of NHPs for P. vivax infection, efforts to produce a costs will be available in October 2015. In six of ten villages, few robust, reliable model of the complete life cycle have been limited, and this index cases and secondary cases were identified, suggesting little local invaluable tool remains elusive. Using recombinant progeny from a genetic transmission. In three of ten villages, many index cases were identified, cross between subpopulations of a P. vivax line with chloroquine sensitive most had a history of travel, and few secondary cases were identified, (VK210) and resistant (VK247) parasites (NIH-1993-S×NIH-1993-R) we suggesting importation with little local transmission. In one of ten villages, are evaluating conditions to maximize production of sporozoites and no cases had a history of travel and many secondary cases were identified, select an adapted line to complete the parasite life cycle using Saimiri suggesting substantial local transmission. To achieve malaria elimination boliviensis monkeys. Infections initiated via intravenous inoculation of in Amhara Region, intervention strategies targeting these patterns of infected erythrocytes varied widely in time to patency and intensity, but transmission and population movement are required. parasitemias reaching ~1% were obtained. Anopheles freeborni and An. albimanus were found to be the most competent vectors among 1629 those tested. Oocyst and sporozoite counts indicated that artificial membrane feeding following serum replacement with human AB+ serum MULTI-COUNTRY ROUTINE DATA QUALITY ASSESSMENT produced the most intense infections. No correlation was found between (RDQA) FOR MALARIA INFORMATION the intensity of mosquito infection and parasitemia or gametocytemia. A more sensitive molecular assay to retrospectively correlate gametocytemia Jeff Bernson1, Michael Hainsworth1, Marie-Reine Rutagwera2, and the male:female sex ratio with transmission success is under John Miller2, Chris Lunga2, Adem Ahmed3, Melkamu Zeleke4, development. Our findings will provide important information regarding Girma Guesses4, Asmamaw Ayenew4, Worku Workie4, Prudence the utility of this New World monkey as a model to study P. vivax biology, Malama5, Kalenga Kakompe5, Mercy Mwanza5, Mulakwa and to facilitate development of novel diagnostics, effective antimalarial Kamuliwo5 drugs and vaccines, which will be indispensible for malaria eradication. 1PATH, Seattle, WA, United States, 2PATH, Lusaka, Zambia, 3PATH, Addis Ababa, Ethiopia, 4PATH, Addis Ababa, Zambia, 5Ministry of Health, Lusaka, Zambia As National Malaria Control Programs increasingly focus on malaria elimination, real time, accurate, and actionable data are critical to target geographies and populations and to optimize the allocation of resources. The MACEPA project assessed the quality of weekly data captured through a mobile phone application built on DHIS2 in Ethiopia and Zambia over a 24-month period to understand how data quality improvement practices can be strengthened to support system needs for rapid and more focal data. Data was captured from 209 health facility catchment areas across four health zones in Amhara Region, Ethiopia, covering an estimated population of 1.6 million in Ethiopia and 220 facility catchments in astmh.org 499 1631 with the aim of assessing the safety, protective efficacy, and immune correlates of protection of immunization with Pv RAS which may guide PHASE 1, DOSE ESCALATION, RANDOMIZED CONTROLLED future vaccine development. Healthy adult volunteers were immunized TRIAL TO EVALUATE THE SAFETY, IMMUNOGENICITY AND with Pv RAS (150 ± 10 cGy) through mosquito bites. Duffy positive (Fy+) EFFICACY OF INTRAVENOUSLY ADMINISTERED ATTENUATED individuals (n=21) were randomly assigned to either experimental (Exp, PLASMODIUM FALCIPARUM SPOROZOITE VACCINE IN n=14) or control group (Ctr, n=7), and received bites from irradiated P. TANZANIAN ADULTS: PRELIMINARY RESULTS vivax-infected and non-infected mosquitoes, respectively. Additionally, Duffy negative (Fy-) volunteers (n=7) were assigned to a third group and Said A. Jongo received bites of infected non-irradiated mosquitoes in order to assess Ifakara Health Institute, Bagamoyo, United Republic of Tanzania the response to non-attenuated parasites. After each immunization, patients were followed-up with clinical assessments and safety laboratory A Phase 1 study of PfSPZ Vaccine administered IV at doses ranging from tests. After completing a total of seven immunizations, volunteers were 2,000 to 135,000 PfSPZ in USA showed the vaccine is safe, well-tolerated subjected to a P. vivax sporozoite infectious challenge. A total of 20 and immunogenic in malaria naïve population in the U.S. It is important volunteers completed the infectious challenge phase (12 Exp, 3 Ctr and 5 to know early on if there are differences with endemic population. The Fy-). Exp volunteers received a mean of 430 (362-497) infective Pv-irrad- present double blind placebo controlled trial was conducted at the spz mosquito bites, Ctr, 934 (895-963) non-infective bites and Fy- 442 Bagamoyo Clinical Trials Unit of the Ifakara Health Institute in Tanzania (358-487) infected non-irradiated bites. All infected volunteers developed and aimed at demonstrating that doses of 135,000 and 270,000 PfSPZ symptoms except for one, with a mean incubation period of 9.9 days are safe, immunogenic and effective in African population as in USA. A (range 8-13), and a mean pre patent period 12.6 days (range 11-14). total of 73 healthy adult male subjects were enrolled according to pre- The immunization model with Pv RAS was safe and sterile immunity defined inclusion and exclusion criteria into five groups. The 1st group of 3 was achieved in five experimental volunteers (42%) with an average volunteers were given 3 ascending doses of 30,000, 135,000 and 270,000 dose of 418 infectious bites and Fy- volunteers remained negative. The PfSPZ each, at 4 weeks interval for demonstration of safety. The 2nd and overall protection was lower than expected, probably because the planed 3rd groups had 20 out of 24 subjects per group given 5 vaccinations of minimal dose was not achieved in all the volunteers (1000 infective bites). 135,000 and 270,000 PfSPZ respectively while 4 out of 24 subjects in High throughput immune analyses and correlates of protection will be each group were blinded normal saline controls. After the 5th vaccination, presented. all subjects in the 2nd and 3rd groups were challenged with controlled human malaria infection (CHMI) at 3 weeks and at 24 weeks. The 4th 1633 group had 6 subjects receiving 5 vaccinations of 270,000 PfSPZ and were challenged with CHMI at 24 weeks after the 5th vaccination. The fifth DIRECT VENOUS INOCULATION: AN INNOVATIVE METHOD group had 16 subjects who were used as unblinded normal saline controls FOR ADMINISTERING WHOLE SPOROZOITE MALARIA for 2nd and 3rd groups during the CHMI at 3 weeks (2 subjects per group) VACCINES THAT IS SAFE, WELL TOLERATED, IMMUNOGENIC and at 24 (6 subjects per group) after the 5th vaccination. The primary AND HIGHLY PROTECTIVE outcomes were safety and tolerability after each vaccination as well as protective efficacy after CHMI with PfSPZ homologous Challenge (NF54). Thomas L. Richie1, Robert A. Seder2, Benjamin Mordmüller3, Other important outcomes were immune responses after PfSPZ vaccine. Judith E. Epstein4, Mahamadou S. Sissoko5, Sara A. Healy6, Seif A. Preliminary results suggest that the vaccine given at 135,000 PfSPZ and Shekalaghe7, Bertrand Lell8, Gloria P. Gómez-Pérez9, Ally Olotu7, 270,000 PfSPZ is as safe and well tolerated in Tanzanian adults as in naïve Said A. Jongo7, Alexandra L. Singer4, Kirsten E. Lyke10, Matthew US population. The assessment of efficacy using controlled human malaria B. Laurens10, Kristopher M. Paolino11, Julie E. Ledgerwood2, Peter infection for the second, third and fourth groups is underway and will be F. Billingsley1, B. K.L. Sim1, Eric R. James1, Anita Manoj1, Barney presented. Potential future trials to establish effective dose in different age S. Graham2, Claudia A. Daubenberger12, Christopher V. Plowe10, groups will be also be discussed. Marcel Tanner12, Pedro L. Alonso13, Salim Abdulla7, Patrick E. Duffy6, Ogobara K. Doumbo5, Peter G. Kremsner3, Stephen L. 1632 Hoffman1 1Sanaria Inc., Rockville, MD, United States, 2Vaccine Research Center, PROTECTIVE EFFICACY OF PLASMODIUM VIVAX RADIATION National Institute of Allergy and Infectious Disease, National Institutes ATTENUATED SPOROZOITES IN HUMAN VOLUNTEERS of Health, Bethesda, MD, United States, 3Institute of Tropical Medicine, 4 Myriam Arévalo-Herrera1, Juan M. Vásquez-Jiménez2, Andrés B. University of Tübingen, Tübingen, Germany, Naval Medical Research 5 Amado-Garavito2, Mary López-Pérez2, Andres F. Vallejo2, Angélica Center, Silver Spring, MD, United States, Malaria Research and Training 6 Castellanos2, Nora Cespedes2, Sergio A. Ochoa-Orozco2, Michelle Center, University of Bamako, Bamako, Mali, Laboratory of Malaria Larmat-Delgado2, Nora Martínez2, Juliana Henao-Giraldo2, Karen Immunology and Vaccinology, National Institute of Allergy and Infectious Molina-Gómez2, David A. Forero-Peña2, Cristhian Morales-Plaza2, Diseases, National Institutes of Health, Rockville, MD, United States, 7 8 Johanna Trejos3, Lucía Buriticá2, José Oñate4, Ramón Amaya5, Ifakara Health Institute, Bagamoyo, United Republic of Tanzania, Centre 9 Freddy Giraldo5, Cristian Beltrán5, Ricardo Palacios6, Sócrates de Recherches Médicales de Lambaréné, Lambaréné, Gabon, ISGlobal - 10 Herrera7 University of Barcelona, Barcelona, Spain, Center for Malaria Research, Institute for Global Health, University of Maryland School of Medicine, 1Malaria Vaccine and Drug Development Center and Faculty of Baltimore, MD, United States, 11Walter Reed Army Institute of Research, Health, Universidad del Valle, Cali, Colombia, 2Malaria Vaccine and Silver Spring, MD, United States, 12Swiss Tropical and Public Health Drug Development Center, Cali, Colombia, 3Asoclinic Inmunnologia, Institute, Basel, Switzerland, 13World Health Organization Global Malaria Cali, Colombia, 4Centro Médico Imbanaco, Cali, Colombia, 5Hospital Programme, Geneva, Switzerland Universitario del Valle, Cali, Colombia, 6Meridional R&D, São Paulo, Brazil, 7Malaria Vaccine and Drug Development Center and Caucaseco Scientific The oral, intramuscular, subcutaneous (SC) and intradermal (ID) routes Research Center, Cali, Colombia are often selected to inoculate humans with antigenic material for the purpose of inducing long term, protective immunity. The intravenous Immunization of human volunteers with radiation-attenuated sporozoites (IV) route, while standard for cellular or humoral immunotherapies and (RAS) of Plasmodium falciparum has shown to be highly protective immunoprophylaxis (e.g., hepatitis B immune globulin), has not generally against infectious challenge with live sporozoites. Due to the lack of P.vivax been used. Sanaria and collaborators are now testing the IV route for a in vitro cultures, development of a vaccine based on RAS to this species vaccine immunogen – whole Plasmodium falciparum (Pf) sporozoites has lagged behind. A phase 1/2, controlled clinical trial was conducted (SPZ) – to facilitate targeting the liver. Clinical grade vaccine product

astmh.org 500 was first manufactured in 2008, consisting of aseptic, purified, radiation 1635 attenuated cryopreserved PfSPZ meeting FDA standards for parenteral injection (PfSPZ Vaccine). Initial trials showed high-grade (100%) CHEMOPROPHYLAXIS VACCINATION (CVAC) OF RHESUS protection against Pf with IV injection through an indwelling catheter MACAQUES USING PLASMODIUM KNOWLESI SPOROZOITES (IV line), as previously published, but not when injected by the ID or SC AND THE ANTIMALARIAL DRUG PYRIMETHAMINE: routes (Epstein et al Science, 2011). Because it is impractical to consider ESTABLISHING A REGIMEN THAT COMPLETELY PREVENTS immunizing large numbers of individuals by placing an IV line and then DEVELOPMENT OF BLOOD STAGES injecting through it, and to improve operability for mass administration campaigns to eliminate malaria, direct venous inoculation (DVI) has been Agnes Mwakingwe1, Sara A. Healy1, Erin Gabriel2, Irfan Zaidi1, developed. A small-bore (25 gauge) needle is inserted, blood “flashback” Lynn Lambert1, Sachy Orr-Gonzalez1, Junhui Duan1, Dariyen is documented, and the PfSPZ are injected rapidly. This often painless Carter1, Brandi Butler1, Jen C. Hume1, Charles Anderson1, Sumana procedure has been performed 913 times to inject PfSPZ into 305 adults Chakravarty3, Stephen L. Hoffman3, Patrick E. Duffy1 in the US, Germany, Spain, Mali, Tanzania, Gabon and Equatorial Guinea. 1National Institutes of Health/Laboratory of Malaria Immunology and When used for PfSPZ Vaccine, DVI induces high-grade protection after Vaccinology/National Institute of Allergy and Infectious Diseases, Rockville, 3 doses. The injections cause limited local and essentially no systemic MD, United States, 2National Institutes of Health/National Institute of reactogenicity, and there have been no allergic reactions or disenrollments Allergy and Infectious Diseases/Biostatistical Research Branch, Rockville, due to adverse events. Moreover, injection of infectious PfSPZ (PfSPZ MD, United States, 3Sanaria Inc., Rockville, MD, United States Challenge) by DVI induces Pf infection consistently, and when study subjects receive concurrent oral chloroquine, PfSPZ Challenge given by DVI Chemoprophylaxis Vaccination (CVac) involves inoculation of Plasmodium induces high levels of protective immunity. Based on the excellent safety, sporozoites under antimalarial drug coverage, and CVac using chloroquine tolerability, infectivity and potency record in adults, the first trials of PfSPZ (CQ) has been shown to induce potent and long-lasting immunity in administered to infants and children by DVI will be initiated in 2015. humans and animals. The contribution of blood stage immunity versus liver stage immunity to protection has been a point of controversy. We 1634 seek to induce highly effective immunity in humans with CVac regimens that kill parasites during liver stage development thus completely inhibiting USE OF FLUOROSPOT ASSAY TO ASSESS IFNG, IL2, AND exposure to blood stages. We have conducted a study of a CVac drug IFNG PLUS IL2 RESPONSES AGAINST WHOLE PLASMODIUM schedule in Rhesus monkeys. Rhesus macaques were inoculated with FALCIPARUM SPOROZOITES AND SELECTED ANTIGENS 12,500 purified, cryopreserved, P. knowlesi sporozoites (PkSPZ) by direct AFTER IMMUNIZATION WITH RADIATION-ATTENUATED venous injection (DVI). Monkeys subsequently received oral pyrimethamine (PYR; 1 mg/kg) treatment, in an attempt to kill liver stage parasites and SPOROZOITES ADMINISTERED BY MOSQUITO BITES prevent emergence of blood stage infection. An Up/Down study design Harini Ganeshan, Jun Huang, Maria Belmonte, Steve Abot, Arnel was implemented to evaluate the appropriate timing of PYR following Belmonte, Joanne Lumsden, Sharina Reyes, Jo Glenna Banania, PkSPZ DVI. Groups of macaques were dosed with PYR on either days 1, Charlotte Fedders, Anatalio Reyes, Yolanda Alcorta, Alicia 2 (Group 2, n=4) or on days 2, 3 (Group 3, n=7) post PkSPZ. qRT-PCR Simmons, Carlos Vasquez, Santina Maiolatesi, Alexandra Singer, and blood smears were performed from day 5 to day 27 post PkSPZ Bradley Hickey, Eileen Villasante, Judith Epstein, Martha Sedegah inoculation, to detect subpatent and patent parasitemia respectively. Naval Medical Research Center, Silver Spring, MD, United States All macaques (n=11) in Groups 2 and 3 were blood smear and qRT-PCR negative at all time points after PkSPZ inoculation. All control macaques In vivo depletion experiments in animals have shown that protective that did not receive PYR were qRT-PCR and blood smears positive by day 6 immunity induced by radiation-attenuated sporozoites (RAS) is dependent and day 8, respectively. Upon second and third vaccinations, administered on CD8+ T cells (mice and non-human primates) and IFNg (mice). Based 4 weeks apart, all macaques in Groups 2 and 3 remained negative for on results from our previous clinical trial where 50% (5 of 10) of subjects subpatent and patent parasitemia. Results from homologous challenge immunized with RAS were protected after controlled human malaria (2,500 PkSPZ DVI) to evaluate development of protective immunity will be infection (CHMI), the number of bites required to achieve the same presented. This study provides evidence that PYR following PkSPZ CVac level of 50% protection was calculated and used for the current study. can prevent blood stage infection in non-human primates, thus guiding Among the 11 subjects who received an average of 1,027 bites over 5 the design for an upcoming human trial of CVac with PYR. immunization-sessions, 6 were protected after CHMI (55%), allowing for the study of protective immune effector mechanisms and/or surrogate markers of protective immunity. Of the possible 5000 antigens predicted to be present in Plasmodium falciparum (Pf), the specific antigens involved in protective immunity induced by RAS vaccine is unknown. Using the highly robust FluoroSpot assay that assesses single cells simultaneously secreting two cytokines, IFNg and IL2, we measured T cell responses to purified aseptic sporozoites (SPZ) using freshly isolated peripheral blood mononuclear cells (PBMC) from subjects prior to each of the 5 immunizations, and before and after CHMI. We also assessed T cell responses against overlapping 15-mer peptide pools of four standard Pf proteins that have been evaluated in clinical trials, including CSP, AMA1, SSP2/TRAP, and CelTOS. All true immunized subjects, but none of the mock immunized, developed IFNg and IL2 T cell responses to SPZ. The highest magnitude and frequency of responses was detected at 28 days post first immunization. At pre-CHMI, there was a trend towards higher magnitude of responses and percent responders in protected subjects vs. non-protected subjects, but this did not reach statistical significance. As expected, responses against the four antigens tested were of lower magnitude and prevalence than the responses against whole SPZ. Interestingly, all pre-CHMI responses decreased in protected and increased in non-protected subjects post-CHMI. A possible hypothesis to explain this finding will be discussed. astmh.org 501 1636 1637 SAFETY AND EFFICACY OF DIRECT VENOUS INOCULATION A MODEL FOR DEPLOYMENT OF CRYOPRESERVED PFSPZ WITH RADIATION ATTENUATED PLASMODIUM FALCIPARUM VACCINE FOR FOCAL ELIMINATION OF MALARIA ON BIOKO NF54 SPOROZOITES (PFSPZ VACCINE) IN HEALTHY MALIAN ISLAND ADULTS Eric R. James1, Adam J. Ruben1, Aderonke O. Awe1, Henry Mahamadou S. Sissoko1, Sara A. Healy2, Abdoulaye Katile1, Huang1, José Raso2, Peter F. Billingsley1, Thomas L. Richie1, Ally Bourama Kamate1, Yacouba Samake1, Kourane Sissoko1, Amagana Olotu3, Alli Hamad3, Chris Schwabe4, Dianna Hergott4, Carl Maas5, Dolo1, Karamoko Niare1, Amadou Niangaly1, Merepen A. Guindo1, Marcel Tanner6, Anita Manoj1, Betty K. Sim1, Salim Abdulla3, Erin Gabriel3, Michael Fay3, Irfan Zaidi2, Freda Omaswa4, Eric Stephen L. Hoffman1 James4, Anita Manoj4, Anusha Gunasekera4, B. Kim Lee Sim4, 1Sanaria, Rockville, MD, United States, 2Ministerio de Sanidad y Bienstar Peter Billingsley4, Thomas L. Richie4, Michael Walther2, Stephen L. Social, Malabo, Equatorial Guinea, 3Ifakara Health Institute, Bagamoyo, Hoffman4, Patrick E. Duffy2, Ogobara Doumbo1 United Republic of Tanzania, 4Medical Care Development International, 1Malaria Research and Training Center, Mali-NIAID ICER, University Silver Spring, MD, United States, 5Marathon Oil Corporation, Houston, TX, of Science, Techniques and Technologies of Bamako, Bamako, Mali, United States, 6Swiss Tropical Public Health Institute, Basel, Switzerland 2Laboratory of Malaria Immunology and Vaccinology, National Institute PfSPZ Vaccine, composed of aseptic, purified, radiation-attenuated, of Allergy and Infectious Diseases, National Institutes of Health, Rockville, cryopreserved, P. falciparum (Pf) sporozoites (SPZ) is being assessed MD, United States, 3Biostatistical Research Branch, National Institute of in multiple clinical trials in the USA, Europe and Africa. The goal is to Allergy and Infectious Diseases, Rockville, MD, United States, 4Sanaria Inc, finalize a 3-dose regimen that induces high level (>80%), durable (>6 Rockville, MD, United States months) protection against controlled human malaria infection and A double blind, randomized Phase 1/2 clinical trial was conducted in Mali, natural exposure by heterologous/heterogeneous Pf parasites. The PfSPZ, West Africa to assess the safety, immunogenicity and protective efficacy being eukaryotic organisms, are cryopreserved and stored and distributed of Sanaria® PfSPZ Vaccine administered via direct venous inoculation through a liquid nitrogen vapor phase (LNVP) cold chain. The clinical (DVI) against natural malaria exposure in healthy 18-35 year old adults. development plan has a goal of licensure by mid to late 2018 for non- Twelve volunteers (safety group) received 2 doses of PfSPZ Vaccine (Day immune travelers and early 2019 for use in targeted focal elimination 0: 1.35x105 and Day 14: 2.7x105) and 88 volunteers received 5 doses of campaigns, for which it will serve as an ideal tool alone or in combination 2.7x105 PfSPZ Vaccine or normal saline (Day 0, 28, 56, 84, 140; total dose with other control measures. The first campaign is planned for Bioko of 13.5 x 105). The incidence and severity of local and systemic adverse Island, Equatorial Guinea. Bioko is ~2,000 km2 and has a population events occurring within 7 days after each dose were solicited. During the estimated for 2018 of ~300,000, concentrated in the capital, Malabo. malaria transmission season, volunteers were examined and blood smears The island is accessible by automobile, 95% of houses are currently obtained every 2 weeks for 20 weeks in total, with the primary efficacy mapped, and 85% of residents enumerated using a tablet-based endpoint being time to first positive blood smear. Injection site pain, Campaign Management Information System. Vaccine will be airfreighted headache, fatigue, myalgia, and pyrexia were the most frequent solicited to Malabo in large LNVP dry shippers each containing 5 x 104 cryovials adverse events in both vaccine groups. There was no significant difference and transferred at a central store to a LNVP cryobank or directly into small in local site reactogenicity, solicited systemic adverse events, or laboratory LNVP dry shippers for transport to the immunization clinics. Options for abnormalities between PfSPZ Vaccine and control volunteers. In this adult vaccinating Bioko’s population include fixed clinics, mobile clinics, and population, malaria transmission was intense with 93% (41/44) of the door-to-door vaccination. Each will be tested in a trial of 3,000 subjects in control group having at least one positive blood smear. Vaccine efficacy 2017. The LNVP dry shippers (free-standing, independent of electricity) will beginning 28 days after the last dose of PfSPZ Vaccine and through the serve both for delivery and for temporary storage on a rotating schedule next 20 weeks by estimated by cox proportional hazard 48% (15 , 69) to fixed or mobile clinics. Each dry shipper will hold up to 1,000 single P-value: 0.01 and by proportional analysis was 29% [8, 47], p = 0.006. dose vaccine vials. Plans include immunizing 15,000 people per day and Immunogenicity, measured by PfCSP antibody responses by ELISA, was not completing each immunization round in 4 weeks. The assumptions and predictive of individuals who remained blood smear negative throughout challenges of this and other approaches will be discussed. As the first the transmission season. The study demonstrates that repeated DVI such focal elimination campaign, Bioko Island will serve as a crucial test of administration of the PfSPZ Vaccine in a healthy adult African population the distribution logistics for PfSPZ Vaccine and as a model for subsequent was easy to administer, safe, well tolerated and efficacious in an intense campaigns. seasonal malaria transmission area of Mali. To our knowledge, this is the highest estimated protective efficacy against Pf parasitemia for 6 month 1638 follow-up vaccination of African adults. We are now working on altering the immunization regimen to increase immune responses and protective ASSESSING AND INCREASING THE POTENCY OF efficacy. PLASMODIUM FALCIPARUM SPOROZOITES FOLLOWING CRYOPRESERVATION Adam J. Ruben1, Eric R. James1, Aderonke O. Awe1, Henry Huang1, Sumana Chakravarty1, Michelle Laskowski1, Enni Fomumbod1, Soundarapandian Velmurugan1, Patricia De La Vega1, Maria Orozco1, Anita Manoj1, Sandra M. Riera2, Sangeeta M. Bhatia2, B. Kim Lee Sim1, Stephen L. Hoffman1 1Sanaria Inc., Rockville, MD, United States, 2Massachusetts Institute of Technology, Cambridge, MA, United States Sanaria has a unique capability to manufacture aseptic, purified Plasmodium falciparum (Pf) sporozoites (SPZ), which are stored in liquid nitrogen vapor phase until clinical use. The effectiveness of thermostabilization is shown by 100% protection of volunteers against controlled human malaria infection (CHMI) after immunization with radiation-attenuated PfSPZ (PfSPZ Vaccine); 100% infection following

astmh.org 502 injection of infectious PfSPZ (PfSPZ Challenge); and 100% protection 1640 against CHMI when chloroquine is given concurrently with PfSPZ Challenge (PfSPZ-CVac approach). These results using cryopreserved PfSPZ, THE NF54-BASED WHOLE-ORGANISM PFSPZ VACCINE IN THE unprecedented in clinical vaccinology, indicate that Sanaria’s PfSPZ are CONTEXT OF GLOBAL GENETIC DIVERSITY OF PLASMODIUM potent and infective. They are also concordant with the results of 4 in FALCIPARUM: IMPLICATIONS FOR SELECTION OF VACCINE vitro assays we use to monitor PfSPZ viability and potency: a membrane AND CHALLENGE STRAINS integrity assay, 3- and 6-day hepatocyte assays that assess PfSPZ infectivity in hepatocytes, and an axenic culture assay that measures PfSPZ Kara A. Moser1, Elliott F. Drábek1, Amed Ouattara2, Cesar transformation in cell-free culture. By these assays, cryopreservation leads Arze1, B. Kim Lee Sim3, Stephen L. Hoffman3, Judith E. Epstein4, to losses of ~10%, 5%, 5% and 40%, respectively, compared to freshly Christopher V. Plowe2, Joana C. Silva1 dissected PfSPZ, while the micropatterned cellular co-culture (MPCC) assay 1Institute for Genome Sciences, University of Maryland School of Medicine, integrates multiple aspects of viability and shows cryopreservation losses Baltimore, MD, United States, 2Center for Malaria Research, Institute for of 85% to 90%. These reductions compare very favorably with those of Global Health, University of Maryland School of Medicine, Baltimore, MD, other live vaccine agents after thermostabilization but also indicate that United States, 3Sanaria Inc., Rockville, MD, United States, 4U.S. Military process improvements could enable more efficient manufacturing and Malaria Vaccine Program, Malaria Department, Naval Medical Research lower cost of goods. To this aim, Sanaria has focused on improving 3 Center, Silver Spring, MD, United States areas using Pf, P. vivax (Pv) and P. yoelii (Py) SPZ: cryoprotectant additive Genetic diversity in Plasmodium falciparum (Pf) is an obstacle to mixtures, freezing protocols, and thawing methods. Combining several broadly efficacious malaria vaccines. The attenuated whole-organism approaches, we have doubled the infectivity and potency of cryopreserved malaria vaccine PfSPZ Vaccine is based on the African strain NF54, the PySPZ in vivo. In the MPCC assay infectivity has been increased by 2- to parental stock of the reference Pf isolate 3D7. Controlled human malaria 3-fold for both PfSPZ and PvSPZ. When integrated into manufacturing infection (CHMI) trials are underway to replicate initial promising results processes in the future, these improvements are expected to reduce by from homologous CHMI, and to assess heterologous protection using the 2- to 3-fold the numbers of PfSPZ required to achieve high-level protective South American strain 7G8. The degree of genetic dissimilarity between efficacy or infectivity after administration of PfSPZ Vaccine, PfSPZ-CVac, or NF54 and strains used in CHMI, as well as to circulating strains in natural PfSPZ Challenge, respectively. populations, can assist in the interpretation of protective efficacy, in the identification of additional challenge strains, and in the determination 1639 of whether regional-based or multivalent whole-organism vaccines are THEY SAID IT COULD NOT BE DONE: MANUFACTURING needed. To this end, we utilized whole-genome sequencing data from 32 PFSPZ VACCINES AT SCALE FOR MALARIA ELIMINATION clinical isolates from Africa and southeast Asia (SEA), which we compared with NF54, 7G8, and NF135 (the latter an isolate from SEA and potential B. Kim Lee Sim1, Anita Manoj1, Tao Li1, Abraham Eappen1, Eric vaccine component). We generated SNP calls relative to 3D7 for a panel R. James1, Sumana Chakravarty1, Adam M. Richman1, MingLin Li2, consisting of ~1 million validated variable positions in protein-coding Richard E. Stafford1, Adam J. Ruben1, Yun Wu2, Peter F. Billingsley1, genes. We identified an average of 4,200, 4,500 and 5,300 SNPs in Stephen L. Hoffman1 samples from East and West Africa and SEA, respectively. Similarly to 1Sanaria Inc., Rockville, MD, United States, 2Protein Potential LLC, clinical samples from SEA, NF135 differs from 3D7 in 5,280 SNPs, while Rockville, MD, United States the difference between 7G8 and 3D7, at 4,722 SNPs, is intermediate between that of African and of SEA samples. With no SNPs called, Sanaria® PfSPZ Vaccine and PfSPZ-CVac are highly protective vaccines NF54 is identical to 3D7 in all nucleotide positions in the panel. Principal targeting Plasmodium falciparum (Pf) that are currently in clinical trials coordinate analysis using genetic distances between samples showed a in the US, Europe and multiple countries in Africa. The immunogen clear separation of strains from Asia and Africa according to the first two comprises aseptic, purified, cryopreserved, metabolically active whole Pf coordinates, with NF135 clustering with the former. NF54 clustered more sporozoites (SPZ) attenuated by irradiation or an antimalarial drug. The closely with strains from West Africa, and 7G8 appears in the periphery PfSPZ consortium of international investigators met on March 11-12, of the African clade according to the first four components, suggesting 2015 in Germany to develop plans to urgently move these promising clear differences but close ancestry between them. These results suggest PfSPZ vaccines forward. Evidence that such radiation attenuated PfSPZ that heterologous challenge studies demonstrating efficacy of PfSPZ in administered to humans by mosquito bite could confer sterile protection preventing infection against 7G8 would be very encouraging for the has been available since the 1970s. Why then was this approach not prospect of its efficacy in Africa. developed as a vaccine? In large part this was due to the misconception that such a vaccine that met regulatory and cost of good standards could 1641 not be manufactured. The idea that aseptic mosquitoes, highly infected with PfSPZ, could be reared and the PfSPZs harvested was considered MECHANISTIC CHARACTERIZATION OF THE COMPLEMENT an impossible dream. Compounding this notion was the thought that RECEPTOR 2 DERIVED PEPTIDE P28 AS A POTENT ADJUVANT purifying these PfSPZs and stabilizing them for pharmaceutical use was FOR VACCINES not possible. Sanaria’s manufacturing team has optimized the Pf life cycle in compliance with current Good Manufacturing Practices to obtain Elke S. Bergmann-Leitner, Casey Storme, Heather Hosie, >1.5x105 infectious PfSPZ/ aseptic mosquito. Nonetheless, there continues Elizabeth Duncan, Tatyana Savransky, Evelina Angov to be disbelief that a mosquito can ever be raised as an aseptic organism. Walter Reed Army Institute, Silver Spring, MD, United States Sanaria’s aseptic mosquitoes are quality controlled to pass USP<71> sterility tests that are mandated for aseptic manufacture. But how can Second generation malaria vaccines are currently being identified with PfSPZs be harvested from each mosquito salivary gland in a manner that the help of reverse vaccinology, which takes advantage of genome- and is compatible with GMP at scale? Our operators harvest at average rates proteome-based antigen discovery. Targeting immune responses to of 3 mosquitoes/minute. Thus a single lot of 1x103 vials of PfSPZ vialed at antigens expressed on sporozoites ideally impacts the ability of parasites 1.5x105 PfSPZ per vial requires a team of 6 dissectors working for 2 hours; to migrate to the liver and/or infect hepatocytes. The Plasmodium a yield of 3x103doses of PfSPZ-CVac. Our automated dissection intends on Cell-Traversal protein for Ookinetes and Sporozoites (CelTOS) plays an harvesting 1 mosquito/sec. Our cryopreservation methodology stabilizes essential role in parasite movement in both, mosquitoes and vertebrates, PfSPZ for >4 years. This presentation will de-mystify our manufacturing and is required for successful infection. We previously characterized the process and explain the specifics of how we intend to manufacture for ability of a CelTOS-based protein vaccine to induce protective immunity Phase 3 clinical trials and product launch. in preclinical models using conventional adjuvants. To overcome the

astmh.org 503 shortcomings plaguing malaria vaccines, i.e., requirement for large However, similar to other microbial vaccine candidates the polymorphic antigen doses and short duration of protection, we employed a peptide nature of this ligand represents a serious problem that may compromise adjuvant that has been shown to greatly enhance the immunogenicity efficacy of a DBP vaccine. In particular there is the tendency for immunity of circumsporozoite protein (CSP). The peptide is based on the minimal to be strain specific. Our hypothesis is that polymorphic dominant B cell binding site for complement receptor 2 (CD21) of complement factor C3d. epitopes of DBP represent an evasion mechanism to misdirect immune Antigen uptake and activation studies with bone marrow derived dendritic responses away from functional, conserved epitopes. Consistent with cells revealed superiority of the PfCelTOS-p28 chimeric protein over the this interpretation, the dominant B cell epitopes in DBP are polymorphic wildtype PfCelTOS. Mice were immunized with different doses, containing surface-exposed motifs adjacent to the dimer interface but these variable or lacking extraneous adjuvant (Montanide) to determine the optimal dose residues are generally not important for binding the erythrocyte receptor of the vaccine for a subsequent challenge with heterologous P. berghei DARC. To overcome the inherent bias towards strain immunity, we sporozoites. The cellular analysis revealed a) that significant IFN-γ and IL-4 previously evaluated an engineered DBP mutant DEKnull that partially responses were induced even in the absence of extraneous adjuvant, and overcame strain-specific immunity. In the current study we have evaluated b) superiority in the magnitude of the responses compared to the wildtype three additional novel engineered DBP immunogens that altered (1) PfCelTOS. Immunization with 100 fold lower dose of the chimeric protein variant epitopes, (2) functional residues, and (3) residues for dimerization. (0.1 µg PfCelTOS-p28) had a higher efficacy (80%) than immunization Each strategy altered the nature of functional antibodies elicited and with adjuvanted wildtype protein (10 µg). Studies are underway to importantly design #1 induced more broadly neutralizing antibodies determine the longevity of the protective response. In conclusion, against a range of diverse allelic variants. The successful results indicate a targeting a protein vaccine to CD21 using this peptide adjuvant can greatly potential approach that can be used generally to improve efficacy of other enhance immunity and can also bypass the need for extraneous adjuvant. malaria vaccine candidates. Structural studies into these novel antigens are currently underway. 1642 1644 THE COMBINED IMPACT OF TRANSMISSION-BLOCKING DRUGS AND RTS,S VACCINES IS SYNERGISTIC? IDENTIFICATION AND CHARACTERIZATION OF NEW PLASMODIUM VIVAX ANTIGENS AS POTENTIAL TARGETS Ellie Sherrard-Smith, Leanna Upton, Sara Zakutansky, Katarzyna FOR PRE-ERYTHROCYTIC VACCINES AGAINST VIVAX Sala, Azra Ghani, Thomas S. Churcher, Andrew Blagborough MALARIA Imperial College London, London, United Kingdom Mindy Leelawong1, Julio A. Ventocilla1, Karina P. Leiva1, Emily The Malaria Vaccine Roadmap aims to develop a vaccine that provides Smith2, Kimberly A. Edgel2, Gissella Vasquez1, Robert Gerbasi1, 80% protective efficacy against Plasmodium falciparum by 2020. The Eileen Villasante2, Andres G. Lescano1, Joao Aguiar2, Geral most advanced malarial vaccine is currently the pre-erythrocytic vaccine Christian Baldeviano1 RTS,S which targets the circumsporozoite protein (CSP) and has been 1 2 shown in clinical trials to reduce the clinical incidence of malaria in U.S. Naval Medical Research Unit - 6, Callao, Peru, Naval Medical children by 46% (range 40 - 77%). It is thought to be most efficacious Research Center, Silver Spring, MD, United States in regions of low transmission. Methods to reduce mosquito-to-human Despite the large global burden of Plasmodium vivax (Pv) infection, there transmission within a given region prior to vaccine application could is a dearth of promising vaccine candidates against vivax malaria. Four enhance the vaccine’s overall effectiveness. One approach could be the vaccines have progressed to clinical trials, three of which are based on use of partially effective transmission blocking interventions (TBIs) which the abundant sporozoite surface protein, the circumsporozoite protein. aim to reduce human-mosquito transmission. Using mosquito-vertebrate To identify additional promising pre-erythrocytic vaccine antigens, data systems we estimate the combined impact of a TBI candidate (atovaquone) from a high-throughput P. falciparum (Pf) antigen screening project was and a pre-erythrocytic vaccine (which targets CSP in a similar manner to used. The most immunogenic proteins were selected based of their ability RTS,S and has an estimated efficacy of approximately 50%) to determine to induce antibodies and cytokine production in T cells from volunteers whether the different interventions are antagonistic, additive or synergistic. immunized with radiation attenuated Pf sporozoites. Two of the Pf A mathematical model is developed which captures the population proteins, falstatin, a cysteine protease inhibitor, and the gamete egress and dynamics of the parasite in the mosquito and mouse population and is sporozoite traversal protein (GEST) are expressed in the sporozoite and liver used to estimate the mosquito-to-vertebrate and vertebrate-to-mosquito stages and are capable of inducing protection in a P. yoelii rodent model. transmission probabilities and how they change following the introduction We expressed full-length PvFalstatin and PvGEST using an optimized wheat of vaccine. The functional relationship between the probability of blood- germ cell-free expression system protocol. Antibodies to both falstatin stage infection and quantity of oocysts in the mosquito mid-gut does not and GEST were measured by ELISA in individuals naturally infected with P. change with TBI treatment but the number of oocysts is reduced at lower vivax. Additionally, we assessed the capacity of these proteins to induce biting rates (and eliminated at 1 or 2 bites after 4 successive generations). cytokine production in T cells from P. vivax-infected individuals living in The estimated probability of transmission to the vertebrate is therefore endemic areas in the Peruvian Amazon. We will present data that indicate lower with TBIs compared to control estimates. We present and discuss the that lessons from P. falciparum antigen discovery may provide a promising potential benefits of using TBIs with RTS,S-like vaccines to reduce malarial and valid platform for identifying potential vivax vaccine candidates. transmission. 1645 1643 IMPORTANCE OF CHOOSING THE RIGHT ANIMAL MODEL A NEWLY ENGINEERED MUTANT OF THE PLASMODIUM FOR THE DOWN-SELECTION OF SECOND GENERATION CSP VIVAX DUFFY BINDING PROTEIN ENHANCES INDUCTION OF BASED VACCINES BROADLY NEUTRALIZING ANTIBODIES Anthony May1, Mike Porter1, Farhat Khan1, Margot Debot1, Aziz Francis B. Ntumngia1, Miriam T. George1, Edwin Chen2, Niraj H. Qabar1, Norman Waters1, Phillipe Saudan2, Sheetij Dutta1 2 1 Tolia , John H. Adams 1Walter Reed Army Institute of Research, Silver Spring, MD, United States, 1University of South Florida, Tampa, FL, United States, 2Washington 2Cytos Biotechnology, Schlieren, Switzerland University School of Medicine, St. Louis, MO, United States Plasmodium falciparum Circumsporozoite protein (CSP) remains the The vital role Plasmodium vivax Duffy binding protein (DBP) in blood- most promising malaria vaccine candidate. We have expressed a near stage development justifies its consideration as a vaccine candidate. astmh.org 504 full-length soluble recombinant CSP in E. coli. The protein contains the status. In this pilot study, seroreactivity to RH5 was less prevalent among conserved N-terminal region, NANP repeats and the C-terminal region mothers and less correlated between mothers and newborns than for of PfCSP. It is widely believed that adjuvanted soluble CSP would not be AMA1 or MSP variants. PM may alter breadth of seroreactivity in mothers sufficiently immunogenic to confer protection against parasite challenge and their newborns. Protein microarrays may be a userful tool that will and that particulate delivery platforms are a way to overcome this hurdle. allow us to determine the influence of PM and maternal antibody transfer We investigated whether conjugating the soluble CSP to a nanoparticle to the fetus on potential vaccine candidates. would substantially augment its immunogenicity as compared to adjuvanted soluble CSP. A recombinant capsid protein of bacteriophage 1647 Qb that assembles into a 25 nm particle was used as a carrier. CSP was chemically conjugated to the Qb virus-like particle (VLP) and the INDUCING BOTH PROTECTIVE ANTIBODIES AND CD8 T CELLS immunogenicity of the resulting VLP vaccine was tested in C57Bl/6 mice. BY PRIME-BOOST WITH LIVE ATTENUATED VACCINE Alum adjuvanted Qb -CSP induced higher antibody titersthan soluble CSP. Sumana Chakravarty1, Yun Wu2, Minglin Li2, Richard E. Stafford2, Upon challenge with a transgenic P. berghei parasite that expresses the Meredith L. Leong3, Peter Lauer3, Dirk G. Brockstedt3, Thomas full-length P. falciparum gene, the CSP and Qb-CSP vaccines showed high W. Dubensky3, Steven G. Reed4, Chris Fox4, Shahid M. Khan5, level of sterile protection. The differences between soluble and particulate Chris Janse5, Ahmed M. Salman5, Patrick E. Duffy6, David Jones6, CSP was most pronounced after the 1st vaccination and particulate Stephen L. Hoffman1, B. Kim Lee Sim2 presentation most strongly influenced the titers of the repeat region. Since immunogenicity in mice does not always translate to humans we also 1Sanaria Inc., Rockville, MD, United States, 2Protein Potential LLC, tested the Qb-CSP and soluble CSP vaccine in the Rhesus monkey model. Rockville, MD, United States, 3Aduro Biotech, Inc., Berkeley, CA, United Unlike mouse data, no significant difference in the immunogenicity of States, 4Infectious Disease Research Institute, Seattle, WA, United States, Alum adjuvanted CSP and Qb-CSP was observed in Rhesus. While potent 5Leiden University Medical Center, Leiden, Netherlands, 6Laboratory of immunogenicity and protection was observed in mice, Alum adjuvanted Malaria Immunology and Vaccinology, National Institute of Allergy and CSP and Qb-CSP were not highly immunogenic in the Rhesus model. The Infectious Diseases, National Institutes of Health, Bethesda, MD, United availability of transgenic parasite challenge strains allows us to use mice States as a go-no-go model for vaccine progression, however our data shows There are >2x108 cases and 6x105 deaths due to Plasmodium falciparum that mice may be much more sensitive to Alum based formulations and (Pf) annually, despite $2B/yr spent on malaria control. The malaria vaccine, particulate vaccines than higher primates. Hence Rhesus immunogenicity RTS,S/AS01 is safe and delays clinical malaria onset by 30-50% depending should remain as the final go-no-go criteria for down-selecting second on age group. Protection may be primarily mediated by antibodies generation CSP based vaccines for human trials. against the repeat region and some CD4+ T cell responses against the C’ terminus of PfCSP. The vaccine does not induce meaningful CD8+ T 1646 cell responses. A vaccine for the military and travellers needs to provide >80% protective immunity for at least 6 months. We hypothesize that BREADTH OF MALARIA VACCINE TARGET ANTIGEN by adding highly functional, protective CD8+ T cell responses to antibody SEROREACTIVITY AND PLACENTAL TRANSFER AMONG responses against the PfCSP, such long lived protective immunity can be MOTHER-NEWBORN PAIRS IN MALAWI achieved. We use live-attenuated Listeria monocytogenes (Lm) as a Jenny A. Walldorf1, Jason A. Bailey1, Sarah Boudová1, Titus vaccine platform and use its properties of effectively stimulating robust, Divala1, Randy Mungwira2, Patricia Mawindo2, Jozelyn Pablo3, Algis multi-functional, cell-mediated immunity, as a result of its intracellular Jasinskas3, Rie Nakajima3, Amed Ouattara1, Matthew Adams1, lifecycle and ability to infect, deliver antigen and stimulate DCs in vivo. Terrie Taylor2, Philip L. Felgner3, Christopher V. Plowe1, Mark A. Our strategy for improving protective efficacy of our recombinant (r) Travassos1, Miriam K. Laufer1 PfCSP vaccine as compared to RTS,S/AS01 is to, 1) Include N’-terminus sequences containing neutralizing antibody and T cell epitopes to diversify 1Center for Malaria Research, Institute for Global Health, University of and increase potency of the antibody and cellular responses to PfCSP; 2) Maryland School of Medicine, Baltimore, MD, United States, 2Blantyre Conjugate rPfCSP to a carrier protein to increase antibody titers; and 3) Malaria Project, University of Malawi College of Medicine, Blantyre, Boost with attenuated rLm expressing PfCSP (Lm-PfCSP) to enhance CD8+ Malawi, 3Division of Infectious Diseases, Department of Medicine, T cell responses. We demonstrate that priming with rPfCSP in adjuvant and University of California, Irvine, CA, United States boosting with Lm-PfCSP induces high levels of PfCSP-specific inhibitory In young infants, malaria vaccine efficacy may be inhibited by maternal antibodies and CD8+ and CD4+ T cells. Conjugating rPfCSP to a carrier antibody interference with potential vaccine targets. Little is known further enhances the antibody response to PfCSP by >8 fold as compared about the comparative efficiency of transplacental transfer of antibodies to unconjugated rPfCSP. Most importantly, 100% of mice immunized with targeting different Plasmodium falciparum antigen variants and the adjuvanted rPfCSP and boosted with Lm-PfCSP were protected against effect of placental malaria (PM) infection. PM is one of several factors sporozoite challenge with a transgenic rodent malaria parasite which thought to inhibit antibody transfer. We used a protein microarray to express PfCSP in place of PbCSP. The high levels of inhibitory antibodies assess breadth of seroreactivity to 314 target malaria vaccine antigens as assessed by inhibition of liver stage development, impressive in vivo in 32 mother-newborn pairs in Malawi. The array included 264 apical protection and assessment of long term memory provides impetus for membrane antigen 1 (AMA1), 20 merozoite surface proteins (MSP) 1 urgent development of this strategy. and 2, and 30 reticulocyte-binding protein homologue 5 (RH5) protein variants. At delivery, maternal peripheral and cord blood samples were obtained. Placentas were inspected for histological and molecular evidence of PM. The categorical definition of seroreactivity was median fluorescent intensity (MFI) 2 standard errors above the mean for 10 malaria-naïve controls for each antigen variant. Of all mothers, 80% (95%CI: 78-81) were seroreactive across AMA1 variants, 75% (95%CI: 70-81) to MSP, and 33% (95%CI: 26-40) to RH5 variants. Breadth of seroreactivity was greater among mothers with evidence of PM than without. Categorical mother-newborn outcomes were concordant in all three antigen groups by McNemar’s test while Spearman correlation of continuous MFIs was 0.74, 0.83, and 0.35 for AMA1, MSP, and RH5 respectively. Maternal-newborn correlation results for each antigen group were similar stratifying by PM

astmh.org 505 1648 emulsion or liposome), as determined by ELISA against synthetic peptides or region-specific recombinant polypeptides using sera from two rhesus RECOMBINANT EXPRESSION, PURIFICATION AND monkey trials and multiple mouse studies in which immunization with IMMUNIZATION STUDIES OF NOVEL PRE-ERYTHROCYTIC either monomeric forms or chemical conjugates to ExoProtein A or other VACCINE ANTIGENS IN THE PLASMODIUM YOELII MOUSE carriers was examined. To date, chemical conjugation of a recombinant MALARIA MODEL CSP to a carrier protein formulated in an adjuvant other than Alhydrogel has provided the best evidence for enhancement of the breadth of the Daniel Shaji, Charles Anderson, Weili Dai, Solomon Conteh, antibody response to include the processed N-terminal region as well as Dariyen Carter, Lynn Lambert, Nicholas MacDonald, Emma K. a 5 - 100 fold increase in the overall CSP-specific response in mice. These Barnafo, Kelly Rausch, Andrew Orcutt, Sarah Brockley, Holly preclinical results are significant in context to the rationale design of a Torano, Patrick E. Duffy second-generation CSP vaccine. Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, 1650 MD, United States LIMITED EFFICACY OF RTS,S VACCINE AGAINST MALARIA The pre-erythrocytic (PE) stage is a metabolically highly active but MAY BE ATTRIBUTED TO LACK OF T CELL EPITOPE symptomatically silent preparatory phase of the Plasmodium life cycle. CONSERVATION Intervening to kill the parasite at this stage prevents the symptomatic blood stage of infection, and is an attractive vaccine target. Using Andres G. Nunez1, Ryan Tassone1, Lauren Levitz2, Jonathan J. microarray analysis and DNA vaccination, 8 genes were previously Juliano2, Steven Meshnick2, Frances Terry3, William D. Martin3, identified as up-regulated in Liver Stage parasites and able to induce Anne S. De Groot1 partial protective immunity against PE infection. For further studies of 1University of Rhode Island, Providence, RI, United States, 2University these vaccine candidates, we prepared their P. yoelii orthologues as of North Carolina, Chapel Hill, Chapel Hill, NC, United States, 3EpiVax, recombinant proteins. Five genes were expressed as recombinant protein Providence, RI, United States with C terminal His tag in insect cells. Proteins Py370w and PyMIF4 were in soluble form when expressed in insect cells and could be purified In a recent clinical trial, the RTS,S vaccine against malaria achieved under native conditions using Ni-NTA column. Proteins PyMAL7, PyLISP1 efficacies of 55.8% and 31.3% for protection against the first clinical and PySHMT were initially insoluble and were purified under denaturing episode in children (5-17 months) and infants (6-12 weeks), respectively. conditions in presence of 6M GuHCL and subsequently refolded using While promising, these results leave much room for improvement. appropriate buffer conditions. Prior to formulation with adjuvants, the One reason for the limited success of RTS,S may be that the strain refolded PyMAL7 and PyLISP1 proteins were then passed over detergent of circumsporozoite protein (csp) included in the vaccine is poorly removal column to remove detergent present in the refolding buffer, and representative of circulating strains in endemic areas. Using sequences detergent from refolded PySHMT was removed by passing over a second from 57 unique csp variants collected in Liongwe, Malawi, we applied a Ni-NTA column. Proteins PySAP1, Py1995c and Py305w were expressed novel informatics algorithm called EpiCC (Epitope Content Comparison) and purified from E. coli under denaturing conditions and the proteins to determine relatedness among variants at the T cell epitope level. refolded using appropriate buffer conditions. Immunization studies of EpiCC uses HLA-DR binding predictions generated by the EpiMatrix tool these proteins have been initiated in mice, and details of the results will be to quantify the likelihood that a candidate vaccine strain will induce presented. protection against other strains, based on the nature and similarity of their T cell epitopes. According to EpiCC, the csp strain included in RTS,S 1649 had a low degree of T cell epitope relatedness compared to the other variants. The relationships among the variants at the T cell epitope level ROLE FOR CHEMICAL CONJUGATION TO ENHANCE THE differed from the phylogeny of the whole genome in many cases. If the BREADTH AND QUANTITY OF PLASMODIUM FALCIPARUM csp T cell epitopes in the RTS,S vaccine are not well conserved among RECOMBINANT CIRCUMSPOROZOITE PROTEIN-SPECIFIC the strains found in malaria-endemic areas, the vaccine may only confer ANTIBODIES partial protection. Lack of epitope coverage may explain why RTS,S has not achieved better efficacy in clinical trials. This concept can be broadly David L. Narum1, Joan Aebig1, Kelly Rausch1, Randall F. Howard2, expanded to sample data over multiple malaria-endemic areas. EpiCC Charles Anderson1, Darrick Carter2, Lynn Lambert1, Steve G. Reed2, may provide an objective approach to aid in strain selection for vaccine Patrick Duffy1, David Jones1 development. 1National Institutes of Health, Rockville, MD, United States, 2Infectious Disease Research Institute, Seattle, WA, United States 1651 The circumsporozoite protein (CSP) remains a significant vaccine target due PRELIMINARY RESULTS OF A RANDOMIZED, CONTROLLED, to the success of RTS,S. The antigenic component of RTS,S is comprised of DOUBLE-BLIND, SINGLE-CENTER PHASE 1 CLINICAL TRIAL about two-thirds of the native CSP including the immunodominant NANP TO EVALUATE SAFETY, TOLERABILITY, IMMUNOGENICITY repeat region and the thrombospondin repeat-like (TSR) domain fused to AND EFFICACY OF CAF01 AND ALUMINUM HYDROXIDE AS the hepatitis B surface antigen. We and others have recently shown that ADJUVANTS FOR THE MALARIA VACCINE CANDIDATE GMZ2 the N-terminal region of the CSP is also a target for antibody blockade of hepatocyte invasion. Furthermore, we observed that in Anopheles IN HEALTHY ADULT AFRICAN VOLUNTEERS mosquitoes, a fragment of approximately 70 amino acids is cleaved from Ulysse Ateba Ngoa1, Ayola Akim Adegnika1, Jean Claude Dejon the N-termini and then within the salivary gland the CSP changes its Agobe1, Marguerite Massinga-Loembe1, Michael Theisen2, Peter shape to protect both the N- and C-terminal regions against antibody G. Kremsner3, Benjamin Mordmüller4 recognition prior to hepatocyte invasion. Thus, our development efforts 1Centre de Recherches Médicales de Lambaréné/Albert Schweitzer have focused on the evaluation of two recombinant forms of the CSP, Hospital, Lambaréné, Gabon, 2Statens Serum Institut, Copenhagen, one mimicking the unprocessed form or full-length protein (EcCSP) and Denmark, 3Institut für Tropenmedizin, Tübingen, Germany, 4Institut für the other mimicking the cleaved form (PpCSP) identified in salivary gland Tropenmedizin, Tübingen, Germany sporozoites. The N-terminus of CSP is poorly immunogenic compared to the NANP repeat region and the TSR domain. This was observed regardless GMZ2 is a malaria vaccine candidate consisting of conserved domains of of the adjuvant formulation tested (Alhydrogel, oil-in-water stable the two Plasmodium falciparum asexual blood-stage antigens merozoite

astmh.org 506 surface protein 3 (MSP3) and glutamate rich protein (GLURP). The antigens Significant communication activities had accompanied all the process. In were selected based on sero-epidemiological and functional studies parallel, pharmacovigilance system strengthening was set up because of and showed excellent safety, tolerability, and immunogenicity in pre- the characteristic of the drugs used and the relatively important quantity clinical studies when adjuvanted with aluminium hydroxide. The vaccine administered to children within such a short time. candidate GMZ2/aluminum hydroxide has been clinically developed up to Phase 2. Results of a Phase 2 trial in African children are still pending 1653 but preliminary data support the very good safety and tolerability profile of GMZ2. In general, data from the four trials suggest that improved FIELD TESTING OF A PYRETHROID QUANTIFICATION KIT formulations may result in stronger efficacy and a vaccine with potential IN VILLAGES COVERED BY INDOOR RESIDUAL SPRAY IN health benefits. Therefore, combination of GMZ2 with a more potent MULEBA, TANZANIA adjuvant is the rational next step in the clinical development. CAF01 is a novel adjuvant, which has demonstrated good safety, tolerability and Lauren Wright, Harparkash Kaur, Natacha Protopopoff, Mark improved immunogenicity profile when combined with various vaccine Rowland candidates. The current GMZ2/CAF01 study is performed to compare London School of Hygiene & Tropical Medicine, London, United Kingdom safety, tolerability, immunogenicity and efficacy of GMZ2 formulated Insecticide treated nets (ITN) and indoor residual spraying (IRS) are two with CAF01 to a control vaccine (Rabies) and 100 μg GMZ2 in aluminium of the primary methods of malaria prevention in Africa. In order for hydroxide, the best studied GMZ2 regimen so far. The study has started these methods to be effective it is essential that adequate concentrations in April 2015. A total of 50 participants were randomized and received of insecticide are present on nets and wall surfaces to kill mosquitoes. vaccinations. Participants receive three times control vaccine (n = 8; Group There is no easy assay to quantify insecticide levels without expensive A), 100 μg GMZ2 formulated in alum (n = 12; Group B), 30 μg GMZ2 laboratory equipment and procedures. To address this, LSHTM has formulated in CAF01 (n = 8; Group C) or 100 μg GMZ2 formulated in developed a simple field-applicable kit for monitoring pyrethroid residues CAF01 (n = 22; Groups D and E). Five weeks after completion of the on insecticide-treated nets- the Pyrethroid Quanitification Kit (PQK)-which vaccination regimen participants of groups A, B, C and D will receive a can be adapted to other types of treated surfaces. During the initial trial direct venous inoculation of 3200 PfSPZ Challenge to test for the efficacy the PQK kit was calibrated against a variety of sprayed surfaces and with of the vaccine. Follow up of the study participants will end six months different concentrations of lambdacyhalothrin before being taken into after the administration of the last vaccine injection. We will report the the field. Mosquito cone bioassay was conducted to show whether the result of the preliminary analysis of the GMZ2CAF01 study. The safety surface concentrations of insecticide detected by the PQK were sufficient profile, the tolerability as well as the efficacy of the GMZ2 candidate to kill a susceptible strain of mosquitoes. Houses in six villages were vaccine formulated with CAF01 will be discussed. visited 3 months after IRS had been conducted in Muleba, Tanzania. The samples were analysed in the field using a handheld spectrophotometer. 1652 In each house, five areas of the wall were examined to give an indication of insecticide distribution and within-wall variation. Results showed that SEASONAL MALARIA CHEMOPREVENTION the actual spraying results differed from expectation. Preliminary results IMPLEMENTATION IN CHILDREN FROM THREE TO 120 showedthat only 28% of houses had all rooms sprayed, leaving 72% of MONTHS EXPERIENCE IN THE FOUR SOUTHERN REGIONS IN houses partially sprayed, and insecticide concentration varied dramatically SÉNÉGAL across sprayed walls. The PQK is an easy to use quality assurance tool for Mamadou L. Diouf, Medoune Ndiop, Mady Ba, Julie Twing, monitoring of pyrethroid application rates and improving the quality of IRS Ibrahima Diallo, Moustapha Cisse, Seynabou Gaye, Alioune campaigns. Badara Gueye, Mame Birame Diouf Ministry of Health, Dakar, Senegal 1654 Because malaria still remains a major cause of disease and death in infants MULTIPLE PYRETHROID INSECTICIDES RESISTANCE and children, NMCP strives to reduce drastically these morbidity and MECHANISMS IN ANOPHELES GAMBIAE S.S. FROM mortality among children. For this aim, Seasonal malaria chemoprevention MALARIA SURVEILLANCE SITES IN NIGERIA (SMC) is adopted as a new intervention in malaria control policy after Samson T. Awolola1, Adedayo Oduola2, Adedapo Adeogun1, a long process launched in March 2012. According to WHO criteria Abiodun Olakiigbe1, Monday Tola3 the target areas for SMC are the four regions mentioned above. Drugs administration lays on door to door campaign strategy with community 1Nigerian Institute of Medical Research, Lagos, Nigeria, 2Department of volunteers. On the first day, the volunteers, trained by health agents in Zoology, University of Ilorin, Kwara State, Ilorin, Nigeria, 3Nigerian Institute health facilities, administer drugs to the children under surveillance of of Medical Research/University of Lagos, Lagos, Nigeria mothers or children guardians. For the 2 remaining days, mothers have to Insecticide resistance in Anopheles gambiae sensu stricto is a major substitute to the volunteers. In 2014, SMC Campaign CPS was conducted concern to malaria control. Resistance is mainly due to target-site in the four areas with three cycles covering the higher transmission season insensitivity arising from a single point mutation, often referred to as (August, September and November). The target was enlarged to the old knockdown resistance (kdr). Metabolic-based resistance mechanisms children from 3 to 120 months (624 139). This enlargement of the target, associated with elevated level of monooxygenase and Glutathione-S- compared with WHO recommendations (3 to 60 months,) was due to Transferase (GST) have also been implicated but to a lesser extent. Here vulnerability sliding towards the ages from 60 to 120 months as shown we report the co-existence of both resistance mechanisms in populations by the epidemiologic data on malaria morbidity in Senegal. The campaign of An. gambiae s.s. from malaria surveillance sites in Nigeria. Anopheles results were very satisfactory since the coverage rates for the 3 passages, larvae were collected from 12 malaria surveillance sites located in 3 are respectively 98, 63%, 97, 85% and 98, 04%. However, it should be ecological zones (north-central, south-west and south-south) in Nigeria. noted that behind these beautiful coverage rates, many challenges have All Anopheles tested belonged to the An. gambiae complex. An. to be faced to achieve such results. Indeed, considering the innovation gambiae s.s. was predominant (82.5%) and found at the 12 sites. An. of the intervention, its and and the strong Community component, it arabienis represented 17.2% but found at 3 sites. Mosquitoes from was necessary to set up an operative system allowing an availability of three sites located in the south-south and north-central were 100% the commodities, management tools supports and accessories on the susceptible to pyrethroid insecticides (permethrin and deltamethrin). sites and to prepare the actors to roll the strategy as recommended. In Mosquito susceptibility level to pyrethroids was 55-70% at the remaining addition, regular coordination and a follow-up with an effective data sites. Bioassay, synergist and biochemical analysis carried out on resistant collection and transmission system, was one of the key-success elements. and susceptible An. gambiae s.s. from the 12 sites revealed 35-60% astmh.org 507 of the West African kdr mutation in the resistant mosquitoes. Resistant a technical working group which developed a checklist and interview mosquitoes synergized using pyperonyl butoxide before insecticide guide to gather follow-up information on number of households that exposure showed a significant increase in mortality compared with the acquired nets, hung nets, slept under nets, their reasons for not using nets non-synergized. Biochemical assays showed significant increased levels of and sources of information about nets. Interviewers from each LGA were monooxygenase activities in the resistant mosquito at six sites in addition trained to use the checklist and recognize appropriate net hanging and to significant increased in GST level at two sites, indicating the presence use. Twelve interviewers were assigned to each Ward of each LGA. A total of multiple pyrethroid resistance mechanisms at these malaria surveillance of 2,696,476 net cards were issued to households based on two nets per sites. This current survey of insecticide resistance in Anopheles provides household, and 2,626,966 nets (97.4%) were redeemed. Retention rate baseline for resistance monitoring and highlights the need for routine in sampled households was 97.1%, while hanging rate of those retained resistance surveillance as an integral part of malaria control. was 71.8%%. Overall 69.6% household members reported that they slept under a net the previous night. A greater proportion of pregnant 1655 women (92.1%) reported using nets compared to children below 5 years of age (82.3%) and other household members (63.3%). Main reasons INTERMITTENT PREVENTIVE TREATMENT IN PREGNANCY: for not using nets included feeling hot (44.5%), inability to hang the net INCREASING THE DOSES IN BURKINA FASO (19.7%) and concern about the chemical used to treat the net (11.4%). Akwa Ibom is located in Nigeria’s highest malaria transmission zone. Hence Ousman Badolo1, Stanislas P. Nebie1, Mathurin Dodo1, Thierry there is need to use LLINs throughout the year. In contrast between 2013 Ouedraogo1, Rachel Waxman1, William R. Brieger2 DHS (14.1% residents slept under LLIN) and current results is stark and 1Jhpiego, Baltimore, MD, United States, 2Johns Hopkins University, implies that net use may likely decline as nets age. Even 1-2 months out Baltimore, MD, United States from a campaign there are people who are not hanging and using nets. In Burkina Faso, Antenatal Care (ANC) is a national platform for malaria Continuous systems for community level education and reinforcement and in pregnancy prevention and control. The 2010 Demographic and Health health system-based routine distribution for periods between campaigns Survey showed a good initial ANC registration rate (95%), but over are needed. 56% of pregnant women in rural areas do not register until their second or third trimester. Thus they may have missed the full regimen of ANC 1657 services including Long Lasting Insecticide-treated nets and intermittent preventive treatment of malaria in pregnancy (IPTp). In 2010 only 10.6% LLIN DISTRIBUTION CAMPAIGN PROCESSES: LESSONS of pregnant women nationally and 8.4% in rural areas received two LEARNED AND CHALLENGES FROM AKWA IBOM STATE, doses of IPTp. The United States Agency for International Development- NIGERIA supported Improving Malaria Care (IMC) project in Burkina Faso has been John Orok1, Bright Orji2, Enobong Ndekhedehe2, William R. providing technical assistance and training to health districts and their Brieger3 ANC staff on implementing updated (2012) WHO IPTp guidelines. The 1Ministry of Health, Akwa Ibom State, Uyo, Nigeria, 2Jhpiego, Baltimore, recommended provision of IPTp at every ANC visit from the 13th week MD, United States, 3Johns Hopkins University, Baltimore, MD, United of pregnancy onward leads to the possibility of 3 or more doses per States woman. The new guidance was incorporated into the update of Burkina Faso’s malaria strategy and has been disseminated since September 2014. Long Lasting Insecticide-Treated Nets (LLINs) protect users from malaria Annual data from the Health Management and information System for only if they reach the home. A smoothly functioning distribution is 2014 from three districts (Batie, Po and Ouargaye) and 61 health clinics essential to ensure nets reach their end users. Routine distribution at clinics where IMC has been working were collected and summarized. A total of helps to maintain supplies, but mass campaigns are also needed to replace 26,909 women registered for ANC. Of these 89.7%, 73.2% and 39.8% nets on a wide scale. The recent LLIN mass campaign in Akwa Ibom State attended ANC twice, three and four times respectively. Of those registered Nigeria offers lessons and challenges on this process. A State support team 84.1%, 73.2% and 18.8% received IPTp once, twice and thrice. Eleven was set-up and estimated the total nets needed on one net to 2 people. (17.7%) had not started the updated IPTp guidance. The Ministry of A total of 21,167 different cadres of personnel were recruited from Health also experienced stock-outs of sulfadoxine-pyrimethamine. Based supervisory to outreach jobs. One-day training was conducted in batches on this slow implementation and uptake of IPTp3+, the IMC project in in each of the 31 Local Government Areas (LGAs). To begin household collaboration with the National Malaria Control Program is examining ways mobilizers issued net cards and registered household members Town to strengthen antenatal malaria prevention including capacity building for announcers helped in demand creation. A private firm was hired bring ANC staff and community IPTp provision. 2,715,160 nets to 1,242 delivery points. A reporting tool tracked and monitored the distribution process. Reports flowed from the distribution 1656 points to the Ward supervisor, the LGA team leader and on to the state technical support team. The State team met at the end of each day to USE OF LONG-LASTING INSECTICIDE-TREATED BEDNETS IN review activities and address challenges and re-strategize. The distribution AKWA IBOM STATE NIGERIA AFTER A MAJOR DISTRIBUTION lasted from 18-22 December, 2104. Overall, thirty-five thousand CAMPAIGN households were mobilized, and no settlement was reported omitted. 2,715,160 nets were distributed, and 88,049 nets remained in the LGAs, Enobong U. Ndekhedehe1, John Orok2, Bright C. Orji1, William R. while 23,080 were left in the central store for mob-up. Unfortunately 145 Brieger3 50-net bales were missing. Mobilization led to active involvement of the 1Jhpiego, Baltimore, MD, United States, 2Ministry of Health, Akwa Ibom faith-based leaders, traditional rulers and members of the national youth State, Nigeria, Uyo, Nigeria, 3Johns Hopkins University, Baltimore, MD, service corps scheme. Despite advocacy, state political officials focused United States more on upcoming elections that the net distribution. Although demand While long lasting insecticide-treated nets (LLINs) have made a major dent was created and short term need was met, more attention is needed to in the incidence of malaria in Africa, LLINs need to be replaced at intervals. longer term use and supplies for routine services. The remaining supplies Akwa Ibom State Ministry of Health conducted a mass net distribution unfortunately were affected by security lapses and lost nets and may not in 2010 during which 1.8 million LLINs in the 31 local government areas serve the needs of complimentary routine distribution. The State needs (LGAs/Districts). An estimated 2.7 million nets were acquired with Global to assess the long term costs and sustainability of such massive efforts in Fund support for replacement distribution in November and December terms of meeting its malaria control needs. 2014. To learn about the outcome of the exercise, the Ministry organized a follow-up household survey in all LGAs in January 2015. The state formed astmh.org 508 1658 children under 5 years old were 18.3%, 9.9% and 10.1%, respectively. Heads of households mentioned other uses of LLIN such as for fishing SUSCEPTIBILITY STATUS OF ANOPHELES GAMBIAE S.L. TO and protecting crops. Despite substantial progress achieved over the last INDOOR RESIDUAL SPRAY INSECTICIDES FROM A SIX SITE seven years in malaria prevention in DRC, the use of LLIN among the BIENNIAL SURVEY PROJECT, UGANDA, 2009-2013 pygmy populations in the health zone of Wamba remains low. LLIN mass distribution planners should develop mechanisms to reach autochthone Michael Okia1, Ranjith de Alwis1, John Rwakimari1, James populations including a participatory process, inclusion of these key Kirunda1, Betty Mpeka1, Denis Ambayo1, Constantine Muwonge1, population representatives in decision making, targeted communication, Kenneth Ssaka1, David Hoel2, Claudia Corredor-Medina2, William and procurement of smaller size LLIN. G. Brogdon2 1Abt Associates, Inc., Kampala, Uganda, 2Centers for Disease Control and 1660 Prevention, Atlanta, GA, United States USE OF GIS-BASED HOUSEHOLD MAPPING SYSTEM TO Insecticide resistance threatens vector control interventions in Uganda, IMPROVE PLANNING, IMPLEMENTATION AND MONITORING past studies having shown the development of resistance in Ugandan OF MALARIA CONTROL STRATEGIES IN BIOKO ISLAND vector populations. We followed up on the 2009 national insecticide susceptibility study to investigate possible changes in susceptibility levels Guillermo Garcia1, Jason Kleps2, Alfred W. Hoadley3, Jose Luis in Anopheles gambiae s.l. to DDT, six pyrethroid, two organophosphate Obama Nsue1, Jose Osa Osa Nfumu1, Telesforo Eyegue Abuy1, and two carbamate insecticides collected from six sentinel surveillance Restituto Mangue Avue1, Jeremias Nzamio Mba Eyono1, Teobaldo sites across Uganda in 2011 and 2013 using the WHO bioassay test Babo1, Marcos Mbulito Ivanga1, Rosa Patricia Richard Ateme1, Nico kit. Resistance to DDT (mortality <90%), occurred in Wakiso, Tororo Alonso-Harper4, Roland Wango4, Roland Wango4, Sandra Fuentes4, and Kanungu Districts. In Apac and Kitgum Districts where IRS using Megan Perry4, Dianna B. Hergott1, Christopher Schwabe4 carbamate insecticides occurred the prior three years, mortality to DDT 1Medical Care Development International, Malabo, Equatorial was 91.5% and 94%, respectively. There was reduced mortality in An. Guinea, 2Towson University, Towson, MD, United States, 3Medical gambiae s.s. to almost all pyrethroids tested from the six sites except Care Development, Inc., Augusta, ME, United States, 4Medical Care for etofenprox in Kitgum District (92%). Mortality rates >98% were Development International, Silver Spring, MD, United States observed in An. gambiae s.s. populations to both organophosphate and carbamate insecticides across all test sites, except for propoxur As it is in many malaria-endemic countries, the informal housing pattern in Tororo (81%). An. gambiae s.s. in Uganda is resistant to DDT and in Equatorial Guinea without street names and building numbers makes most pyrethroid insecticides but is susceptible to organophosphate and malaria control difficult to effectively plan, implement and monitor. carbamate insecticides, while Anopheles arabiensis appears susceptible Beginning in 2012, the Bioko Island Malaria Control Project (BIMCP) to DDT. An. arabiensis was found to predominate in the IRS districts of created a geo-referenced mapping system that assigned each household Apac and Kitgum following rotation to carbamate insecticides, suggesting a unique identifier similar to an address. The Island was divided into 1 that An. arabiensis is not resistant to DDT and indicating that IRS greatly km2 sequentially numbered map areas, which in turn were sub-divided reduced An. gambiae s.s. populations. Data from Tororo and Kanungu into 100m2 sequentially numbered sectors. Using printed high resolution Districts indicate that there is reduced susceptibility to carbamates, strongly satellite images of each sector that clearly identified each building, a indicating the need for routine annual monitoring for insecticide resistance local field team assigned a sequential number to each household in each from around the country. building in each sector. Buildings with more than one household were ascribed a unique number for each household. Households residing in 1659 multi-story buildings received a floor identifier. The concatenation of the map area, sector, household number, and floor level yielded a unique LLIN USE IN THE PYGMY COMMUNITY IN THE HEALTH identifier, which was printed on a sticker glued to each household OF ZONE OF WAMBA, NORTHEAST OF THE DEMOCRATIC entryway, and subsequently recorded on all spray cards and LLIN REPUBLIC OF CONGO distribution forms. Areas of the island where satellite images were not available were mapped using GPS by a team that drove every road, walked Joris L. Likwela1, Norbert Mandana2, Marcel Lama3, A. every footpath, and identified every building/household. The information Brevezosek4 from the field maps was then digitized in ArcGIS. Field teams updated 1National Malaria Control Program, Kinshasa, Democratic Republic of the household database during IRS rounds in 2013 and 2014, and a the Congo, 2University of Uele, Isiro, Democratic Republic of the Congo, mass LLIN distribution in 2015. This has enabled the BIMCP to effectively 3Association Santé Familiale/Population Services International, Kinshasa, plan, implement and monitor vector control activities and respond to the Democratic Republic of the Congo, 4Nancy School of Medicine, University substantial housing growth due to the economic boom on the Island. of Lorraine, Nancy, France By being able to track IRS and LLIN supply to households and link this to annual survey data, the BIMCP has had an improved understanding of Autochthones are one of the three groups of key populations in need factors that contribute to increased parasite prevalence and to stratify of malaria control interventions. A key population is defined as a the Island in terms of transmission characteristics and service coverage. In community that is highly affected by malaria and which has limited areas such as Bioko where informal housing patterns exist, the GIS-based access to malaria control interventions. This study assessed LLIN access mapping system instituted by the BIMCP allows for improved planning, and use among pygmies, an autochthone population, in the health implementation and monitoring of malaria control activities. zone of Wamba, Province Orientale in DRC. A descriptive cross sectional study was conducted among pygmy populations in the health zone of Wamba from 17-22 February 2014, 4 years after the previous LLIN distribution campaign (2010) in order to establish a baseline data prior to the 2014 LLIN distribution campaign. Data was collected through interviews with heads of households using structured questionnaires. Data was entered using EPIDATA and analysed using SPSS for Windows. 602 heads of households in pygmy populations or their representatives were interviewed. The median household size was 4. The persons surveyed lived mostly in huts (57%) or small houses (43%). The proportion of households owning at least one LLIN, the use of LLIN by pregnant women and

astmh.org 509 1661 test samples from three spots arrayed from the top left to the bottom right of a sprayed wall. Six qualitative outcomes are measured ranging from DESIGN AND DEPLOYMENT OF A GIS-BASED CAMPAIGN “Well Sprayed” where all three samples comply with WHO concentration INFORMATION MANAGEMENT SYSTEM FOR PLANNING, norms, to “Not Sprayed” where all three have no insecticide. Sprayers MANAGING AND MONITORING MALARIA CONTROL who do not satisfy the “Well Sprayed” outcome receive intensified training INCLUDING FUTURE VACCINATION ON BIOKO ISLAND and supervision. Repeated poor performance can lead to dismissal. A first evaluation in 2014 revealed that 6% of sprayers achieved a “Well Dianna B. Hergott1, Christopher Schwabe1, Guillermo Garcia2, Sprayed” status and 4% a “Not Sprayed” status. Data from the current Andrew Taylor3, Benjamin Heasly3, Nathan Lienhardt3, Jessenia IRS round at various time intervals will be presented. Program performance Knowles2, Bruce MacLeod3 is assessed using Lot Quality Assurance Sampling (LQAS) and IQKs to 1Medical Care Development International, Silver Spring, MD, United States, determine if effective insecticidal coverage has been achieved (i.e., that 2Medical Care Development International, Malabo, Equatorial Guinea, at least 80% of 19 randomly selected communities each in turn have at 3University of Southern Maine, Portland, ME, United States least 80% of 19 randomly selected houses sprayed with the recommended insecticide concentration). The samples from all lots are then pooled to Medical Care Development International (MCDI) and the University of derive an effective insecticidal coverage rate for the Island as a whole. Southern Maine (USM) are developing an Android-based tablet application These data for the current round will be presented. The ability to randomly for planning, managing and monitoring community-based malaria control select, locate and test via IQK houses reportedly sprayed the prior day has on Bioko Island called the Campaign Information Management System markedly improved the quality of IRS on Bioko Island, virtually eliminating (CIMS). The CIMS is currently deployed for IRS and LLIN distribution falsification, and enabling the project to better evaluate its performance. and keep-up and will later be used for managing rapid case detection and treatment, highly focused control around residual hotspots, and possibly mass vaccination with a transmission-blocking vaccine. The CIMS 1663 includes four modules, two of which leverage pre-existing open source PREVALENCE OF ACUTE GASTROENTERITIS AMONG U.S. applications developed by USM and other partners - OpenHDS, a health MILITARY PERSONNEL DEPLOYED TO HONDURAS DURING and demographic surveillance system, and MOTECH, a suite of mhealth 2014-2015 tools that include technology for integrating with telcom systems to send voice or text messages to individuals/patients based on defined calling Mark P. Simons1, Giselle Soto1, Faviola Reyes2, Nathanael D. criteria. The CIMS modules include: (1) a geo-referenced household listing Reynolds1, Jamie Fraser3, Ricardo Aviles2, David Wolken2, David and associated member census based on OpenHDS; (2) an individual Tribble3, Ramiro Gutierrez4, Mark Riddle4 identification system that uniquely identifies all residents; (3) a set of 1U.S. Naval Medical Research Unit-6, Lima, Peru, 2U.S. Joint Task Force campaign participation applications developed in ODK that track individual Bravo, Comayagua, Honduras, 3Uniformed Services University of the or household participation in various campaigns; and (4) a cell phone- Health Sciences, Bethesda, MD, United States, 4U.S. Naval Medical based notification system using MOTECH which notifies households Research Center, Silver Spring, MD, United States about impending campaign events, follows-up on missed contacts, and encourages participation in future events. When engaging households Acute gastroenteritis (AGE) is a leading cause of lost duty days in military during campaigns, field workers select enumerated households from a personnel, and vaccine candidates against common diarrhea pathogens hierarchical geographic selection system. Household information can be are in phase II clinical trials. The need for field sites to evaluate vaccine updated in real time, accounting for population movement or construction efficacy in deployed personnel is a strategic need for the U.S. military of new houses. Campaign participation information is then entered and collaborating partners. Thus, we established Soto Cano Air Base in separately for IRS, LLINs, or any other type of campaign. These data are Honduras as a field site for clinical trials in Latin America including an stored in distinct data sets on a central server (cloud or local). The CIMS on-site lab for stool cultures and reference capacity at NAMRU-6 in Peru. provide an easy-to-use, adaptable and scalable solution for planning, Additionally, post-deployment surveys were integrated into medical out- managing and monitoring malaria control campaigns that is particularly processing to capture unreported cases of AGE. To date, 36/168 (21.4%) well suited for countries heading towards elimination. personnel evaluated in the post-deployment surveys reported experiencing diarrhea during a 6-9 month deployment (mean 3.2 different episodes, 1662 range 1-10). The most common symptoms reported were cramps (43.9%), nausea (40.3%), fever (26.3%), vomiting (14.3%), with 2 (3.5%) persons UTILIZING IQKS AND A CAMPAIGN INFORMATION reported experiencing bloody diarrhea, and the median number of loose MANAGEMENT SYSTEM (CIMS) FOR IMPROVED QUALITY stools in a 24 hour period was 4 (range 2-15). Eleven (19.3%) persons CONTROL OF INDOOR RESIDUAL SPRAYING reported experiencing lost duty time (range 1-4 days), 29 (50.8%) experienced decreased performance (range 1-10 days), and 8 (14.0%) Godwin Fuseini1, Wonder Philip Phiri1, Guillermo Garcia1, Raul reporting being sick in quarters. Further, 22 (38.6%) persons reported Nguema Ncogo Oyana1, Anita Eyang Obama1, Jesus Nazareth to the clinic and 4 (7.0%) needed IV fluids. From passive surveillance, Buatiche1, Arcadio Edu Mico1, Valeriano Oluy Nsue Maye1, Aveika 85 persons reported to the clinic with diarrhea and 36 (42.9%) met the Akum1, Luis Segura1, Dianna B. Hergott2, Christopher Schwabe2 case definitions of moderate-severe diarrhea. From these 36 patients, 1Medical Care Development International, Malabo, Equatorial Guinea, 3 (8.3%) samples were positive by primary stool culture, with Shigella, 2Medical Care Development International, Silver Spring, MD, United States Salmonella, and Aeromonas each identified. The remaining samples were positive for lactose-fermenting Gram-negative rods consistent with IRS programs have traditionally faced challenges ensuring that: (1) sprayers potential pathogenic E. coli subtypes. These samples are being analyzed at do not falsify spray records; (2) rooms within houses are sprayed well NAMRU-6 by multiplex PCR using the Luminex Gastrointestinal Pathogens (i.e. without coverage gaps and with a sufficient amount of insecticide Panel (GPP) as well as multiplex PCR detection of pathogenic E. coli applied); and, (3) effective insecticidal coverage has been achieved in each virulence factors, norovirus RT-PCR, and stools ova and parasite exam. spray area. The Bioko Island Malaria Control Project (BIMCP) has instituted These findings highlight the impact of diarrhea on military operations and a quality control procedure to address these challenges using Insecticide provide the information/logistics needed to establish Soto Cano as a site Quantification Kits (IQKs) to test houses randomly selected from a for phase I-IV clinical trials. Campaign Information Management System (CIMS) that maps in real time the houses reportedly sprayed each day. Sprayer performance is assessed at various intervals during a spray round by randomly selecting a house per sprayer from those recorded in the CIMS the previous day. IQKs are used to

astmh.org 510 1664 in the MAL-ED cohort study. We will test for fecal Reg1B in monthly and diarrheal stools for all children up to 12 months of age. We hope to assess AN ORAL CHOLERA VACCINATION CAMPAIGN COVERAGE the relationship between Reg1B and stunting in this cohort and determine SURVEY, HAITI 2014 a normal fecal Reg1B level in our population, an important step towards using this test in the clinical setting. Eleanor M. Burnett1, Jeannot Francois2, Nandini Sreenivasan1, Kathleen Wannemuehler1, Papa Coumba Faye3, Rania A. Tohme1, 1666 Paul Adrien2, Yves Gaston Deslouches2, Melissa Etheart4, Amber Dismer1, Roopal Patel4, Kashmira Date1 CLIMATIC INFLUENCES ON ENDEMIC CHOLERA IN KALEMIE, 1Centers for Disease Control and Prevention, Atlanta, GA, United States, DEMOCRATIC REPUBLIC OF THE CONGO 2Ministry of Public Health and Population, Port au Prince, Haiti, 3Pan- 1 2 1 American Health Organization, Port au Prince, Haiti, 4Centers for Disease Kerry L. Shannon , Didier Bompangue , Andrew Azman , Sean 1 3 1 Control and Prevention, Port au Prince, Haiti Moore , Benjamin Zaitchik , Justin Lessler 1Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United As part of a 10-year cholera elimination plan in response to the 2010 States, 2Research and Training Unit of Ecology and Control of Infectious cholera outbreak in Haiti, the Haitian Ministry of Public Health and Disease Control, Microbiology Department, Faculty of Medicine, University Population (MSPP) has proposed vaccinating 600,000 persons living in of Kinshasa, Kinshasa, Democratic Republic of the Congo, 3Department areas with high cholera attack rates and poor access to healthcare, clean of Earth and Planetary Sciences, Johns Hopkins University, Baltimore, MD, water, and basic sanitation with a two dose oral cholera vaccine (OCV). United States During August –September 2014, MSPP conducted its second OCV campaign targeting 185,314 persons in certain areas of 3 departments: We examined associations of environmental factors with cholera incidence Artibonite, Centre and Ouest. This was the first time vaccine from the in Kalemie, a city by Lake Tanganyika in the Democratic Republic of global OCV stockpile was used in Haiti. We conducted a multi-stage Congo. From January 2002 to February 2012 Kalemie had a total of stratified cluster survey to assess OCV coverage by department. We 20,559 suspected cholera cases averaging 39 per week (IQR 12-52). Cases sampled 80 enumeration areas (EAs) using stratified random sampling appear year-round with two annual peaks, atypical of Africa. The region and 20 households were selected in each EA. In each selected household, has a single rainy season that peaks between November and January and a general and an individual interview were conducted; one person per a single dry season from May-August. Climatic factors were estimated age group (1-4 years, 5-14 years, and ≥ 15 years) was randomly selected through remote sensing and considered as lagged variables in analyses for interview. Overall, 1,489 household and 3,201 individual interviews from 0 to 30 weeks before the week of cholera incidence. Factors included were conducted. Coverage estimates and 95% confidence intervals (CI) Lake Tanganyika height, temperature and chlorophyll a, maximum and were calculated accounting for the design. Two-dose OCV coverage was minimum weekly air temperatures, precipitation, solar radiation, and water 74% (95% CI: 64, 82), 64% (56, 72), and 48% (40, 56) in Artibonite, in the top meter of the soil column. In univariate models, cholera incidence Centre, and Ouest, respectively, and drop-out after the first dose was 7%, was most associated with chlorophyll a levels (Pearson correlation = 0.23) 8%, and 2%, respectively. Children 1 to 14 years were more likely to be and maximum and minimum weekly air temperatures one week prior vaccinated than persons ≥15 years old (p<0.01); in Centre, females were (Pearson correlation = 0.26 and 0.27 respectively). Multivariable negative more likely to be vaccinated than males (p=0.03). The most common binomial regression models including climatic factors were compared reason for not receiving any OCV doses was being absent during the based on Akakie Information Criteria and mean-squared prediction campaign in Centre and Artibonite and not hearing about vaccination error using ‘hold one year out’ cross validation. The best model by activities in Ouest. The most common reason for receiving only one dose both methods included: Lake Tanganyika water level, temperature and was being absent during the second round of campaign in all three chlorophyll a, soil water content of top meter of soil, rainfall, net solar departments. While coverage in Artibonite and Centre was comparable radiation, and minimum/maximum air temperature at varying time lags. with that in other OCV campaigns in Haiti and elsewhere, outdated 4.4% of weekly case counts were above and 21.9% below the cross population estimates and inadequate social mobilization might have validation predictive interval. These climate factors explain 36.3% of the contributed to lower coverage estimates in Ouest. Future OCV campaigns week-to-week variation in cholera. Cholera incidence is clearly associated in Haiti should be informed by more up to date population estimates and with climatic factors, however, models based on solely on climate fail to robust social mobilization activities. predict many major variations in cholera incidence. In Kalemie, 61% of the weeks when cases exceeded the prediction interval occurred in years 1665 with documented large-scale power outages and influxes of migrant populations. Improved predictive models using increased local knowledge EXPLORING REG1B AS A POTENTIAL MARKER OF of factors impacting the epidemic may allow us to better evaluate effective INTESTINAL HEALTH interventions such as vaccination campaigns. Allissia Anne Gilmartin1, Rashidul Haque2, William A. Petri, Jr.1 1667 1University of Virginia, Charlottesville, VA, United States, 2International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh HARD BLOOD AGAR IN THE ISOLATION OF ARCOBACTER SPP Environmental enteropathy (EE) is a gut disorder characterized by intestinal inflammation without overt diarrhea that occurs in individuals exposed Rito Zerpa1, Jorge O. Alarcon1, Lilian Patiño2, Edwin Correa3 over time to poor sanitation and hygiene. In children from low-income 1Instituto de Medicina Tropical “DA Carrion”, UNMSM, Lima, Peru, countries EE, is implicated as a cause of malnutrition, oral vaccine failure 2Instituto Nacional de Salud del Niño, Lima, Peru, 3Universidad Peruana and impaired cognitive development. Unfortunately, a lack of direct and Cayetano Heredia, Lima, Peru specific diagnostic tests has made it challenging to study EE. We have developed a fecal ELISA for Reg1 to test it as a potential biomarker of Arcobacter spp., is currently considered emerging zoonotic pathogen; small intestinal health. Reg1 plays a role in gut health and is known isolation by conventional methods in developing countries is difficult and to be up-regulated in a variety of enteric infections and inflammatory expensive, sometimes by contamination with bacteria such as Proteus. conditions. Our laboratory has previously found that fecal Reg1 predicted Here, we present the hard blood agar (HBA) as a simple culture medium future stunting through the first two years of life when measured in for the isolation of Arcobacter spp. We worked with 100 human fecal 12-week-old children in birth cohorts from Bangladesh and Peru. We are samples and 100 animals (50 pigs and 50 cattle) for the isolation of currently testing Reg1 for its ability to independently predict gut damage Arcobacter spp.; using the HBA and Columbia Blood Agar (CBA), both in approximately 220 children from Mirpur, Bangladesh who were enrolled with the method of the filter (0.45um porosity), and microaerophilic astmh.org 511 incubation with the method of Klebsiella and closing or sealing of the respectively). DNA was extracted directly from fecal samples collected inoculated plate with rubber bands obtained from powder-free latex from 226 children during May 2008 and April 2009, in Fortaleza, Ceará, gloves. Incubation at 28 ° C and read after 24-48 hours. The identification Brazil. A questionnaire was applied to characterize clinical symptoms. of Arcobacter was only based on their phenotypic characteristics. Conventional PCR was performed for detection of C. jejuni strains and Arcobacter was isolated 3/100 (3%) of human specimens in CBA, and investigation of nine virulence genes. The identification of C. jejuni was 4/100 (4%) in HBA; in animals: in cattle 10/50 (20%) was isolated in CBA, performed using hipO gene, providing 19,5% (44/226) of positivity. The and 28/50 (56%) in HBA; in 18/50 pigs (36%) was isolated in CBA, and presence of C. jejuni´s virulence-associated genes encoding proteins 35/50 (70%) in HBA. Hard blood agar (HBA) is an effective, simple and related to pathogenesis of the micro-organism were detected in the inexpensive alternative culture medium for the isolation of Arcobacter following proportions of C. jejuni-positive DNA samples: racR, 97.7% spp., even in samples with Proteus passing through the filter and by (43/44), dnaJ, 88.6% (39/44), and flaA, 79.5% (35/44); - related to swarming on cultures, masking and difficult isolation of Arcobacter. bacterial adhesion and colonization; ciaB, 97.7 % (43/44); pldA, 45.4% (20/44) and pVir 0% (0/44) - related to invasion, and cdtABC in 95.4% 1668 (42/44) related to cytolethal distending toxin (CDT). These data showed that C. jejuni were detected in a significant percentage of children aged VIRULENCE GENES AND ANTIMICROBIAL RESISTANCE IN 0-36 months with moderate to severe diarrhea. Virulence genes related SHIGELLA SPP. ISOLATED FROM CHILDREN WITH DIARRHEAL to bacterial adhesion, colonization and cytotoxicity were detected in a DISEASES REQUIRING MEDICAL CARE IN FORTALEZA, great proportion of C. jejuni-positive samples, while invasion-related CEARA, BRAZIL virulence genes were detected in lower frequency. The distribution profile of virulence genes from C. jejuni was not correlated with the clinical Ila F. Lima, Pedro H. Medeiros, Marjorie M. Guedes, Mariana D. presentation of the disease, suggesting that maybe other virulence genes Bona, Alexandre Havt, Aldo A. Lima or host factors such as nutritional status are important in defining the Federal University of Ceara, Fortaleza, Brazil clinical severity of diarrheal diseases associated with C. jejuni. Shigella spp. is one of the most prevalent etiological agents of enteric infection. This study aimed to determine circulating species, virulence 1670 genes and antimicrobial resistance profile of Shigella spp. obtained from EVIDENCE FOR GASTROINTESTINAL CARRIAGE OF a cross-sectional study of moderate to severe childhood diarrhea in CLOSTRIDIUM DIFFICILE AMONG CHILDREN IN THE Fortaleza, Ceara, Brazil. Fecal specimens and clinical data were collected from May 2008 to April 2009 and 63 Shigella strains were isolated by PERUVIAN AMAZON RIVER BASIN standard microbiological methods. Immunoagglutination assay was Heather Clark1, Rajasree Roy1, Rosa Burga2, Ricardo Abadie2, employed for species characterization and four multiplex-PCRs were Henry Montilla-Guedez1, Anne Huyler1, Loan Nguyen1, Claudio developed to detect 14 sequences encoding virulence genes (ial, set, Rocha2, Hamilton Tilley2, David Craft1 virF, sen, sigA, pic, sepA, ipaA, ipaB, ipaC, ipaD, icsB, Stx and virB). 1Pennsylvania State College of Medicine, Hershey, PA, United States, 2U.S. Antimicrobial susceptibility tests were performed using the Kirby-Bauer Naval Medical Research Unit - 6, Iquitos, Peru disk diffusion method with 13 antimicrobial discs commercially available. The most prevalent Shigella species were S. flexneri and S. sonnei (43%, Diarrheal disease is a leading cause of death and illness in developing 27/63 for both), followed by S. dysenteriae (8%, 5/63) and S. boydii (6%, countries and is responsible for nearly one in five child deaths worldwide 4/63). The protease associated with mucosal binding (pic), enterotoxin each year. Unsafe water, poor sanitation, and inadequate hygiene are the 1(set) and protein associated with cell invasion (sepA) genes were major risk factors for the spread of disease. Belen is an impoverished river significantly associated with S. flexneri infection (p=0.0002, p<0.0001 dwelling community without public sewage systems and trash disposal. and p<0.0001, respectively), while other virulence genes showed no There are few laboratory based studies on infectious gastroenteritis in difference among species. The concomitant presence of pic, set and sepA this community and none on the prevalence of Clostridium difficile. was correlated with intense abdominal pain (p=0.0379) and multi-drug This study examines the prevalence of C. difficile in children ages 5 resistance to at least three drugs (p=0.0028), being sulfamethoxazole/ and under in Belen. With local IRB approval and informed consent from trimethoprim + tetracycline + ampicillin + chloramphenicol the most heads of households, 206 stool samples were collected from children 5 frequent pattern. This study suggests that more severe shigellosis is caused and under from May to October 2014. All samples were analyzed for by S. flexneri carrying the virulence genes pic, set and sepA. These strains C. difficile antigen (glutamate dehydrogenase) or toxin (A and B) using also present multi-drug resistant phenotype, indicating a link between C. difficile QUIK CHEK (TechLab, Blacksburg, VA). All stool samples virulence and antimicrobial resistance pressure selection and evolution. were accepted irrespective of consistency. Sixteen of 206 stool samples (7.77%) assayed showed antigenic (Ag) or toxigenic (Tox) evidence of 1669 C. difficile; two samples (0.97%) for toxigenic strains (Ag+ / Tox+), 13 samples (6.31%) for non-toxigenic strains (Ag+ / Tox-), and one sample CLINICAL PRESENTATION AND VIRULENCE GENES PROFILE (0.49%) was positive for toxin only (Ag- / Tox+). This is the first laboratory FROM CAMPYLOBACTER JEJUNI INFECTION ISOLATED FROM based study assessing the prevalence of C. difficile in this community CHILDREN WITH MODERATE TO SEVERE DIARRHEA IN and provides strong evidence for childhood carriage of non-toxigenic, FORTALEZA, CEARÁ, BRAZIL and more limited evidence for toxigenic, strains of C. difficile. These studies will be augmented in the future by culture and/or nucleic acid Herlice N. Veras, Josiane S. Quetz, Ila F. Lima, Ana K. Santos, amplification for genes coding for all virulence factors associated with C. Pedro H. Medeiros, Alexandre Havt, Luís C. Rey, Aldo A. Lima difficile. Unfortunately, symptomatic vs. asymptomatic data could not Federal University of Ceara, Fortaleza, Brazil be consistently ascertained, but future studies associating symptoms and the presence of C. difficile could lead to a better understanding of the Campylobacter spp. is considered the most common cause of bacterial epidemiology of non-nosocomial, community-acquired C. difficile in the gastroenteritis. This study characterized C. jejuni virulence-associated Amazon River Basin. To date, there is no data linking C. difficile carriage genes that may play a role in C. jejuni pathogenicity in children aged 0-36 to the environment, hygiene practices or socioeconomic factors in Belen. months who required emergency medical care due to moderate to severe Additional investigations of other etiologies of infectious gastroenteritis diarrheal disease. It is part of a project entitled “‘Diarrhea Enteric Card are also ongoing. (DEC)’ aiming to develop PCR-based multiplex diagnose assay for bacterial enteric pathogens. The project was approved by the local and national ethical committees in Brazil (HIAS 80/06 and CONEPE 13523/2007,

astmh.org 512 1671 1673 INCORPORATING MODEL UNCERTAINTY INTO PREDICTIONS ORAL CHOLERA VACCINE STUDIES IN CHOLERA ENDEMIC OF THE BURDEN OF TYPHOID FEVER SETTINGS IN BANGLADESH Marina Antillon, Forrest W. Crawford, Virginia E. Pitzer Firdausi Qadri Yale University, New Haven, CT, United States International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh Upcoming efforts in vaccination against typhoid fever require an assessment of the baseline burden of disease in countries at risk. Model- Bangladesh has one of the world’s highest burden of endemic cholera based estimates are a feasible alternative to costly and time-consuming with an estimated 350,000 cholera cases and over 4,500 deaths annually. field-based estimates of typhoid fever incidence. In most countries, A serious need therefore exists for control of cholera using vaccines and typhoid incidence data is not collected, and therefore current estimates other preventive measures. Over the last few years large scale vaccination of incidence are based on interpolation of data from 32 studies. Recent studies are being conducted with the whole cell oral cholera vaccine (OCV) estimates of typhoid burden are based on models that have not been Shanchol in high risk urban as well as rural populations. The objective of assessed for predictive accuracy. Furthermore, estimates of age-specific such studies is to assess the feasibility of delivery as well as effectiveness incidence are based on assumptions about how the age distribution of vaccination program utilizing the existing national immunization varies with incidence, rather than empirical estimates of age-specific infrastructure of Bangladesh. Vaccine coverage was 65% and protection heterogeneity. An understanding of the difference in incidence attributable was 53%, which was evident in all age groups and sustained for 2 to age is imperative to guide upcoming vaccine policies. Therefore, it is years. In a study in a rural setting in Bangladesh carried out in 65,000 necessary to identify readily-available predictors of typhoid incidence, such participants and the OCV program was successful and 92% of the as access to clean water, access to improved sanitation, country-level Gross vaccinees receiving the first dose of vaccine also returned for the second Domestic Product, etc. We developed a random-intercept, mixed effects dose. In addition we have recently conducted a single dose oral cholera model fit to data from 32 population-based studies of typhoid incidence, vaccine study to determine if only one dose can be protective, a strategy 17 of which report incidence for different age groups. We used Bayesian very important for use in epidemics and outbreaks. The oral cholera model averaging to incorporate uncertainty around the estimates of the vaccines need to be stored at 2-8 °C. This is one of the limiting factors predictors as well as the uncertainty in model selection. The current re- for delivery of vaccines in resource poor settings globally. We therefore analysis permits prediction of the overall as well as age-specific incidence studied, if storage of vaccine at higher temperatures (25°C, 37°C and of typhoid fever, as well as the associated uncertainty, in low- and middle- 42°C) resulted in similar safety and immunogenicity compared to vaccine income countries. stored in the cold. The vaccine is safe, well tolerated and satisfactory immune response is elicited. The OCV studies were feasible and effective 1672 using government facilities. These studies demonstrate that the Shanchol can be delivered to all age groups using resources already available in EPIDEMIOLOGIC FEATURES OF DIARRHEAL DISEASE DUE the country. Strategies to plan and implement OCV uptake in national TO AEROMONAS SPP. AND PLESIOMONAS SHIGELLOIDES immunization programmes in high risk hotspots is needed for Bangladesh. INFECTIONS IN KAMPONG CHAM, CAMBODIA Studies to assess vaccination strategies, target age groups for vaccination, uptake, feasibility as well as cost-effectiveness analyses need to be made Andrew F. Vaughn using the same approach as used for other immunisation programmes U.S. Naval Medical Research Unit – 2, Phnom Penh, Cambodia which have been successful in Bangladesh and such studies are being To investigate the possible etiological agents of diarrheal disease in planned. Cambodia, a cohort based study was conducted from August 2012 to March 2015. The US Naval Medical Research Unit Two (NAMRU-2) 1674 Detachment Phnom Penh in collaboration with the Cambodian National IFN- ; HAS DIRECT ANTI-ENTEROAGGREGATIVE E. COLI Institute of Public Health (NIPH) conducted active surveillance among four villages in Kampong Cham Province, Cambodia. Subjects self reported PROPERTIES AND IS NECESSARY FOR RESILIENCE TO SEVERE 훾 symptoms to study staff and were also followed on a weekly basis. Stool EAEC-INDUCED ENTEROPATHY IN ZINC-DEFICIENT MICE samples were collected from subjects if they presented with symptoms Glynis Kolling, David Bolick, Luther Bartelt, Richard Guerrant of acute diarrhea defined as 3 or more loose stools within 24 hours or 2 University of Virginia, Charlottesville, VA, United States loose stools associated with gastrointestinal complaint within 24 hours. Study subjects were comprised of 2,921 adults and 1,749 children (aged Enteroaggregative E. coli is a major cause of early childhood diarrhea and < 18 years old). There were 258 Aeromonas spp. and 266 Plesiomonas growth impairment. Descriptions of EAEC-diarrhea are typically mucoid shigelloides isolates identified from 2,603 specimens collected and with occasional leukocyte products. While increased fecal IL-8 has been tested between August 2012 and March 2015. Study data indicates seen in symptomatic patients with EAEC infection, and mutations in the that adults have a higher risk of being infected with Aeromonas spp. IL-8 promoter that lead to increased IL-8 expression also associate with (OR=1.4, 95%CI: 1.1-1.9) or P. shigelloides (OR=1.9, 95%CI: 1.5-2.6). symptomatic disease, other inflammatory mucosal pathways such as the Subjects who worked in retail settings (shop owners or workers) also had IL23-IL17 and IFN- ; axis relevant to other enteropathy-inducing pathogens a higher risk of being infected with P. shigelloides (OR=2.0, 95%CI: are less well understood, and could contribute to disease during EAEC 1.2-3.3) whereas the participants who were students or worked at home infection. In a murine훾 model of EAEC-induced enteropathy we have tended to have lower risk (OR=0.7, 95%CI: 0.5-0.8). Abdominal pain previously shown that zinc deficiency both up-regulates aggR-regulated and mucus laden stool are the two symptoms significantly associated EAEC virulence genes and alters host inflammatory responses leading to with the infection of these two pathogens (p< 0.05). Lack of access to increased Il8 and Mcp1 expression, mucus production, Muc2 expression, clean drinking water (filtered or boiled) or lack of sanitary toilet facilities and Cftr expression, increased Il17, but decreased Il23, Il6, Tnfalpha, were identified as increased risk factors for positive stools. 52.3% and and Il1beta. To interrogate the role of the IL17-IL23 axis we infected 70.2% of Aeromonas spp. positive subjects and 55.6% and 70.3% of P. zinc-deficient IL17RKO mice with the virulent EAEC042 strain. IL17RKO shigelloides positive subjects did not have access to clean water or toilet mice were protected from weight loss, more rapidly cleared EAEC, and facilities, respectively. The prevalence of these pathogens appears to be demonstrated a 5-fold increased expression of IFN- ;. Neutralization correlated with inadequate access to sanity water and toilet facilities. of IFN- ; reverted the resilient IL17RKO mice to a susceptible wild-type phenotype. IFN- ; demonstrated direct effects in vitro훾 , inhibiting EAEC growth훾 in a dose-dependent manner. Further studies are planned to 훾 astmh.org 513 confirm this new recognition of anti-EAEC properties of IFN- ;, and twenty tested samples to ensure that there was no PCR contamination. whether genetically determined alterations in mucosal inflammatory The internal audits allowed identification of several minor challenges responses may promote host resiliency to enteropathogens despite훾 the and a major one: non-collection of critical samples, a situation that was disadvantage of severe micronutrient deficiency. promptly corrected. Further laboratory audits did not identify other major findings. Monitoring of positive controls through LJC allowed identification 1675 of problems with primers and probes used for qualitative PCR, triggered reagents replacement and minimized inter-assay variation. Monitoring ISOLATION AND SPECIES IDENTIFICATION OF GRAM- of standard curves through LJC led to exclusion of the results from one POSITIVE BACTERIA FROM THE CANNED FOOD BY plate out of 72, where key values of the standard curve were found to be SEQUENCE CHARACTERIZATION AT GYRB LOCUS: A PUBLIC out of the defined acceptable range. EQA results identified a risk of PCR HEALTH IMPORTANCE contamination in the sodC gene and promoted development of stricter rules to be applied in our molecular biology laboratories. No non-template Irshad M. Sulaiman, Emily Jacobs, Steven Simpson, Khalil negative control was positive during the entire course of the study. All Kerdahi staff working on this cross-sectional study were trained to apply these high Food and Drug Administration, Atlanta, GA, United States standards. Large-scale epidemiological studies should be conducted with QC standards approaching the ones required in clinical trials. Adopting The primary mission of FDA is to enforce the Food, Drug and Cosmetic these standards allowed us to identify critical issues during the course of a Act and regulate food, drug and cosmetic products. FDA uses presence study of meningococcal carriage and to correct them promptly. of pathogenic microorganisms in these commodities as one of the regulatory action criteria and to ensure that the goods are safe for human consumption. This study was conducted to assess the effectiveness 1677 of pathogen control in a canned food facility located in the United DETECTION OF NEISSERIA GONORRHEA USING CULTURE States. A total of 9 unopened recalled canned food jars from the same AND NUCLEIC ACID AMPLIFICATION TEST IN FIVE HEALTH lot containing Black Bean Corn Poblano Salsa were initially examined by conventional microbiologic protocols. Of these, while analyzing 8 FACILITIES IN GHANA subsamples for each sample, all subsamples of one of the containers Naiki Puplampu1, Helena Dela1, Eric Behene1, Shirley Nimo- was found positive for the presence of slow growing rod-shaped, Paintsil1, Kwesi Addo2, Edward Owusu Nyarko3, Cynthia Kwakye4, Gram-positive facultative anaerobic bacteria. Species identification of 8 Nehkonti Adams1 recovered Gram-positive bacterial isolates from the positive unopened 1Naval Medical Research Unit - 3, Ghana Detachment, Accra, Ghana, jar was accomplished by our recently developed protocol based on DNA 2Noguchi Memorial Institute for Medical Research, University of Ghana, sequencing of PCR amplified gyrB gene products. Multiple alignments Legon, Accra, Ghana, 3Ghana Armed Forces Public Health Department, confirmed all 8 generated gyrB gene sequences to be identical. These Accra, Ghana, 4Ghana Health Service, Accra, Ghana sequences matched 99% (2-point-mutation) with the published sequence of Lactobacillus fermentum sequence available in public domain Neisseria gonorrhea is one of the major etiologies of sexually transmitted (GenBank Accession No. AP008937). Thus, the gyrB-based molecular infections (STIs) and when left untreated can lead to serious complications diagnostic protocol can be used as a suitable genetic marker for rapid such as pelvic inflammatory disease, ectopic pregnancy, infertility in detection of Lactobacillus in the canned food monitoring program of women and sterility in men. Microscopic examination and microbial culture public health importance. are common techniques used in gonorrhea diagnostics; however both are insufficiently sensitive and/or specific. Noninvasive techniques utilizing 1676 newer technology such as antigen detection by immunoassay and nucleic acid amplification tests (NAATs) have become more acceptable because STRINGENT QUALITY CONTROL MEASURES ALLOWS of their precision, suitability and time-saving aspects. The objective of PROMPT IDENTIFICATION OF CRUCIAL PROBLEMS TO this study is to determine the percentage of N. gonorrhea positive cases OPTIMIZE THE RELIABILITY OF MENINGOCOCCAL CARRIAGE occurring among Ghanaian military members using culture and NAAT. SURVEYS Urethral or endocervical swabs and urine samples were obtained from consenting patients presenting with STI symptoms at five health facilities. Jacinta Okeakpu1, Aderonke Odutola1, Sheikh Jarju1, Ebenezer Swabs were cultured on Modified Thayer-Martin agar and colonies Foster-Nyarko1, Anna Roca1, Beate Kampmann1, Umberto subcultured on chocolate agar. N. gonorrhea isolates were identified D’Alessandro1, Martin Antonio1, Caroline Trotter2, James Stuart3, by gram staining, catalase as well as oxidase tests. Purified colonies were Olivier Manigart4, Brian Greenwood for the MenAfriCar confirmed using the API-NH. Urine samples were tested by NAAT. Of 679 Consortium3 specimen screened, 25.4% was positive for gonorrhea by NAAT and 6.9% 1Medical Research Council, The Gambia Unit, Fajara, Gambia, 2University by culture. All specimens positive by culture were also positive by NAAT. of Cambridge, Cambridge, United Kingdom, 3London School of Hygiene & Compared to culture, NAAT performed better in identifying gonorrhea Tropical Medicine, London, United Kingdom, 4London School of Hygiene & in STI-symptomatic patients presenting to health facilities in Ghana. Our Tropical Medicine and MRC, The Gambia Unit, London and Fajara, United finding demonstrates that NAAT could be beneficial in testing high-risk Kingdom groups or patients who are culture negative but have persistent symptoms. We conducted a cross-sectional study to identify carriage of Neisseria meningitidis among 1000 schoolchildren in Fajara, The Gambia, to 1678 evaluate improved detection methods. We conducted this study using DETECTION OF LEPTOSPIRA-SPECIFIC ANTIBODIES USING quality control (QC) standards applied to clinical trials. In addition to RECOMBINANT LIPL32, LIPL41, LIGA, AND LIGB IN ENZYME- developing Standard Operating Procedures, Study Operations and LINKED IMMUNOSORBENT ASSAY Laboratory Operations Manuals and ensuring documented training of staff, we conducted regular internal audits of field and laboratory Hua-Wei Chen, Heather Lukas, Kira Becker, Giulia Weissenberger, activities. We verified the ability of the laboratory team to perform the Wei-Mei Ching tests through enrolment in External Quality Assessment (EQA). We Naval Medical Research Center, Silver Spring, MD, United States performed regular monitoring of positive controls used for qualitative PCR and of standard curves used for quantitative PCR through Levey- Leptospirosis is caused by the infection of spirochetes of the genus Jennings charts (LJC). We used non-template negative controls every Leptospira. This zoonotic disease has become widespread in developing nations, particularly those located in tropical areas. In the early stage of the astmh.org 514 bacterial infection, the disease can be treated with antibiotics. However 1680 leptospirosis is often misdiagnosed due to its nonspecific symptoms and lack of good diagnostic tests which can be easily performed at the clinical DEVELOPMENT OF A LUMINEX TREPONEMAL ANTIBODY site. The current standard method for diagnosis of leptospirosis is the ASSAY FOR LARGE-SCALE SURVEILLANCE AND IMPACT microscopic agglutination test (MAT). This assay requires live cultures, EVALUATION OF GLOBAL YAWS ERADICATION PROGRAM not only technically complex but also time-consuming. In an effort to replace MAT with a test that does not require live cultures, we produced Diana Martin1, Gretchen Cooley1, Brook Goodhew1, Oriol Mitja2, highly purified recombinant antigens, rLipL32, rLipL41, rLigA, and rLigB, Arnold Castro1, Cheng Chen1, Allan Pillay1, Patrick Lammie1, and evaluated their performance individually and a cocktail of 1:1:1:1 Penias Moses3, Tun Ye1, Ron Ballard1 combination in ELISA to detect IgG and IgM antibodies specific for 1Centers for Disease Control and Prevention, Atlanta, GA, United States, Leptospira using a panel of 429 human sera (337 MAT positive and 92 2Lihir Medical Institute, LIhir, Papua New Guinea, 3Lihir Medical University, MAT negative sera). The positive samples had MAT titers greater than 100 Lihir, Papua New Guinea against one or several of 18 serovars from 5 major pathogenic Leptospira Yaws, a non-venereal treponemal infection, is characterized by species (L. interrogans, L. kirschneri, L. borgpetersenii, L. noguchii, papillomatous and ulcerative skin lesions. Mid 20th-century mass- and L. weilii). There were 145 (43%) samples that showed either treatment campaigns resulted in a significant reduction in yaws cases, but detectable IgG or IgM against rLipL32; 177 (53%) samples against rLipL41; resurgence of the disease occurred after the campaigns were dismantled. 216 (64%) samples against rLigA; and 228 (68%) samples against rLigB. Recently, interest in yaws eradication was renewed after demonstration There were 5, 15, 16, and 23 patient sera that had specific antibodies that a single oral dose of azithromycin is efficacious treatment for against only one antigen rLipL32, rLipL41, rLigA, and rLigB, respectively. yaws. Serological diagnosis of yaws requires detection of two distinct Combining the detection results of IgG and IgM from these four individual antibodies: one against a treponemal antigen that indicates exposure to antigens, the overall sensitivity is close to 90% but the specificity is only infection (such as the Treponema pallidum particle agglutination [TPPA] 65%, based on the MAT reference method. The overall sensitivity and or hemagglutination [TPHA] assay) and one against a non-treponemal specificity of the cocktail of 1:1:1:1 combination was 82% and 86%, antigen (such as the rapid plasma reagin [RPR]) that can discriminate active respectively. These results showed that an ELISA using the combination of from past infections. Unfortunately, the RPR test cannot be automated recombinant antigens has the potential to replace the reference method for use in large-scale, integrated serosurveillance platforms. We therefore MAT. Further optimization of the relative amount of each antigen in the sought to assess the quantitative correlation of individual treponemal final formulation to increase the overall sensitivity by ELISA is underway. antigens on a Luminex® multiplex bead-based immunoassay platform against standard serological tests for yaws. A total of 847 serum and 1679 dried blood spot specimens were collected as part of yaws surveillance LEPROSY NEW CASE DETECTION TRENDS AND THE EFFECT projects in Ghana, Vanuatu, and Papua New Guinea (PNG). Specimens OF PREVENTIVE INTERVENTIONS IN PARÁ STATE, BRAZIL: A were run at 1:400 dilutions on a Luminex assay to test for IgG antibodies directed against the recombinant treponemal antigens p17 (rp17) and MODELING STUDY TmpA. Results were compared to those obtained using TPPA/TPHA Haroldo J. de Matos1, David J. Blok2, Sake J. de Vlas2, Jan Hendrik assays and quantitative RPR test. Compared to the TPPA/TPHA, reactive Richardus2 concordance of rp17 was 98.8% (331/335), while reactive concordance of 1Instituto Evandro Chagas, Belem, Brazil, 2Erasmus MC, Rotterdam, TmpA was only 84.8% (284/335). When comparing anti-TmpA reactivity Netherlands against RPR titers we observed a strong correlation that was not seen with rp17 responses. A significant increase was noted in TmpA reactivity Leprosy is still a public health problem in Brazil. Although the overall with increasing RPR titers (R2 =0.975 for Ghana and Vanuatu and 0.94 number of new cases is declining, there are still areas with a high disease for PNG). Our results suggest that TmpA could be used as a treponemal burden, in particular Pará State. We aim to predict future trends in new antigen marker for recent or active infection. Further validation will assist case detection rate (NCDR) and explore the potential impact of contact in development of a tool that could useful to help yaws surveillance and tracing and chemoprophylaxis with single-dose rifampicin on NCDR in impact monitoring of global yaws eradication programs. Pará State. We used SIMCOLEP, an existing individual-based model for the transmission and control of M. leprae in a population structured 1681 by households. The model was quantified to mimic the NCDR trend of leprosy in Pará state between 1990 and 2012. The baseline scenario (i.e. LARGE THROUGHPUT SCREENING AND COMPUTATIONAL continuation of current control) includes multidrug therapy, passive case APPROACHES FOR IDENTIFYING COMPOUNDS EFFICACIOUS detection and BCG vaccination of infants. Leprosy data was obtained AGAINST THE OBLIGATE INTRACELLULAR PATHOGEN, from the SINAN databases. We also investigated the impact of two RICKETTSIA interventions: 1) contact tracing, and 2) contact tracing in combination with administering chemoprophylaxis to contacts. All interventions start Alexander Lemenze, Alexander Perryman, James Occi, Joel in 2015 with predictions made until 2050. The modelled trend in Pará Freundlich, Nancy Connell State after 2012 shows a continuous downward trend, reaching the Rutgers GSBS Newark, Newark, NJ, United States official elimination target of 10 per 100,000 annual new cases by 2028. Rickettsia is a genus of arthropod vectored, obligate intracellular bacteria Systematic contact tracing in combination with chemoprophylaxis to that is the etiological agent of multiple spotted fevers and typhus diseases, household contacts would bring the achievement of elimination forward most notably Rocky Mountain Spotted Fever and epidemic typhus. Various to 2026. Contact tracing would increase the number of detected cases in historical and novel Rickettsial diseases are constantly re-emerging as the first 9 years, but in the long run would drop below the number in the major human pathogens such as R. parkerii causing Tidewater Spotted baseline scenario. Administering chemoprophylaxis would prevent almost Fever that is spreading with climate change up the Eastern coast of the 10% of new detected cases since the start of the intervention in the long United States. In recent years, antibiotic resistance has been documented run. Our study indicates that the leprosy incidence will further decrease in clinical cases requiring physicians to resort to more toxic treatments in Brazil. Elimination of leprosy as a public health problem can possibly and therefore new drug compounds are needed for anti-Rickettsial be achieved around 2028 in Pará state. This moment could be brought development. Rickettsia’s obligate intracellular nature presents challenges forward by two years through systematic contact tracing in combination not usually present in drug screening protocols, which we aimed to with chemoprophylaxis. overcome here. By transforming R. canadensis with pRMA18dRGA (Wood et al) expressing Green Fluorescent Protein we are able to utilize

astmh.org 515 fluorescence to measure inhibition of growth of R. canadensis in the no ongoing robust programme is targeted to control the disease. Using in- Vero cell line when exposed to drug-like compounds. After validation depth interviews, key informant interviews and focus group discussion, the and optimization of the conditions for compound screening, we have perceptions of the people were ascertained. Clinical presentation of the begun to screen 2,000 compounds from the Microsource Compound ulcers were also gathered from infected persons. This lasted from January Library. Toxicity for each compound was also assessed as a factor in the to March 2015. Male and female are equally affected in the distribution obligate intracellular nature of Rickettsia. The compounds that are active of the ulcer with the lower limb mostly affected, late presentation results in vitro against Rickettsia will be further analyzed through a Bayesian in complications such as chronic ulcer, contractures and disability. Myths algorithm to calculate predictive values for future compounds’ activity associated with Buruli ulcer includes that it is caused by witches and or lack thereof. This Bayesian algorithm has been used previously by wizards, enemies and offended deities. it is believed that only native our and collaborating laboratories to identify compounds active against juju doctors can cure the disease. The ulcer perpetuates poverty cycle Mycobacterium tuberculosis and Staphylococcus aureus. By adapting as affected people are not able to farm thereby reducing the income in methods for large throughput screening and combining data produced addition to the treatment bills spent in appeasing the deities and paying with the Bayesian algorithm we aim to find novel compounds active the juju doctors. Women are mostly affected by stigma which reduces the against Rickettsia spp, and produce a baseline database for future drug chances of marriage of affected young women. The key challenges are, discovery. the area is inaccessible because of poor terrain, the educational status is low, medical facilities with qualified personnels are limited. There is 1682 predominance of native juju doctors and sorcerers who perpetuates the superstition and myths. Poverty also affects their health seeking behaviour. IN VITRO ANTIMICROBIAL ACTIVITIES OF “ANTIBACT”, There is need for health education and enlightenment in the area to AN HERBAL MEDICINAL PRODUCT AGAINST CLINICAL make the people understand the aetiology of the disease, remove myths BACTERIAL ISOLATES and superstition and thereby encourage early health seeking, diagnosis and treatment. There is need for research in the area to know further the 1 1 1 Felix C. Mills-Robertson , Cynthia I. Onyeka , Samuel C. Tay , determinants and distribution of the disease in the area. Poverty alleviation 2 3 3 Willimas Walana , Salomey Acheampong , Michael Odame , and empowerment programmes should be provided in addition to 3 Maxwell Antwi improved Orthodox health facilities. 1Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, 2School of Medicine and Health Sciences, University for Development 1684 Studies, Tamale, Ghana, 3Centre for Plant Medicine Research, Mampong- Akwapim, Ghana EXAMINATION OF TETANUS VACCINATION AND In vitro antimicrobial activities of ethanol and aqueous “Antibact”, SEROPREVALENCE DATA BY PROVINCE IN CHILDREN UNDER herbal products consisting of a combination of the leaves and branches 5 YEARS OF AGE FROM 2007 AND 2013 IN THE DEMOCRATIC of four different plants were evaluated against twenty one pathogenic REPUBLIC OF CONGO bacteria. Saponins, reducing sugars, phenolics, polyuronides, and Hayley Ashbaugh1, Sue Gerber2, Reena H. Doshi1, Patrick triterpenes were the major phyto-constituents of both the aqueous and Mukadi3, Nicole A. Hoff1, Jean-Jacque Muyembe3, Emile ethanol “Antibact”. The LD50 analysis revealed the products were safe Okitolonda4, Anne W. Rimoin1 (LD50>5000 mg/kg bodyweight) for in vivo use. All the isolates (100%) 1University of California Los Angeles, Fielding School of Public Health, Los were resistant to at least five of the 12 antibiotics used in the study. In Angeles, CA, United States, 2Bill & Melinda Gates Foundation, Seattle, total, the aqueous “Antibact” inhibited the growth of 5 out of the 21 WA, United States, 3National Institute for Biomedical Research, Kinshasa, (23.81%) microbes used with an average zone of inhibition of 9.73 ± 0.35 Democratic Republic of the Congo, 4Kinshasa School of Public Health, mm while thirteen (61.90%) out of the 21 microbes used were susceptible Kinshasa, Democratic Republic of the Congo to the ethanol “Antibact”, with an average inhibition zone of 10.80 ± 0.18 mm. The minimum inhibitory concentration (MIC) of the aqueous Critical evaluation of an immunization program is key to identifying areas “Antibact” ranged from 4.00 to 32.00 mg/ml and 0.50 to 8.00 mg/ml of need and to ensuring efficacious and efficient resource allocation. We for the wild and standard strains respectively. In the case of the ethanol compared tetanus vaccination rates (determined by either maternal recall “Antibact” the MIC ranged from 2.00 to 8.00 and 1.00 to 2.00 mg/ or vaccination card) by province for children 12-23 months of age in the ml for the wild and standard strains, respectively. The average minimum Democratic Republic of Congo (DRC) from the 2007 (n=1,585) and 2013 bactericidal concentration (MBC) for the aqueous “Antibact” was 32.00 (n=3,366) Demographics and Health (DHS) Surveys. A seroprevalence mg/ml while thatof the ethanol “Antibact” was ranged from 4.00 to survey was also completed in tandem with the 2013 DHS Survey in which 16.00 mg/ml and 4.00 to 8.00 mg/ml for the wild and standard strains, Dried Blood Spots (DBS) were collected from participants to determine respectively. Thus, both aqueous and ethanol “Antibact” are safe for IgG antibodies against tetanus for 8,116 children 6-59 months of age. human use and also effective against some pathogenic bacteriaevaluated Overall tetanus vaccination coverage (doses 1-3) in the 2007 DHS study in vitro with the ethanol “Antibact” showing better antimicrobial activity. for children 12-23 months of age was 70.6%, 59.1%, and 45.0%, respectively. In the 2013 study, overall tetanus vaccination coverage (doses 1683 1-3) of children 12-23 months of age was 81.2%, 73.8%, and 60.5%, respectively. Tetanus seroprevalence was lowest in Maniema (20.1%) and MEETING THE CHALLENGES OF BURULI ULCER IN ANAMBRA Katanga (27.8%) provinces. In 2007, DTCoq vaccine coverage for children STATE NIGERIA 12-23 months of age in Maniema was 51.9%, 38.3%, and 17.4%; and in Katanga was 60.4%, 51.6%, and 38.6%. In 2013, DTC/Pentavalent Amobi L. Ilika1, Valentine C. Ilika2, Chidozie Aniemena1, Frances vaccine coverage for children 12-23 months of age in Maniema was N. Ilika3 73.8%, 66.7%, and 47.2%; and in Katanga was 67.3%, 60.1%, and 1 2 Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria, Anambra 51.3%. Tetanus seroprevalence was highest in North Kivu (51.8%) and 3 State University Teaching Hospital, Awka, Nigeria, London School of Kinshasa (51.3%) provinces. In 2007, DTCoq vaccine coverage for children Hygiene and Tropical Medicine, London, United Kingdom 12-23 months of age in North Kivu was 93.4%, 91.1%, and 83.3%; and Buruli Ulcer remains a great public health problem in riverine areas of in Kinshasa was 94.6%, 87.9%, and 81.1%. In 2013, DTC/Pentavalent Anambra State, Nigeria. It is a debilitating disease affecting the social and vaccine coverage for children 12-23 months of age in North Kivu was economic life of the people who are essentially poor peasant farmers. It 94.4%, 91.1%, and 87.0%; and in Kinshasa was 97.8%, 95.8%, and is shrouded with myths, superstitions, stigma and discrimination which 83.7%. Although reported tetanus vaccination coverage has improved affect early and prompt health seeking behaviour. Yet it is neglected and in the DRC, the low seroprevalence of tetanus antibodies, as well as the astmh.org 516 divergence between reported coverage and seroprevalence warrants 1686 re-examination of current immunization and surveillance strategies. This data suggests that geographical disparities exist that may require novel WHICH DISTRICTS ARE ENDEMIC FOR TRACHOMA: or intensive strategies for effective immunization programs in certain METHODS AND RESULTS OF TRACHOMA ASSESSMENT IN provinces. TANZANIA 1685 Jeremiah M. Ngondi1, George Kabona2, Mathias Kamugisha3, Alistidia Simon4, Edward Kirumbi2, Deogratias Damas5, Andreas DO TRACHOMA ASSESSMENTS PREDICT DISTRICTS Nshala5, Kathryn Crowley6, Lisa Rotondo6, Upendo J. Mwingira2 ENDEMIC FOR TRACHOMA? COMPARISONS OF RESULTS 1RTI International, Dar Es Salaam, United Republic of Tanzania, 2Neglected FROM TANZANIA, UGANDA, BENIN AND DEMOCRATIC Tropical Disease Control Program/MoHSW, Dar Es Salaam, United Republic REPUBLIC OF CONGO of Tanzania, 3National Institute for Medical Research, Dar Es Salaam, United Republic of Tanzania, 4Sightsavers, Dar Es Salaam, United Republic 1 2 2 Jeremiah M. Ngondi , Upendo J. Mwingira , Edward Kirumbi , of Tanzania, 5IMA World Health, Dar Es Salaam, United Republic of 3 4 4 Patrick Turyaguma , Wilfrid Batcho , Bio A. Amadou , Jean Tanzania, 6RTI International, Washington, DC, United States Ndjemba5, Janvier Kilangalanga5, Achille Kabore6, Anne Haggen7, Jean Jacques Tougoue6, Kathryn Crowley6, Phil Downs6, Lisa By January 2014, baseline surveys of trachoma have been completed in Rotondo6 76 of 161 districts in Tanzania. The remaining 85 districts had unknown trachoma prevalence although most were suspected to be endemic. 1RTI International, Dar Es Salaam, United Republic of Tanzania, 2Neglected Establishing trachoma endemicity was needed to plan for implementation Tropical Disease Control Program/MoHSW, Dar Es Salaam, United Republic of the SAFE (surgery, antibiotics, facial cleanliness, environmental change) of Tanzania, 3Ministry of Health, Kampala, Uganda, 4Ministry of Health, strategy in order to meet GET 2020 goals. We describe trachoma Cotonou, Benin, 5Ministry of Health, Kinshasa, Democratic Republic assessments undertaken to prioritize districts for population based of the Congo, 6RTI International, Washington, DC, United States, 7RTI prevalence surveys. The trachoma assessment was undertaken in 54 International, Kampala, Uganda un-surveyed rural districts and two urban districts contiguous to highly Prior to SAFE implementation, baseline population based prevalence trachoma endemic districts. The assessment comprised three activities: surveys (PBPS) of trachoma must be undertaken to facilitate planning. 1) key informant interviews with the district medical officers (or district Trachoma assessments (TA) are a rational approach for prioritizing eye-care coordinator or district NTD coordinator); 2) desk reviews to resources for PBPS. We compared: methods of TA, results of TA and document data on trachomatous trichiasis over the last five years (2009 to results of PBPS undertaken in four countries. In Tanzania, TA in 56 districts 2013); and 3) spot checks in 2 villages per district to examine 50 children included: review of health facility TT data; and assessment of TF and TT in aged 1-9 years and 50 people aged 15 years and above, in each village, two villages. PBPS were prioritized where villages had ≥ 5% TT or ≥15% for active trachoma signs (trachomatous inflammation follicular [TF] and TF, and districts that reported ≥30 TT cases over 5 years. In Uganda, key trachomatous inflammation intense [TI]), and trachomatous trichiasis (TT), informant interviews and review of clinical records were done in 8 districts. respectively. Key informant interviews revealed that majority (85.7%) PBPS criteria included: ≥10 TT cases for 2 consecutive years; >40% of of the 56 districts perceived that there were areas in their district with health workers identified TT as a problem; and districts bordering areas trichiasis; however, 15 (27.8%) districts did not have any data on trichiasis. with TF prevalence ≥10%. In Benin, Communes in 4 northern districts Based on the proposed criteria (proportion of TT ≥5% among 15 years and were assessed and criteria for PBPS were: bordering districts in neighboring above, or active trachoma ≥15% in children aged 1-9 year, or at least 30 countries with TF ≥10%; and reported TT surgery data. In Democratic TT cases reported over previous five years) a total of 19 (33.9%) districts Republic of Congo (DRC), TA included: investigation of TT cases seen at were found to be eligible for population based surveys of trachoma. health facilities in Orientale, Equateur and Katanga; and assessment of TT The trachoma assessment provides a rational approach for deciding cases seen in the community in North and South Kivu Provinces. Criteria areas where resources for population based surveys and subsequent for PBPS were: ≥10 TT cases seen at health facility; ≥10 TT cases seen in implementation of the SAFE strategy will be prioritized. Baseline surveys in the community; and heath zones bordering countries where TF prevalence the 19 districts will enhance Tanzania’s progression toward elimination of was ≥10%. PBPS were done using GTMP methods. In Tanzania, of 19 (out trachoma by the year 2020. of 56) districts prioritized for PBPS, two had TF prevalence ≥10% and none had TT prevalence ≥1%. PBPS in four (out of 8) districts in Uganda showed 1687 TF prevalence and TT prevalence <10% and <1%, respectively. In Benin, 11 (out of 27) communes had PBPS of which two had TF prevalence ≥10% THE SHRINKING TRACHOMA MAP IN TANZANIA: RESULTS and 3 had TT prevalence ≥1%. In DRC, 32 (out of 99) health zones were OF BASELINE SURVEYS IN 31 DISTRICTS prioritized for PBPS. PBPS have been completed in 10 health Zones where 1 1 2 TF prevalence ≥10% and TT prevalence ≥1% was recorded in 4 and 8 the Upendo J. Mwingira , George Kabona , Mathias Kamugisha , 1 1 3 health zones, respectively. Results suggest that TA have been beneficial Bernard Kilembe , Edward Kirumbi , Alistidia Simon , Deogratias 4 5 2 in identifying priority areas for PBPS. The PBPS provide important data for Damas , Alphonsina Nanai , Mwelecele Malecela , Maria 1 3 6 7 SAFE implementation; however, trachoma endemicity was low in most of Chikawe , Christina Mbise , Kathryn Crowley , Harran Mkocha , 8 6 9 the areas surveyed. Patrick Masae , Lisa Rotondo , Jeremiah M. Ngondi 1Neglected Tropical Disease Control Program/MoHSW, Dar Es Salaam, United Republic of Tanzania, 2National Institute for Medical Research, Dar Es Salaam, United Republic of Tanzania, 3Sightsavers, Dar Es Salaam, United Republic of Tanzania, 4IMA World Health, Dar Es Salaam, United Republic of Tanzania, 5World Health Organization, Dar Es Salaam, United Republic of Tanzania, 6RTI International, Washington, DC, United States, 7Kongwa Trachoma Project, Dodoma, United Republic of Tanzania, 8Kilimanjaro Christian Medical Centre, Moshi, United Republic of Tanzania, 9RTI International, Dar Es Salaam, United Republic of Tanzania Blinding trachoma is prevented through the surgery, antibiotics, facial cleanliness and environmental improvement (SAFE) strategy. Prior to SAFE implementation, baseline surveys of trachoma are recommended. As of 2012, only 61 out of 161 districts had been mapped from 2004 astmh.org 517 to 2006. Trachoma was suspected to be more widespread therefore Survey findings suggest that the ultimate intervention goal for TF of further surveys were required for planning SAFE implementation. Between <5%TF has been attained in 19 districts therefore MDA with Zithromax® 2012 and 2014, trachoma baseline surveys were undertaken in 31 un- should be stopped and surveillance surveys undertaken after 2 years. surveyed districts. In 2012 and 2013, 12 at risk districts were selected However, in the remaining districts at least 3 rounds of MDA and a single based on proximity to known trachoma endemic districts, while in 2014, round of MDA are recommended in 5 and 4 districts, respectively; before trachoma assessments were undertaken and 19 districts prioritized for further impact surveys are done. However, in many districts TT still remains baseline surveys. A multi-stage cluster random survey sampling was a serious public health problem and therefore trichiasis surgery is required applied whereby 20 villages (clusters) and 36 households per cluster were to clear the TT backlog. surveyed. Eligible participants, children aged 1-9 year and people aged 15 years and above, were examined for trachoma using the WHO simplified 1689 grading system. A total of 23,199 households were surveyed and 105,092 participants (4.3% of those enumerated) examined for trachoma signs. A IMPACT OF MASS DRUG ADMINISTRATION ON TRACHOMA total of 44,516 children aged 1-9 years were examined for trachomatous PREVALENCE IN 7 DISTRICTS OF THE FAR NORTH REGION IN inflammation-follicular (TF) while 65,256 people aged 15 years and above CAMEROON were examined for trachomatous trichiasis (TT). Prevalence of TF varied 1 2 3 by district ranging from 0.1%; 95% confidence interval [CI] (0.02-0.4) Assumpta Lucienne Bella , Blaise Noa Noatina , Julie Akame , 3 3 4 in Serengeti to 12.8%; 95% CI (8.3-19.3) in Chunya. TT prevalence was Yannick Nkoumou , Ann Tarini , Yaobi Zhang lowest in Misungwi [0.04; 95%CI (0.01-0.2)] and highest in Kibaha [2.5%; 1Ministry of Public Health, Yaounde, Cameroon, 2Independent Consultant, 95%CI (1.8-3.4). Two districts (Ngara and Chunya) had TF ≥10% while 3 Yaounde, Cameroon, 3Helen Keller International - Cameroon, Yaounde, districts (Chunya, Korogwe and Kibaha) had TT prevalence ≥1%. Based Cameroon, 4Helen Keller International Regional Office for Africa, Dakar, on the survey findings only two districts qualify for implementation of the Senegal full SAFE strategy. Trichiasis is still a public health problem in three districts Cameroon is known to be endemic with trachoma in the northern regions. and community based TT surgery services should be considered to prevent Disease mapping in 2010-2011 in the Far North region of the country blindness due to trachoma. Although prevalence of trachoma was lower identified 13 health districts (HDs) with prevalence of trachomatous than previously suspected, in most districts, the findings will facilitate inflammation, follicular (TF) of more than 10% in children aged 1-9 implementation of SAFE in endemic districts. years. These HDs were therefore qualified for district-level mass antibiotic treatments as well as intensive implementation of other components of 1688 the World Health Organization (WHO) endorsed SAFE (Surgery, Antibiotic treatment, Facial cleanliness and Environmental improvement) strategy. PROGRESS TOWARDS ELIMINATION OF TRACHOMA IN Of the 13 HDs, 7 completed 3 rounds of mass drug administration with TANZANIA: RESULTS OF IMPACT SURVEYS IN 28 DISTRICTS good coverage and qualified for impact assessment. A cross-sectional, George Kabona1, Jeremiah M. Ngondi2, Edward Kirumbi1, descriptive, cluster randomized survey was conducted in May-July 2014 Mathias Kamugisha3, Alistidia Simon4, Christina Mbise4, Andreas in the 7 HDs to estimate the prevalence of TF in order to determine Nshala5, Patrick Masae6, Harran Mkocha7, Deogratias Damas5, whether the criteria for stopping mass treatment with azithromycin Alphonsina Nanai8, Kathryn Crowley9, Lisa Rotondo9, Upendo J. had been achieved. A sample of 12,377 children aged 1-9 years was Mwingira1 surveyed. The WHO simplified trachoma grading system was used for the recording of cases. Findings showed that average prevalence of TF in 7 1Neglected Tropical Disease Control Program/MoHSW, Dar Es Salaam, HDs decreased from 20.58% (95% confidence interval: 19.9% - 21.2% United Republic of Tanzania, 2RTI International, Dar Es Salaam, United in 2010 to 2.04% (95% confidence interval: 1.79 - 2.30%) in 2014. Republic of Tanzania, 3National Institute for Medical Research, Dar Es The TF prevalence in each HDs was 6.49% (Meri), 5.75% (Pette), 0.37% Salaam, United Republic of Tanzania, 4Sightsavers, Dar Es Salaam, United (Bourha), 0.90% (Hina), 0.28% (Koza), 0.37% (Mogode), and 0.29% Republic of Tanzania, 5IMA World Health, Dar Es Salaam, United Republic (Roua). Five out of 7 HDs surveyed reached TF prevalence of <5% and of Tanzania, 6Kilimanjaro Christian Medical Centre, Moshi, United Republic met the criteria of stopping mass antibiotic treatment. Two HDs, Meri and of Tanzania, 7Kongwa Trachoma Project, Dodoma, United Republic of Pette, recorded TF prevalence from 5-9.9% and will receive one additional Tanzania, 8World Health Organization, Dar Es Salaam, United Republic of round of treatment before conducting an additional impact assessment Tanzania, 9RTI International, Washington, DC, United States survey, according to the WHO recommendations. The World Health Organization recommends evaluation of the surgery, antibiotics, facial cleanliness and environmental change (SAFE) strategy 1690 after at least three years of implementation. We investigated the prevalence of trachomatous inflammation-follicular (TF) in children aged FILARIAL/LEISHMANIA CO-ENDEMNICITY IN TWO DISTINCT 1-9 years and trachomatous trichiasis (TT) in people aged 15 years and REGIONS OF MALI above in 28 districts. Surveys were conducted in districts where SAFE had 1 1 1 been implemented for 3 years or more. Cluster random survey design Moussa B. Sangare , Yaya I. Coulibaly , Siaka Y. Coulibaly , 1 1 2 2 was used to select the sample. Districts were stratified into three to four Michel E. Coulibaly , Ilo Dicko , Moussa Sissoko , Sibiri Samake , 3 4 5 sub-districts and 10 to13 villages (clusters) randomly selected in each sub- Thomas B. Nutman , Jesus Valenzuela , Ousmane Faye , Shaden 4 4 3 district. Households were selected in using systematic random sampling. Kamhawi , Fabiano Oliveira , Roshanak T. Semnani , Seydou 2 In sampled households, children aged 1-9 years were examined for TF Doumbia and persons aged 15 years and above were examined for TT using World 1Mali International Center for Excellence in Research, Filariasis Unit, Health Organization (WHO) simplified grading system. A total of 41,641 Bamako, Mali, 2Mali International Center for Excellence in Research, households were surveyed. A total of 77,133 children aged 1-9 years and Leishmaniasis Unit, Bamako, Mali, 3National Institutes of Health, Bethesda, 110,763 people aged 15 years and above were examined for trachoma MD, United States, 4National Institutes of Health, Rockville, MD, United signs. District prevalence of TF ranged from 0.5%; 95% confidence States, 5Centre National d’Appui à la lutte contre la Maladie, Bamako, Mali interval [CI] (0.5-1.3) in Karagwe to 14.1%; 95%CI (10.9-18.1) in Kilindi. Filarial infections are a major public health problem that can lead to District prevalence of TF was below the 5% threshold for stopping mass debilitating outcome such as the hydroceles and elephantiasis seen in drug administration (MDA) in 19 districts. Prevalence of TF was ≥10%, and lymphatic filariasis (LF). Phlebotomus duboscqi, the sand fly vector for between 5% and 9.9% in five and four districts, respectively. Prevalence Leishmania major (Lm) parasites, is found in areas endemic for LF in Mali. of TT by district ranged from 0.1%; 95% CI (0.0-0.2) in Kondoa to 2.9%; To determine whether there may be potential interactions between the 95% CI (2.2-3.9) in Lindi with 11 districts with TT prevalence of ≥1%. presence of filarial infections and of Lm, the prevalence of the two major astmh.org 518 filarial infection found in Mali (W. bancrofti [Wb] and M. perstans [Mp]) 1692 in two ecologically distinct regions - Tieneguebougou/Bougoudiana in Kolokani district (North Sudan savannah area) and Boundioba in the PROVIDING SURGICAL CARE IN RURAL HAITI: LESSONS district of Kolondieba (South Sudan Savannah area) -- was assessed as LEARNED AND PROGRESS MADE was the prevalence of coincident delayed type hypersensitivity (DTH) 1 1 1 responses to leishmanin as measured by skin test (LST). A total of 930 Ruth L. Bush , Penelope S. Anthony , Katie A. Coble , J. Scott 1 2 volunteers aged from 18 to 65 years were included from the two endemic Thomas , J. Patrick Lataillade areas. Prevalence rates for the Wb-specific circulating filarial antigen 1Texas A&M College of Medicine, Bryan, TX, United States, 2Living Word (CFA) were 7.69% (15/195), 3.04% (7/230) and 10.30% (52/505) while Haiti, Miramar, FL, United States the Mp microfilaremia prevalence rates were 11.79% (23/195), 4.35% Surgical care in undeveloped poor countries is often lacking, only (10/230) and 9.50% (48/505), for Tieneguebougou, Bougoudiana occurring at large regional hospitals. Rural residents may not have the and Boundioba, respectively. Interestingly, the prevalence rates based financial means for care or the ability to travel. For the past 12 years, a on LST for exposure to Lm infection were 25.12% (49/195), 8.88% team of medical professionals have been performing surgical procedures (15/169) and 2.04% (8/393), respectively, in each of these villages. Single in a remote Haitian village in communication with the local Minister of filarial infection was more common in the study population 15.16% Health. The College of Medicine has established a short-term global (141/930) than DTH response to Lm within the filarial infected subjects health elective for medical students and surgery residents. The purpose 9.03% (14/155) (Chi2=4.076, p=0.044). Microfilaremia prevalence was of this study was to review our experience providing surgical care to a comparable in Kolokani (7.76 %) and Kolondieba (9.50 %) (p=0.35) profoundly underserved region. From 2003-2015, surgical procedures have while CFA prevalence was significantly higher in Kolondieba (p=0.0040) been performed solely under local anesthesia. Early on, procedures were as well as DTH response in Kolokani (p<0.0001). These findings establish performed in a large room with separate areas for pre and postoperative the existence of co-endemnicity of filarial infections and Lm infections in care. Later, an on-site multi-room clinic was constructed with sinks, regions in Mali. Additionally, because of the potential interaction between improving sanitary conditions. One surgical faculty, 4 circulating nurses, 3 differing immune-mediated responses seen in chronic filarial infections and nursing students, 6 surgical residents (elective began 2009), and 2 medical in Lm infection, more detailed and integrated approach to these infections students (elective began 2013) have participated. Utilities are limited and is needed in co-endemic regions. alternative sterilization techniques employed. The procedures performed have included ventral and inguinal hernias (198), lipoma excisions (31), 1691 abscess drainages (31), thyroglossal duct cystectomy (2), skin cancer and THE EFFECTIVENESS OF AN ENHANCED ANTENATAL CARE large keloid excisions (15), and other (58). There have been no deaths and only 5 complications. Two hypertensive patients developed hematomas PACKAGE FOR THE CONTROL OF MALARIA AND ANAEMIA requiring evacuation and 2 patients had recurrence of their inguinal IN PREGNANCY IN GHANA hernias prompting the change to a mesh repair in 2005. One hernia repair Gifty D. Antwi1, Harry K. Tagbor1, Imelda Bates2 was aborted due to extensive scar tissue and the patient sent to a regional hospital. The global burden of surgical disease needs to be addressed 1Kwame Nkrumah University of Science and Technology, Kumasi, Ghana, on numerous fronts, including the most underserved and remote rural 2Liverpool School of Tropical Medicine, Liverpool, United Kingdom populations. The local conditions and volunteer expertise need to be The prevalence of malaria and anaemia in pregnancy remains high despite matched so that excellent, appropriate, and safe care is provided. Trainees efficacious antenatal care (ANC) interventions being available for more will benefit from the experience as well as on the addition of components than two decades. Sub-optimal uptake of the interventions due to non- of cultural education and global surgery ethics. Above all, participants participation of pregnant women in ANC may be a contributory factor. We must demand “Primum non nocere” or “First, Do No Harm”. hypothesized that participation of pregnant women in their ANC would improve adherence to ANC recommendations and lead to better health 1693 outcomes. A cluster randomized trial was conducted to assess the effect of pregnant women’s participation on the risk of anaemia and malaria CHILD MALNUTRITION IN ECUADOR: RESULTS FROM THE parasitaemia during pregnancy. The intervention consisted of ANC staff ECUADORIAN NATIONAL HEALTH AND NUTRITION SURVEY showing pregnant women their rapid malaria test (RDT) and haemoglobin (ENSANUT-ECU) (Hb) colour scale (HCS) results to encourage their participation. The control 1 2 1 1 group had routine care. We also assessed the feasibility and acceptability Winnie Chu , Wilma B. Freire , Saurabh Mehta , Jere D. Haas , 1 of the intervention. The overall mean age, gestational age and Hb at Julia L. Finkelstein baseline were 26.4yrs, 17.3 weeks and 110 g/l, respectively, and similar in 1Cornell University, Ithaca, NY, United States, 2Ministry of Health of both groups; 10.7% had asymptomatic parasitaemia; 74.6% owned ITN Ecuador and the Universidad San Francisco de Quito, Ecuador, Quito, of whom 48.8% slept under it the night prior to enrolment. The adjusted Ecuador risk ratio by 8 weeks of follow up and at 36-40 weeks gestation in the The burden of child malnutrition in Latin America is high, although there intervention versus the control was 0.97 (95% CI: 0.78-1.22) and 0.92 is limited data from Ecuador. The recent Ecuadorian National Health and (95% CI: 0.63-1.34) for anaemia and 1.17 (95% CI: 0.68-2.04) and 0.83 Nutrition Survey is the first national level nutrition survey since 1987, and (95% CI: 0.27-2.57) for parasitaemia. The adjusted risk ratio for low birth provides a unique opportunity to examine the burden of malnutrition weight was 0.93 (95% CI: 0.44-1.97) and for sub-optimal pregnancies in children in Ecuador. Socio-demographic and anthropometric data (abortions, intra uterine foetal deaths and still births) was 0.77 (95% CI: (n=9,145) and venous blood samples (n=2,049) were collected. The 0.17-3.52) in the intervention group versus the control. Integration of prevalence of anemia, micronutrient deficiencies (zinc, vitamin A, iron, the HCS and the RDT into ANC was feasible and acceptable. Both ANC vitamin B12, folate), and stunting (LAZ<-2), underweight (WAZ<-2), staff and pregnant women perceived some improvement in pregnant wasting (WLZ1), and obesity (BMIZ>2) were calculated and mapped women’s adherence to ANC recommendations although clear evidence of using ArcGIS. Binomial and linear regression models were used to a biological effect was not found. The effect may have been diluted out examine the associations of anemia, micronutrient deficiencies, and by the concurrent introduction of RDTs into routine ANC during the time WHO anthropometric indicators and socio-demographic characteristics. of the study and some implementation challenges of the enhanced ANC The prevalence of child stunting (25.0%), underweight (5.0%), wasting package at the ANC clinics. (2.3%), and overweight (30.0%) was high. Micronutrient deficiencies were common in children, particularly zinc deficiency (Zn<65.0 μg/ dL; 25.0%), anemia (Hb<11.0 g/dL; 16.0%), and vitamin A deficiency (retinol0.05); however, the prevalence of anemia was higher in Coastal astmh.org 519 Ecuador (22%; RR: 1.65, 95% CI: 1.36-2.00, p<0.01), compared to all developed a real-time PCR assay for the detection of pathogenic strains other regions. Lower maternal education predicted increased prevalence of Leptospira. Here, we evaluated the Leptospira Assay for analytical of child anemia (19%; RR: 1.40, 95%: CI: 1.10-1.77, p<0.01) and vitamin sensitivity and specificity as well as the stability of organism in various A deficiency (19%; RR: 1.41, 95% CI: 1.11-1.79, p<0.01). The prevalence specimen types. Patient samples were spiked into common sample types, of child stunting was significantly higher in rural compared to urban areas urine, whole blood, and cerebrospinal fluid (CSF), and stored for varying (30% vs. 21%; p<0.01), and in the Sierra (29%, RR 1.32, CI 1.22-1.44, times and temperatures. Samples were then extracted using the MagNA p<0.01). Indigenous children had the highest prevalence of stunting (39%; Pure LC automated platform, and subjected to Real-Time PCR using RR: 2.17, 95% CI: 1.97-2.39, p<0.01). Findings suggest that the burden primers and probes specific to the 16S gene of pathogenic Leptospira. of child malnutrition is high in Ecuador, including anemia, micronutrient The Leptospira Assay, which could be completed in 5 hours, detected deficiencies, and stunting, particularly in urban and coastal settings. Leptospira interrogans, L. weilii, L. santarosai, L. borgpetersenii, L. Further understanding of the burden and distribution of child malnutrition kirschneri, and L. noguchii, but did not detect nonpathogenic strains will inform the design of targeted interventions. Leptospira biflexa, L. meyeri, and L. wolbachii. The Leptospira Assay detected as little as 600 cells/ml from blood, 150 cells/ml from urine, 1694 and 75 cells/ml from CSF. Several stability studies were performed, which demonstrated that, even for molecular testing, Leptospira were stable USE OF INTERFERON-Γ RELEASE ASSAYS FOR THE in urine for only 1 hour after spiking at room temperature, and for less DIAGNOSIS OF TUBERCULOSIS IN PATIENTS WITH than 1 day at 4°C. However, Leptospira were stable in urine for 30 days CONCURRENT MALARIA INFECTION IN TANZANIA at -20°C and stable in blood and CSF for 2 days, 7 days, and 30 days at room temperature, 4°C, and -20°C, respectively. Therefore, it is highly 1 2 2 Camilla H. Drabe , Nyagonde Nyagonde , Filbert Francis , Michala recommended that urine samples are shipped frozen. With a turn-around 1 2 1 3 V. Rose , Martha M. Lemnge , Ib C. Bygbjerg , Morten Ruhwald , time of 24 hours and increased analytical sensitivity, especially in frozen 1 1 Pernille Ravn , Lasse S. Vestergaard samples, the Leptospira real-time PCR assay is an improvement over 1University of Copenhagen, Copenhagen, Denmark, 2National Institute culture. for Medical Research, Tanga, United Republic of Tanzania, 3Statens Serum Institut, Copenhagen, Denmark 1696 Latent tuberculosis can be diagnosed with interferon- release assays ULTRASOUND FINDINGS OF TROPICAL CONDITIONS IN A (IGRAs). However, several conditions have been shown to interfere with IGRA performance, including concomitant glucocorticoidγ treatment, COHORT OF SOUTH ASIAN IMMIGRANTS SEEN IN VICENZA, smoking, and human immunodeficiency virus (HIV) and helminth co- ITALY infection. It remains yet unknown whether concurrent malaria infection Maria T. Giordani1, Paolo Fabris1, Luca Lazzarini1, Roberta Narra2, also affects IGRA performance; however, the well-established immune- Enrico Brunetti3 modulating effects of malaria suggest this may be the case. We aimed in 1Infectious and Tropical Diseases Department, san Bortolo Hospital, this clinical study in Tanzania to assess the effect of acute Plasmodium Vicenza, Italy, 2Department of Clinical Surgical Diagnostic and Pediatric falciparum infection on the performance of two different IGRA tests: Sciences, University of Pavia, Pavia, Italy, 3Division of Infectious and Tropical QuantiFERON-TB Gold in-tube (QFT-GIT) assay and the IFN-gamma- Diseases IRCCS San Matteo Hospital Foundation-University of Pavia, Pavia, inducable protein 10 (IP-10) release assay. Study participants included Italy adults with confirmed uncomplicated P. falciparum malaria attending Muheza District Hospital in north-eastern Tanzania as part of a larger trial Immigrants from developing countries are a potential source of looking at malaria treatment efficacy and safety in patients co-infected imported tropical conditions, including transmissible diseases. While with HIV. A total of 241 adults were included: 184 patients with malaria illegal immigrants mostly come from sub-Saharan Africa crossing the (88 co-infected with HIV) and 57 patients with HIV infection only. Patients Mediterranean sea, Asian immigrants generally travel legally to Italy and with malaria received the standard six-dose treatment with artemether- receive less medical attention. We describe the epidemiological, clinical lumefantrine, and QFT-GIT and IP-10 release assays were performed prior and sonographic findings in a cohort of 145 Asian immigrants admitted to treatment on day 0 and again on day 7 and day 42 after treatment. to our Infectious Diseases and Tropical Medicine Department in Vicenza, Independently of HIV, significantly lower INF- and IP-10 responses to Italy, from 2000 to 2014. Their countries of origin were India (45 patients, mitogen-stimulation were observed in patients with concurrent malaria 31%),Bangladesh (72 p., 49.6%) and Pakistan (28 p., 19.3%).In all compared to patients without malaria, with negative correlations observed patients, point of care ultrasound (PoC-US) was performed in the first between parasite density and INF- and IP-10 levels. These alterations week of admission and during the hospital stay.The main diagnosis at reverted after malaria treatment. Malaria infection did not influence QFT- discharge was: tuberculosis (TB) in 31 cases (21.3 %, 13 pulmonary TB, GIT testing results as such, while a higher proportion of IP-10 release 18 extrapulmonary TB), acute viral hepatitis in 29 cases (20 %, 10 HEV, assays showed indeterminate results during acute malaria. Our findings 2 HAV, 4 HBV, 2 of unknown origin); 12 patients had acute-on-chronic suggest that malaria infection interferes with IGRA performance through viral or alcoholic liver damage, in another three cases acute hepatitis impairment of INF-γ and IP-10 responses. We therefore recommend being was associated with Dengue Fever. 15 patients (10.4% ) had typhoid or cautious when interpreting IGRA results in patients with malaria and that paratyphoid fever, 15 (10.4%) had pneumonia, 8 meningitis (5.51%), testing for tuberculosis be postponed until after completion of malaria and 11 soft tissue infections (7.58%). Parasitic diseases (malaria, liver treatment. amebiasis, trichuriasis, toxoplasmosis and scabies) accounted for 8 cases (5.51 %). Only two patients (1.37 %) tested positive for HIV. The main 1695 ultrasonic findings were: hepatomegaly (52, 35.8%), fatty liver (48 , 33.1 %), splenomegaly (39, 26.8 %), pleural, pericardial and/or abdominal DEVELOPMENT OF A REAL-TIME PCR DIAGNOSTIC FOR effusions (42, 28.9%), lymph nodal abscesses, both superficial and deep PATHOGENIC LEPTOSPIRA (12, 8.27%), coarse liver pattern (8, 5.5%) hepatic and splenic abscesses (7, 4.8%).Most patients (120, 82.75 %) had recently traveled to their Erik P. Johnson, Dale A. Schwab country of origin or were recently immigrated and had an imported Focus Diagnostics, San Juan Capistrano, CA, United States infectious condition. Immigrants from South Asia visiting friends and The current gold standard for the direct detection of Leptospira in clinical relatives (VFR) need more clinical attention from the ID specialist. PoC-US is specimens is culture in semi-solid media, which requires up to 26 weeks of helpful in diagnosing and managing tropical conditions in this population, growth. In addition, leptospires lose viability in urine, a common sample as it allows identification of relevant, and sometimes pathognomonic type, within hours after collection. To address these drawbacks, we have findings in these conditions. astmh.org 520 1697 and the time of evaluation (90%). Myalgia was also highly prevalent at both moments (90% and 48%, respectively). Squeeze test was positive CLINICAL, LABORATORY AND EPIDEMIOLOGICAL PROFILE in 34 (50%) and 30 (44%) patients when performed in hands and feet, AND TREATMENT OF SEVERE SCHISTOSOMIASIS MANSONI respectively (kappa: 0.82, p<0.01). Overall, patients had low grip-strength, IN A TEACHING HOSPITAL IN SÃO PAULO CITY, BRAZIL especially those who had positive as compared to negative squeeze tests (12.5 kg vs. 16.3 kg, p<0.05; respectively). A positive squeeze test (in Maíra Reina Magalhães, Maria Cristina Carvalho Espírito-Santo, hands), but not the grip-strength, was more likely among patients with Naíma Mortari, Expedito José Luna, Ronaldo Cesar Gryschek higher antibody levels: 6% higher probability of positivity per 1 NTU Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil increase in antibody levels (OR=1.06, 95%CI: 1.01 - 1.12). The handgrip maneuver and the squeeze test may contribute to a better characterization Schistosomiasis remains a public health problem in Brazil. The aim of of rheumatic complications and correlate with the antibody’s response. this study was to evaluate the clinical, epidemiological and laboratory Whether these tools are useful to assess prognosis deserves further profile of patients with severe forms of schistosomiasis assisted at evaluation the Schistosomiasis Outpatient Clinic of the Hospital das Clinicas of the University of São Paulo. This is a case series study evaluating 42 outpatients’ records. We developed a data collection questionnaire from 1699 patients’ medical records and described their clinical and laboratory data. IMPACT OF MALARIA RAPID DIAGNOSTIC TESTS ON In addition, we made a comparison between patients with and without PATIENTS’ SUBSEQUENT TREATMENT-SEEKING, COSTS AND splenomegaly. The clinical, epidemiological and laboratory profile showed HEALTH OUTCOMES: RESULTS FROM THE ACT CONSORTIUM the following: predominance of males 57.1% (24/42); 100% (42/42) had the hepatosplenic form of the disease; 68.3% of patients (28/42) had Heidi Hopkins, Philippa West, Shunmay Yeung, Clare Chandler, just elementary school education and mean age of 48.24 years. Among ACT Consortium RDTs in Context Working Group the symptoms that led the patient to seek medical attention, presence London School of Hygiene & Tropical Medicine, London, United Kingdom of an enlargement in any organ was more prevalent: 55.3% (12/36). There was a statistically significant association between splenomegaly Malaria rapid diagnostic tests (RDTs) are intended to have a beneficial and thrombocytopenia (p <0.004) between splenomegaly and leukopenia impact on management of suspected malaria, and on health outcomes (p <0.046), and only 2.5% (1/22) of patients presented with bleeding. and other patient-related outcomes. The ACT Consortium includes several Regarding specific treatment, 54.2% (13/24) of patients used Praziquantel studies designed to test operational strategies for artemisinin combination and 45.8% (11/24), Oxaminiquine. Patients used the following non- therapy (ACT) and RDT implementation in various settings, providing an specific drug therapy: 65% (26/40) Propranolol, 90% (36/40) Omeprazole, opportunity to draw on data from multiple projects that have introduced and 43.6% (39/42) Aluminum Hydroxide 92.9% (39/42) of patients RDTs across a range of clinical, social, and epidemiological contexts, and in required an upper endoscopy, 85% (39/40), sclerotherapy, 62.5% (25/15), public, private retail, and community health service sectors. The impact of elastic bandages, and 28.2% (11/39) underwent surgery. This preliminary RDTs on case management is presented in a separate abstract; this analysis study allowed us to observe the clinical, epidemiological and laboratory focuses on events after the clinical consultation, including subsequent profile of patients treated in an outpatient clinic far from endemic areas treatment seeking, patient costs, and self-reported health outcomes. Data for schistosomiasis, while pointing out that medical and endoscopic were examined from eight studies comparing scenarios where RDTs were treatment, in combination with outpatient treatment can be effective made available to control scenarios where RDTs were not made available. in preventing bleeding and surgical treatment. The severe forms of this Preliminary analysis of three data sets shows that where RDTs were helminthiasis require an interdisciplinary outpatient follow-up. introduced, the proportion of patients seeking further care after the initial consultation increased in one high-transmission setting where community 1698 health workers offered only ACT; this was not the case in another setting in retail drug shops which offered non-ACT alternatives for RDT-negative CHIKUNGUNYA RHEUMATISM DURING THE SUBACUTE patients. The same data sets indicate that patient or caregiver report PHASE OF THE DISEASE AND ITS CORRELATION WITH IGG of symptomatic recovery is approximately equivalent whether or not ANTIBODIES: FINDINGS FROM AN OUTBREAK IN COLOMBIA RDTs are available. Full results will include analysis by health care sector, epidemiology, patient age, routine and reference diagnostic results, and Elsa M. Rojas Garrido1, Maria C. Miranda Montoya1, Victor M. treatment prescribed at the initial consultation. This ongoing analysis Herrera Galindo1, Adriana M. Gómez Bernate1, Luisa V. Galviz aims to elucidate features associated with variation in post-consultation Gómez2, Luz A. Rey Caro1, Luis A. Villar Centeno1 outcomes in order offer tailored guidance for policy and program 1Centro de Investigaciones Epidemiológicas, UIS., Bucaramanga, Colombia, development for RDT introduction in other areas. 2Departamento de Medicina Interna, UIS., Bucaramanga, Colombia Chikungunya rheumatism (CHIK-r) includes a broad spectrum of disorders 1700 ranging from mere pain to frank arthritis with severe incapacity, however, ASSESSMENT OF RISK FACTORS FOR PRETERM BIRTH AND the burden of this complication, its clinical features, and its relationship CONTRIBUTIONS OF PREMATURITY TO FUTURE RISK OF with the immunological response have not been fully characterized, ADVERSE OUTCOMES IN A BANGLADESHI BIRTH COHORT especially in areas where the disease has been recently introduced. We evaluated 78 adults with clinical diagnosis of Chikungunya (CHIK) fever E. Ross Colgate1, Dorothy M. Dickson1, Marya P. Carmolli1, and persistent musculoskeletal symptoms after 15 days of disease’s onset, Rashidul Haque2, Masud Alam2, Josyf C. Mychaleckyj3, Uma in the context of an outbreak in Capitanejo, Colombia. CHIK infection was Nayak3, Mary Claire Walsh1, Sean A. Diehl1, Firdausi Qadri2, confirmed in 73 patients (mean age: 59 years; 23% male; median disease’s William A. Petri3, Beth D. Kirkpatrick1 duration: 46 days) using micro-capture ELISA for IgG. Antibody levels were 1University of Vermont College of Medicine, Burlington, VT, United States, expressed in NovaTec units (NTU). Patients underwent a clinical evaluation 2International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, focused on the determination of rheumatic symptoms and a physical Bangladesh, 3University of Virginia, Charlottesville, VA, United States exam that included the squeeze test (in hands and feet) and the handgrip maneuver (Jamar dynamometer). The association between antibody levels Preterm birth has been identified by the WHO as a major global public and clinical signs of rheumatic involvement was evaluated using multiple health problem and accounts for more infant deaths in the first month logistic regression, adjusting for age, sex, and disease’s duration. Arthralgia of life than any other cause. South Asia has the highest rates of preterm was the most frequently reported symptom at disease’s onset (97%) birth. We followed a birth cohort of 700 healthy infants from the urban slums of Dhaka, Bangladesh for 2 years. We examined factors contributing astmh.org 521 to preterm birth and whether prematurity led to increased risk for adverse 1702 outcomes related to rotavirus vaccine efficacy and any diarrheal illness in the first year of life. In our cohort, gestational age assessments using the NATIONAL SEROPREVALENCE OF MEASLES, TETANUS AND Dubowitz-Ballard scale were completed on a subset of 381 children at RUBELLA AMONG CHILDREN AGED 6-59 MONTHS IN THE enrollment (0-7 days after birth) by a trained medical officer. Among 381 DEMOCRATIC REPUBLIC OF CONGO children, 32% were born preterm (32-36 weeks gestation). We examined predictors of prematurity including child’s gender, birth order, mother’s Reena H. Doshi1, Nicole A. Hoff1, Patrick Mukadi2, Sue Gerber3, age and BMI, and delivery status (cesarean vs vaginal). No association Stephen Higgins4, Emile Okitolonda5, Jean-Jacques Muyembe- was found between preterm birth and infant or maternal characteristics, Tamfum2, Anne W. Rimoin1 nor with cesarean delivery. To survey associations between prematurity 1University of California Los Angeles Fielding School of Public Health, Los and increased risk for adverse outcomes, we used univariate and logistic Angeles, CA, United States, 2National Institute for Biomedical Research, regression analysis to examine incidence and duration of rotavirus and Kinshasa, Democratic Republic of the Congo, 3Bill & Melinda Gates all-cause diarrhea in the first year of life; infant rotavirus-specific IgA at Foundation, Seattle, WA, United States, 4Dynex Technologies, Chantilly, 6 and 18 weeks of age; enteric co-pathogen burden at 10 weeks; serum VA, United States, 5Kinshasa School of Public Health, Kinshasa, Democratic zinc at 6 and 18 weeks; and incidence of diarrhea-related serious adverse Republic of the Congo events in the first year. Prematurity was not found to predict increased Serosurveys are a direct and accurate method to assess population risk for any of these outcomes. In a population with high prevalence of level immunity and can provide critical insight into immunity gaps and childhood malnutrition, prematurity notably may explain a portion of operational program efficiency. In collaboration with the Demographics described malnutrition in our cohort: 59% of stunted children (HAZ<-2SD) and Health Survey (DHS) we assessed population immunity to vaccine- at enrollment were also assessed as premature, as were 50% of children preventable diseases in the Democratic Republic of Congo. We screened with WAZ<-2SD and 39% with WHZ<-2SD at enrollment. Preterm birth 8,117 children aged 6 to 59 months for IgG antibodies against measles, was not associated with increased risk of malnutrition by one year of rubella and tetanus using dried blood spots (DBS) collected during the age. Future analyses will include assessment of prematurity and cognitive 2013 DHS. DBS were tested using the Dynex Multiplex M2 platform, function outcomes up to age 2 years which may indicate clear targets for an automated enzyme-linked immunosorbant assay at the National public health interventions to prevent preterm births. Laboratory for Biomedical Research in Kinshasa. Seropositivity rates for children in three age categories were determined for measles, tetanus, and 1701 rubella antibodies, respectively. Children aged 6 to 8 months had rates of SAFETY EVALUATION OF FIXED-DOSE 18.3, 46.7, and 14.0%; children 9 to 11 months had rates of 40.1, 43.6, DIHYDROARTEMISININ-PIPERAQUINE COMBINATION IN A and 23.9%; and children 12 to 59 months had rates of 73.1, 31.8 and 39.3% seropositivity for the three diseases described. VPD seroprevalence REAL LIFE SETTINGS varied by province as well, ranging from 51.4-81.6% for measles, 20.1- Abraham R. Oduro1, Seth O. Owusu-Agyei2, Margaret Gyapong3, 51.8% for tetanus, and 19.3-52.5% for rubella. The lowest seropositivity Fred N. Binka4 rates for tetanus and measles were seen in Katanga and Maniema 1Navrongo Health Research Centre, Navrongo, Ghana, 2Kintampo Health provinces. The prevalence of rubella was highest in Bandundu. The low Research Centre, Kintampo, Ghana, 3Dodowa Health Research Centre, seroprevalence of measles and tetanus antibodies indicate that large-scale Accra, Ghana, 4University of Allied Health Sciences, Ho, Ghana immunity gaps exist across the DRC. The large percentage of children exposed to rubella in the absence of a vaccine, suggests widespread Uncommon and rare reactions with delayed onset may not be detected circulation of the virus throughout the country. In DRC, there is an before new medicines are licensed. Post-licensure surveillances are immediate need to re-evaluate immunization strategies for these vaccine carried out to expand the evidence base of products characteristics for preventable diseases. which marketing authorization were granted. Using the established INDEPTH-network safety monitoring platform the study evaluated safety 1703 of dihydroartemisinin-piperaquine as first-line treatment for malaria across different settings in Ghana. Key questions answered were the HOSPITALIZATIONS IN IMMIGRANTS AND NON- safety of the drug when used under usual conditions and assessment of IMMIGRANTS WITH CHRONIC HEPATITIS C INFECTION IN the occurrence of adverse events. Health and Demographic Surveillance QUEBEC areas of Navrongo, Kintampo and Dodowa research centres located in the northern, middle and coastal belts of Ghana were used. From September Rhiannon L. Kamstra1, Laurent Azoulay2, Russell Steele3, Marina 2013 to June 2014 a prospective, observational, study was carried Klein4, Christina Greenaway5 out. Participants were males and females, age >6 months, weighing ≥ 1Centre for Clinical Epidemiology, Lady Davis Research Institute for 5kg, ability to take oral medications, acute febrile illness and informed Medical Research, Jewish General Hospital, Department of Epidemiology, consent. Detailed clinical enquiry was conducted. Data analysis involved Biostatistics and Occupational Health, McGill University, Montreal, descriptive characteristics and adverse events coded using MedDRA® QC, Canada, 2Centre for Clinical Epidemiology, Lady Davis Research System Organ Class classification. The protocol received approval from Institute for Medical Research, Department of Epidemiology, Biostatistics the Ghana Health Service Ethics Review Committee, Ghana Food and and Occupational Health, McGill University, Montreal, QC, Canada, Drugs Authority and was registered with Clinicaltrials.gov (NCT02199951). 3Department of Mathematics, McGill University, Montreal, QC, Canada, Approximately 95.5% (4563/4777) patients comprising 52% females 4Division of Infectious Diseases, McGill University Health Center. and 48% children < 6 years of age. Overall 347 adverse with incidence Department of Epidemiology, Biostatistics and Occupational Health. McGill rate of 76/10000 population. Characteristics associated with adverse University, Montreal, QC, Canada, 5Division of Infectious Diseases, Jewish effects were body mass index and parasite density. The commonest events General Hospital, Centre for Clinical Epidemiology, Lady Davis Research according the MedDRA® Coding per 10000 population were infestations Institute for Medical Research, Jewish General Hospital. Department of (465), gastrointestinal disorder (103), Respiratory conditions(46), thoracic Epidemiology, Biostatistics and Occupational Health, McGill University, disorders(44), Nervous system disorders (26) and Skin disorders (26). In Montreal, QC, Canada conclusion, fixed-dose dihydroartemisinin-piperaquine combination is very Chronic hepatitis C (HCV) causes considerable morbidity and mortality safe in African population with malaria in real life settings in Canada due to liver cirrhosis, liver failure and liver cancer that could be prevented through early screening and treatment. Immigrants are an underappreciated group at risk for HCV, often originating from high

astmh.org 522 prevalence countries. This study characterized all-cause and liver-related 1705 hospitalizations in HCV-infected immigrants compared to non-immigrants. We performed a retrospective population-based cohort study of all ACUTE FEBRILE SYNDROME IN COLOMBIAN NORTHWEST HCV cases in the Quebec mandatory disease reporting database from 1 2 2 1998 to 2007. Cases were deterministically linked to hospitalization Maria F. Yasnot , Maria C. Velasco , Virginia C. Rodriguez and outpatient services databases. Liver-related hospitalizations were 1Universidad de Cordoba, Monteria, Colombia, 2Grupo de Investigaciones identified through discharge diagnoses and procedure codes. A total of Microbiológicas y Biomédicas de Córdoba, Universidad de Cordoba, 20,139 linked cases of chronic HCV were reported from 1998-2007, 9% Monteria, Colombia (N=1,821) of whom were immigrants. At HCV diagnosis, immigrants were Fever is one of the most characteristic symptoms of infectious diseases, older (47.6 vs. 43.2y, p<0.05), more likely to be female (46.7 vs. 31.9%, sometimes the only one or the most important. A few time of fever, p<0.05), and to have liver cancer (0.93 vs. 0.31%, p<0.05). The mean usually due to self-limited viral processes or noninfectious diseases. time to HCV diagnosis after arrival was 9.8 ± 6.9 years. Non-immigrants When fever persists more than two weeks, it is considered prolonged as had a 3-10 fold higher prevalence of HCV-related risk factors, including a result of an infectious disease in many cases, but also in malignancy, drug or alcohol abuse, and HIV. Non-immigrants were more likely to be autoimmune or hematologic diseases, metabolic disorders and vascular hospitalized at least once during follow-up compared to immigrants (49.3 disorders. The febrile syndrome is the most common and nonspecific, It vs. 35.8%, p<0.05 with hospitalization rates of 31.3 vs 18.2 /100 PY). is defined as sudden onset of fever and less than seven days duration in Immigrants were as likely to have at least one liver-related hospitalization patients who have not been identified signs or symptoms related to an (7.8% vs. 7.1%), however in-hospital deaths were more likely to be liver infectious focus. Infectious disease to discard in the course of a febrile related among immigrants as compared to non-immigrants (57.9% vs syndrome are diverse, such as tuberculosis, typhoid fever, brucellosis, 41.8%, p<0.01). The most common primary discharge diagnoses for non- sepsis, endocarditis, localized infections, urinary tract infections, rickettsia immigrants were mental disorders (20.5%) and injury/poisoning (10.3%) and viral processes. On this study, were evaluate five infectious agents whereas for immigrants they were liver-related (11.6%) and neurologic (dengue virus, Plasmodium sp., Brucella spp., Leptospira sp., and disorders (10.2%). Higher all-cause hospitalizations in non-immigrants Salmonella sp.) that are cause of febrile illness at the Córdoba department likely reflects more prevalent lifestyle comorbidities. The higher prevalence in Colombia, using molecular and immunological techniques to identified. of liver cancer and in-hospital deaths due to liver disease in immigrants Dengue contributes 40% of all cases, followed by malaria with 20%. highlights the importance of early HCV screening and treatment in this Was not possible to determine the etiology of 36% of patients and 2% population. of leptospirosis. Only one patient showed co-infection with dengue and malaria; brucellosis and salmonellosis is not evident as the etiologic agent 1704 of febrile syndrome in this study. INCIDENCE OF TROPICAL DISEASES IN THE US MILITARY 2004-2013 1706 Elizabeth Blazes1, Leslie Clark2, David Blazes3 EPIDEMIOLOGIC CHARACTERISTICS OF ACUTE NEUROLOGIC DEFICIT IN ELDERLY PEOPLE FROM A DEVELOPING COUNTRY 1Sidwell Friends School, Washington, DC, United States, 2Armed Forces Health Surveillance Center, Silver Spring, MD, United States, 3Uniformed Mentor Ali Ber Lucien1, Claudia Pierre2 Services University of the Health Sciences, Bethesda, MD, United States 1National Laboratory of Public Health, Port-au-Prince, Haiti, 2Quisqueya Understanding the impact of tropical disease on health is important to University, Port-au-Prince, Haiti the US military, because many service-members travel overseas to areas Elderly patients are vulnerable people and neurologic disorders are a very where there is a high risk of acquiring these illnesses. To understand the important public health problem which carries a risk of loss of autonomy. scope of this risk, we quantified the incidence of the five most important In developing countries like Haiti, few data exist about neurologic tropical diseases in the military from 2004 to 2013 using the Defense disorders. The aim of this study was to describe epidemiologic patterns Medical Surveillance System (DMSS), a continuously expanding relational of elderly people with acute neurologic deficit from Haiti. It was a data base that documents military and medical experiences of service retrospective cohort study conduct in the internal medicine ward from a members throughout their careers. Standard ICD9 codes for the following big teaching hospital in Port-au-Prince: La Paix Hospital. The study period diseases were included: Dengue, Leptospirosis, Leishmaniasis, Malaria, and was 1st January 2012 to 31 October 2014. Criteria of inclusion: all adults Helminths. Descriptive techniques were used to calculate the incidence patients admitted in the internal medicine ward with acute neurologic rates in the military over the period of time between 2004 and 2013. deficit and older than 65 years old. The criteria of exclusion were: charts Overall, there were a total of 10,941 cases of the five tropical diseases, non available. 525 elderly patients were hospitalized during this period and an incidence rate of 60.4 cases per 10,000 person-years. Most of and 124 had acute neurologic disorder. A systematic sampling was applied those cases were Helminths, which had a total of 8,398 cases over the over the registry of the site. One patient over two was included in the ten years, and an incidence rate of 46.4 cases per 10,000 person-years. study. Data from 62 patients were analyzed. Mean age was 75 years old, Leishmaniasis was the next most common illness, at 1,327, or an incidence 32 (51.6%) patients were female. 45 (72.5%) had previously hypertension; rate of 4.7 cases per 10,000 person-years. Malaria and leptospirosis were 7 (11.2%) had diabetes; 8 (13%) were at their second acute episode. less common, with 860 and 95 cases respectively, yielding incidence rates Only 16 (25.8%) patients came in less than 6 hours at the hospital. 18 of 4.8 and 0.5 cases per 10,000 person-years. In all the diseases, there (29%) had a blood systolic pressure > 220mnHg or a diastolic pressure > seems to be a general downward trend from 2004 to 2013, possibly a 120 mmHg. 25(40.32%) patients died and 50% of them before 3 days. result of decreasing deployments to tropical areas or better conditions 12 patients (19.35%) had a coma; 20 (32.25%) had obnubilation, 13 encountered in those areas where travel occurred. (20.9%) had seizure and 24 (38.70%) had speech disorders. 15 (24.19%) patients had facial palsy; 27(43.54%) had a left motor neurologic deficit, 3 (4.83%) had a neurologic deficit located at right inferior limb and 14(22.58%) had neurologic deficit at right superior and inferior limbs. All of the 17(27.41%) patients who realized a CT scan done it after 24 hours of hospitalization. 12 (70.58%) of them were ischemic stroke while the 5 (29.41%) others were hemorrhagic stroke. In our cohort, 25 (40.32%) patients died. 50% of those who survived had a length of stay of 8 days

astmh.org 523 while it was only for those who died of 3 days. It is very important to bearing on the individual and overall public health burden of endemic develop Point of Care technologies for neurologic emergencies at low communities. Although a clear distinction in immunogenetic profiles in economic cost for developing countries. response to LF is known to occur between overt clinical manifestations such as pathology and sub-clinical disease, it is unclear whether patent 1707 infections are distinct from latent states in sub-clinical disease. In a Ghanaian study, 101 single nucleotide polymorphisms (SNPs) and 1 PREVALENCE AND DETERMINANTS OF TRYPANOSOMA insertion/deletion polymorphism from 48 candidate genes were selected CRUZI INFECTION AMONG CITIZENS OF BOLIVIAN DESCENT for a case-control study. Genotyping was done for 302 patent and 389 LIVING IN MUNICH, GERMANY latent unrelated individuals. SNPs in 9 genes [Caveolin-1 rs926198 (PATT = 0.03), Desmoplakin rs2076299 (PATT = 0.01), Endothelin-1 rs5370 (PATT 1 2 1 Stefan Hohnerlein , Miriam Navarro , Nicole Berens-Riha , = 0.04), GJA4 rs1764391 (PATT = 0.01), IFN-gamma rs2069707 (PATT = 1 1 1 Peter Seiringer , Charlotte von Saldern , Sarah Garcia , Michael 0.049), IGF-1 rs2946834 (PATT = 0.002), NOD-1 rs736781 (PATT = 0.047), 1 1 1 Hoelscher , Thomas Loescher , Michael Pritsch NOD2/Card15 rs1000331 (PATT = 0.005), TLR-4 rs5030725 (PATT = 9E-4)] 1Division of Infectious Diseases and Tropical Medicine, Medical Center of and the TLR-2 gene insertion/deletion (-196 to -173 base pairs) (PATT = the University of Munich (LMU), Munich, Germany, 2Fundación Mundo 0.04) were associated with patent infection. Haplotype analysis yielded Sano, Madrid, Spain haplotypes of SNPs in two genes that were significantly associated with Chagas disease (CD) affects 7 million humans worldwide and is responsible infection status. AT in the IGF-1 gene was significantly associated with for 10,000 estimated deaths annually. Due to increased population patent infection (Monte-Carlo method with 200,000 simulations), while mobility, CD has become an international health issue. Migration of the haplotype GT was significantly associated with latent infection (Global Latin-American migrants from Spain (most CD-affected country in P = 1.5E-5). The haplotype CG in the IFN-γ gene was also associated Europe) to other European countries is increasing lately. Germany lacks with latent infection (Global P = 0.04). Our findings suggest that SNPs in surveillance data. A cross-sectional, descriptive study was started in angiogenic and inflammation genes are associated with patent infection 2013 as a pilot project to determine the prevalence and determinants and that the two states of sub-clinical disease are distinct chronic states in of CD among citizens of Bolivian descent living in Munich, Germany. LF disease pathogenesis. Participants completed a questionnaire in order to collect socio-economic and medical data. Peripheral blood was drawn and specific antibodies 1709 against Trypanosoma cruzi antigens were determined by ELISA and IFAT. MEDIATORS OF VASCULAR PERMEABILITY AND LYMPH/ If positive, PCR, clinical staging and management of CD was initiated. A qualitative research was conducted through 2 interviews (one women ANGIOGENESIS ARE MARKERS FOR HYDROCELES CAUSED T.cruzi+, one women with unknown serological status) and a focus group BY WUCHERERIA BANCROFTI INFECTION (3 subjects T. cruzi-), all in Spanish language, in order to assess the impact Chrisinta Weier1, Anna Albers1, Linda Batsa-Debrah2, Sunny of CD for individuals and the Bolivian community. Between June 2013 Mante3, Sabine Mand1, Birgit Stoffel-Wagner1, Ute Klarmann- and June 2014, 43 citizens of Bolivian descent living in Munich could be Schulz1, Alex Debrah4, Kenneth Pfarr1, Achim Hoerauf1 enrolled. Four participants (9.3 %) were T. cruzi +, two of these also in 1University Hospital of Bonn, Bonn, Germany, 2Kumasi Centre for PCR. Two of them were treated with benznidazole. Two of the T. cruzi Collaborative Research into Tropical Medicine, Kumasi, Ghana, 337 Military + subjects had a mother with CD. A total of 55.8% of all participants Hospital, Accra, Ghana, 4Kwame Nkrumah University of Science and (2 of the 4 T. cruzi +) had no knowledge about symptoms of CD and Technology, Kumasi, Ghana 30.2% (1/4 T. cruzi +) about ways of transmission. A total of 27.9% (0/4 T. cruzi +) had donated blood in the past without prior serological Lymphatic filariasis, caused by the filarial nematode Wuchereria tests on CD, 62.8% (3/4 T. cruzi +) were motivated to donate blood bancrofti, is a disease that affects over 120 million people. Most and 53.5% (3/4 T. cruzi +) to donate organs. Regarding qualitative individuals have no or just mild pathology, whereas others have severe research, lack of knowledge about CD, stigma and fears associated with pathology including lymphedema (~7% of infected individuals) or CD were identified. Regarding the lack of epidemiological data about hydrocele (50% of infected men). Hydrocele is a painful swelling of CD in Germany and the absence of measures controlling non-vectorial the scrotum caused by accumulation of lymph fluid. The aim of this transmission, the prevalence in this pilot study is alarming. Prevalence study was to identify biomarkers of hydrocele due to filarial infection. and determinants of CD in Germany have to be investigated further Hydrocele fluid was collected as part of a Volkswagen Foundation funded in a nationwide study and sensible control strategies with information study investigating the use of doxycycline therapy in hydrocele patients. campaigns should be put in place. Eight hydrocele samples were analyzed: 3 treated, 3 control and 2 European idiopathic hydrocele samples. Using Isobaric Tags for Relative 1708 and Absolute Quantitation (iTRAQ) the relative protein content of the 8 samples was measured simultaneously. Placebo samples were analyzed SINGLE NUCLEOTIDE POLYMORPHISMS IN ANGIOGENIC AND against doxycycline and idiopathic samples. From the iTRAQ results we INFLAMMATION PATHWAY GENES ARE ASSOCIATED WITH identified ~1000 proteins that were up- or down-regulated in the placebo PATENT LYMPHATIC FILARIASIS samples. Prioritization of the results identified 9 proteins that were significantly higher in lymphatic filariasis hydrocele fluid (placebo): the 1 1 2 Jubin Osei-Mensah , Linda Batsa-Debrah , Anna Albers , Lydia androgen receptor, angiopoietin 2, cystatin C, fibronectin, heparan sulfate 2 3 4 1 Lust , Felix Brockschmidt , Christine Herold , Yusif Mubarik , Tim extracellular region, IGFBP-2 and -6, osteopontin and VCAM-1. These 3 3 2 2 Becker , Holger Fröhlich Fröhlich , Kenneth Pfarr , Achim Hoerauf , proteins are mediators or interact with mediators of vascular permeability 5 Alex Debrah and lymph/angiogenesis. Androgen receptor, fibronectin, IGFBP-2 and 1Kumasi Centre for Collaborative Research into Tropical Medicine, Kumasi, -6, osteopontin, and down-stream pathway factors are being analyzed in Ghana, 2University Hospital of Bonn, Bonn, Germany, 3University of Bonn, hydrocele fluid and plasma as markers of lymphatic filariasis hydrocele that Bonn, Germany, 4Universit of Bonn, Bonn, Germany, 5Kwame Nkrumah could aid in early diagnosis and interventions to prevent or reverse disease. University of Science and Technology, Kumasi, Ghana Two-thirds of people with bancroftian lymphatic filariasis (LF) have sub-clinical disease or are asymptomatic and present as microfilaremic individuals (patent infections) or amicrofilaremic individuals who are antigen-positive (latent infections). These sub-groups are crucial to the continued transmission of Wuchereria bancrofti and have a direct astmh.org 524 1710 1712 UTILITY THICK SMEAR OF LARGER VOLUME FOR THE CHRONIC INFECTION WITH LITOMOSOIDES SIGMODONTIS DIAGNOSIS OF MANSONELLA OZZARDI IN THE PERUVIAN PROTECTS AGAINST ANAPHYLAXIS IN ORALLY SENSITIZED AMAZON MICE Salomon Durand, Dolores Rimarachin, Alejrandro Quiroz, Robert Laura E. Kropp, Edward Mitre V. Gerbasi, Andres G. Lescano Uniformed Services University, Bethesda, MD, United States U.S. Naval Medical Research Unit - 6, Callao, Peru Anaphylaxis is a life-threatening condition that can result from IgE- Although filariasis Mansonella ozzardi is very common in some regions mediated allergy. It is becoming increasingly prevalent in western of the Peruvian Amazon, little is known about its clinical presentations, countries and results in approximately 1,500 deaths a year in the its actual distribution in the Amazon Basin and its role in aggravation of United States. In this study we investigated the therapeutic potential other diseases. This filariasis is considered a neglected disease in the world. of helminths on systemic anaphylaxis in orally sensitized mice. BALB/c One of the major constraints to learning more about this condition is the mice were sensitized by weekly oral gavage with ovalbumin (OVA) plus difficulty of diagnosis. The Knott test, which is the gold standard for the Staphylococcal enterotoxin B (SEB) or mock sensitized with PBS for a diagnosis of this disease, is difficult to perform, and not done routinely period of two months. Two weeks after completion of sensitization mice in rural setting. For these reasons, we conducted a study to determine were infected with Litomosoides sigmodontis, a rodent filarial parasite, the sensitivity of the thick smear for malaria and a thick smear modified or mock infected with PBS. Ten weeks post-infection mice were challenge with increased blood volume compared to the Knott test for the diagnosis by intraperitoneal injection of 0.4 mg of OVA. Basal temperature was of this disease. The study was conducted in a rural community in the evaluated every 5 minutes for 30 minutes following OVA-challenge. Peruvian Amazon of approximately 500 inhabitants where we knew there OVA-sensitized and mock-infected mice dropped an average of 2.6 was a high prevalence of M. ozzardi. Nearby and accessible houses were degrees Centigrade by 30 minutes. In contrast, OVA-sensitized mice selected and after obtaining consent, samples of 5 ml of blood were taken that were infected with L. sigmodontis experienced no change in core from the arm of participants to perform a thick smear in a 6 µL volume of body temperature. As expected, PBS-sensitized mice that were infected blood, similar to that performed for the diagnosis of malaria, and 2 thick with L. sigmodontis or mock infected exhibited no change in core body smears of 60 µL, each of which were stained with giensa. A Knott test was temperature during the 30 minutes post-challenge. Thus, chronic infection also performed. The sensitivity and specificity were calculated. Samples with L. sigmodontis appears to prevent anaphylaxis in mice with pre- were taken from 91 persons over 5 years. 56/91 (61.5%) of the samples existing allergy. Identifying the mechanisms underlying this phenotype were M. ozzardi-positive by Knott test. The sensitivity of the thick smear could be important in developing novel therapeutics to treat allergic was only 58.9% (CI 45.8-70.8) while the sensitivity of a thick film of 60 µL disease. was 75.0% (CI 62.3- 84.4) and the sensitivity of two thick smear of 60 uL was 82.4% (CI 70.1-90.0). The specificities of all smears were 100%. In 1713 conclusion, the sensitivity, simplicity, and practicality of two thick smears of 60 uL would allow for sufficiently accurate diagnosis of filariasis by M. PHARMACOKINETICS OF ORALLY ADMINISTERED ozzardi in field studies and in rural health facilities. DIETHYLCARBAMAZINE AND ALBENDAZOLE IN FERRETS (MUSTELA PUTORIUS FURO) 1711 So Young Kim, Edward Mitre CHEMOKINE PROFILE OF HUMAN INTESTINAL Uniformed Services University of the Health Sciences, Bethesda, MD, HELMINTHIASIS IN AGBOR NIGERIA United States Ebube M. Odoya1, Onyeabuchi Patric Nmorsi2, Reginah E. A major obstacle to eliminating lymphatic filariasis is a lack of effective Ohenhen2, Clement Isaac2 macrofilaricidal drugs, medications that are active against the adult stage of these parasites. Drug development has been hindered by the lack of a 1Nigerian Institute for Trypanosomiasis Research, Vom, Nigeria, 2Ambrose small mammal model of lymphatic infection that develops clinical disease. Alli University, Ekpoma, Nigeria We have established a previously developed ferret model of LF. In our The study provides information on chemokine 5(CXCL-5) and chemokine model, 150 Brugia malayi L3’s are injected subcutaneously in the right 11(CXCL-11)profile in human intestinal helminthisis in Agbor Delta hind limb of ferrets. The adult worms reside in the lymphatic vessels, cause State, Nigeria.Feaces were examined using formo-ethol concentration histologic and clinical lymphangitis, and develop permissive infections with method and Karto-Katz techniques. Sera from 72 volunteers infected the production of circulating L1 stage microfilarial worms. The objective with helminthes and 8 uninfected controls were subjected to chemokine of this study is to describe the pharmacokinetics of known anthelmintic evaluation using ELISA techniques.Eggs of intestinal helminthes identified drugs in our model in order to evaluate the suitability of ferrets for filarial were those of Ascaris lumbricoides (26.6%), Trichuris (5.8%), drug testing. To achieve this, we administered a single oral dose of Hookworm (3.6%); Tapeworm and larvae of Strongyloides had 0.9% diethylcarbamazine (DEC) or albendazole (ALB) by gavage to healthy adult and 0.4% respectively. Plathyhelminthes had Schstosoma mansoni, ferrets. In our experiment, 3 ferrets were given doses of: DEC 50mg/kg, 7.6%; S. intercalatum 6.3% and Fasciola, 1.3%. CXCL-11 concentration DEC 250mg/kg, ALB 40mg/kg, or ALB 200mg/kg. The ferrets underwent showed no significant difference in expression between males and females four blood draws at baseline, 1 hour, 4 hours, and 24 hours after (3500.00±42.08)pg/ml and their control subjects (2891±11.31)pg/ml. treatment. Plasma samples were analyzed by LC-MS/MS. The peak drug In CXCL-5, infected males (3839±2190.20)pg/ml showed no significant concentration for the low dose DEC was 1010 ng/ml and occurred at the difference relative to male control (3549±3123.49)pg/ml (p>0.05). 1 hour timepoint. Peak concentration for high dose DEC was 6200 ng/ml In the contrary, CXCL-5 concentration was high in infected females and occurred at 4 hours. Peak drug concentrations for low and high dose (7015.20±2190.20) pg/ml than in female control (1107.0±7391.77)pg/ albendazole were 270 and 80 ng/ml, respectively. For both low and high ml (x2 =3796.20, p<0.001=124.84 ). In conclusion, elevated concentration dose albendazole the peak drug concentration was measured at 1 hour. In of CXCL-5 in serum of volunteers infected with intestinal helminthes both DEC and ALB groups, the drugs reached the lower limit of detection implicates this chemokine as an important biomarker in the immunology by 24 hours. Based on our limited timepoints to date, we can estimate of intestinal helminthiasis especially in subclinical cases. that the half-life for low dose DEC is 3-5 hours and the high dose is 12-15 hours. In humans, the half-life of DEC is 8 hours. The estimated half-life of ALB in ferrets is 2-3 hours for the high dose. In humans the half-life

astmh.org 525 of ALB is 10 hours. These findings give a foundation for determining established ONCHOSIM model to investigate how much the time-to- antifilarial drug pharmacokinetics in ferrets. Future studies will utilize more elimination can be reduced by various strategy adjustments for different timepoints and include other agents. settings. Our results show that doubling the frequency of treatment from yearly to 6-monthly reduces remaining program duration by about 40%. 1714 Similar reductions can be achieved by continuing annual mass treatment with a more effective drug like moxidectin, or - if the achieved coverage INVESTIGATING EARLY INFECTION STATUS OF THE FILARIAL is too low - by increasing treatment coverage to usual levels. The relative PARASITE BRUGIA MALAYI IN LABORATORY ANIMAL reductions in time-to-elimination do not depend much on the pre-control MODELS endemicity level and number of treatment rounds provided thus far. Test and treat approaches may be needed for Loa loa co-endemic areas where Erica J. Burkman, Christopher C. Evans, Molly D. Savadelis, ivermectin mass treatment is contraindicated or compliance is poor due to Michael T. Dzimianski, Andrew R. Moorhead perceived risk of side effects. We recommend that measures are taken to University of Georgia, College of Veterinary Medicine, Athens, GA, United improve treatment coverage where needed. Further, biannual treatment States should be considered when interventions are not yet fully scaled-up, or Lymphatic filariasis (LF) is a mosquito-borne disease caused by the parasitic where pre-control levels are exceptionally high. Where these adjustments nematodes Wuchereria bancrofti and Brugia malayi. These parasites are expected to still be insufficient for achieving elimination by 2025, other are a major cause of morbidity globally, with an estimated 120 million strategies could be considered, including 3-monthly mass treatment, the people infected. Brugia malayi is the preferred laboratory model for LF addition of vector control through ground larviciding, or the use of more due to the fact that non-primate hosts can become infected. For over efficacious drugs for mass treatment or selective treatment of carriers. The 30 years, the domestic cat has been utilized as the primary non-rodent cost-effectiveness, feasibility, and acceptability of different policy options experimental model for B. malayi. However, only approximately 25% should be taken into account. of felines become patent and maintain a microfilaremia of >1000 mf/ ml, which is necessary for life cycle maintenance. The primary test to 1716 determine infection status is the presence of circulating microfilariae (mf), FIELD COMPARISON OF THE BINAX FILARIASIS NOW which are detectable as early as 4 months. The cost of maintaining this animal model is relatively high, and it would be beneficial to be able to CARD TEST AND THE ALERE FILARIASIS TEST STRIP FOR detect a biomarker to indicate infection status before mf are observed. In DETECTION OF WUCHERERIA BANCROFTI CIRCULATING order to compare host susceptibility in another experimental model, we FILARIAL ANTIGENS also examined B. malayi-infected canines, which have been implicated as Cédric B. Chesnais1, Sébastien Pion1, Naomi P. Awaca2, François a reservoir in endemic areas. Ten male domestic cats and eight adult male Missamou3, Gary J. Weil4, Michel Boussinesq1 and three adult female, heartworm-negative, beagle dogs were infected 1Institut de recherche pour le Développement, Montpellier, France, by subcutaneous injection of 400 (cat) or 500-1,000 (dog) B. malayi third- 2Ministère de la Santé publique, Kinshasa, Democratic Republic of the stage larvae. We monitored complete blood counts (CBCs), lymphedema, Congo, 3Ministère de la santé publique, Brazzaville, Republic of the Congo, and microfilaremia. Filarial infections are known to induce a strong Th2 4Washington University School of Medicine, St. Louis, MO, United States response. Therefore, we examined eosinophil levels in the blood, with the hypothesis that animals with high eosinophilia would become infected, The Global Program to Eliminate Lymphatic Filariasis (GPELF) recommends but would not develop a patent infection. However, sequential CBCs use of tests for circulating filarial antigens (CFAs) to identify areas that monitored over the period of one year showed that cats maintained a require mass drug administration (MDA), to assess the impact of MDA, high eosinophilia regardless of their infection status. Canine eosinophil and for post-MDA surveillance. We compared the Binax Now Filariasis levels were all within normal established reference ranges, even though card test (ICT) with the recently released Alere Filariasis Test Strip (FTS). 50% would become patent. These results may indicate that eosinophils Comparisons were conducted in two sites that were endemic for LF: do not play a role in the initial response to infection in the dog and cat (1) a pre-MDA village in the Democratic Republic of Congo (DRC), and and provide further insight into the role of LF pathogenesis in these animal (2) a village in the Republic of Congo after two years of semiannual models. MDA with albendazole. The FTS detected 44.8% more subjects with filarial antigenemia (all subjects positive by FTS and negative by ICT 1715 were amicrofilaraemic) than the ICT (42/187 vs 29/187) in the DRC study site. The difference in the sensitivity of the tests was much higher HOW CAN ONCHOCERCIASIS ELIMINATION IN AFRICA BE in the community under MDA, where the FTS detected 93.2% more ACCELERATED? MODELING THE IMPACT OF STRATEGY infected subjects (only one subject amongst the 41 who were positive ADJUSTMENTS by FTS and negative by ICT was microfilaraemic) than the ICT (85/697 vs 44/697); one subject (amicrofilaremic) was positive by ICT and negative Wilma A. Stolk1, Grace Fobi2, Afework H. Tekle2, Honorat G. by FTS. When tests were scored with a semiquantitative scale 0-3, mean Zouré2, Luc E. Coffeng1, Annette C. Kuesel3, Samuel Wanji4, scores were about 1 unit lower with the ICT compared to the FTS. A Daniel A. Boakye2, Sake J. De Vlas1, Jan H. Remme5, Jean-Baptiste portable densitometer (Konica FD-5) was used in DRC to measure the Roungou2, Michel Boussinesq6 intensity of the T line in a sub-sample of 124 FTS (from which 16, 28, 1Erasmus MC, Rotterdam, Netherlands, 2African Programme for 24 and 56 were visually scored 0, 1, 2 and 3, respectively). We found a Onchocerciasis Control (World Health Organization/APOC), Ouagadougou, significant correlation between the semi-quantitative visual scores and the Burkina Faso, 3World Health Organization/TDR, Geneva, Switzerland, intensities of the T lines assessed on the spot by the densitometer (rho = 4University of Buea, Buea, Cameroon, 5Consultant, Ornex, France, 6Institut 0.93, P-value < 0.001). Intensities of the T lines were also reassessed at de Recherche pour le Développement, Montpellier, France different intervals to assess the stability of test results. Post hoc intensity Great progress has been made towards elimination of onchocerciasis in measurements showed a high correlation with the original values up to Africa by annual ivermectin mass treatment. Some countries are already 8 days. These results confirm that the FTS is more sensitive than the ICT, close to elimination and might stop interventions before 2020. Other especially with lower levels of infection. Densitometry can be used to countries are lagging behind, e.g. due to a late start, very high pre-control objectively read FTS as a means of quality control for visual readings. endemicity level, implementation problems or contraindications for the implementation of ivermectin mass treatment. To eliminate onchocerciasis in these countries before 2025, interventions must be intensified or alternative treatment strategies must be implemented. We used the astmh.org 526 1717 hit rate, ii) expansion of SAR around hits, iii) discovery of novel hit chemotypes, iv) scaffold hopping, and v) probing new areas of chemical EFFECT OF AN INJECTABLE LONG-ACTING FORMULATION OF space. We will also present an analysis of the physicochemical properties IVERMECTIN ON ONCHOCERCA OCHENGI of A-AWOL active compounds. Michel Boussinesq1, Peter Enyong2, Patrick N. Chounna 1719 Ndongmo2, Sébastien D. Pion1, Christophe Roberge3, Georges Gaudriault3, Samuel Wanji2 A FIELD COMPARISON BETWEEN TWO RAPID DIAGNOSTIC 1Institut de recherche pour le Développement, Montpellier, France, TESTS FOR DETECTING WUCHERERIA BANCROFTI ANTIGEN 2Research Foundation for Tropical Diseases and the Environment, Buea, IN HUMAN WHOLE BLOOD Cameroon, 3MedinCell S.A., Jacou, France Yao-Chieh Cheng1, Delma Beaso2, Nelly Sanuku2, Lindy Marken2, Additional tools and strategies are needed to reach the objective of James K. Suamani2, Samson Satofan2, Bart Lombore2, Peter M. onchocerciasis elimination set at 2025, and the most urgent requirement Siba2, James W. Kazura1, Christopher L. King1 is the availability of a safe macrofilaricidal drug. In this context, a pre- 1Case Western Reserve University, Cleveland, OH, United States, 2Papua clinical trial was conducted in Cameroon to evaluate the effects of an New Guinea Institute of Medical Research, Maprik, Papua New Guinea injectable long-acting (12 months) formulation of ivermectin on the microfilariae (mf) and adult stages of Onchocerca ochengi. Ten female Seventy-two countries are currently endemic for lymphatic filariasis. The Gudali zebu cattle (age: 3 years) naturally infected with the parasite were Global Program to Eliminate Lymphatic Filariasis uses rapid filarial antigen injected subcutaneously with either 500 mg ivermectin (group 1, N=4), testing to identify endemic areas where mass drug administration (MDA) is 1000 mg ivermectin (group 2, N=4) or the vehicle (group 3, N=2). Four needed and to monitor these areas in post-MDA surveillance. Two filarial subcutaneous nodules and a skin sample were collected from each animal antigen tests are currently available: the Alere Filariasis Test Strip and the at each time-point (before and 6 and 12 months after treatment). Before BinaxNOW Filariasis card test. Because of lower cost and greater stability, treatment, the average O. ochengi microfilaridermia was similar in the the test strip will likely replace the card test in a few years. In only one 3 groups (471.6, 222.4 and 263.8 mf per gram of skin, respectively). Six published study from Liberia, the strip test is about 20-30% more sensitive months after treatment, all treated animals were free of skin mf whereas compared to the card test. Whether the test strip compares similarly to the two controls (vehicle group) still showed high mf densities (mean: the card test in other filarial endemic areas has not been examined. We 319.3 mf/g). Twelve months post-dose, the same trend in the reduction compared the two tests using 216 samples collected from Papua New of microfiladermia was observed, except for one treated animal which Guinean communities. Capillary blood was collected by finger prick during had one microfilaria in its skin sample. This animal had the highest mf the night. The test strips were run using 75 μL of blood at the point of density before treatment (1336.0 mf/g) and received the lower dose of collection. The card tests were run the following morning using 100 μL of ivermectin (500 mg). The two animals of the control group showed an blood collected in 500 µL, EDTA-coated BD Microtainer tubes. Both test average mf density of 850.4 mf/g. None of the animals showed any local strip and card test were accessed at 10 minutes after the application of or general adverse effect after injection and during the 12-month period. their required amounts of blood. Seventy-one of 216 subjects (32.9%) The viability and fecundity of adult worms will be assessed by histology were test strip positive compared to twenty-three of 216 (10.6%) that and by embryograms and the plasma concentrations of ivermectin will be were card test positive. For the positive test strips, 18.3% had 1+ reactivity, assessed by liquid chromatography-mass spectrometry. All these results 36.6% had 2+ reactivity, and 45.1% had 3+ reactivity compared to will be presented at the meeting. Should the long-lasting effect observed 95.7%, 4.3%, and 0% respectfully for the card tests. Only individuals on the mf densities be due to a macrofilaricidal effect, the new sustained- with strong reactivity in the test strips showed reactivity in the card release formulation of ivermectin might be an additional tool to accelerate tests. Microfilarial counts show that card tests may have had decreased the elimination of human onchocerciasis in specific settings. sensitivity as three of ten microfilarial positive blood smears had negative card test readings. Although further investigation is needed for the 1718 suspected decreased sensitivity of the card tests, these initial results show that the Alere Filariasis Test Strip has much greater sensitivity compared to ANTI-WOLBACHIA (A-WOL) DRUG DISCOVERY: LIGAND the BinaxNOW Filariasis card test. These could have important implications BASED VIRTUAL SCREENING COMBINED WITH HTS for determining cut-off thresholds for when an area is considered filariasis free or for when transmission interruption has occur. Neil Berry1, Paul O’Neill1, Jaclyn Bibby1, Steve Ward2, Mark Taylor2 1University of Liverpool, Liverpool, United Kingdom, 2Liverpool School of Tropical Medicine, Liverpool, United Kingdom 1720 Filariasis inflicts serious health problems throughout tropical communities causing lymphatic filariasis (elephantiasis) and onchocerciasis (river A NOVEL APPROACH TO IMPROVE THE BIOAVAILABILITY OF blindness). These diseases infect 120 million people worldwide, ranking FLUBENDAZOLE BY USING A SPRAY DRIED FORMULATION IN filariasis as one of the leading causes of global morbidity.1 Wolbachia JIRDS, RATS AND DOGS is a bacteria that lives inside the cells of the filarial worms. As the filaria 1 2 3 are dependent on Wolbachia bacteria survival, eliminating the bacteria Sophie Lachau-Durand , Marieke Voets , Petros Psathas , Peter 2 with novel-antibiotic drugs would kill the filaria and deliver a new and Boeykens practical solution for eradicating these debilitating diseases. Through 1Janssen Infectious Diseases, Beerse, Belgium, 2Janssen Research & targeting the Wolbachia bacteria, we aim to discover novel antibiotic Development, Division of Janssen Pharmaceutica N.V, Beerse, Belgium, anti-Wolbachia (A-WOL) therapy which will deliver safe macrofilaricidal 3Janssen Research & Development, LLC, Raritan, NJ, United States activity with superior therapeutic outcomes compared with the current Flubendazole (FBZ) is an anthelmintic with low oral bioavailability in the current gold standard, doxycycline. Our present hit identification its currently marketed formulations indicated for the treatment of Soil activities involves an iterative combination of HTS and ligand based virtual Transmitted Helminths. In view of the potential development of FBZ for screening, with the results of each screen (active and inactive compounds) the treatment of filariasis (onchocerciasis and lymphatic filariasis), aiming informing computational models which are utilised to select the next at systemic exposure, a new formulation with increased bioavailability set of compounds for screening with the aim of improving both hit rate has been developed. This new formulation of amorphous solid dispersion and diversity of the hits. We will present the background, methodology of FBZ, is manufactured using a modified high temperature spray dried and successes of our approach in our iterative compound selection and technology (HSDT). It was administered at 1, 5, 10, 20 and 40 mg/kg as a screening approach. Through our approach we will show i) an increased astmh.org 527 single dose and at 5 and 20 mg/kg for 5 days in jirds, at 20 mg/kg in rats 1722 and 35 mg/kg in dogs. Flubendazole and its 2 metabolites (Hydrolyzed and Reduced FBZ) were measured in jird, rat and dog plasma and in jird tissues STRENGTHENING LOCAL HEALTH SYSTEMS TO ADDRESS (liver, lymph nodes, spleen and skin). After oral administration in jirds, LYMPHATIC FILARIASIS MORBIDITY IN A RESOURCE-LIMITED

Cmax and AUC values increased less than dose proportionally, from 1 to 5 SETTING: A MORBIDITY MANAGEMENT PROJECT IN THE mg/kg/day, and increased dose proportionally, from 5 to 40 mg/kg/day. LINDI AND MTWARA REGIONS OF TANZANIA After repeated administration, the exposure was similar at 5 mg/kg and was lower at 20 mg/kg/day compared to the equivalent single dose. The Deogratias Damas1, Maria Chikawe2, R. Shaban3, Larry Akoko4, plasma concentrations of its 2 metabolites were lower compared to FBZ. In Ally Mwanga4, Sarah Craciunoiu5 tissues, 0.5 h after administration, FBZ was largely distributed in the liver, 1IMA World Health, Dar es Salaam, United Republic of Tanzania, 2Ministry evenly in spleen and lymph nodes and less in skin compared to FBZ plasma of Health and Social Welfare, NTD Secretariat, Dar es Salaam, United concentration. Same pattern was seen in all doses and after repeated Republic of Tanzania, 3Lindi Regional Hospital, Lindi Region, United administration. The distribution of its 2 metabolites was slightly different Republic of Tanzania, 4Muhimbili National Hospital, Dar es Salaam, United with much higher liver concentrations than for FBZ. In rats and dogs, after Republic of Tanzania, 5IMA World Health, Washington, DC, United States oral administration, exposure was drastically increased compared to the In Tanzania, lymphatic filariasis (LF) affects over 6 million people leading marketed formulation. The plasma exposure of its 2 metabolites ranged to a high burden of LF associated hydrocele: a fluid-filled enlargement of between 0.55 to 0.67 compared to the FBZ exposure in rats and between the tunica vaginalis sac around the testes. The economic, physical, and 1.8 and 2.9 in dogs. In conclusion, the new FBZ formulation, using HSDT, psychosocial impact of hydrocele is devastating not only for the individual, improved drastically the bioavailability of FBZ after oral administration in but also for the family and community. In the Lindi and Mtwara regions jirds, rats and dogs. These encouraging data allowed to design efficacy alone, hydrocele backlog was estimated at 8000 men awaiting hydrocele studies in jirds with a broad range of FBZ doses and to start the toxicology surgery in 2011. However, most patients did not access surgeries due to program in rats and dogs. the following: 1) inability to pay as almost 90% of patients depend on out of pocket payment; 2) an inadequate number of skilled clinicians to 1721 perform surgeries; 3) limited medical supplies; and 4) patients’ fear of MODEL-BASED GEOSTATISTICAL MAPPING OF THE PRE- undergoing a non-emergency surgery under general anesthesia. To address CONTROL PREVALENCE OF ONCHOCERCA VOLVULUS IN these obstacles, the project focused on strengthening the local health WEST AFRICA system by pooling resources from stakeholders (donor, MOH, national referral hospital, regional/district hospitals, and communities) to allow for Simon O’Hanlon1, Hannah Slater1, Robert Cheke2, Boakye surgeries free of charge and to provide required supplies. Experienced Boatin3, Luc Coffeng4, Sébastien Pion5, Michel Boussinesq5, Wilma surgeons mentored 40 local doctors and nurses on hydrocelectomy using Stolk4, María-Gloria Basáñez1 sac partial excision technique under local anesthesia. Also, clinicians were 1Imperial College London, London, United Kingdom, 2University of provided a small incentive to conduct surgeries over weekends to avoid Greenwich at Medway, Chatham, United Kingdom, 3University of interfering with regular weekly duties. By strengthening the local health Ghana, Accra, Ghana, 4Erasmus MC, Rotterdam, Netherlands, 5Institut workforce, pooling resources, and increasing availability of supplies, over de Recherche pour le Développement and University of Montpellier 1, 2000 patients accessed high quality, safe hydrocelectomy over 24 months; Montpellier, France almost 6 times the annual average of hydrocelectomy surgeries performed regionally before the intervention. This intervention can be sustained The initial endemicity (pre-control prevalence) of onchocerciasis has been through increased local capacity and ownership of the hydrocele surgery shown to be an important determinant of the feasibility of elimination by methodology within district level staff. mass ivermectin distribution. We present the first geostatistical map of microfilarial prevalence in the former Onchocerciasis Control Programme in 1723 West Africa (OCP) before commencement of antivectorial and antiparasitic interventions. Pre-control microfilarial prevalence data from 737 villages NOVEL ANTHELMINTICS FROM FILAMENTOUS FUNGI ACTIVE across the 11 constituent countries in the OCP epidemiological database AGAINST FILARIAL WORMS AND SOIL TRANSMITTED were used as ground-truth data. These 737 data points, plus a set of HELMINTHS statistically selected environmental covariates, were used in a Bayesian model-based geostatistical (B-MBG) approach to generate a continuous Jeffrey N. Clark1, Meagan Tillotson1, Jessica Carter1, Brenda K. surface (at pixel resolution of 5 km x 5km) of microfilarial prevalence in Hansen1, Blaise Darveaux1, Sheila M. Mitchell1, Cedric J. Pearce1, West Africa prior to the commencement of the OCP. Uncertainty in model Nicolas H. Oberlies2 predictions was measured using a suite of validation statistics, performed 1Mycosynthetix, Inc, Hillsborough, NC, United States, 2University of North on bootstrap samples of held-out validation data. The mean Pearson’s Carolina Greensboro, Greensboro, NC, United States correlation between observed and estimated prevalence at validation Mycosynthetix, Inc. owns one of the world’s largest (55,000), diverse locations was 0.693; the mean prediction error (average difference and unique collections of filamentous fungi which were sourced from a between observed and estimated values) was 0.77%, and the mean variety of ecosystems worldwide. We reported previously that a number absolute prediction error (average magnitude of difference between of natural product compounds and a few fungus extracts active against observed and estimated values) was 12.2%. Within OCP boundaries, many nematodes which cause serious neglected diseases in humans 17.8 million people were deemed to have been at risk, 7.55 million to as well infections in animals. We continue to exploit the medicinal and have been infected, and mean microfilarial prevalence to have been 45% pharmaceutical potential of this large library. The targets of the current (range: 2-90%) in 1975. This is the first map of initial onchocerciasis work include Brugia malayi microfilaria (BmMF) representing filariasis, prevalence in West Africa using B-MBG. Important environmental and Haemonchus contortus L1 stage larvae (HcL1) and Strongyloides predictors of infection prevalence were identified and used in a model stercoralis L3 stage larvae (SsL3) representing soil transmitted helminth out-performing those without spatial random effects or environmental (STH) infections. We screened 4,048 crude fungal extracts and 90 pure covariates. Results may be compared with recent epidemiological mapping compounds against these three parasites in our 96-well plate based efforts to find areas of persisting transmission. These methods may be systems. Following fungus re-growth and confirmation of activity of extended to areas where data are sparse, and may be used to help inform original extract hits, 12 (BmMF), 16 (HcL1) and 9 (SsL3) fully active extract the feasibility of elimination with current and novel tools. hits were identified. Many of these hits were produced by filamentous fungi not previously shown to produce anthelmintic metabolites, including

astmh.org 528 Polyporales spp. and others. De-replication procedures to identify the behavioral trends at VCT centers. This paper reports on findings from five chemical structures of the active metabolites are ongoing, but data thus years of data from a VCT and treatment center in Yeka neighborhood in far indicates that many are novel compounds. Of the 90 pure compounds Addis Ababa. A preliminary analysis of intake forms from 13,192 clients tested, 22 were fully active against HcL1, 63 were fully active against demonstrated an overall rate of positive HIV tests of 7.6% with a decrease BmMF and 11 were fully active against SsL3. The most potent compounds from 9.8% in 2009 to 6% in 2014. Demographic variables significantly were active to 12.5 µM vs HcL1, 0.39 µM against BmMF and 6.25 µM associated with a positive HIV test included female gender, pregnancy, vs SsL3. One of the active pure compounds we identified was enniatin increasing age, presenting as an individual for testing (as opposed to with D which has been shown previously to be active against parasites, thus a partner), marriage or widowhood, unemployment, and lower income validating our natural product de-replication/screening paradigm. We groups. The majority of clients reported their primary reason for testing will continue to evaluate extracts and pure compounds against these was to plan for the future. This study adds to the currently scant peer- three targets over the next few months and will provide an update at the reviewed literature on VCT in Addis Ababa, suggests a trend of declining meeting. In conclusion, from our fungal collection we continue to find rates of HIV at the VCT center, and identifies demographic characteristics interesting, novel and potent compounds against nematode targets of associated with higher HIV rates. If the proportion of people testing at VCT importance. centers is truly declining in the area this center is located, this study may help target testing outreach efforts towards higher-risk populations. 1724 1726 EFFECTS OF FLUBENDAZOLE ON FILARIAL NEMATODES: A TRANSCRIPTOMIC APPROACH LEPROMATOUS LEPROSY AND HIV CO-INFECTION ASSOCIATED WITH PHENOMENON OF LUCIO VERSUS Maeghan O’Neill1, Cristina Ballesteros1, Lucienne Tritten1, Weam IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME Zaky2, Erica Burkman3, Jianguo Xia1, Steven A. Williams2, Timothy G. Geary1 Nora M. Cardona-Castro1, Hector A. Serrano-Coll1, Juan C. 1McGill University, Ste Anne de Bellevue, QC, Canada, 2Smith College, Beltran-Alzate1, Sonia M. Buitrago2 Northampton, MA, United States, 3University of Georgia, Athens, GA, 1Instituto Colombiano de Medicina Tropical - CES, Sabaneta, Antioquia, United States Colombia, 2Empresa Social del Estado Jose Cayetano Vásquez, Puerto Boyacá, Santander, Colombia The use of microfilaricial drugs for the control of onchocerciasis and lymphatic filariasis necessitates prolonged yearly dosing. Prospects for Diffuse lepromatous leprosy (DLL) is a severe clinical outcome of elimination or eradication of these diseases would be enhanced by lepromatous leprosy. A new species, Mycobacterium lepromatosis, availability of a macrofilaricidal drug. Flubendazole (FLBZ), a benzimidazole was identified from a group of Mexican patients with DLL, and severe anthelmintic, is an appealing candidate macrofilaricide. FLBZ has leprosy reactional state type 3 (phenomenon of Lucio). Clinically, the demonstrated profound and potent macrofilaricidal effects in a number immune hypersensitivity triggered by bacterial antigens is associated with of experimental filarial rodent models and one human trial. Unfortunately, constitutional symptoms, necrotizing vasculitis, sepsis, and in some cases FLBZ was deemed unsatisfactory for use in mass drug administration death. In addition, the advent of HIV and routine use of highly effective (MDA) campaigns due to its markedly limited oral bioavailability. However, antiretroviral therapy (HAART) in patients with Hansen’s disease, may relate a new formulation that provided sufficient bioavailability following oral to other events as immune reconstitution inflammatory syndrome (IRIS), administration could render FLBZ an effective treatment for onchocerciasis which may occur in 40% of patients with HIV and HAART. In patients and LF. Identification of drug derived effects is important in ascertaining with HIV-leprosy, IRIS has been generally associated with inflammatory a dosage range which is detrimental to the worm. Evaluation of processes such leprosy-reactions type1, in contrast current clinical case drug-induced damage to tissues is challenging. In previous studies, shows a leprosy reaction type 3 or phenomenon of Lucio: Female, 37 histochemical analysis of morphological damage following exposure to years old, on 07/13 consulted by one month of recurrent febrile episodes FLBZ indicated that damage to tissues required for reproduction and and multiple skin ulcers in lower limbs. On physical examination patient survival can be achieved at pharmacologically relevant concentrations. has signs as pinna edema, loss of the bilateral external third of eyebrows, However, histological damage is difficult to assess and there are individual chronic indurated lesions in abdomen, and pigmented scarring lesions differences in scoring of severity. The current study addressed this issue by in lower limbs. In addition, patient has skin ulcers with burning pain taking a transcriptomic approach to confirm effects observed histologically associated with local edema and serous-hematic and purulent discharge. and identify genes which were differentially expressed in FLBZ treated Patient refers weight loss of 4 kg in 6 months. She relates that seven days adult females worms (100 nM - 5 μM). Comparative analysis across ago her spouse died by AIDS. Laboratory exams confirm HIV infection and treatment levels and time provided an overview of the processes which leprosy. Multidrug therapy (MDT-MB) initiated with dapsone + rifampicin are affected by FLBZ exposure. The list of regulated genes correlates + clofazimine. HIV treatment abacavir/lamivudine plus lopinavir/ritonavir. with reproductive effects observed via histology in previous studies. This After three weeks of treatment for HIV and leprosy, patient consulted with study revealed transcriptional changes in genes involved in embryo and multiple skin blisters, with reticular pattern in upper limbs and proximal larval development, as well as cuticular synthesis. This data supports the third of the lower limbs. Ulcer lesions in multiples sizes and different indication that flubendazole acts predominantly on rapidly dividing cells, stages, dirty bottom, some of them necrotic with erythematous borders, and provides a basis for selecting markers of drug-induced damage. numbness in legs and hands. DNA extracted from skin biopsy tested by Sanger sequencing technique ruling out the infection caused by M. 1725 lepromatosis. Results reported M. leprae European genotype 3-I as the cause of DLL. DECLINING HIV RATES AT A VOLUNTARY COUNSELING AND TREATMENT CENTER IN ADDIS ABABA, ETHIOPIA 2009-2014 Demetri A. Blanas1, Chantal E. Ghanney1, Kim Nichols2 1Icahn School of Medicine at Mount Sinai, New York, NY, United States, 2African Services Committee, New York, NY, United States Voluntary counseling and testing (VCT) plays a key role in increasing access to HIV diagnosis and linkage to care. In Addis Ababa, Ethiopia’s capital, where the rate of HIV is estimated to be 5%, there has been little published in the peer-reviewed literature regarding HIV epidemiologic, and astmh.org 529 1727 ulceration and inflammation from non-sexually transmitted pathogens, most importantly Schistosoma hematobium, which is highly prevalent in PERINATAL HIV INFECTION AND HEALTH RELATED QUALITY SSA. None considered ulcers infected with streptococci, staphylococci, or OF LIFE IN SCHOOL AGED UGANDAN CHILDREN fungi, common in the region. Treating one genital infection may have little effect on HIV incidence when other infections are untreated. Flaws in the 1 2 1 Allan K. Nkwata , Sarah K. Zalwango , Florence N. Kizza , Juliet design of the post-Mwanza trials render them unsuitable to inform HIV- 1 1 1 2 N. Sekandi , Robert Kakaire , Robert Kakaire , Noah Kiwanuka , prevention policy for treatment of cofactor infections. Given the evidence 1 1 Christopher C. Whalen , Amara E. Ezeamama that STIs and other genital infections, including urogenital schistosomiasis, 1The University of Georgia, Athens, GA, United States, 2Makerere promote HIV transmission and acquisition, cofactor treatment should be University College of Health Sciences, Kampala, Uganda considered an important method for reducing HIV incidence in SSA and elsewhere. This study was undertaken to evaluate the impact of perinatal human immunodeficiency virus (HIV) infection on health-related quality of life (QOL) among 166 Ugandan children 6 -18 years old. We implemented 1729 a clinic-based retrospective cohort study among perinatally HIV infected CD31 EXPRESSION ON CD4+ CELLS: A POSSIBLE METHOD and exposed children of HIV-positive women and HIV-negative perinatally FOR QUANTITATION OF RECENT THYMUS EMIGRANT CD4 unexposed children from Kampala, Uganda. Perinatal HIV infection was diagnosed by the end of breastfeeding via DNA PCR. Current negative HIV- CELLS IN RESOURCE-LIMITED REGIONS status was confirmed by HIV rapid-diagnostic test. Child QOL was assessed Ramia Zakhour, Dat Tran, Guenet Degaffe, Cynthia Bell, with self-report version of pediatric QOL inventory. Four QOL domains Elizabeth Donnachie, Weihe Zhang, Norma Pérez, Laura (physical, emotional, social and school functioning) each with scores Benjamins, Gabriela Del Bianco, Gilhen Rodriguez, James R. ranging from 0 (least QOL) to 100 (highest QOL) were defined. Descriptive Murphy, Gloria P. Heresi analyses estimated means, standard deviations (SD), numbers and University of Texas Health Science Center, Houston, Houston, TX, United percentages by perinatal HIV status. Multivariable linear regression models States were used to estimate HIV-related differences (β) in QOL scores and 95% confidence intervals (CI). HIV-infected (n=56), exposed negative (n=56) and HIV infected individuals with combined antiretroviral therapy (cART) with unexposed children (n=54) were enrolled. Mean age was 10.8 (SD 3.48) long term viremia suppression may remain clinically stable or progressively years and 77(45.8%) were females. QOL scores in the social functioning deteriorate. For cART suppressed patients, conventional clinical status domain were similar by child HIV status (p=0.9385). However, perinatally measurements such as CD4% or HIV viral load are poor predictors of long HIV-infected children performed worse than HIV-exposed negative and term clinical outcome. Measurements of recent thymus emigrant T-cells HIV-unexposed children in the physical (p=0.0006), emotional (p=0.0253) (RTE) have been shown to have predictive value. However, established and school (p<0.0001) functioning domains. Perinatally HIV infected methods for measurement of RTE (T-cell receptor excision circles or children scored significantly lower on Global QOL compared to HIV- complex FACS) are difficult to deploy to regions where most HIV infections exposed negative (β=-5.7, 95%CI: -10.7, -0.7) and HIV-unexposed (β=- occur and where cART is becoming widely available. Literature review 6.6, 95%CI: -11.6, -1.6) after adjusting for child’s age, sex, nutritional suggests that direct measurement of CD31 expression on CD4+ cells status, relationship to caregiver, and caregiver’s age and educational level. provides a simple measure of RTE CD4+ cells. To test this hypothesis, we QOL scores were similar for HIV exposed negative and unexposed children. reviewed records of 69 perinatally infected HIV+ [median (IQR) 13.0 (8.6) In conclusion, perinatal HIV-infection is a significant predictor of low QOL. years, 54% female, 71% black] and 51 HIV- children [1.6 (5.6) years, 51% Specific interventions to mitigate HIV related disadvantage in the physical, female, 63% black] attending UTHealth, Houston clinics between January emotional and school functioning QOL domains may enhance functional 2010 and September 2012 for whom CD4+CD31+ were measured. HIV survival in children living with HIV. disease was well controlled by cART [2.2 (1.5) log10 HIV RNA copies/ml, 33% (12%) CD4+]. In HIV- and HIV+ groups CD4+CD31+% correlated 1728 negatively with age [Spearman’s ρ=-0.525, p<0.001 and ρ=-0.475 (p<0.001), respectively] and values were slightly higher in females; HIV AND TROPICAL COFACTORS: LESSONS FROM THE STI- expected patterns for RTE. And, CD4+CD31+% values fell within ranges TREATMENT TRIALS IN SUB-SAHARAN AFRICA of normal values established using conventional methodology. Our results show that direct measurement of CD4+CD31+ cells in peripheral blood 1 2 Larry Sawers , Eileen Stillwaggon gives results with numerical and biological characteristics consistent with 1American University, Washington, DC, United States, 2Gettysburg College, those expected for CD4+ RTE. This technique can be easily performed in Gettysburg, PA, United States technical and budget limited settings. The capacity to measure RTE in the Substantial evidence indicates that sexually transmitted infections (STIs) absence of sophisticated laboratory support should prove useful for both promote HIV transmission by producing genital ulcers, inflammation, and clinical management and research. viral shedding. The burden of untreated STIs is far higher in sub-Saharan Africa (SSA) than in any other region. Ten randomized controlled trials in 1730 SSA examined the effect of STI control on HIV incidence. Only the first EVALUATION OF THE OUTCOME OF CHILDREN ON trial in Mwanza produced statistically significant results. Consequently, support for STI treatment for HIV prevention faded. The 9 post-Mwanza ANTIRETROVIRAL THERAPY IN CAMEROON: A FOUR YEAR trials suffered from insufficient exposure contrast due to ethical RETROSPECTIVE COHORT STUDY considerations that required essential STI treatments for controls. The Gabriel L. Ekali1, Gilbert Tene2, Joelle Sobngwi3 small differences in interventions in treatment and control arms led to 1National AIDS Control Committee and Biotechnology Center, Yaounde small differences in STI outcomes between arms. Substantial treatments I University, Yaounde, Cameroon, 2Centers for Disease Control and for controls also explain their reduced risky sexual behavior that in turn Prevention, Yaounde, Cameroon, 3Catholic University of Central Africa, led to similar STIs outcomes between arms. The trials tested alternative Yaounde, Cameroon treatments of bacterial or viral STIs but not both and were thus subject to confounding from STIs not considered in the trial design. None of the Although Antiretroviral Therapy (ART) has significantly improved the lives trials examined genital morbidity from infections other than STIs that of those infected with Human Immunodeficiency Virus (HIV), access for could enhance HIV transmission or acquisition. Thus none of the trials children still remains low. The goal of our study was to assess 12 month addressed potential effect modification from biological interactions in outcome of HIV-infected children on ART in Cameroon. A retrospective the genital microbial community. None of the trials considered genital cohort study was carried out in 25 treatment centers in 3 of 10 regions astmh.org 530 (North West, South West and Center), harboring over 60% of pediatric 1732 patients nationwide. Children who initiated ART between January 2007 and December 2010 were included. De-identified socio-demographic, OLDER AND FORGOTTEN: MENOPAUSE SYMPTOM clinical and biological were extracted from hospital records and analyzed EXPERIENCE OF HIV POSITIVE AND NEGATIVE WOMEN IN using SPSS version 16. Survival was estimated by Kaplan Meier method. IBADAN, NIGERIA χ2 and Cox proportional hazards were used to determine predictors of mortality. P values < 0.05 were considered significant and ethical clearance Olubukola Christianah Omobowale was obtained from the Institutional Review Board of the School of Health University College Hospital, Ibadan, Nigeria Sciences, Catholic University of Central Africa. A total of 1,867 children Globally,not only are people living longer with HIV/AIDS, but there is <15 years were included in the study. 50.2% were females, mean age also a significant increase in older individuals becoming infected .As the was 62.2 ± 4.8 months. Over 50% were <60 months old, 20.7% had human immunodeficiency virus (HIV) epidemic enters its third decade, one or both parents dead and 63.7% had severe clinical disease (WHO a high percentage of women with HIV will also be entering menopause clinical stage III or IV) at ART initiation. Of the 7.1% (110/1558) who had their lives extended by improvements in antiretroviral therapies.This study tuberculosis (TB) at baseline, only 48.2% were on TB treatment. Over half aims to determine and compare the menopause symptom experience (57.8%) were on Cotrimoxazole at baseline. Complete data for outcome and perceived health status among HIV positive and negative women. A analysis was available for 328/1867. After 12 months, 71.3% (234/328) comparative, hospital based study was conducted among HIV positive and were still alive and in care, 9.8% (32/328) were dead and 17.4% (57/328) negative menopausal women. Focus group discussions were conducted were lost to follow up. Severe clinical disease (Chi2=104, p<0.001), age among menopausal women attending the ARV and General Outpatient < 12 months (Chi2=16.4, p=0.001), presence of TB (Chi2=5.9, p=0.022) clinics at the University College Hospital Ibadan, Nigeria with the use of a and hemoglobin level <8g/dL (Chi2=13, p=0.001) were all significantly focus group discussion guide. Opinions of discussants on knowledge and associated to death. Predictors of mortality were severe clinical disease experience of menopausal symptoms, perceptions about the menopause (aHR=16.6, p<0.001), TB presence (aHR=4.1, p=0.007) and age < 12 and the different coping strategies were explored. Six focus group months (aHR=5.6, p=0.009). Outcome of children on ART in Cameroon is discussions were conducted among women aged 40 and 60 years in each poor. Improving retention in care, strengthening community engagement of the two groups.Data was analysed thematically. The majority of the and building capacity of service providers are priorities if outcome needs to discussants had adequate knowledge of menopausal symptoms with most be improved. of them reporting vasomotor symptoms and musculoskeletal symptoms. In both groups, perceptions about the menopause were generally positive 1731 as most of them opined that the menopause means freedom from sexual HIV, TUBERCULOSIS AND HIV/TB CO-INFECTION IN activity and child birth. Concurrent health conditions mentioned include: MACHALA, ECUADOR hypertension, osteoporosis, depression and reduced libido. Older women with HIV infection reported higher occurrences of these conditions. Abigail G. Fessler1, Saurabh Mehta1, Efraín Beltrán-Ayala2, Coping strategies reported include belonging to a support group and Anita L. Arichábala Wilches2, Anna M. Stewart-Ibarra3, Julia L. seeking information from health care workers. In conclusion, menopause Finkelstein1 may induce many of the same metabolic changes that are being observed 1Cornell University, Ithaca, NY, United States, 2Ministry of Health, Machala, with HIV infection, and this may complicate the health and quality of life Ecuador, 3SUNY Upstate Medical University, Syracuse, NY, United States of aging women with HIV infection. There’s a need for the formulation of methods and interventions that will help these women in coping with the Tuberculosis (TB) is a leading cause of death among HIV-infected double burden of HIV infection and symptoms of menopause. individuals worldwide. The incidence of HIV in Ecuador has increased considerably in the past 15 years, and Ecuador has one of the highest 1733 burdens of HIV/TB co-infection in the Americas. We examined the burden of HIV, tuberculosis, and HIV/TB co-infection in Machala, Ecuador, a LOW NUMBER OF NERVOUS SYSTEM INFECTIONS AMONG coastal city in southern Ecuador near the Peruvian border. A total of 4012 ADMISSIONS IN SHELUI TANZANIA WITH STABLE/LOW 398,919 records were analyzed from a citywide database of clinic visits PREVALENCE OF HIV in Machala, Ecuador in 2014. Binomial regression was used to examine the associations of HIV, tuberculosis, and HIV/TB co-infection with socio- Gertruda Mikolasova1, Veronika Sladeckova2, Vladimir Krcmery3, demographic factors. There were 321 HIV cases, 1,210 tuberculosis cases, Martin Duris2, Andrea Gughova2, Kristina Badanicova2, Zuzana and 60 HIV/TB co-infection cases in 2014. The burden of HIV (RR: 3.16, Paukovova2, Lenka Michalikova4, Jaroslava Brnova4, Emilia 95% CI: 2.54-3.94, p<0.0001) and HIV/TB co-infection (RR: 4.91, 95% Mihalska2, D. Jacko2, Juraj Benca1, Monika Jankechova2, T. Oelnik2 CI: 2.91-8.30, p<0.0001) was highest in adults aged 19 to 34 years, 1St. Elizabeth University, Bratislava, Slovakia, 2St. Francis Dispensary, compared to all other age groups. In contrast, the risk of tuberculosis St. Elizabeth Tropic Programme, Shelui, United Republic of Tanzania, was highest among older adults (50-64y: RR: 3.27, 95% CI: 2.87-3.73, 3Institution of Microbiology, Medical School, Commenius University, p<0.0001; ≥65y: RR: 2.21, 95% CI: 1.87-2.60, p<0.0001), compared to Bratislava, Slovakia, 4Trnava University, Faculty of Health Sciences and other age groups. Men had a greater risk of being infected with HIV (RR: Social Work, Trnava, Slovakia 3.10, 95% CI: 2.48-3.89, p<0.0001), tuberculosis (RR: 3.53, 95% CI: In sub-Saharan Africa, several countries did substantial progress in 3.14-3.97, p<0.0001), and HIV/TB co-infection (RR: 8.70, 95% CI: 4.52- decreasing HIV prevalence, such as Coastof Kenya, Central Tanzania and 16.73, p<0.0001), compared to women. The burden of tuberculosis was North Uganda, when HIV prevalence dropped from 20-25% in 2000-2010 higher in HIV-infected men, compared to HIV-infected women (24.9% vs. to 5-10% in 2010-2015. The aim of this study has to asses prevalence/ 8.9%; p<0.05). In summary, the burden of HIV, tuberculosis, and HIV/TB occurrence of opportunistic HIV related in central and peripheral nervous co-infection was relatively high in coastal Ecuador, with nearly one in five system infections in post Highly active antiretroviral therapy (HAART), HIV-infected patients presenting with TB co-infection. Active surveillance in area of central Tanzania with stable HIV transmission. Shelui region is efforts are needed to screen for HIV/TB co-infection and drug resistance in located in central Tanzania between Arusha and Mwanza in a dry climate this setting. area in altitude of 1000 metres. HIV prevalence in 2013 was 4,3% and in 2014 was 5,6%. A decade ago, according to the local statistic of Health Dispenzary in Shinquida (50km) in 2003 was 14,7%. We separated from the 4012 admissions from January 2013 to December 2014 all neuroinfections and double checked in monthly reports their occurence in

astmh.org 531 2013 - 2014. Within12 months, 4012 patients was treated on out patients 1735 basis, in Shelui St. Francis Dispenzary, and any 79 neuro-infections (less than 1%) were repeated (majority of them 24 (61%) was herpes zoster DEVELOPMENT AND DESIGN OF AN OBSERVATIONAL infection (HZV) with local manifestation along the peripheral only 5 (22%) IMPACT EVALUATION OF IMMEDIATE ANTIRETROVIRAL were HIV positive. 15 cases have had severe malaria, with central nervous THERAPY ON HIV INCIDENCE AMONG HIV-POSITIVE MEN symptomatology (coma or serious neuropsychic event (seizures)). No one WHO HAVE SEX WITH MEN IN SHANGHAI, CHINA case of TBC neuritis, cryptoccocal meningitis or toxoplasma encephalitis were observed among HIV positive cases. In conclusion, in time of HAART Joshua Mendelsohn1, Liviana Calzavara1, Hua Cheng2, Mona and decreasing of HIV prevalence, only minimum number of central Loutfy3, Ann Burchell4, Laiyi Kang2, Canada-China Team nervous opportunistic infections appeared and therefore prophylaxis of 1University of Toronto, Toronto, ON, Canada, 2Shanghai Centers for opportunistic neuroinfections is not indicated, as it has been considered in Disease Control and Prevention, Shanghai, China, 3Women’s College pre/or early HAART era. Hospital, Toronto, ON, Canada, 4Ontario HIV Treatment Network, Toronto, ON, Canada 1734 For people living with HIV and AIDS, antiretroviral therapy (ART) provides DEVELOPMENT AND EVALUATION OF THE NON- life-saving clinical benefits. Immediate ART initiation after HIV diagnosis INSTRUMENTED NUCLEIC ACID AMPLIFICATION (NINA) has also been shown to be highly effective at reducing HIV transmission ELECTRICITY-FREE PLATFORM FOR ACUTE AND EARLY risk within heterosexual HIV-serodiscordant couples; however, equivalent evidence for men who have sex with men (MSM) has been limited to a INFANT HIV-1 DETECTION IN LOW-RESOURCE SETTINGS few observational studies in high-income settings. Although immediate Robert Burton, Dylan Guelig, David H. McAdams, Steven treatment after HIV diagnosis (i.e., treatment as prevention), regardless Diesburg, Paul LaBarre of CD4 count, is now considered best practice for key populations PATH, Seattle, WA, United States including MSM, the evidence in support of this policy in most real-world settings is inadequate. In China, where HIV incidence is increasing among In low-resource and resource compromised settings (LRS), limited access to the general population and especially among MSM, immediate ART centralized medical facilities presents a critical barrier to timely diagnosis following diagnosis is being considered by public health authorities as a and treatment, of infectious diseases. Inadequate diagnostic laboratory possible strategy to reduce transmission. We have proposed a strategic infrastructure results in inaccurate diagnoses, lost test results, delays to international collaboration between the University of Toronto and the treatment, and loss to follow-up associated with specimen collection and Shanghai Centers for Disease Control and Prevention (Shanghai CDC) transportation to centralized health centers and subsequent response. to conduct a three-phase observational impact evaluation that will The most accurate molecular diagnostic tests with low limits of detection investigate: (1) background HIV care indicators (i.e., the cascade of HIV (LODs) and high clinical sensitivity and specificity are only available care including linkage to care, ART initiation, retention in care, adherence, through laboratory-based testing and more recently through portable and viral suppression) drawing on routinely collected surveillance data nucleic acid amplification tests (NAATs). To ensure accurate diagnostics are (n=9,284); (2) HIV care outcomes among HIV-positive MSM who select available to everyone, PATH has developed a non-instrumented nucleic immediate ART (CD4>=500 cells/µL) or the current standard of care acid amplification (NINA) device that enables disposable isothermal (CD4<500 cells/µL) (n=236); and (3) transmission risk among the HIV- amplification by thermally coupling an exothermic chemical reaction to negative partners (n=360). Methods will include a retrospective study of an engineered phase change material (PCM) in an easy-to-use, low-cost the Shanghai CDC database and a prospective cohort study among HIV- heater. This patented, electricity-free heating platform approach can be positive MSM and their HIV-negative partners. The present work outlines used to provide highly sensitive isothermal molecular diagnostics away the scope of this international collaboration, elaborates upon key local and from the traditional laboratory setting. The US Centers for Disease Control global research gaps, and presents the proposed study design, anticipated and Prevention (CDC) has developed a reverse transcription loop-mediated challenges, and limitations. This study is poised to make significant isothermal amplification (RT-LAMP) assay for HIV-1 that amplifies nucleic scientific contributions to the global evidence-base for HIV prevention and acid from a prepared whole-blood specimen. As nucleic acid amplification to strengthen HIV care outcomes in China and globally. is the preferred method for acute HIV infection and early infant detection (EID), the introduction of this point-of-contact NAAT diagnostic will 1736 reduce the time to detection for HIV-1 infection by up to three weeks as compared to the currently used serology-based rapid diagnostic ASSESSMENT OF VECTOR SURVEILLANCE CAPACITY IN THE tests (RDTs). We present data on the design and manufacturing of 150 US DEPARTMENT OF DEFENSE FOR EMERGING VECTOR- miniaturized single-use disposable NINA heaters, the lyophilization and BORNE DISEASE THREATS stabilization of RT-LAMP reagents, and a qualitative HIV-1 assay. These data demonstrate our current status toward the goal of an inexpensive, easy-to- Koya C. Allen, Jean-Paul Chretien, Amy Peterson, Rohit A. use molecular RDT for acute and early infant HIV infection detection. Chitale Armed Forces Health Surveillance Center, Silver Spring, MD, United States With the emergence of vector-borne diseases, such as chikungunya virus (CHIKV), it is necessary to assess the state of preparedness for the US Department of Defense (DoD) to detect and respond to vector-borne disease (VBD) threats. Assessments are required for vector surveillance activities and prevention strategies for DoD personnel in areas at risk. A risk assessment was needed to evaluate the threat of CHIKV to the US, measure DoD capabilities for rapid detection of cases, and capacity for vector surveillance. The evaluation identified gaps in current capabilities for responding to emerging vector-borne disease threats, and strategies for capacity-building to apply to current surveillance programs. The four- tiered data collection and analysis strategy employed was 1) a review of DoD policy; 2) a workshop on strengthening DoD surveillance and detection for CHIKV and Dengue; 3) semi-structured interviews and observations; and, 4) a review of DoD vector surveillance programs.

astmh.org 532 Qualitative analyses of interview and field notes data included analytical 1738 coding and deductive reasoning to determine and translate themes for identifying gaps. The resultant themes were: 1) variation in capabilities; PEER LED DISCUSSIONS: A KEY ELEMENT OF CARE FOR 2) a demand for resources; and, 3) a need for communication and YOUNG ADULTS WITH HIV collaboration. Major gaps identified were in operational surveillance and organizational structure. Laboratory capabilities varied by region and Raghuveer Puttagunta, Elizabeth Thoyakulathu, Sherri Bogard service, which caused ‘Reactionary Surveillance’ instead of prevention. Baylor College of Medicine, Houston, TX, United States Moreover, military-civilian collaboration varied by need and program. In the USA the incidence of HIV infection in young people (13 to 24 years The workshop resulted in six recommendations for preparedness; policy old) continues to increase, accounting for 1 in 4 new infections. These development, long-term research, improved risk assessments and improved newly infected young people are at a critical juncture in the management collaboration. DoD vector surveillance capabilities for emerging threats are of their chronic disease while transitioning into adulthood. To support this high; however, resources were lacking and efforts, often unstructured and population, we sponsored an environment for Houston’s young adults disparate. Improved civilian-military collaboration can improve efficiency with HIV that supports personal capacity building through peer support and effectiveness of national VBD preparedness by using an integrated and learnt coping mechanisms. A weekly advocacy and wellness group approach to surveillance among biosurveillance partners. was established in May 2014. The typical meeting agenda encompassed dinner, social activities, peer-led discussion of personal challenges and 1737 a short didactic session. On a monthly basis, individual interviews and COMPARISON OF VIROLOGICAL OUTCOMES IN HIV ongoing needs assessment were conducted. Over the past 30 group meetings, the attendance ranged from 1 to 5 participants, with an INFECTED CHILDREN AND ADOLESCENTS ON COMBINATION age range of 18 to 27 years old. The group consists of individuals from ANTIRETROVIRAL THERAPY, WITH AND WITHOUT HISTORY multiple ethnicities and different education levels, sexual orientations, and OF TUBERCULOSIS DURING ELEVEN YEARS OF FOLLOW UP sero-concordant/discordant relationships. Of the participants, 66% have IN CAMBODIA attended over 5 meetings. During the meetings clients speak about their Andrea Shahum1, Joseph J. Eron1, Vladimir Krcmery2, William C. health, and specifically how HIV has affected their lives. Topics discussed Miller1 include medication adherence, disclosure, grief, substance abuse, and life skills such as interview techniques and budgeting. When some feel they 1University of North Carolina, Chapel Hill, NC, United States, 2St. Elizabeth have nowhere else to go, the group has provided an outlet for participants University College of Health and Social Science, Bratislava, Slovakia to share their dreams and goals while also unloading some emotional The immunological interaction between human immunodeficiency virus burden. The wellness group is an opportunity for individual young adults (HIV) and Mycobacterium tuberculosis (MTB) is bi-directional, with MTB with HIV to engage peers outside the clinical setting, empowering them to increasing HIV viral replication possibly by inducing T-cell activation. But overcome personal obstacles, achieve career goals, and be an active citizen the impact of MTB disease on long-term virological response to combined of the community. antiretroviral therapy (cART) in MTB/HIV co-infected children and adolescents is unknown. We retrospectively analyzed a longitudinal cohort 1739 of 107 Cambodian HIV positive children (vertically infected) on cART continuously enrolled into 2 pediatric programs between 2003 and 2014. NOVEL APPROACHES IN THE DIAGNOSIS OF CUTANEOUS Children resided in a unique living setting that ensured a high degree LEISHMANIASIS of medication adherence. Median follow-up was 86 months (11-134). Henk Schallig1, Emily Adams2, Gerard Schoone1, Inge Versteeg1, Median age was 7.0 years (1-15) at entry and 7.5 years (1.4-15.6) at cART Maria Gomez3, Ruby Rios3, Ricardo Marquez3, Alexandra Cossio3, initiation. Most children (n=60, 53%) had CD4 count ≤ 15% at the time of Yasuyoshi Mori4, Nancy Saravia3, Audrey Albertini5 enrollment. Based on symptoms and radiographic evidence, 47 (44%) of 1 2 107 were diagnosed with active MTB infection. TB prevalence was 29.9%; Royal Tropical Institute, Amsterdam, Netherlands, Royal Tropical Institute the TB incidence rate was 61.5/100 children-years. From 47 co-infected and Liverpool School for Tropical Medicine, Amsterdam and Liverpool, 3 children, 18 (38%) had virological failure of the first line (NNRTI-based) Netherlands, Centro Internacional de Entrenamiento e Investigaciones 4 5 regimen, compared with 11 (18%) with no history of MTB (p=0.02). Total Médicas, Cali, Colombia, Eiken Diagnostics, Tochigi, Japan, Foundation of 7 (21%) developed a recurrent episode of active MTB while on cART, 4 for Innovative New Diagnostics, Geneva, Switzerland with evidence of virological failure (p=0.41). In a Cox proportional hazards Current methods to diagnose leishmaniasis have limitations due to the model, children with co-infection were more likely to experience virological fact that they lack sufficient sensitivity and/or specificity, are difficult failure, as compared to children without MTB (HR 2.2, [95% CI 1.1, 4.2], to conduct and often require invasive sample methods. Furthermore, p=0.02). After adjusting for age and using a left-truncated analysis (180 variation in clinical accuracy of molecular diagnostic methods for days post-cART), HR was 1.85, [95% CI 0.95, 3.8]. Active MTB infection, leishmaniasis is commonly observed depending on sample source, even if treated, appears to influence long-term virological outcomes of method of DNA recovery and molecular test and few attempts have been cART among HIV positive children and adolescents. The most apparent made to compare these variables. Our research collaboration is seeking impact on virological outcomes was seen after 24 months of cART. High new methods in sampling and molecular methods that ultimately can clinical recurrence of MTB among HIV positive children in both groups, be employed near patient. Swab and aspirate samples from lesions of with and without virological failure, suggests that standard MTB treatment patients with suspected cutaneous leishmaniasis (CL) were evaluated was suboptimal at preventing recurrence or cART was unable to restore alongside standard diagnosis by microscopy or culture of parasites from optimal MTB responsiveness. lesion material. Three DNA extraction methods were compared: Qiagen on swab and aspirate specimens, Isohelix on swabs, and boil/spin of lesion aspirates. Recovery of Leishmania DNA was evaluated for each sample type by real-time PCR (18S rDNA). Swab sampling combined with Qiagen DNA extraction was the most efficient recovery method for Leishmania DNA , and the most sensitive (97%; 95% CI:91%-100%) and specific (84%; 95% CI:64%-95%) approach. Swab sampling of lesions was painless, simple to perform and coupled with standardized DNA extraction enhances the feasibility of molecular diagnosis of CL. To allow for near patient molecular testing we have developed an isothermal Pan-Leishmania LAMP assay for diagnosis of CL, which was evaluated astmh.org 533 in a prospective cohort trial of 105 clinical CL suspects in South-West and an insufficient understanding of basic kinetoplastid biology. These Colombia. Swab samples were processed for DNA extraction using the and other challenges have left drug discovery programs heavily reliant Qiagen Blood and Tissue kit. Microscopy was performed on skin scrapings upon phenotypic screening of compound collections against parasites in of ulcers, aspirate samples were cultured, LAMP and qPCR performed culture. However, in the absence of understanding the mode of action on extracted DNA. A composite gold standard comprising of microscopy (MoA) or the specific targets of phenotypically active compounds, chemical AND/OR culture positivity was used to calculate the diagnostic accuracy optimization to improve pharmacokinetics or avoid toxicity is difficult to of LAMP and qPCR. LAMP was 95% sensitive (95% CI: 87.22 % to 98.53 achieve, leading to unacceptably high attrition rates. To address these %) and 86% specific(95% CI: 67.32 % to 95.88 %). This molecular test is issues, we have established a multiplex platform for the determination of more sensitive and specific than microscopy and culture alone. MoA. Several hundred anti-kinetoplastid compounds have been identified through phenotypic screening of libraries, providing well-validated 1740 cell-active chemical matter encompassing a diverse range of chemical scaffolds. The diversity of the cell-actives suggests that multiple undefined TOOLS FOR IMPROVED MANAGEMENT OF VISCERAL MoAs are in play. Our MoA-platform incorporates a battery of chemical, LEISHMANIASIS: CLINICAL EVALUATION OF THE RK28 RAPID biological and genetic tools, and the orthogonal basis of the platform DIAGNOSTIC TEST AND ASSESSMENT OF AN ANTIGEN- provides particular strength in determination of the interactions between DETECTION TEST OF CURE actives and the parasite. This should yield high value insights into MoA, mechanisms of drug resistance and molecular targets. The utility of this 1 2 2 Randall F. Howard , Maowia Mukhtar , Asim O. Abdoun , approach will be discussed in terms of developing compounds as potential 3 4 4 Hashim Ghalib , Marleen Boelaert , Joris Menten , Rosanna therapies and as tools for the dissection of kinetoplastid biology. Peeling5, Raodoh Mohamath1, Malcolm S. Duthie1, Dinesh Mondal6, Asrat Hailu Mekuria7, Aarthy Vallur1, Steven G. Reed1 1742 1IDRI, Seattle, WA, United States, 2IEND, Khartoum, Sudan, 3Universite de Lausanne, Epilanges, Switzerland, 4ITM, Antwerp, Belgium, 5London ESTIMATING THE COSTS OF IDENTIFYING HUMAN AFRICAN School of Hygiene & Tropical Medicine, London, United Kingdom, TRYPANOSOMIASIS CASES USING A NEW DIAGNOSTIC 6International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, FRAMEWORK IN UGANDA Bangladesh, 7Addis Ababa University, Addis Ababa, Ethiopia Paul R. Bessell1, Charles Wamboga2, Enock Matovu3, Robert Prompt diagnosis and treatment of visceral leishmaniasis (VL) provide Ssekubugu4, Sylvain Biéler5, Joseph M. Ndung’u5 the best clinical outcome. The rK39 Rapid Diagnostic Test (RDT) has 1Epi Interventions Ltd., Edinburgh, United Kingdom, 2Ministry of Health, multiple advantages over invasive tissue biopsies and microscopy for the Kampala, Uganda, 3Makerere University, Kampala, Uganda, 4Rakai Health confirmation of clinical diagnosis, but low sensitivity (~80%) has been Sciences Program, Kalisizo, Uganda, 5FIND, Geneva, Switzerland reported in Africa. We conducted a clinical study to validate our previous observation that an RDT based on the rK28 antigen can improve the Human African trypanosomiasis (HAT) cases in Uganda that are caused confirmation of VL in Africa. VL was diagnosed in 206 enrolled Sudanese by the gambiense subspecies of the protozoan parasite Trypanosoma patients by Leishmania parasite detection in lymph node or bone marrow brucei have been declining in recent years. To maintain this decline, HAT aspirates, while another 79 enrolled patients were negative and considered cases must be identified early in their infection, but prior to 2013 only four as controls. rK28 RDTs were conducted with both whole blood and facilities were equipped with HAT screening tests. In 2013 a program was sera, then evaluated by blinded interpretation. The rK28 RDT had a high launched to strengthen the passive surveillance infrastructure, here we specificity when developed with whole blood (WB; 100%) and serum evaluate the cost-effectiveness of this program. The program equipped (97.7%) and exhibited good sensitivity (WB, 92.5%; serum, 94.5%). all 197 public healthcare facilities in the focus with new Rapid Diagnostic Performance was favorable when compared with a Direct Agglutination Tests (RDTs). To confirm presence of the pathogen, positives by RDT Test performed on the same sera (92.9% specificity and 83.5% sensitivity). were referred to one of 12 facilities that were equipped with enhanced Two blinded readers scored a given WB or serum sample the same on the microscopy. For those not confirmed by microscopy, a blood sample stored rK28 RDT 99.2% and 100% of the time, respectively. A reader scored one on filter paper was transported by motorcycle to one of three facilities individual’s paired WB and serum RDT results the same (“reproducibility”) equipped with loop mediated isothermal amplification of DNA (LAMP) 93.8% of the time. As a means to monitor parasite burden and response equipment. To estimate the costs of running the program and costs of to drug treatment, we have also developed a test, the Leishmania identifying each case we use an epidemiological model of the surveillance Antigen DetectTM ELISA (LADE), to directly detect L. donovani antigens system and incorporate costs in this model. Data on costs (incurred by in VL patient urine. LADE had >90% sensitivity on VL urine from Sudan the program and by those screened) and epidemiological parameters (N=64), Bangladesh (N=13), and Ethiopia (N=46) and 88% sensitivity were collected during the program. By June 2014, 5,036 RDTs had been on samples from Brazil (N=43). The test had 100% specificity (N=88). performed and had identified 7 cases from 200 positive RDTs. Facilities had To confirm LADE’s utility in monitoring treatment, urine samples were been enrolled in the program gradually from August 2013 until February collected from Ethiopian VL patients on a drug treatment plan. ELISA ODs 2014. We estimate that over one calendar year, an average 11,162 people were highest at time of diagnosis and decreased during treatment: A would be screened, identifying 16 cases per year (at contemporaneous 95% positivity by LADE at day 0 fell to 21% at day 30, and to zero by day prevalence), at a total cost of 129,700 USD which is 8,360 USD per case 180. Thus, LADE provides a non-invasive, semi-quantitative tool to detect identified or 658 USD per facility per year. We have demonstrated that parasite products during acute infection. Taken together, the rK28 RDT large scale passive screening can be implemented in a cost-effective and LADE represent tools that can fill existing gaps in VL management. manner across an entire HAT focus. This model of easy access to screening through the nearest healthcare facility is a framework that can be used in 1741 other countries. Following a shrinkage in the HAT focus, this project was streamlined by reducing the extent of coverage of RDT facilities in July DEFINING DRUG MECHANISM OF ACTION: LEVERAGING 2014. These results are being updated accordingly and will be modelled to PHENOTYPIC HITS AGAINST KINETOPLASTIDS estimate costs as prevalence declines. Sonia Moniz, Susan Wyllie, Richard Wall, David Gray, Paul Wyatt, Mark Field, David Horn, Alan Fairlamb, Ian Gilbert University of Dundee, Dundee, United Kingdom The development of new drugs for the treatment of kinetoplastid diseases remains a challenge, hampered by few validated drug targets astmh.org 534 1743 processes to determine the likely incidence of HAT by 2020. Formerly these health zones have relied on detection and treatment of cases to reduce COMPARISON OF THE PERFORMANCE OF THE SD BIOLINE disease burden, however introducing vector control may be necessary HAT RAPID TEST AND CATT IN VARIOUS DIAGNOSTIC to reach and sustain elimination of HAT. The impact of active screening ALGORITHMS FOR GAMBIENSE HUMAN AFRICAN campaigns as a control strategy is analysed by investigating the effect TRYPANOSOMIASIS of screening frequency and proportion of the population screened upon disease prevalence. Likewise the benefit of vector control as an additional Crispin Lumbala1, Paul R. Bessell2, Pascal Lutumba3, Sylvain strategy is assessed. Due to the highly heterogeneous nature of disease Baloji1, Sylvain Biéler4, Joseph Ndung’u4 and control strategies in different geographic foci it is key to use robust 1PNLTHA, Kinshasa, Democratic Republic of the Congo, 2Epi Interventions models in conjunction with high quality regional data to ensure resources Ltd., Edinburgh, United Kingdom, 3University of Kinshasa, Kinshasa, are effectively used to achieve elimination. Democratic Republic of the Congo, 4FIND, Geneva, Switzerland Early diagnosis of human African trypanosomiasis (HAT) relies on screening 1745 large numbers of at-risk individuals. Screening for HAT has been carried DISSEMINATED LEISHMANIASIS: AN EMERGING, SEVERE out with the card agglutination test for trypanosomiasis (CATT), which AND DIFFICULT TO TREAT DISEASE IN BRAZIL is limited by its requirement for cold storage, electricity and its multi-test packaging format. Recently, Standard Diagnostics (SD)/Alere developed Paulo R. Machado, Maria das Graças Brito, Luiz H. Guimarães, an individually formatted and thermostable rapid diagnostic test (RDT). Albert Schriefer, Edgar M. Carvalho Evaluation studies found that the SD BIOLINE HAT RDT prototype was less Federal University of Bahia, Salvador, Brazil sensitive and specific than CATT. The prototype was optimized and we present a study to evaluate the performance of CATT and the optimized Disseminated leishmaniasis (DL) has been characterized by multiple RDT in the Democratic Republic of the Congo. The study followed a and pleomorphic cutaneous lesions, including papules, nodules and clinical trial format. Participants were enrolled actively by four mobile ulcerations, distributed in more than two noncontiguous parts of the teams, and passively at four healthcare facilities in three provinces. Each body. Besides the great number of cutaneous lesions ranging from ten participant was tested with the RDT and CATT, participants positive by to hundreds, the severity of the disease is revealed by the presence of CATT were retested with CATT on 1:8 diluted plasma (CATT 1:8), and systemic symptoms like fever and chills during the dissemination phase, positives to CATT or RDT were tested by visual inspection for motile as well as nasal mucosal involvement in up to 44% of the cases. We have parasites in body fluids. Cases were those with visible parasites. Results documented an increased frequency in the number of DL caused by L. were analysed in four algorithms - RDT and CATT as standalone tests braziliensis in the endemic area of Corte de Pedra, Bahia, Brazil. DL was and each test followed by CATT 1:8. During five months 131 cases and a rare disease, responsible for 0.2% of all cutaneous leishmaniasis (CL) 13,527 controls were enrolled. The sensitivity of the RDT was 92.0% (95% cases identified from 1978 to 1984. DL accounted for 1.9% and 3.9% confidence intervals (CIs) = 86.1, 95.5), and was significantly higher than of cases of CL from 1992 to 1998 and from 2004-2008 respectively, CATT, which was 69.1% (95% CIs = 60.7, 76.4). The sensitivity of all the indicating that it has become an emerging form of leishmaniasis. Although algorithms decreased when followed by CATT 1:8, to 52.8% (95% CIs = the reasons for the development of DL have not been established, it 44.1, 61.3) for the RDT and 59.2% (95% CIs = 50.4, 67.4) for CATT. The involves a complex and poorly understood network involving L. braziliensis specificity of the RDT was 97.1% (95% CIs = 96.8 - 97.4), significantly polymorphism, host immune response, and the environment. We lower than CATT which was 98.0% (95% CIs = 97.8, 98.2). Specificity was have evaluated the peripheral and in situ production of cytokines and over 99.5% when a positive screening test was retested with CATT 1:8. chemokines in DL, where a decrease in the type 1 immune response in the Agreement between readers was very good. This study has demonstrated peripheral blood appears to be caused by the attraction of Leishmania- that an algorithm in which the SD BIOLINE HAT RDT is used for screening activated T cells to the multiple cutaneous lesions where few parasites may is optimal for case detection in both passive and active screening settings. be found. Interestingly, DL patients were HIV negative and without other However, its lower specificity will increase the burden on screening teams systemic immunosuppression. DL is a hard to treat disease and the majority by generating more false positives. of DL patients need more than three courses of meglumine antimoniate, or the use of 1.5 to 2 gr of amphotericin B deoxycholate for 45 to 60 days 1744 to cure. We have treated twenty DL patients with liposomal amphotericin B with a total dosage ranging from 22 to 35 mg/kg administered in 7 to ARE WE NEARLY THERE YET? MODELLING SLEEPING 14 days and found 65% of cure rate, compared with 28% of cure rate SICKNESS ELIMINATION using 30 days of meglumine antimoniate in its highest dosage of 20mg/ kg/day. Our data show that DL in Brazil is an emerging and severe form Kat S. Rock1, Steve J. Torr2, Matt J. Keeling1 of CL that represents a therapeutic challenge with an important socio- 1University of Warwick, Coventry, United Kingdom, 2Liverpool School of economic impact. Tropical Medicine, Liverpool, United Kingdom The number of cases of Gambian human African trypanosomiasis (HAT) 1746 has declined in recent years, however it has previously remained unclear DEVELOPMENT OF A HIGH SENSITIVITY LATERAL FLOW if elimination of the disease as a public health problem can and will be ASSAY FOR DETECTION OF TRYPANOSOMA CRUZI achieved by 2020. Despite being targeted by the WHO in the London INFECTION IN LOW COMPLEXITY TESTING ENVIRONMENTS 2012 declaration, no detailed quantitative assessment of the impact of existing and proposed control strategies had been carried out in relation Alejandro Castellanos1, Omar A. Saldarriaga1, Hayley Sparks1, to this aim. Here, mathematical modelling techniques are utilised to Gustavo A. Vallejo2, Nisha Garg1, Peter C. Melby1, Bruno L. Travi1 address the feasibility the WHO goals, in particular focusing on answering 1University of Texas Medical Branch, Galveston, TX, United States, this question for two high-endemic health zones in the DRC. Traditional 2Universidad del Tolima, Ibagué, Colombia assumptions such as considering Gambian HAT to be solely anthroponotic and supposing that tsetse cannot ever acquire infection after their first Chagas disease, despite global control efforts, still is a major health blood-meal are challenged by fitting the model to human incidence data challenge in several countries of Latin America, with an estimated 8-10 from the DRC. Using a framework which incorporates the multiple disease million of acute or chronically infected people. Control programs have stages as well as current screening, diagnostics and treatment practices, decreased vector-transmitted Chagas disease yet blood transfusion, this predictive model uses our current understanding of the biological organ transplant and principally congenital disease which accounts for >14,000 cases annually, are of major concern. Serology is frequently astmh.org 535 difficult to interpret and of little value for congenital infections. 1748 Parasitological methods used to detect Trypanosoma cruzi infections have suboptimal sensitivity (microscopy, culture, and xenodiagnosis) or PHARMACOKINETICS AND PHARMACODYNAMICS OF require infrastructure, equipment and trained personnel unattainable MILTEFOSINE IN CHILDREN AND ADULTS WITH CUTANEOUS in endemic areas. PCR has shown to be more sensitive than other LEISHMANIASIS CAUSED BY LEISHMANIA VIANNIA parasitological methods or serology to detect early infections. This is a critical aspect of Chagas management since early treatment is associated Maria Adelaida Gomez1, Maria del Mar Castro1, Anke Kip2, with greater therapeutic efficacy. We developed an innovative point of Alexandra Cossio1, Adriana Navas1, Eduardo Ortiz1, Thomas C. care molecular test to diagnose Trypanosoma cruzi infection that does Dorlo2, Nancy G. Saravia1 not require expensive equipment and the results are read in < 1 hour. 1CIDEIM, Cali, Colombia, 2Utrecht University, Utrecht, Netherlands We used the kinetoplast DNA minicircle as target for designing primers A population pharmacokinetics phase IV clinical trial was conducted to and probes. Trypanosoma DNA was extracted with the Qiagen® kit and comparatively analyze the pharmacokinetics and pharmacodynamics parasite detection was achieved using isothermal Recombinase Polymerase of miltefosine in children and adults. The protocol was approved and Amplification coupled with Lateral Flow (RPA-LF) assay for visual analysis monitored by the institutional ethical committee. Sixty patients presenting of the amplification product. The test sensitivity was similar to real time with cutaneous leishmaniasis, 30 children of 2 to 12 years of age, and PCR (reference test), detecting 0.1 T. cruzi per reaction. Preliminary results 30 adults of 18 to 60 years of age, participated this study. Plasma and using a small number of T. cruzi (n= 10) and T. rangeli (n= 5) strains intracellular drug concentrations were measured by mass spectrometry showed that the RPA-LF detected both parasite species. However, T. in samples obtained during treatment and six months following initiation rangeli could be distinguished from T. cruzi when the RPA products were of treatment, at which time therapeutic outcome was defined. Fifty-two run in a 1% agarose gel, giving 300 bp or 190 bp band sizes, respectively. patients cured, failure occurred in 5 children, and 3 patients were lost to This could be relevant in regions where both parasite species are being follow-up. Plasma and intracellular miltefosine concentrations were overall, transmitted. The RPA-LF test could be a practical tool to manage Chagas lower in children compared to adults. Exposure to miltefosine, estimated disease in endemic areas with resource-limited health infrastructure. by the area under the curve and Cmax, was significantly lower in children (p<0.01). Molecular evidence of Leishmania persistence was obtained 1747 in 43% and 28% of the study participants respectively, at the end of NON-INVASIVE FUNCTIONAL CARDIAC MONITORING IN treatment and 90 days after beginning of treatment. The dynamics of in A MOUSE MODEL OF CHAGASIC CARDIOMYOPATHY TO vivo parasite clearance were not predictive of the outcome of treatment. Significant and strong inverse correlations between end of treatment EVALUATE A NEW THERAPEUTIC VACCINE (EoT) parasite loads and intracellular EoT and Cmax concentrations were Meagan A. Barry, Jonathan L. Respress, Kathryn M. Jones, Qian established. Leishmania strains were isolated from 76.6% of patients. Wang, Maria Elena Bottazzi, Michael J. Heffernan, Peter J. Hotez Strains were isolated from 3 of 5 patients who failed treatment, of which Baylor College of Medicine, Houston, TX, United States two presented low in vitro susceptibility to miltefosine, potentially contributing to treatment failure. Our results revealed fundamental New estimates from the World Health Organization indicate that 1.17 pharmacokinetic differences for miltefosine in children and adults, which million people suffer from chagasic cardiomyopathy in Latin America. evidently influence the outcome of treatment. The results include the first Initially, cardiac dysfunction is characterized by conduction disorders, intracellular pharmacokinetic profiles of an antileishmanial drug in adult which can then progresses to cardiomyopathy and even sudden cardiac and pediatric patients and their relevance in the therapeutic efficacy of death. We have utilized state-of-the-art non-invasive functional cardiac drugs against intracellular parasites. These findings provide the knowledge monitoring offered by a core facility at Baylor College of Medicine as base for optimizing the therapeutic regimen in the pediatric population, an innovative approach to evaluate new therapeutics in a mouse model while reducing the risk of loss of drug susceptibility. of chagasic cardiomyopathy. Current pharmacological treatments are plagued by significant side effects and poor efficacy. There is an urgent 1749 need for new treatment modalities. A therapeutic vaccine has potential advantages that include reduced adverse effects, cost savings, and the ANTIPARASITIC POTENTIAL OF EXTRACELLULAR potential to be used as a replacement for current therapies or when paired METABOLITES FROM MARINE ACTINOMYCETES AGAINST with chemotherapy. Our laboratory has previously shown promising cell- LEISHMANIA (VIANNIA) PERUVIANA AND L. (V.) mediated protective immunity and therapeutic efficacy of a nanoparticle BRAZILIENSIS vaccine in an acute mouse model of Chagas disease. In order to test new treatment modalities in a model that mimics key aspects of human Nadia R. Galindo-Cabello1, Nyshon Rojas-Palomino2, Gloria disease, we have optimized a mouse model of chagasic cardiomyopathy. Minaya-Gómez2, Jorge León-Quispe1 When female ICR mice (Taconic Biosciences, Inc) are infected with 500 1Universidad Nacional Mayor de San Marcos, Lima, Peru, 2Instituto trypomastigotes of a H1 strain originally isolated from a patient in Yucatán, Nacional de Salud, Lima, Peru Mexico, 70% of the mice survive through the acute phase of the disease Actinomycetes are recognized as producers of pharmacological and and enter into the chronic stage. Of these mice, 22% have evidence of industrial compunds. In the last decades, the discovery of new metabolites ECG abnormalities in the early chronic stage of disease including altered isolated from the terrestrial actinomycetes has decreased and the basal heart rates, ectopic activity, and conduction blocks. As these mice researches have focused on searching unexplored habitats, like the marine progress further into chronic infection 17% show severe conduction environment. The vast majority of compounds produced by actinomycetes blocks by echocardiography. Currently, we are evaluating our therapeutic are antimicrobial and few have antiparasitic activity. This study aims at vaccine in this mouse model of chagasic cardiomyopathy. This work determining the antiparasitic potential of actinomycetal extracellular optimizes a mouse model of chagasic heart disease, and utilizes non- metabolites isolated from marine actinomycetes against Leishmania invasive functional cardiac monitoring as a novel translational technique to (Viannia) peruviana and L. (V.) braziliensis. In order to carry out this evaluate new therapeutic vaccines against Chagas disease. study, a preliminary evaluation of antiparasitic activity in vitro with 13A1, EIIIA, EIIB and EIIIC strains against promastigotes of two species of Leishmania has been made; the results of this test showed that EIIB strain had the higher inhibitory activity. The EIIB strain was identified as a member of the genus Streptomyces using rRNA method. The minimum concentration of butanolic extract of actinomycete EIIB who filed the

astmh.org 536 anti-Leishmania activity was 15 000 μg/mL for L. (Viannia) peruviana the presence of T. cruzi by detecting circulating antigens presents an and L. (V.) braziliensis. The preliminary chemical characterization of the undeniable advantage and an indication of an active infection. The present extract confirmed the presence of coumarins. In conclusion, the results study was intended to produce polyclonal antibodies that could be further demonstrated the production of metabolites from marine actinomycetes used for T. cruzi antigen detection. Three two-year old female alpacas with antiparasitic activity, which have a great potential in the biomedical (Vicugna pacos) were immunized with three different Trypanosoma and pharmacological field. cruzi antigens: TESA-antigen, somatic proteins and membrane proteins. Each animal was immunized with 300 ug of each antigen by subcutaneous 1750 route, employing Freud complete and incomplete adjuvant (50:50). Blood samples were taken before and after immunization. Sera obtained EFFECT OF THE ADDITION OF PENTOXIFYLLINE ON THE after centrifugation were stored at -20 ºC until use. Presence of specific THERAPEUTIC AND INFLAMMATORY RESPONSE IN PATIENTS antibodies was followed by Western-Blot using antigen obtained from WITH CUTANEOUS LEISHMANIASIS: A RANDOMIZED T. cruzi Y strain. The antibodies showed a specific reaction against their PLACEBO CONTROLLED TRIAL respective antigen. The highest antibody titer was observed after the three immunization. When human urine spiked with parasite TESA antigen Alexandra Cossio-Duque, Maria del Mar Castro, Adriana Navas, was tested against these whole alpaca sera, antibodies from alpacas Liliana Valderrama, Lyda Cuervo-Pardo, Ricardo Marquez, Sandra immunized with membrane proteins performed the best. Additionally, J. Jojoa, Ruth M. Castillo, Maria A. Gómez, Nancy Gore Saravia this polyclonal antibody did not react with other human urine proteins. Centro Internacional de Entrenamiento e Investigaciones Médicas, Cali, Antibodies induced in alpaca would represent an alternative diagnostic Colombia tool for the detection of parasite antigens in urine. The inflammatory response is an important factor in the therapeutic response of cutaneous leishmaniasis (CL). Co-adjuvant use of 1752 immunomodulators may improve the efficacy or outcome of treatment. USE OF IGY EGG YOLK ANTIBODIES FOR THE DETECTION OF This study sought to determine whether the addition of pentoxifylline TRYPANOSOMA CRUZI ANTIGENS (PTX) to meglumine antimonite (MA) treatment improves therapeutic response in CL patients and to determine the effect of PTX on the Alessandra Romero-Ramirez1, Edith Malaga1, Edgar A. inflammatory response. A randomized, double-blind, “Add on” placebo- Florentini1, Ines Cabello2, Rosina Camargo2, Fernando Recuenco2, controlled trial was conducted in 2 centers in Colombia. The protocol was Maritza Calderon1, Manuela Verastegui1, Caryn Bern3, Robert H. approved and monitored by the institutional ethical committee. Seventy- Gilman4, Holger Mayta1 five parasitologically diagnosed patients were randomly allocated by 1Universidad Peruana Cayetano Heredia, Lima, Peru, 2Universidad Nacional computer. Inclusion criteria: age 18-65 years, lesion >1 month evolution, Mayor de San Marcos, Lima, Peru, 3University of California, San Francisco, multiple lesions or single lesion ≥ 3 cm. Intervention: intramuscular MA Lima, Peru, 4Johns Hopkins University School of Medicine, Lima, Peru (20 mg/ kg /day x 20 days) plus oral PTX 400 mg thrice daily (n=36). Control: MA plus placebo (n=37). Expression of inflammatory genes Chagas disease, an infection caused by Trypanosoma cruzi, remains cxcl10,cxcl5,ccl2, IL1b, ptgs2 and csf1 was evaluated by qRT-PCR in one of the most important health problem especially in Latin America. peripheral blood mononuclear cells from CL patients, before and after Diagnosis of the disease is based on antibody detection; for a correct antimonial treatment, in combination with either PTX (n=12) or placebo diagnosis the World Health Organization recommends that at least two of (n=12). Therapeutic response and adverse events were assessed at the the so-called conventional test (indirect hemagglutination (IHA), indirect end of treatment 5, 7, 13 and 26 weeks. Seventy participants (93%) were immunofluorescence (IIF) and the ELISA immunoenzymatic test) should analyzed by intention to treat (ITT) and forty-eight (64%) per protocol be performed. However antibody detection is not always an indicative of (PP). Treatment failure was 12/34 (35.3%) for PTX vs. 9/36 25% placebo; current or active infection. Detection of T. cruzi circulating antigens in (OR: 1.63; 95% CI: 0.58 - 4.5). PP failure rate was 6/20 (30%) for PTX and body fluids might be an important diagnostic tool. Circulating antigens 5/28 (17.8%) for placebo (OR: 1.97; 95% CI: 0.50 - 7.68). No differences are present only if parasites are present. The objective of the present between overall frequency and severity of adverse events were found study was to develop IgY (egg yolk antibodies) against different parasite (PTX=142 vs. placebo=140). Expression of inflammatory mediators at the fractions, the developed antibodies will be further tested as a tool for end of treatment was not altered by addition of PTX to MA. However, antigen detection in infected individuals. Eight New Hampshire strain therapeutic failure was associated with significant overexpression of IL1β hens were subcutaneously immunized every 14 days for two months and Ptgs2 (p<0.05) irrespective of the study group. Addition of PTX to with three different T. cruzi antigens: 1F8 (commercial flagellar antigen), standard treatment of CL did not modify the therapeutic response in this TESA, and membrane proteins. Eggs were collected before and after each population with early mild to moderate CL, or alter the gene expression of immunization. The IgY was extracted using chloroform or polyethylene the evaluated inflammatory mediators. glycol techniques. IgY yield was compared by protein concentration using Bradford. Presence of anti-T. cruzi IgY was corroborated by indirect 1751 immunofluorescence using cultured T. cruzi Y strain epimastigotes. The chloroform showed to be the more efficient than the polyethylene glycol ANTIBODY DEVELOPMENT FOR TRYPANOSOMA CRUZI for purification of IgY from egg yolk. IgY antibodies show to be specific ANTIGEN DETECTION for their respective antigens as showed by immunofluorescence. Further studies will be oriented to determine if those antigens are useful for 1 1 1 1 Edith Malaga , Noelia Angulo , Sofia Astupina , Remo Gonza , antigen detection in body fluids of infected individuals. Edgar A. Florentini1, Ines Cabello2, Alessandra Romero-Ramirez1, Rosina Camargo2, Manuela Verastegui1, Maritza Calderon1, Caryn Bern3, Robert H. Gilman4, Holger Mayta1 1Universidad Peruana Cayetano Heredia, Lima, Peru, 2Universidad Nacional Mayor de San Marcos, Lima, Peru, 3University of California, San Francisco, Lima, Peru, 4Johns Hopkins University School of Medicine, Lima, Peru Chagas disease is an infection caused by the protozoan parasite Trypanosoma cruzi. According to World Health Organization, between 8 to 10 million people in the world are infected. Currently, routine diagnosis is based on antibody detection but antibodies remain detectable even after a successful therapy and eradication of parasites. Confirmation of astmh.org 537 1753 between the infected and uninfected bedbugs. Fecundity and fertility indexes were moderately higher in the infected cohort. The prevalence of NADPH-OXIDASE AN ESSENTIAL ENZYME FOR THE the infection at time of death was 95% (N=274). These results suggest EXPANSION AND ACTIVATION OF CD8+ T CELLS DURING that T. cruzi infection does not affect negatively either the survival rate, TRYPANOSOMA CRUZI INFECTION or the fecundity and fertility indexes in bedbugs. The implications of these findings on the vectorial capacity of C. lectularius and its possible role as Monisha Dhiman1, Nisha Jain Garg2 a vector of Chagas disease are discussed. 1Central University of Punjab, Bathinda, Bathinda, Punjab, India, 2University of Texas Medical Branch, Galveston, TX, United States 1755 We investigated the significance of NADPH oxidase in the development A BAYESIAN MODEL FOR IDENTIFYING AND PREDICTING of protective immunity to an intracellular pathogen Trypanosoma cruzi THE DYNAMICS OF URBAN INSECT INFESTATIONS that causes Chagas disease. C57BL/6 p47phox-/- mice, as compared to wild-type (wt) mice succumbed within 30 days post-infection (pi) to Erica MW Billig1, Jason A. Roy1, Michelle E. Ross1, Drew J. low doses of T. cruzi and exhibited inability to control tissue parasites. Dolgert2, Michael Z. Levy1 P47phox-/- bone-marrow and splenic monocytes were not compromised 1University of Pennsylvania, Philadelphia, PA, United States, 2Cornell in maturation, phagocytosis and parasite uptake capacity. The deficiency University, Ithaca, NY, United States of NOX2-mediated oxidative burst was compensated by higher levels of iNOS/NO. activity and inflammatory cytokine (TNF-α, IFN-γ, IL-1β) release Analyses of epidemics are complicated by several factors, including the by p47phox-/- macrophages as compared to wt controls infected by T. fact that the true dispersal mechanism of disease agents and the precise cruzi. The splenic activation of Th1 CD4+T cells and tissue infiltration infection times of patients are often unobserved. Instead, we often of immune cells in T.cruzi-infected p47phox-/- mice was comparable or observe the infection state of each unit at discrete time intervals. For higher than that noted in infected/wt mice. However, generation and example, consider a recent study of the Chagas disease vector Triatoma activation of type 1 CD8+T cells was severely compromised in p47phox-/- infestans in Arequipa, Peru. The data are limited to observed insect mice. In comparison, wt mice exhibited a robust T. cruzi-specific CD8+T presence at each household at three time points over several years. In cell response with type 1 (IFN-γ+TNF-α>IL-4+IL-10), cytolytic effector addition, we observe the number of insects at each household, although (CD8+CD107a+IFN-γ+) phenotype. Macrophage activation of NOX2 with measurement error. To address these challenges, we propose a novel and oxidative burst is suggested to kill T. cruzi that causes Chagas susceptible-infected-detected-removed model that incorporates the counts disease. However, the role of NOX2 in generation of protective immunity of vectors at each house and complex spatial dispersal dynamics observed and whether these mechanisms are deregulated in the event of NOX2 in Arequipa. The fully Bayesian method is used to augment the data, deficiency are not known, and examined in this study. NOX2/ROS activity estimate the dispersal parameters, and determine posterior infestation in macrophages signals the development of antigen-specific CD8+T cell risk probabilities of households for future treatment. We investigate the response. In the event of NOX2 deficiency, a severely compromised CD8+T properties of the model with simulation studies and analyze the Chagas cell response was generated leading to increased parasite burden, tissue disease vector data to create an informed control strategy. pathogenesis and mortality. 1756 1754 BED BUGS AS VECTORS OF TRYPANOSOMA CRUZI SURVIVORSHIP OF TRYPANOSOMA CRUZI-INFECTED BED Michael Z. Levy1, Renzo Salazar2, Ricardo Castillo-Neyra2, Aaron BUGS (CIMEX LECTULARIUS) Tustin3, Katty Borrini-Mayori2, Sherrie Xie1, Cesar Naquira2 Renzo S. Salazar Sanchez1, Ricardo Castillo Neyra2, Casey 1University of Pennsylvania, School of Medicine, Philadelphia, PA, United Bartow McKenney2, Katty Borrini Mayorí1, Carlos Condori Pino1, States, 2Universidad Peruana Cayetano Heredia, Sede Arequipa, Arequipa, César Náquira1, Michael Z. Levy2 Peru, 3Johns Hopkins, Baltimore, MD, United States 1Universidad Peruana Cayetano Heredia, Arequipa, Peru, 2Center for Through a series of experiments we show that bed bugs (Cimex Clinical Epidemiology and Biostatistics, University of Pennsylvania School of lectularius) can acquire Trypanosoma cruzi by feeding on infected mice, Medicine, Philadelphia, PA, United States transmit it back to susceptible animals during cohabitation (in which the The resurgence of the common bedbug (Cimex lectularius) has created mice ate them) and by the usual route (through their feces). Whether a difficult public health problem around the world. Recently, we showed bed bugs are, or will become, epidemiologically important vectors of the the vectorial competence of C. lectularius into laboratory conditions, parasite remains unclear. To address the issue we develop a modified Ross- proving that the common bedbug can transmit Trypanosoma cruzi to MacDonald model of vector-borne T. cruzi transmission and apply it to mice and can get infected when fed on T. cruzi-carrying mice. T. cruzi is both a traditional vector, Triatoma infestans, and Cimex lectularius. In the causative agent of Chagas disease, a vector-borne disease transmitted relation to some key parameters of the model, such as the ratio of vectors by triatomine bugs and an increasing problem in many countries of to hosts and the biting rate of the vector, bed bugs are more worrying the Americas. Specialized literature has reported that the infection than T. infestans. We consider the death rate of the vector, and run with T. cruzi in triatomines, their natural vector, affects negatively their experiments to assess whether T. cruzi might increase mortality among development, survival and reproductive index. Being the vector survival bed bugs or triatomines. It does not. We consider the range of hosts an important component of vectorial capacity, we studied the effect of and feeding preferences of each insect. We show that triatomines can the T. cruzi infection on C. lectularius survival. A cohort study of 280 only support sustained T. cruzi transmission when exposed to a rather T. cruzi-infected bedbugs and 240 uninfected bedbugs was carried complex host community; we discuss whether such conditions exist in out in Arequipa – Peru, in the Zoonotic Disease Research Group lab. houses, hotels, and other environments affected by bed bugs in the US To get infected first instar bedbugs were fed on 4 female BALB/c mice and abroad. (Mus musculus) previously infected by intraperitoneal inoculation with 2 x 103 trypomasgotes (T. cruzi Arequipa strain TC35) in 100 ul. We fed them weekly for a month on mice and after that they were fed on uninfected guinea pigs until death. The same conditions were applied to the uninfected bedbug’s cohorts. We evaluated weekly vector survival, nymphal development, fecundity and fertility and T. cruzi presence in the infected cohorts. The statistical results showed no difference in survivorship astmh.org 538 1757 from the queue after successful identification and subsequent treatment with insecticides. Using stochastic queueing models, we project the rate A CASE: CONTROL STUDY OF POSSIBLE RISK FACTORS FOR at which household infestations can be successfully eliminated, allowing CUTANEOUS LEISHMANIASIS IN SOUTHERN SRI LANKA us to evaluate the cost of eliminating infestation in a neighborhood as a function of participation rates in blanket residual insecticide campaigns 1 1 Udeshika L. Kariyawasam , Yamuna D. Siriwardana , Chathura and the efficacy of subsequent community-based surveillance programs. S. Edirisuriya2, Upul Senerath1, Nadira D. Karunaweera1 1Faculty of Medicine, University of Colombo, Colombo, Sri Lanka, 1759 2Epidemiology Unit, Ministry of Health, Colombo, Sri Lanka TRYPANOSOMA CRUZI IN PATIENTS WITH ESOPHAGEAL Leishmaniasis is a tropical disease that has not been given due priority, in ACHALASIA IN A NON-ENDEMIC AREA OF COLOMBIA spite of its importance as a parasitic disease associated with high morbidity and mortality. Cutaneous leishmaniasis (CL) in Sri Lanka is caused by L. Santiago Panesso-Gomez1, Iván E. Rodríguez-Mantilla1, donovani. Transmission patterns were different in Southern and Northern Paola Lasso2, Paula Pavia2, Alejandro Orozco3, Adriana Cuellar4, Sri Lanka according to previous studies indicating the need for large scale Concepción J. Puerta2, Belén E. Mendoza de Molano5, John M. studies. Therefore, current study examined the prevalence and risk factors González1 of CL in Matara District, Southern Sri Lanka. Total of 2260 individuals from 1Grupo de Ciencias Básicas Médicas, School of Medicine, Universidad de 4 District Secretariat divisions (DSDs) were screened by house to house los Andes, Bogota, Colombia, 2Laboratorio de Parasitología Molecular, survey using an interviewer administered questionnaire. Patients with skin School of Sciences, Pontificia Universidad Javeriana, Bogota, Colombia, lesions were investigated by light microscopy/culture/PCR. Prevalence was 3Investigación y Desarrollo Sistemas Clínicos, Bogota, Colombia, 4Grupo calculated and a case control study was conducted to identify risk factors. de Inmunobiología y Biología Celular, School of Sciences, Pontificia The study population had an age ranged between 1-90yrs (median=43 Universidad Javeriana, Bogota, Colombia, 5Gastroenterology Section, ±17.31), low monthly income (<20, 000 LKR, 52.8%) and male to Hospital Universitario Fundación Santa Fe de Bogotá, Bogota, Colombia female ratio of 1:2(males 31.7%, females 68.3%).Out of 80 clinically suggestive cases only 38 was laboratory confirmed. District prevalence Esophageal achalasia is a motility disorder of the esophagus, which can was 0.03%. Over 50% of the patients were identified from the DS of be secundary to chronic Trypanosoma cruzi infection. Few studies have Dickwella (55.3%), while lowest number of cases was from Devinuwara been conducted in Latin America regarding the prevalence of esophageal (2.6%). Case clustering nature was observed as significant in GIS map achalasia as a manifestation of Chagas Disease and none in Colombia. (Nearest neighbor ratio 0.46, p=0.000). The risk factors identified were The main purpose of this ongoing project is to determine the prevalence un-plastered brick walls (P<0.05, OR 41.4), abysmal usage of mosquito of anti-T.cruzi antibodies in patients diagnosed with esophageal repellents (p<0.05, OR 10.3), low income (p<0.05, OR 33.4), excessive achalasia and to detect the parasite by polymerase chain reaction (PCR) in time (>4 hrs/day) spent outdoors (p<0.05, OR 22.5) and unawareness individuals found to be seropositive who attended to the Gastroenterology of leishmaniasis (p<0.05, OR 10.76). Improper clothing while outdoors, section in a referral hospital in Bogotá, Colombia; a non-endemic area. common water source as the mode of water supply and having animal This cross-sectional study was carried out in adult patients (18-65 years) shelters in their gardens within 200m were not associated with the risk diagnosed with impaired esophageal motility. Blood samples were taken to of acquiring the disease. Both peri-domestic and outdoor factors seem assess antibodies against T. cruzi by IFAT and presence of T. cruzi’s DNA to be associated with leishmaniasis transmission in the study area. Spatial by conventional PCR and qPCR. In total 30 patients have been evaluated clustering of cases was observed. This may be due to the behavior of with an average age of 47 (± 15.8 SD) years, including 14 men and 16 host coinciding with that of the vector, sand fly. Awareness regarding women; 75% of volunteers live in Bogotá, yet only half of them were the disease and appropriate control measures are urgently required to born there. Most denied to having lived in rural housing and currently minimize further spread. all reside in urban areas. Near 90% referred no family history of Chagas disease and 70% had never undergone blood transfusion. Four out of the 1758 30 patients were positive for anti-T. cruzi by IFAT (current seroprevalence is 13.3%), and, only one of these patients had parasite DNA detected by QUEUEING ANALYSIS OF A CHAGAS DISEASE CONTROL conventional PCR and detection by qPCR was positive, but below DNA CAMPAIGN equivalent to 1x10³ parasites. The parasite genotype was identified as TcI. This is the first study that associates esophageal achalasia and T. cruzi in Maria T. Rieders, Michael Levy, Karthik Sethuraman, Chagas Colombia. ELISA test will be carried out to confirm the antibodies results. Disease Working Group in Arequipa, Peru University of Pennsylvania, Philadelphia, PA, United States 1760 This work investigates the economic impact of public health intervention MAPPING OF HUMAN AFRICAN TRYPANOSOMIASIS RISK IN in an ongoing Chagas disease control campaign in Arequipa, Peru. A DRC AND MODELING OF POTENTIAL PATHS TO ELIMINATION critical component of preventing and studying the spread of disease are door-to-door campaigns of public health inspectors, followed by Alexander M. Upfill-Brown1, Caitlin A. Bever1, Matthew Steele2, insecticide application by exterminators to eradicate the vector infestation Noelle Huskins2, Jacquie Makabuza3, Pascal Lutumba4, Philip A. of households. The success of the campaign depends on adequate Eckhoff1, Crispin Lumbala3 household participation as well as on the success of identifying infested 1Institute for Disease Modeling, Bellevue, WA, United States, 2Bill & households. We apply queueing theory to evaluate the rate of treatment Melinda Gates Foundation, Seattle, WA, United States, 3Programme and associated costs over time. In our queueing model, a household that National de Lutte Contre la THA, Kinshasa, Democratic Republic of the is infested enters the queue of houses that will require treatment. Unlike Congo, 4University of Kinshasa, Kinshasa, Democratic Republic of the conventional queueing systems, however, the customers (houses) joining Congo the queue are invisible and need to be identified before being scheduled for treatment. An infested house becomes visible either via notification by While surveillance suggests Human African Trypanosomiasis (HAT) its inhabitants or through a successful search by a team of public health incidence has decreased markedly over the past 15 years_from 26,318 inspectors. A multi-armed bandit procedure is being applied to optimize recorded cases in 1998 to 5,983 cases in 2012_transmission remains the search for invisible (infested) houses, based on available GIS data and widespread in the Democratic Republic of the Congo (DRC), which findings in previous campaigns. We assume that houses in the queue accounted for 84% of HAT cases globally in 2012. New tools - rapid will continue to spread the disease to noninfected houses at a rate that diagnostic tests (RDT), low-cost vector control, and the oral drug is a function of the time spent in queue. Households are being removed fexinidazole - will hopefully make control of HAT far more effective astmh.org 539 and enable diagnostic and treatment coverage of a much greater 1762 population. In preparation for renewed discussions on elimination, the geographic distribution of HAT risk and associated uncertainties must MOLECULAR CHARACTERIZATION OF AVIAN INFLUENZA A/ be well understood. We develop a spatial statistical model using both H9N2 ISOLATED FROM HUMAN RESPIRATORY SPECIMEN IN active and passive surveillance data for Trypanosoma brucei gambiense EGYPT collected between 2000 and 2014 in DRC to assess the distribution of risk and identify important risk factors. Key uncertainties include how to Mayar M. Said1, Maha Talaat1, Ehab Ayoub1, Mustafa Abdel appropriately address areas with limited records of functional surveillance Aziz1, Manar Mahmoud1, Manal labib2, Samya Omaer2, Amel and the impact of human migration patterns. By fitting the model only Naguib2, Samir El Rifay2, Emad Mohareb1, Amr Kandeel2 to areas reporting cases, we estimate that a substantial number of HAT 1U.S. Naval Medical Research Unit - 3, Cairo, Egypt, 2Ministry of Health infections may go undetected in remote areas. Preliminary mechanistic and Population, Cairo, Egypt modeling suggests elimination will only be feasible in areas with high Since the mid-1990s, two lineages of Low Pathogenic A/H9N2 influenza quality active and passive surveillance. The number of visits required A viruses have circulated in domestic poultry in China and South East by the active surveillance mobile teams to clear the parasite from the Asia. A/H9N2 (G1-like) lineage has circulated in Egypt since 2011. To local population depends on the sensitivity of the RDT used and, as date, few human cases had been reported in China and SE Asia and no interventions reduce prevalence even further, overtreatment considerations human infections have been reported in the Middle East. In this report will have to be weighed. Preventing patient drop-out (patients who fail to we characterize the A/H9N2 virus isolated from a nasopharyngeal and receive their confirmatory diagnosis or to complete treatment) will also be oropharyngeal swabs combined in 2ml viral transport medium VTM, from highly important; in that regard, newly implemented mobile technologies human case with severe acute respiratory infection (SARI), who has been for data collection should enable better tracking of HAT patients through enrolled in sentinel SARI surveillance in Egypt. The total nucleic acid (TNA) encounters with the healthcare system. extracted from VTM tested positive for the matrix (M) gene of influenza A by reverse transcriptase RT-PCR, but negative for the commonly circulating 1761 subtypes in Egypt; seasonal H3 and H1, PdmH1 and avian H5 as well as to EVALUATION OF INSECTICIDE-BASED CONTROL FOR other viral etiologies. TNA was further tested for H7 and H9 by RT-PCR and CHAGAS DISEASE VECTORS IN SOUTHERN ECUADOR was found positive for H9. MDCK cell monolayers in culture tubes were inoculated with 100µl of the combined swab-VTM and monitored for CPE HIGHLIGHTS THE NEED TO FIND NEW STRATEGIES FOR every 24hrs. On day two CPE was observed indicating viral replication. LONG-TERM RISK REDUCTION OF TRYPANOSOMA CRUZI TNA was used for the sequencing of the haemagglutinin (HA) while viral TRANSMISSION RNA extracted from the cell culture lysate was used to sequence the Mario J. Grijalva1, Anita G. Villacis2, Sofia1 Ocaña-Mayorga2, neuramidase (NA) gene by Sanger technique. HA and NA gene sequencing Cesar A. Yumiseva2, Ana L. Moncayo2, Claudia Nieto-Sanchez3, demonstrated a virus with 97% and 98% similarity, respectively, to those Darwin Guerrero2, Esteban G. Baus2 of the H9N2 G1-like lineage, the predominant lineage circulating in the Middle East. Phylogenetic analysis showed close homology to previous 1Tropical Disease Institute, Heritage College of Osteopathic Medicine, A/H9N2 viruses from Egyptian poultry and those from neighboring Ohio University, Athens, OH, United States, 2Center for Infectious Disease Middle-East countries. Co-circulation of A/H5N1 and A/H9N2 has been Research, School of Biological Sciences, Pontifical Catholic University of documented in Egyptian poultry since 2011. Given the risk to human Ecuador, Quito, Ecuador, 3Ohio University, Athens, OH, United States population from zoonotic influenza, in addition to the specter of antigenic Prevention of Chagas disease depends mainly on control of the triatomine shift in co-infected hosts, intensified control measures within the poultry insects that transmit infection. Developing an optimal spraying strategy production sector and increased bird and human surveillance is warranted. requires a detailed knowledge of the vector dynamics as well as the effect of the application of this strategy in the field. A prospective study 1763 to assess the long-term impact of spraying was conducted between 2008 and 2012 in three rural communities in Loja province, southern AN OPERATIONAL EVALUATION OF A SOCIOECONOMIC Ecuador. Entomological searches to detect the infestation of houses with INTERVENTION TO PREVENT TB IN IMPOVERISHED triatomines and its natural infection with trypanosomes was conducted PERUVIAN COMMUNITIES after the application of two different intervention strategies: 1) selective 1 2 3 4 insecticide spraying (2008 and 2010) and 2) community-wide insecticide Tom Wingfield , Marco Tovar , Delia Boccia , Rosario Montoya , 5 6 3 7 spraying (2011). Out of 53 houses searched at baseline (2008), 22 (41.5%) Eric Ramos , Doug Huff , James Lewis , Carlton A. Evans were infested with the vector species Rhodnius ecuadoriensis and 1Universidad Peruana Cayetano Heredia, Lima, Peru and Imperial College, Panstrongylus chinai. The overall entomological data showed a density Lima, Peru, 2Universidad Peruana Cayetano Heredia and Innovación of 12.4; crowding of 29.8 and colonization index 68.2%. Houses infested Por la Salud Y Desarrollo, Lima, Peru, 3London School of Hygiene & at baseline were less likely to be infested after the first round of selective Tropical Medicine, London, United Kingdom, 4Innovación Por la Salud Y insecticide spraying (POR 0.38, CI 95% 0.17-0.89). However, an increased el Desarrollo, Lima, Peru, 5Universidad Peruana Cayetano Heredia, Lima, risk was observed after two rounds of selective spraying (2011) (POR 1.40, Peru, 6School of Public Health, Tulane University, New Orleans, LA, United 95% CI 0.61-3.21). Although the association as not statistically significant, States, 7Universidad Peruana Cayetano Heredia, Lima, Peru and Imperial our data showed that one round of community-wide intervention strategy College, London, United Kingdom had a protective effect on the probability of infestation (POR 0.55, CI The World Health Organisation’s post-2015 global TB strategy identifies 95% 0.25-1.25). Persistent infestations were detected in >20% of houses social protection interventions (including cash transfers) as key pillars after both interventions. Lower infection rates with Trypanosoma cruzi of global TB control but minimal rigorous evidence exists with which to were found at the baseline visit in domicile and peridomicile, 27.3% and guide their implementation. We designed, implemented, and refined 6.3%, respectively. However, these rates dramatically increased during a novel TB-specific social protection intervention that included cash following visits, especially in the peridomicile that reached > 80% in 2011 transfers, which aimed to support TB prevention and cure in resource- and 2012. Full coverage spraying seems to be more effective than selective constrained shantytowns in Lima, Peru. The design of the study was an spraying; however both methods failed to confer long-term protection. household-randomized controlled: newly-diagnosed TB patients from 32 These results remark the need to implement long-term control strategies, impoverished shantytowns of north Lima were eligible to be randomized such as housing improvement and frequent monitoring of domestic and (1:1) to receive the social protection intervention consisting of economic peridomestic environments. support and social activities. Economic support was provided to patient

astmh.org 540 households completing conditional cash transfers: screening for TB in 1765 household contacts and MDR-TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social activities (household COMPARISON OF THE AKONNI BIOSYSTEMS MDR-TB visits and community meetings). Throughout treatment, CRESIPT research MICROARRAY TEST TO THE HAIN LIFESCIENCE GENOTYPE nurses applied a questionnaire concerning health, socioeconomic position, MTBDRPLUS FOR RESISTANCE TO RIFAMPIN AND ISONIAZID and direct (out-of-pocket), indirect (lost income), and total TB-related IN KAZAKH M. TUBERCULOSIS ISOLATES costs. 282 patients were recruited to the study. Lost income contributed half of households’ total costs. The burden of total costs was greater in Yuriy Skiba1, Elina Maltseva1, Lyazzat Musralina1, Gulnara poorer than less poor households (3.5 versus 2 months of that household’s Ismagulova1, Ketan Patel2, Cynthia Zimmerman3, Jolanta S. income respectively, p=0.0007). The 135 patients randomized to the Jacobs4, Paul D. Stamper5 supported arm of the intervention achieved 890 conditional cash transfers 1M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry, Almaty, (80% of potential cash transfers), with an average total of 520 Peruvian Kazakhstan, 2Naval Medical Research Center-Frederick, Frederick, MD, Soles (173 US Dollars) received per household. The conditional cash United States, 3MRIGlobal, Palm Bay, FL, United States, 4MRIGlobal, transfers offset 22% of total costs and 43% of direct costs. Conditional Frederick, MD, United States, 5MRIGlobal, Baltimore, MD, United States cash transfers offset total costs to a greater extent in poorer households Early case detection and rapid treatment reduce Mycobacterium (23% versus 20%) and female patients (26% versus 20%, p=0.02). tuberculosis (MTB) transmission. MTB is considered multidrug-resistant A novel TB-specific social protection intervention has been designed, TB (MDR-TB) when resistant to rifampin and isoniazid, and a test which implemented, refined, and was found to be both acceptable and equitable simultaneously diagnoses MTB and multi-drug resistance (MDR) is urgently in a challenging, impoverished setting. needed. The Akonni Biosystems MDR-TB microarray test (Akonni MDR- TB) (Frederick, MD USA) specifically reports on the presence of rpoB (30 1764 mutations), and katG (2 mutations) and inhA (4 mutations) mutations COMBINATORIAL APPROACH TO PATHOGEN DETECTION IN known to confer resistance to rifampin and isoniazid, respectively. The RESPIRATORY SAMPLES OF UNKNOWN ETIOLOGY assay contains markers for the M. avium complex (MAC), M. tuberculosis complex, and an internal amplification and hybridization control. Similarly, Mariana Leguia1, Maria Silva1, Jane Rios1, Cristhopher Cruz1, the Hain LifeScience GenoType MTBDRplus (Hain MTBDRplus) (Nehren, Michael Wiley2, Carla Prieto2, Gustavo Palacios2, Matthew R. Germany) detects the presence of mutation in rpoB (4 mutations), and Kasper3, Daniel G. Bausch1 katG (2 mutations) and inhA (4 mutations). MRIGlobal partnered with the 1U.S. Naval Medical Research Unit – 6 (Peru), Washington, DC, United M.A. Aitkhozhin Institute of Molecular Biology and Biochemistry (IMBB) States, 2U.S. Army Medical Research Institute for Infectious Diseases, to test 411 extracted isolates from the National Center of Tuberculosis Frederick, MD, United States, 3Global Emerging Infections Surveillance and Problems in Kazakhstan. Isolates indicating a mixed genotypes (26) or Response System, Armed Forces Health Surveillance Center, Silver Spring, presence of MAC (8) were removed from the performance evaluation. MD, United States The Akonni MDR-TB was compared to the Hain LifeScience GenoType MTBDRplus (377 isolates) for rifampin and isoniazid resistance mutations: Emerging pathogens are a continuous threat to public health around percent agreement (95% Confidence Interval) rifampin 93.6% (90.7- the world. Respiratory pathogens in particular, such as those causing 95.9), isoniazid 97.9% (95.9-99.1); sensitivity (95% Cl) rifampin 92.7% influenza-like illnesses and severe acute respiratory infections, are easily (88.9-95.6), isoniazid 98.7% (96.6-99.6); and specificity (95% Cl) rifampin transmissible person-to-person and primarily affect children, the elderly, 95.7% (90.2-98.6), isoniazid 95.4% (88.6-99.2). Isoniazid testing on the and confined populations, such as those in prisons or military bases. Akonni MDR-TB resulted in 1 indeterminate result. Discrepant analysis The U.S. Naval Medical Research Unit No. 6, Lima, Peru, conducts between assays is ongoing with culture to adjudicate. The performance routine surveillance for respiratory pathogens throughout Latin America. characteristics of these assays to detect specific resistance markers is About 60% of the 5,000 respiratory samples collected annually remain further defined, while highlighting the advantages of using a practical and without an identified etiological agent, either because known pathogens quick multiplexed microarray platform in a field forward setting for global are present at sub-threshold levels that render them undetectable to surveillance. traditional PCR-based diagnostics or because pathogens are novel or divergent enough that they cannot be detected using existing 1766 methodologies. We used a combination of both classical (cell culture) and advanced laboratory methodologies (MassTag PCR and next-generation HIGH PREVALENCE OF BORDETELLA PERTUSSIS IN SEVERE sequencing) to screen over 600 samples that showed cytopathic effect on ACUTE RESPIRATORY INFECTIONS IN HOSPITALIZED cell culture but for which no pathogen could be identified. Initial screening CHILDREN UNDER FIVE YEARS IN LIMA, PERU using a highly multiplexed MassTag PCR-based approach identified potential etiologies in 41% of the samples tested, including enterovirus Ivana Pavic-Espinoza, Sandy Bendezu-Medina, Angella Herrera- (39%); human parainfluenza virus 1 (2%), 2 (32%), 3 (2%) and 4 (1%); Alzamora, Maria J. Pons, Adrián V. Hernandez, Juana Del Valle- human metapneumovirus (10%); respiratory syncytial virus A (5%) and B Mendoza (4%); coronavirus OC43 (3%) and 229E (1%); and influenza A virus (1%). Universidad Peruana de Ciencias Aplicadas, Lima, Peru We then conducted unbiased next-generation sequencing on selected samples and identified additional etiologies, including viruses that had Acute respiratory infections (ARI) are the main cause of morbidity and never before been detected in Latin America, such as Saffold virus. Here, mortality in children under 5 years worldwide. Bordetella pertussis we describe our integrated approach to pathogen detection and report is a highly contagious bacterium that can cause serious illness, and our complete findings for over 600 samples collected since 2011. This new approximately half of infected infants less than 1 year old are hospitalized. combinatorial approach to pathogen detection enables rapid identification Also, pertussis immunization series is not completed until six months of known and novel pathogens present in respiratory samples in a modern of age, leaving young infants vulnerable to pertussis. In Peru, pertussis and cost effective manner that should facilitate global respiratory disease is an increasing health problem despite immunization efforts, and the surveillance efforts. role of B. pertussis in ARI is unknown. We determined the prevalence of B. pertussis among children under 5 years old admitted to Hospital Nacional Cayetano Heredia in Lima with diagnosis of ARI between Jan- 2009 and Dec 2010. Epidemiological and clinical features were collected, and presence of B. pertussis was determined by PCR (pertussis toxin and IS481 gene). A total of 596 nasopharyngeal samples among children

astmh.org 541 under 5 years were analyzed. In 114 (19.1%) samples were positive for prolongation of hospital stay of the patient, but also because it results B. pertussis. 32.5% of sample positive to B. pertussis were diagnosed in increased mortality and increases in the costs of patient care. This as viral pneumonia at diagnosis. Importantly, 71.9% of cases were under pulmonary complication develops after 48 to 72 hours of endotracheal 12 months of age and 58.8% have been contact with other ARI infected intubation. To determine the prevalence of disease as a cause of people. Significant differences in clinical symptoms between the total pneumonia associated with mechanical ventilation in adult ICU of a ARI cases and B. pertussis cases were not found. The most frequent health institution in Montería, Córdoba. A retrospective study in the symptoms in B. pertussis cases were fever (100%), rhinorrhea 78%, ICU of a hospital in Montería- Córdoba. Patients with ICU stay and VM cough 71.9% and respiratory distress 60.5%. One child died due to the for more than 48 hours period that meet the criteria of the American infection. B. pertussis cases showed a seasonal distribution with peaks Thoracic Society / Infectious Diseases Society of America (ATS / IDSA). during the months March June and November. This study shows the high for mechanical ventilation associated pneumonia (VAP) and which has prevalence of B. pertussis in infants who were hospitalized due to severe been carried them bronchial secretion cultures or tracheal aspirate were acute respiratory infections in Lima, Peru. Epidemiologic surveillance included. For data collection 1474 medical records of patients admitted programs for B. pertussis are essential in the future in Peru. to the ICU on study time. The information was processed with statistical software SPAD, making a multivariate correspondence analysis (MCA). 1767 Pseudomonas aeruginosa and Klebsiella pneumoniae, were greatest number of isolates with rates equivalent to 39.34% and 27.87%, NOSOCOMIAL TUBERCULOSIS TRANSMISSION: IS AIR respectively, following the order of frequency Acinetobacter baumannii EXCHANGE ADEQUATE IN PATIENT CARE AREAS IN GULU with 16.39%, Escherichia coli and Staphylococcus aureus with 4.92% AND MAKERERE TEACHING HOSPITALS, UGANDA of isolates, the less common bacteria found correspond to Enterobacter aerogenes with 3.28% and Burkholderia cepacia and Serratia 1 2 3 Achilles Katamba , Priscilla Nakiboneka , Gerald Obai , Bruce marcescens with percentages corresponding to 1.64% respectively. VAP 1 Kirenga affects up to 38.36 % (61 of 159 ) of patients admitted to the ICU of the 1Makerere University College of Health Sciences, Kampala, Uganda, institution where the study was conducted, complicating their evolution 2Uganda Ministry of Health, Kampala, Uganda, 3Gulu University, Faculty of , prolonging their stay in the ICU and increasing costs of health services. Medicine, Kampala, Uganda For this reason, more studies should be done to better understand the In Uganda like similar developing countries, tuberculosis (TB) infection epidemiology, pathophysiology and etiology to improve the chances of rates in medical students have been found to higher than that of survival of patients. comparable groups including students in other University programs and adults living in suburbs of the city where the medical school is located. 1769 In addition, a steep increase in prevalence of TB infection from year CHALLENGES IN DIAGNOSIS OF PEDIATRIC TUBERCULOSIS: one (35%) to year five (55%) in a relatively short period suggests that exposure and infection may be related to clinical work, that is exposure A CASE STUDY IN SIAYA COUNTY REFERRAL HOSPITAL, and infection due to nosocomial TB. Thus we undertook the study to WESTERN KENYA assess the adequacy of airborne ventilation in patient areas as per WHO Nicholas O. Otieno1, Stellamaris Oloo1, Evelyne Modi1, Vincent recommendations. We conducted a study in Gulu and Makerere University Omanje1, Jacob Odeny1, Chrispine Wasonga1, Joan Ochieng1, teaching hospitals. The patient areas assessed included: causality/ Rodney Bosire1, Zachary S. Karim2, Prakasha Kempaiah2, Momchilo emergency ward, bronchoscopy rooms, sputum induction rooms, inpatient Vuyisich3, Norman Doggett3, Nick Hengartner3, Paul Fenimore3, wards, laboratories, out-patient departments, and the mortuary. Using an Basil Swanson3, Benjamin H. McMahon3, John M. Ong’echa4, airflow alnor velometer/anemometer placed approximately 15 centimeters Harshini Mukundan3, Douglas J. Perkins2 form the window or door opening, we measured the air speed of each 1University of New Mexico/KEMRI Laboratories of Parasitic and Viral patient-care area at different times of the day in the usual working Diseases, SCRH, Siaya, Kenya, 2Center for Global Health, Department of situation, when all openings are fully open, when all openings half open Internal Medicine, University of New Mexico, Albuquerque, NM, United and all openings closed for 4 measurements per opening per day for States, 3Los Alamos National Laboratory, Los Alamos, NM, United States, three day. In addition data on intensity of use of the different patient 4University of New Mexico/KEMRI Laboratories of Parasitic and Viral areas were classified into minimum use, moderate use and maximum use. Diseases, Kisumu, Kenya Data were computed to determine the Air changes per hour (ACH) for patient-care areas for different intensity of use of the patient care areas. Tuberculosis (TB) has a substantial global prevalence and results in high Preliminary data indicate that the ACH range to as low as 5 to as high as rates of morbidity and mortality. Kenya ranks among the top five TB- 14 ACH. Patient care areas of old building constructed 50 or more years burden countries in sub-Saharan Africa. Although pediatric TB is estimated were more likely to have adequate ACH as per recommendation of WHO at 10.72% for all cases, this figure is likely an underestimation due to even at maximum intensity of use of patient-care areas. Inadequate ACH the challenges associated diagnosis of pediatric TB. Currently, pediatric in patient-care settings may be responsible for nosocomial transmission of TB diagnosis in Kenya relies (primarily) on patient history, physical TB and may explain the high TB infection rates among medical students. examination, chest x-ray, and sputum smear microscopy (if available). Precautionary measures to prevent transmission of airborne infections are However, challenges are substantial when TB diagnosis is based largely recommended. (Abstract changes to be made) on clinical parameters since a number of frequent co-morbid endemic diseases present with common clinical signs and symptoms. For example, 1768 we enrolled a cohort of children (n=1,704, aged 3-36 months) at the Siaya County Hospital, western Kenya (2003-2014), who were followed PREVALENCE OF PATHOGENS AS A CAUSE OF PNEUMONIA longitudinally for 36 months. This particular region has holoendemic ASSOCIATED WITH MECHANICAL VENTILATION IN THE Plasmodium falciparum transmission and the highest prevalence of HIV ADULT ICU OF A HEALTH PROVIDER MONTERÍA- ENTITY IN in Kenya. Although diagnosis of malaria, HIV, and bacteremia were robust CORDOBA, DURING THE YEARS 2011 TO 2014 due to utilization of state-of-the-art diagnostic platforms, diagnosis of pediatric TB presented substantial challenges based on the use of clinical Linda M. Chams, lisy Gracia, Maria F. Yasnot algorithms. In the cohort, 55 children (3.2%) presented with suspected Universidad de Córdoba, Monteria, Colombia TB. However, based on the WHO TB pediatric score chart, only 15 of the 55 suspected cases (27.3%) were confirmed as TB cases (0.88% of the Pneumonia associated with mechanical ventilation (VAP) is one of the cohort). Based on these challenges, we initiated development of diagnostic most serious infections associated with health care, not only for the assays that utilize blood and/or urine samples for TB diagnosis. Towards

astmh.org 542 this end, we are currently investigating the use of novel technologies by immunization. Pneumonia is defined as a cough or cold with fast that employ detection of pathogen biomarkers coupled with sensitive breathing (counted with respiratory timers); while having chest indrawing measurement platforms to facilitate rapid and specific diagnosis of TB from additionally, defines Severe Pneumonia. Between November 2014 and blood and/or urine samples. February 2015, in 7 iCCM-eligible LGAs of Abia State: 6,455 under-fives were seen of which 2,505 had cough/difficulty breathing and 1,230 had 1770 fast breathing (Pneumonia: 19% of all children seen). Of these, 1004 cases were promptly treated with Dispersible Amoxicillin in the community; IMPACT OF PCV7 ON NASOPHARYNGEAL DENSITY, and 226 cases were referred to health facilities. Pneumonia is the leading SEROTYPE DISTRIBUTION AND ANTIBIOTIC RESISTANCE infectious cause of death in children worldwide, and constitute 19% of OF PNEUMOCOCCAL STRAINS ISOLATED FROM PERUVIAN the estimated 756,000 under-five deaths annually in Nigeria. iCCM is CHILDREN an equity-focused strategy of delivering curative treatment of childhood illnesses in the communities outside of health facilities; and is designed 1 2 1 Christiane R. Hanke , Carlos G. Grijalva , Sopio Chochua , Mathias such that more than the hitherto estimated one-third of under-fives can 3 4 5 W. Pletz , Claudia Hornberg , Kathryn M. Edwards , Marie R. access interventions and antibiotics for Pneumonia. In its 4 months of 2 6 6 6 Griffin , Hector A. Verastegui , Ana I. Gil , Claudio F. Lanata , implementation in 7 LGAs in Abia State, 1004 under-fives who may not 1 1 Keith P. Klugman , Jorge E. Vidal have reached the health facilities were managed in the community with 1Hubert Department of Global Health, Rollins School of Public Health, antibiotics and preventable deaths averted. iCCM of Pneumonia is a Emory University, Atlanta, GA, United States, 2Department of Health Policy, veritable strategy for reducing the alarming rates of under-five mortality, Vanderbilt University, Nashville, TN, United States, 3Center for Infectious as well as achievement of Millennium Development Goals in Abia State, Diseases and Infection Control, Jena University Hospital, Jena, Germany, Nigeria. 4Department of Environment and Health, School of Public Health, Bielefeld University, Bielefeld, Germany, 5Vanderbilt Vaccine Research Program, 1772 Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University, Nashville, TN, United States, 6Instituto de Investigacion CHILDHOOD PNEUMONIA IN RURAL MOUNTAINOUS Nutricional, Lima, Peru PAKISTAN: CLINICAL FEATURES AND NASOPHARYNGEAL Pneumococcal conjugate vaccines (PCV) have reduced the burden of CARRIAGE OF VIRAL PATHOGENS pneumococcal disease (PD), and decreased nasopharyngeal carriage Elizabeth D. Thomas1, Julia M. Baker1, Assis Jahan1, Ejaz of vaccine-types. Few data exist from remote rural areas, so here, we Hussain1, Nathan F. Robinson1, Wasiat Hasan Shah1, Fatima investigated the serotype distribution and antibiotic resistance of carriage Aziz2, Shahida Qureshi2, Uzma Bashir Aamir3, Asad Ali2, Syed strains isolated from young children, before and two years after PCV7 Sohail Zahoor Zaidi3, Syed Iqbal Azam4, Saba Wasim4, Zeba A. was introduced, in a prospective cohort study conducted in the remote Rasmussen1, Khalil Ahmed5 Peruvian Andes. Effects of PCV7 on pneumococcal nasopharyngeal 1Fogarty International Center, National Institutes of Health, Bethesda, density, obtained using qPCR reactions, were also assessed. Methods. MD, United States, 2Aga Khan University, Department of Paediatrics and Nasopharyngeal swabs were collected from a sample of children <3 years Child Health, Karachi, Pakistan, 3National Institute of Health, Islamabad, of age in both 2009 and 2011. Pneumococcal strains were isolated, Department of Virology, Islamabad, Pakistan, 4Aga Khan University, quellung-serotyped and tested for susceptibility to antibiotics. Results. Department of Community Health Sciences, Karachi, Pakistan, 5Karakoram Nasopharyngeal prevalence of PCV7 strains decreased from 48% in International University, Gilgit, Pakistan 2009 to 28.8% in 2011, whereas non-PCV7 types increased from 52% to 71.2% (p=.002). Vaccination with PCV7 did not affect overall Childhood pneumonia causes high morbidity/mortality in developing pneumococcal density in children colonized by a PCV7 type but did countries, including Pakistan; the role of viral pathogens is not clear. Two increase median nasopharyngeal density in those colonized with a non- cohort studies of children under 5 years of age were conducted in rural PCV7 type [2009, 1.9x105 cfu/ml vs 2011, 5.5x105 cfu/ml; (p=0.046)]. Oshikhandass village by trained community research workers using weekly The most prevalent serotypes were 19F (13.6%), 23F (12.8%), and active surveillance and WHO defined criteria for pneumonia diagnosis. 6B (12%) in 2009; and 19F (11.2%), 6C (11.2%), and 11A (9.6%) in Pneumonia incidence declined from 44 episodes/100 child years (CY) in 2011. A substantial 3.5-fold increase in carriage of serotype 6C was 1992-1996 to approximately 15/100 CY in 2012-2014. From 2012-2014, observed after PCV7 introduction (p=0.026). Overall antibiotic resistance NP data were available for 184/207 (88.9%) pneumonia cases; 132/184 did not change after vaccine introduction. Most pneumococcal strains (71.7%) of these had NP viral carriage detected using Luminex® and were non-susceptible to tetracycline (97.2%), and to a lesser extent, to Taqman® PCR methods, including RSV (19.6%), and influenza (5.4%). trimethoprim-sulfamethoxazole (56.4%), penicillin (34%), erythromycin A subset of 155 cases tested with Luminex® had entero/rhinovirus (22.4%), chloramphenicol (18.8%) or clindamycin (12.4%). Conclusion. (53.5%), coronavirus (7.7%) parainfluenza (7.1%), adenovirus (6.5%), PCV7 impacted carriage of those serotypes in rural Peru. Replacement metapneumovirus (5.2%) and bocavirus (1.9%). Of 207 pneumonia cases, serotypes had increased density when less PCV7 serotypes were present. 7 (3.4%) had severe pneumonia. Three children were <2 months of age, Peru should consider switching to the PCV13 vaccine to cover the 50 (24.2%) were 2-11 months, and 154 (74.4%) were between 12-59 emerging serotype 6C strain. months; median age at diagnosis was 19 months. At presentation (Day 1), average duration of illness was 2.1 days, 29.0% had wheezing by exam, 1771 and 24.2% had axillary temperature>=100.4 F. Children were followed on Days 3, 5/6 and 14. Total duration of illness, defined as initial duration plus COMMUNITY CASE MANAGEMENT OF PNEUMONIA IN ABIA days until respiratory rate returned to normal as checked by health worker, STATE, NIGERIA was available for 152 cases (73.4%); mean total duration of illness was 5 days (range 3-17). Where respiratory rate was taken at each visit (84.5% Ugo U. Enebeli of cases), most children (63.3%) recovered within 3 days of initiating Federal University of Technology, Owerri, Owerri, Nigeria antimicrobial therapy; 16.4% needed 5 days. Nine children (4.4%) needed This study aims at assessing community management of Pneumonia in referral, mostly on Day 1 (6/66%); 3 were hospitalized and none died. children aged 2-59 months in Abia State using the Integrated Community Community based pneumonia is primarily non-severe and with early Case Management (iCCM) Model. Community Resource Persons detection, referral, and treatment, has low mortality. Enterovirus/rhinovirus (CORPs) in the iCCM model are trained in diagnosis and treatment of and RSV were the main viruses detected, though multiple other viruses Pneumonia; referring of severe cases to the health facilities; following up were found; influenza detection was relatively low. Clinical correlation with such cases; and advising all caregivers on protection against pneumonia viral carriage is underway. astmh.org 543 1773 research, including focus group discussions with 24 CHWs in each country and pile sorting exercises with government stakeholders and NGO BODY COMPOSITION AND VITAMIN D STATUS AMONG partners. CHWs in all countries expressed a ‘felt’ need for new pneumonia PATIENTS WITH TUBERCULOSIS IN RURAL SOUTH INDIA: THE diagnostic devices and automation was a preferred device characteristic. NEED FOR INTEGRATING NUTRITIONAL MANAGEMENT IN The pile sorting exercises favoured the fingertip pulse oximeters due to CARE AND TREATMENT PROGRAMS ease of use and affordability.The pulse oximeters, having not been used under field conditions, underwent laboratory testing for accuracy and Elaine A. Yu1, Julia L. Finkelstein1, John Kenneth2, Bonam robustness (prototypes excluded). All laboratory tested devices passed, Wesley2, Saurabh Mehta1 except one fingertip pulse oximeter. Nine devices (5 pulse oximeters and 1Cornell University, Ithaca, NY, United States, 2Arogyavaram Medical 4 respiratory rate counters) were selected overall for further accuracy Centre, Madanapalle, India evaluation. Health facility accuracy evaluations in the project countries assessed accurate use of each device by CHWs/FLHFWs against reference The evidence base for modifiable nutritional risk factors in patients with standards. In each country 430 children aged 0-59 months were enrolled Tuberculosis (TB) remains inadequate and very little is known about TB’s in the study. Children were presented randomly to the CHW/FLHFW, who association with body composition and micronutrient status in populations was blinded to their condition and true RR. The accuracy evaluation is with high prevalence of undernutrition. The objective of this study was anticipated to finish in June 2015. Preliminary results are encouraging to describe and assess the association between body composition, with health workers able to use all devices being trialled. It is hoped that vitamin D, and active TB among patients at a rural center in South India. by identifying devices that can be used by frontline health workers to Whole and segmental body composition indicators (body fat [%, kg], accurately detect pneumonia symptoms in children aged 0-59 months, this fat free mass [kg], total body water [kg], impedance) were measured by will increase appropriate treatment for pneumonia while improving referral 8-electrode bioelectrical impedance analysis. 25-hydroxyvitamin D serum rates for patients with severe pneumonia. concentration was determined by a chemiluminescence immunoassay, and < 50 nmol/L was defined as deficient. Active TB was defined by acid-fast bacilli sputum smear microscopy, per standard of care, and HIV infection 1775 was determined by TriDot rapid test. The associations between body ACCEPTABILITY OF SELECTED RESPIRATORY RATE COUNTERS composition indicators with vitamin D and TB were assessed in multivariate AND PULSE OXIMETERS FOR USE BY FRONTLINE HEALTH linear regressions, adjusting for other covariates (including demographic WORKERS IN THE DETECTION OF PNEUMONIA SYMPTOMS [sex, age], hemoglobin, immunological and rheological indicators). 11.6% IN CHILDREN IN SUB-SAHARAN AFRICA AND SOUTHEAST of patients had confirmed active TB disease, and 1.5% had HIV infection. Among study participants, mean body weight was 48.7 kg (±13.5). Nearly ASIA 25% of patients had 25 kg/m2. Mean vitamin D status was 51.4 nmol/L Lena Matata1, Kevin Baker2, Akasiima Mucunguzi3, Monica (±26.7), and 54.7% of patients were vitamin D deficient. Average fat Posada4, Tedila Habte5, Karin Källander2 mass was 7.2 kg (±4.3) among individuals with confirmed TB, compared 1Malaria Consortium, Juba, South Sudan, 2Malaria Consortium, London, to 11.2 kg (±7.2) among patients with probable TB. Vitamin D deficiency United Kingdom, 3Malaria Consortium, Kampala, Uganda, 4Malaria was associated with increased body fat (%) and fat mass (kg; all p<0.05), Consortium, Phnom Penh, Cambodia, 5Malaria Consortium, Hawassa, after controlling for other covariates. The results highlight the rampant Ethiopia undernutrition among patients with TB at our clinic in South India and underscore the need for integrating nutritional assessment and counseling Diagnosis of pneumonia, the leading infectious killer of children under in TB care and treatment programs. Further, future laboratory and the age of five, by community health workers (CHWs) and first level longitudinal studies are needed to understand the direction of linkages health facility workers (FLHFWs) is presumptive and based on counting between vitamin D, body composition, and TB along with their relevance respiratory rate (RR). This process can be challenging for frontline health for long-term health. workers in low resource settings and misclassification of the observed RR is common. Malaria Consortium’s Pneumonia Diagnostics project is 1774 identifying the most accurate and acceptable respiratory rate counters and pulse oximeters to support CHWs and FLHFWs in the detection of ACCURACY OF SELECTED DEVICES FOR THE DETECTION OF pneumonia symptoms in children aged 0 to 59 months in Cambodia, PNEUMONIA SYMPTOMS - RESULTS FROM LABORATORY Ethiopia, South Sudan and Uganda. In each country a diverse sample of TESTING AND FIELD EVALUATIONS OF RESPIRATORY RATE 16 CHWs and 6 FLHFWs are provided with a respiratory rate counter or COUNTERS AND PULSE OXIMETERS WITH FRONTLINE pulse oximeter. These devices will have been selected based on results HEALTH WORKERS IN SUB-SAHARAN AFRICA AND of earlier accuracy evaluations and pile sorting exercises with CHWs/ SOUTHEAST ASIA FLHFWs who have previously tried the devices. The CHWs/FLHWs will use the device in routine clinical practice for two months between July and Kevin Baker1, Akasiima Mucunguzi2, Lena Matata3, Monica October 2015, and filmed using them. The recordings will be analysed for Posada4, Tedila Habte5, Karin Källander1 device procedure accuracy, and reactions of the caregiver and their child. 1Malaria Consortium, London, United Kingdom, 2Malaria Consortium, Additionally the CHWs and FLHFWs, as well as a diverse sample of 24 Kampala, Uganda, 3Malaria Consortium, Juba, South Sudan, 4Malaria parents in each country, will be asked to participate in a semi-structured Consortium, Phnom Penh, Cambodia, 5Malaria Consortium, Hawassa, interview on their perceptions of the devices. Anticipated results will give Ethiopia insight into the acceptability of different diagnostic devices for frontline health workers in their daily work, as well as the reactions of caregivers Globally, pneumonia remains the leading infectious cause of death and their children. It is hoped that this unique study will recommend in children under five years. Diagnosis of pneumonia symptoms by accurate and acceptable devices for detection of childhood pneumonia community health workers (CHWs) and first level health facility workers symptoms by frontline health workers in Sub-Saharan Africa and (FLHFWs) is based on counting respiratory rate (RR), which is challenging Southeast Asia. and misclassification of the observed RR is common. Malaria Consortium’s Pneumonia Diagnostics project is identifying the most accurate and acceptable devices to support CHWs and FLHFWs in the detection of pneumonia symptoms in children aged 0 to 59 months in Cambodia, Ethiopia, South Sudan and Uganda. Eight pulse oximeters and four respiratory rate counters were selected for evaluation based on formative

astmh.org 544 1776 role of S. mansoni TRPM8 channels, which in mammals are cold sensitive and activated by icilin. Like capsaicin, icilin induces dramatic hyperactivity SCHISTOSOMA MANSONI: ASSESSING THE FUNCTION OF in adult and larval schistosomes. Suppression of TRPM8 expression strongly MAPK PATHWAY AND OF HISTONE MODIFYING ENZYMES attenuates this increase in icilin-induced motility, but does not affect 5-HT-induced hyperactivity. This is the first demonstration of a TRPM8 1 1 1 Marina M. Mourão , Luiza F. Andrade , Sandra G. Gava , Livia G. agonist-induced pharmacological effect in schistosomes and provides 1 2 1 Avelar , Raymond J. Pierce , Guilherme Oliveira a novel sensitive point for exploring the pharmacology and function of 1Fundação Oswaldo Cruz, Belo Horizonte, Brazil, 2CIIL, Inserm U1019, this channel. Targeted disruption of these channels may provide clues CNRS UMR8204, University Lille Nord de France. Institut Pasteur de Lille, about the roles they play in the parasite and possible strategies for the Lille, France development of new antischistosomal therapeutics. In most organisms, Mitogen-activated protein kinases (MAPKs) and Histone Modifying Enzymes (HMEs) influence a number of important 1778 tissue-specific biological activities such as cell proliferation, survival and, MOLECULAR DETECTION OF SCHISTOSOME AND OTHER differentiation. Those enzymes are increasingly approved as targets PARASITIC HELMINTH INFECTIONS ON A DISPOSABLE for drug development with a growing amount of inhibitors under development. However, to date, the function of HMEs and MAPKs MICROFLUIDIC CASSETTE are uncertain in the parasite Schistosoma. Here, we employed RNA Jinzhao Song, Changchun Liu, Thomas J. Nolan, Michael Mauk, interference to elucidate the roles of 16 HMEs and 5 genes involved in James B. Lok, Haim H. Bau, Robert M. Greenberg MAPK signaling pathway in S, mansoni. First, the selected genes were University of Pennsylvania, Philadelphia, PA, United States chosen based in their putative function and/or for being unique members of their subfamily (ePK) in the parasite. Among the targets are included: Current classical and serological methods for diagnosis of parasitic SmERK1, SmERK2, SmJNK, SmCaMK2, and Smp38 and 1 histone helminth infections have limitations on sensitivity, specificity, and reliability, deacetylases (SmHDAC8), 10 methyltranferases (HMTs), 5 demethylases and are often labor intensive and require specialized training. Nucleic (HDM), from those, 8 were chosen for experimental validation. acid-based methods for detection of free parasite DNA in host blood, Pharmacological inhibition and RNAi were used to elucidate the functional urine, feces, or tissues hold the promise of dramatic increases in diagnostic role of MAPK signaling pathway proteins and HMEs in S, mansoni. After sensitivity and specificity, but often require infrastructure not available RNAi, mice were injected with treated schistosomula and evidenced that in the field. Self-contained, point-of-care molecular detection devices SmHDAC8 and SmJNK are important to the parasite transformation and hold the promise of more extensive and accurate monitoring of infection survival, whereas HDAC8, PRMT3, KDM1/KDM2, SmERK, and Smp38 dynamics and treatment efficacy. Here, we describe a simple, small, fully- seems to be associated in egg production as infected mice had significantly integrated, inexpensive, and disposable microfluidic cassette adapted lower egg burdens and female worms presented underdeveloped for molecular detection of parasitic helminth infections. The cassette, ovaries. Moreover, worms depleted in SmJNK and Smp38 exhibited large or chip, features an array of reaction chambers that house nucleic acid damage in the tegument and, the later enzyme, seems to be involved binding membranes. Nucleic acid capture, washing, amplification, and in the activation of detoxification enzymes. Recently, RNAseq analysis of detection are all combined in a single multifunctional reaction chamber. MAPKs knockdown parasites elucidated the genes which might be under The cassette is endowed with a concentration function since nucleic acids the control of this signaling pathway. Our results help characterize the captured on a flow through membrane serve directly as templates for importance of MAPK pathway and HMEs in the maintenance and survival amplification without elution. This cassette is compatible with isothermal of the schistosome and propose some of these enzymes as valuable drug amplification methods such as loop-mediated isothermal amplification targets to prevent schistosomiasis progress. (LAMP) and reverse transcription (RT)-LAMP. Both monitoring the reaction and thermal control is low-cost and flexible. By adapting LAMP protocols 1777 with this cassette, we show that Schistosoma mansoni DNA is readily detectable on the chip using serum taken from mice as early as one-week PHARMACOLOGICAL SENSITIVITIES OF TRP CHANNELS IN post infection, several weeks prior to the onset of parasite egg production. SCHISTOSOMA MANSONI Furthermore, we show that Dirofilaria immitis DNA is readily detected in plasma samples from infected dogs. These results provide a strategy Swarna Bais, Matthew A. Churgin, Christopher Fang-Yen, Robert for simple, inexpensive, and highly accurate diagnostic monitoring of M. Greenberg schistosome and other parasitic helminth infections on site and in the University of Pennsylvania, Philadelphia, PA, United States clinic. There is an urgent need for new or repurposed antischistosomal agents, as praziquantel is effectively the only drug available for treatment and 1779 control of schistosomiasis, a disease that affects hundreds of millions. Ion BIOMPHALARIA GLABRATA EMBRYONIC (BGE) CELL channels are validated and common targets for current anthelmintics. Transient receptor potential (TRP) channels are a diverse family of channels SUPEROXIDE DISMUTASE (SOD) EXPRESSION PRE-AND essential for sensory transduction and other functions. However, the POST-EXPOSURE TO SCHISTOSOMA MANSONI LARVAL roles and pharmacological sensitivities of these channels are essentially TRANSFORMATION PROTEINS unexplored in schistosomes and other parasitic helminths. We are using Utibe Bickham-Wright, Nathalie Dinguirard, Grzegorz Sabat, TRP channel modulators and RNAi to examine the pharmacological Timothy P. Yoshino sensitivities of TRP channels in schistosomes. The S. mansoni genome predicts representatives of most TRP channel subfamilies, with the notable University of Wisconsin, Madison, WI, United States exception of TRPV, the vanilloid receptor family. Nonetheless, both adult Schistosoma mansoni is one of several species of human blood flukes and larval schistosomes exhibit dramatic hyperactivity in response to that causes schistosomiasis, which continues to afflict over 200 million capsaicin, a selective activator of mammalian TRPV1. Surprisingly, the people worldwide. In resistant strains of the snail intermediate host, majority of this response is attenuated by knockdown of TRPA expression; Biomphalaria glabrata, primary sporocysts are rapidly encapsulated by TRPM7 also contributes to the capsaicin response. Knockdown has no circulating hemocytes and killed by the release of reactive oxygen species. effect on 5-HT-induced hyperactivity. These results indicate that some Superoxide dismutase (SOD) in hemocytes is responsible for the production TRPV-mediated sensory functions may be fulfilled by schistosome TRP of H2O2 and the destruction of encapsulated parasites. An increase in Cu/ channels from other subfamilies, and that schistosome TRP channels likely Zn SOD activity has been linked to the resistant snail strains and further have novel pharmacological properties. We have also been exploring the astmh.org 545 characterization has shown allele specific differences between strains. Cells oxamniquine resistance. The gene involved encodes a sulfotransferase, of the B. glabrata embryonic (Bge) cell-line encapsulate larval S. mansoni SmSULT, required for intracellular drug activation. Resistance has a under in vitro conditions, similar to hemocyte-sporocyst encapsulation recessive basis and occurs when both SmSULT alleles encode for defective reactions. In the present study we investigated if Bge cells, like proteins. Here we examine SmSULT sequence variation in a natural hemocytes, possessed SOD activity, and whether exposure of cells to larval schistosome population in Brazil after 30 years of treatment. Our central transformation proteins (LTP) affected its activity. Molecular, proteomic, aim was to determine (i) the frequency of resistance alleles and (ii) the and enzyme activity assays were used to investigate SOD in Bge cells and number of independent origins of resistance to this drug in a single the effects of exposure to parasite proteins on its expression. Results of parasite population. We collected fecal material containing S, mansoni Cu/Zn SOD allele-specific PCR analysis in Bge cells showed that the A/C eggs, hatched miracidia and stored these on FTA cards. Following whole alleles, previously found to be associated with susceptible B. glabrata genome amplification of DNA, we sequenced the two exons of SmSULT snails, were expressed. A quantitative real-time PCR assay showed an from each miracidia. We amplified miracidial DNA from 189/228 samples increase in Bge cell Cu/Zn SOD transcript levels after exposure to S. (83% success). These included one to 11 miracidia larvae from each of mansoni LTP although changes were not statistically significant. However, 50 patients. We found four mutations that are known or predicted to nanoLC-MS/MS mass spectrometry analysis of Bge cell proteins expressed impair protein function from examination of their position in the SmSULT pre- and post-exposure to LTP showed a significant increase in Cu/Zn crystal structure and/or by biochemical assays. These were (i) the amino SOD in the LTP exposed group. Finally, consistent with proteomic data, acid deletion (Δ142) (ii) a single bp insertion in exon 1 predicted to make Bge cell lysates possess SOD activity, although whether or not this activity a truncated protein product, and (iii) two substitutions (N44H, G206V), is affected by S. mansoni LTP remains to be investigated. Results of this which are predicted to impair binding of the oxamniquine and the co- study demonstrate the expression of Cu/Zn SOD in Bge cells and further factor needed for oxamniquine activation respectively. One other mutation validate the use of this cell line as a model for studying schistosome-snail (N215Y) is not predicted to affect drug activation. Three results are of immune interactions. particular interest: (i) we recovered the Δ142 mutation, responsible for resistance in our genetic cross, in field collected parasite populations (i) 1780 allele frequencies of known or predicted resistance alleles are low (0.04- 0.29%), perhaps consistent with fitness costs associated with carriage GENETIC ANALYSIS OF TRANSMISSION-RELATED TRAITS IN of these alleles (ii) we observed 2-4 independent origins of known or SCHISTOSOME PARASITES predicted resistant alleles. Winka Le Clec’h, Frédéric D. Chevalier, Tim J. Anderson 1782 Texas Biomedical Research Institute, San Antonio, TX, United States Parasite traits associated with transmission success, such as the number POPULATION “EXOMICS” OF SCHISTOSOMA MANSONI of infective stages released, are expected to be optimized by natural Frédéric D. Chevalier1, Winka LeClec’h1, Philip T. LoVerde2, Rafael selection. However, in the trematode parasite Schistosoma mansoni, such Ramiro de Assis3, Guilherme Oliveira3, Safari Kinunghi4, Anouk transmission traits vary significantly within and between different parasite Gouvras5, Bonnie Webster5, Joanne Webster6, Aidan Emery5, David populations and selection experiments demonstrate that this variation Rollinson5, Timothy J. Anderson1 has a strong genetic basis. We are using two approaches to determine 1Texas Biomedical Research Institute, San Antonio, San Antonio, TX, the genetic architecture of this important transmission related life-history United States, 2University of Texas Health Science Center, San Antonio, San trait. First, we used deep sequencing of pooled exomes to compare allele Antonio, TX, United States, 3Centro de Pesquisas René Rachou - Fiocruz/ frequencies across the 363Mb parasite genome in low and high shedding MG, Belo Horizonte, Brazil, 4National Institute for Medical Research, parasites from a single outbred laboratory schistosome population Mwanza, United Republic of Tanzania, 5Natural History Museum, London, (SmLE). This experiment was conducted in triplicate using large parasite United Kingdom, 6Imperial College, London, United Kingdom populations to minimize sampling issues and inbred snail lines to minimize the impact of host genetics. Second, we are conducting three generation We have developed a robust, inexpensive approach for capture and genetic crosses between two laboratory parasite lines (SmBRE and SmLE) sequencing of the ~17Mb Schistosoma mansoni exome that can be that differ >10 fold in numbers of cercariae shed from snails (mean(±se) used for single larval parasites isolated from feces. The approach uses cercariae per shedding, 2929±156 vs. 253±39) for a classical QTL analysis. whole genome amplification of miracidia larvae preserved on FTA cards, The exomes from parents, F1s and F2 progeny from these genetic crosses solution-based capture of exome sequences using 120bp RNA baits, and will be sequenced and the genotype and phenotype data analyzed using Illumina sequencing, and can be extensively multiplexed to reduce costs linkage-based methods. The combination of these two approaches is and simplify sequence library preparation. Here we describe population expected to reveal the genetic architecture of a parasite trait that is critical genomic analysis of exome sequence data from 146 miracidia (one for transmission in an important human pathogen. from each patient sampled) from Brazil, Tanzania and two West African countries (Senegal and Niger). All the African samples come from the 1781 Schistosome Collection At the Natural History Museum (SCAN collection). We detail patterns of genetic variation in autosomal and mtDNA, we INDEPENDENT ORIGINS OF ALLELES CONFERRING characterize SNP variation at candidate vaccine and drug resistance loci, OXAMNIQUINE RESISTANCE IN BRAZILIAN SCHISTOSOME and examine geographic differentiation in allele frequencies to identify PARASITES genome regions under strong directional and balancing selection. Exome sequencing has multiple applications for investigating the population 1 1 1 Winka Le Clec’h , Frédéric D. Chevalier , Nina Eng , Rafael biology and evolutionary genomics of schistosomes. This approach 2 2 3 Ramiro de Assis , Guilherme Oliveira , Philip T. LoVerde , Timothy provides several advantages over other “genome reduction” approaches 1 J. Anderson (eg RADseq) because the sequence captured can be unambiguously 1Texas Biomedical Research Institute, San Antonio, TX, United States, aligned to the parasite genome, coding sequences of central interest to 2Centro de Pesquisas René Rachou - Fiocruz/MG, Belo Horizonte, Brazil, most biologists are determined, and unwanted contaminating DNA is 3University of Texas Health Science Center, San Antonio, TX, United States removed. The evolution of drug and pesticide resistance provides a valuable opportunity to examine adaptation in natural populations. Oxamniquine was used to treat schistosomiasis patients in the 1970s to the late 1990s and several cases of parasite infections resistant to treatment were recorded. Our group has identified the gene and mutations involved in astmh.org 546 1783 1785 EFFECT OF PARASITISM ON THE DISTRIBUTION OF PATTERNS OF REACTIVITY TO SCHISTOSOMA MANSONI EGG SEROTONIN IN THE NERVOUS TISSUES OF BIOMPHALARIA GLYCAN ANTIGENS IN A POPULATION OF TREATMENT-NAÏVE ALEXANDRINA KENYAN SCHOOL CHILDREN Solymar Rolon-Martinez1, Mohamed R. Habib2, Lee O. Vaasjo1, Nina S. Prasanphanich1, Ryan E. Wiegand2, Jasmine A. Landry3, Roger P. Croll3, Mark W. Miller1 Eric M. Ndombi4, Bernard Abudho4, Diana K. Riner5, Megan 1University of Puerto Rico, San Juan, PR, United States, 2Theodor Bilharz L. Mickum1, Diana M. Karanja4, Daniel G. Colley5, Richard D. Research Institute, Cairo, Egypt, 3Dalhousie University, Halifax, NS, Canada Cummings1, W. Evan Secor2 1Emory University, Atlanta, GA, United States, 2Centers for Disease Control Schistosomiasis, or bilharzia, is estimated to affect more than 200 and Prevention, Atlanta, GA, United States, 3Macalester College, St. Paul, million people worldwide. The digenetic trematode worm Schistosoma MN, United States, 4Kenya Medical Research Institute, Kisumu, Kenya, mansoni that causes schistosomiasis employs the freshwater snail genus 5University of Georgia, Athens, GA, United States Biomphalaria as its primary intermediate host. It has been proposed that the transition from the free-living S. mansoni miracidium to Children in schistosomiasis-endemic areas develop partial resistance to parasitic mother sporocyst depends upon uptake of biogenic amines, infection as they age. This resistance is associated with immune responses, e.g. serotonin (5HT), from the snail host. However, little is known about including IgE and IgG, to parasite antigens. Anti-glycan antibodies potential sources of serotonin in Biomphalaria alexandrina tissues and are abundant in schistosome-infected hosts, but their significance in its potential changes during the course of infection. The purpose of this human disease resistance is still unclear. The aim of this study was to investigation was to localize serotonin-like immunoreactivity (5HTli) in the identify glycan epitopes targeted by children in S, mansoni endemic central nervous system (CNS) of B. alexandrina and examine 5HTli at areas, and examine trends of reactivity with age in a population of egg- critical points of the host-parasite interaction. 5HTli fibers were observed positive, treatment-naïve Kenyan school children. Plasmas from both innervating the cephalopedal integument, the major site of S. mansoni egg-positive and -negative children demonstrate reactivity with several miracidium penetration and transformation. However, no peripheral 5HTli epitopes including core xylose/core α3 fucose, F-LDNF, LDN and LDNF neurons were detected. Clusters of 5HTli neurons were observed in the on schistosome glycan microarrays. To explore age-related trends of cerebral, pedal, left parietal, left pleural and visceral ganglia, suggesting such antibodies, we measured IgG and IgM to mock- and periodate- that the peripheral serotonergic fibers originate from the CNS (see also treated S, mansoni soluble egg antigen (SEA), and two parasite cross- Delgado et al. 2012). Specimens infected with S. mansoni were examined reactive glycoproteins, keyhole limpet hemocyanin (KLH) and horseradish at 10 days post infection (10 dpi) and during their shedding stage. The peroxidase (HRP). The ratio of periodate-resistant (primarily non-glycan) total number of central 5HTli neurons decreased from 162.2 ± 40.0 (n = versus total IgG and IgM reactivity to SEA increased with age. IgG to HRP 5) under control conditions to 118.8 ± 11.9 10 dpi and 130.4 ± 6.7 at the and IgM to KLH decreased with age, while IgG to KLH increased. These shedding stage (one-way ANOVA, p < 0.05). Reductions of 5HTli were trends were especially pronounced throughout adolescence. The anti- most evident in the pedal ganglion (control: 33.6 ± 8.8; 18.0 ± 3.7, 10 glycan antibodies detected included a mix of IgG1, G3 and G4. Our results dpi; 25.6 ± 5, shedding; p < 0.05) and the left pleural ganglion (3.2 ± 2.8, suggest that immune recognition of some glycan epitopes is negatively control; 0 ± 0, 10 dpi; 0 ± 0, shedding; p < 0.05). The changes in 5HTli correlated, and others, positively correlated with age. Future studies on the observed following infection by S. mansoni indicate that reductions in function of such anti-glycan antibodies and their pattern of expression in serotonin levels can occur in specific central neurons in parasitized snails human infection could be informative for the improvement of diagnostics and that these changes might contribute to the modifications in several and vaccine development. behaviors that are observed during the course of infection. 1786 1784 GENE REGULATION OF IMMUNE RESPONSES IN SCHISTOSOMIASIS IN REPRODUCTIVE-AGE WOMEN IN BIOMPHALARIA GLABRATA RURAL ZIMBABWE Judith Humphries, Briana Harter, Heather Jost, Eric Ohlrogge, Joseph Freer1, Andrew Prendergast2 Eric Weinlander 1London School of Hygiene & Tropical Medicine, London, United Kingdom, Lawrence University, Appleton, WI, United States 2Queen Mary, University of London, London, United Kingdom Biomphalaria glabrata snails act as the intermediate host to the Schistosomiasis, which is highly prevalent in Zimbabwe, has well- trematode parasite, Schistosoma mansoni. Following S. mansoni recognised complications. However, the epidemiology of schistosomiasis penetration of resistant B. glabrata, parasites are encapsulated by blood in reproductive-age women and the impact of infection during pregnancy cells (hemocytes) and following are killed most likely via host-derived remain poorly understood. In this study we describe the epidemiology reactive oxygen and/or nitrogen intermediates. An immune response such of schistosomiasis in reproductive-age women in rural Zimbabwe. The as this is assumed to depend on altered gene expression to some degree. prevalence and risk factors for infection will be described, using the rich Moreover several studies have shown that the transcriptional profile of baseline dataset that includes demographic and socioeconomic variables, B. glabrata changes in response to stressors such as gram negative and together with extensive data on sanitation coverage, water collection and gram positive bacteria, mechanical wounding, and metazoan parasites, exposure practices. Secondly, we explore associations between maternal as published previously. To date however, only a few transcription factors schistosomiasis and adverse birth outcomes, including i) prematurity have been described in B. glabrata and an understanding of gene ii) low birth weight iii) miscarriage iv) stillbirth and v) neonatal death, regulation in this species is lacking. The NF-kappaB family of transcription stratified by maternal HIV status. Regression analysis for each birth factors has been shown to regulate gene expression in a wide variety outcome, using schistosomiasis as the exposure variable and including a of biological processes, including immune and inflammatory responses. range of covariates known to be associated with adverse birth outcomes As a result, the NF-kappaB pathway is a prospective candidate for (e.g. maternal age, parity, education, hypertension, smoking and alcohol the regulation of immune-related genes in B. glabrata. NF-kappaB use) will be presented. Thirdly, we present the relationship between the homologues have previously been identified in the snail and we have presence of inflammatory biomarkers (C-reactive protein, interleukin-6) in discovered putative kappa-binding sites in the regulatory regions upstream the plasma of 400 pregnant women with and without schistosomiasis. of immune-related genes such as p38 MAPK and Mpeg. Consequently we have examined whether these putative kappa-binding sites are recognized and bound by a B. glabrata NF-kappaB protein through electrophoretic astmh.org 547 mobility shift assays (EMSAs). Furthermore the ability of NF-kappaB the Ministry of Local Government and Housing in Zambia has scaled CLTS to translocate to the nucleus following exposure to PAMPS (pathogen throughout half the country. Included in the CLTS is a mobile-to-web real- associated molecular patterns) including S. mansoni larval transformation time monitoring tool of ODF progress at the village level supported by products was studied. Results support that NF-kappaB can function as a DHIS2 that provides feedback to the community, district and traditional transcription factor and suggest its associated signaling pathway plays a leaders. After 18 months of implementation of CLTS with the real-time role in the immune system in B. glabrata. monitoring the entirety of Chiengi District, Zambia has now certified as ODF despite challenges at the onset of the program. Chiengi District is the 1787 first in Zambia, and likely one of the first in all of sub-Saharan Africa to achieve ODF. CHARACTERIZATION OF THE HUMORAL AND CELLULAR IMMUNE RESPONSES ELICITED BY THE IMMUNIZATION 1789 OF MICE WITH SCHISTOSOMA MANSONI CATHEPSIN B IN THE PRESENCE OF CPG OLIGODEOXYNUCLEOTIDES OR THE ASSOCIATION BETWEEN SEASONALITY AND MONTANIDE ISA 720 VG LEPTOSPIROSIS IN SOUTHERN THAILAND Alessandra Ricciardi, Kittipos Visitsunthorn, John P. Dalton, Sarunyou Chusri, Edward McNeil, Khachornsakdi Silpapojakul Momar Ndao Prince of Songkla University, Hat yai, Songkhla, Thailand McGill University, Montreal, QC, Canada Introduction: Leptospirosis is a worldwide zoonosis with incidence rates Schistosomiasis is the most important human helminth infection due to of between 0.86 and 5.50 per 100,000 populations per year in Songkhla its impact on public health. A vaccine could contribute to a long-lasting Province in southern Thailand. The incidence rate per month during the decrease in disease spectrum and transmission. Our previous vaccine monsoon season was 3-5 times higher and up to 10-15 times higher study using Schistosoma mansoni Cathepsin B (SmCB) resulted in 59% during floods. Objectives: To study the association between the number and 60% worm burden reduction with CpG oligodeoxynucleotides and of leptospirosis cases in Songkhla Province to the seasonal pattern and Montanide ISA720 VG as adjuvants, respectively. Furthermore, antibody climate factors. Methods: We retrospectively reviewed the number of production was significantly augmented in the vaccinated mice; both leptospirosis cases and climate factors including rainfall, temperature, formulations elicited SmCB-specific total IgG endpoint titers > 120,000. relative humidity, light, wind and documentation of flooding from In this study, the role of antibody-dependent cell-mediated cytotoxicity in 1995-2015 and used time series analysis and logistic regression to study SmCB-mediated protection was evaluated by incubating the parasite in the association between them. The time series of monthly number of the presence of pre-immune or immune sera with isolated lung CD45+ leptospirosis cases and climate information were taken and put into cells. These cells were obtained from mice immunized with recombinant analytic model. Results: From 1995 to 2015, there were 1023 cases of SmCB adjuvanted with either CpG oligodeoxynucleotides or Montanide leptospirosis in Songkhla Province. We found the documentation of ISA 720 VG. Cells and sera from adjuvant and saline control animals flooding and 1-month lag of average rainfall were associated with number were also included. SmCB + Montanide induced the highest killing when of leptospirosis cases with odds ratio (95% confidence interval) of 5.3(2.8- immune serum was present; suggesting the contribution of antibodies in 7.8, p-value =0.003) and 1.4(1.1-2.2, p-value=0.04). We also found the cell-mediated parasite killing. In contrast, SmCB + CpG induced constant lack of association between chronological month, temperature, light increased parasite killing which was independent of the addition of and wind. For time series analysis there was no association between any immune sera; implying that only cellular effects were elicited. To further more than 2-month lag climate factors and number of leptospirosis cases. investigate the immunological mechanisms, different cell populations Conclusion: The trend of leptospirosis in southern Thailand was associated were isolated and analyzed. CD8+ cells prominently contributed to with flooding and rainfall within a month. This model was purposed to SmCB + Montanide-induced parasite killing (67%) while CD4+ cells predict the number of leptospirosis cases accurately. were the main effectors in SmCB + CpG-induced parasite killing (64%). Our results elucidate the importance of the adjuvants in influencing the 1790 immune mechanisms involved in parasite killing and protection against schistosomiasis. CAN DIARRHEAL DISEASES BE PREDICTED IN ADVANCE? Md Rakibul H. Khan1, Haidar Aldaach1, Shafqat Akanda2, Anwar 1788 Huq3, Antarpreet Jutla1, Rita Colwell3 1 2 CHIENGI DISTRICT, ZAMBIA OPEN DEFECATION FREE! West Virginia University, Morgantown, WV, United States, University of Rhode Island, Kingston, RI, United States, 3University of Maryland, College Vernon Ngulube1, Rabson Zimba2, Lambwa Chomba3, Philippa Park, MD, United States Crooks4, Oswell Katooka5, David A. Larsen6, Chinyama Lukama5, Diarrheal diseases continues to pose a severe threat in tropical regions Abel Manangi5, Laurie Markle2, Selenia Matimelo5, Paul Mboshya5, where WASH facilities remain marginal and are prone to destruction. Sarrah Muleya7, Engervell Musonda5, Nicolas Osbert4, John With limited efficacy of vaccines, it is important to device alternate Pinfold4, Scott Russpatrick2, Amy Tiwari2, Benjamin Winters2 methods to determine environmental conditions favorable for diarrheal 1 Ministry of Local Government and Housing, Luapula Province, Zambia, diseases. Outbreaks of several vibrio (V. cholerae., V. vulnificus, V. 2 3 Akros, Lusaka, Zambia, Chomba Chiefdom, Chiengi District, Zambia, parahaemolyticus) have characteristic signatures that are associated with 4 5 UNICEF Zambia Country Office, Lusaka, Zambia, Ministry of Local large scale climatic processes. Here, using cholera as one of the signature 6 Government and Housing, Lusaka, Zambia, Syracuse University, Syracuse, diarrheal disease, we present a framework coupling hydrological and 7 NY, United States, Government Council, Chiengi District, Zambia microbiological understanding with satellite remote sensing data to predict Open defecation is a leading risk factor for the transmission of diarrheal environmental conditions for outbreak in several regions of sub-Saharan disease and soil-transmitted helminths. To become open defecation free Africa. Hydroclimatic processes, primarily precipitation and temperature (ODF) households must have access to a latrine with various adequacy are found to be strongly associated with epidemic and episodic outbreak parameters including a smooth, cleanable floor, a lid and a hand-washing of cholera. Using spatial land surface temperature (LST) data from station with soap or ash. Zambia has adopted community-led total satellites along with water accessibility data and population data, we have sanitation (CLTS) as country policy in rural areas. CLTS is a behavior change developed an algorithm to classify regions at risk to cholera. A case study communication campaign where communities are “triggered” through has been piloted to implement the algorithm in five epidemic regions e.g. a discussion about open defecation and consequences of the behavior. Mozambique, Central African Republic, Cameroon, South Sudan and Communities then construct their own latrines. With support from UNICEF, astmh.org 548 Rwanda. Conditions for occurrence of cholera were detectable at least one night. Despite having toilets in their compounds, accessing them after month in advance. Additionally, we will present framework for prediction dark presents severe threat to their personal safety. As a result, women of V. vulnificus, V. parahaemolyticus in several coastal regions of US. are forced to rely on various unhygienic means of relieving themselves. Although fewer women stated they have been attacked while collecting 1791 water, more than 23% reported they felt insecure to gather water for their households at night. Data from semi-structured interviews with 20 women POPULATION-LEVEL INDOOR PM2.5 EXPOSURE ASSOCIATED also revealed a fear of violence or threat in accessing WASH facilities WITH HOUSEHOLD SOLID FUEL USE FOR THE ESTIMATION within the community. Preliminary results demonstrate installing WASH OF THE GLOBAL BURDEN OF HOUSEHOLD AIR POLLUTION infrastructure does not always ensure regular usage in communities, when (GBD 2013) there is an underlying threat of gender-based violence. The lack of safe toilet access at night may give rise to the use of other unsanitary methods Astha KC, Victoria Bachman, Tiffany Ku, Mohammad H. of waste disposal, may force a woman to wait until daylight hours, and/or Forouzanfar, GBD Household Air Pollution Expert Group create psychosocial stress all of which can result in other public health risks Institute for Health Metrics and Evaluation, University of Washington, for women and their families. A systematic and holistic approach is needed Seattle, WA, United States to address gender-based violence to ensure safer and higher access to WASH facilities by the women. Published evidence suggests that there is notable heterogeneity in PM2.5 exposure distribution across geographies due to various socioeconomic and environmental factors. However, there has been limited effort to 1793 quantify average PM2.5 exposure associated with household solid fuel EXPLORING THE IMPACT OF HARMFUL ALGAL BLOOMS use while accounting for this variation. To address this evidence gap, (HABS) ON THE HEALTH OF COASTAL COMMUNITIES IN THE we estimated the population-level PM2.5 exposure associated with household solid fuel use with uncertainty for 138 developing countries GULF OF GUAYAQUIL, ECUADOR from 1980 to 2013.We updated the Global Household Air Pollution Mercy J. Borbor-Cordova1, Gladys Torres2, Bonny Bayot1, J. Database by conducting a systematic review to include studies published Rafael Bermúdez1, Luis Escobar1, Stuart Hamilton3, G. Cristina as of January 2015. The final database comprised of 67 studies conducted Recalde1, Sadie Ryan4, Anna Stewart-Ibarra5 in 16 countries from 8 regions. First, mean 24-hour kitchen PM2.5 1Escuela Superior Politecnica del Litoral, Guayaquil, Ecuador, 2Instituto concentration was estimated using a linear mixed effect model with Oceanografico de la Armada del Ecuador, Guayaquil, Ecuador, 3Salisbury maternal education as a covariate and nested random effect for GBD University, Salisbury, MD, United States, 4Department of Geography and super region, region, and country. Then, ratios of personal exposure to Emerging Pathogens Institute, University of Florida, Gainsville, FL, United average 24-hour kitchen PM2.5 concentration for men, women, and States, 5Center for Global Health and Translational Science, SUNY Upstate children were calculated separately. Finally, average personal exposure Medical University, Syracuse, NY, United States was calculated for men, women, and children by applying the ratio of personal exposure and kitchen concentration to the average 24-hour Here we present a methodological framework and initial findings from kitchen PM2.5 concentration for all 138 countries.Our analysis showed a transdisciplinary study of harmful algal blooms (HABs) and public that mean PM2.5 exposure associated with household solid fuel varies health effects in coastal Ecuador. There is a growing scientific consensus geographically. Maternal education was a significant predictor of mean that the public health and economic impacts of HABs are indicative of 24-hour PM2.5 kitchen concentration (p-value: 0.016). The estimated a global epidemic. We have developed a methodological framework to mean 24-hour PM2.5 kitchen concentration was highest in Ethiopia 691 explore the natural and anthropogenic drivers of HABs (red tides) in an µg/m3 (95% CI: 226-1750) and lowest in Costa Rica 103 µg/m3 (95% CI: estuarine-coastal gradient, and the potential linkages to the public health 14.5-396) in 2013. The pooled ratio of personal to kitchen area PM2.5 of three coastal communities in the Gulf of Guayaquil, Ecuador. Previous concentration was highest for women 0.73 (95% CI: 0.66-0.81) and research identified more than 100 “red tide” events in the gulf since lowest for men 0.43 (95% CI: 0.37-0.50).Informed by a global database 1968; about 77% of these were associated with the death of fish, birds, spanning 16 countries our model captured geographic variation in indoor or shrimp; however, there is a lack of specific epidemiological information PM2.5 exposure that was instrumental in estimating the global burden linking HABs to local public health impacts. To address this gap, we are of household air pollution for GBD 2013. Future estimates would benefit conducting a comprehensive eco-epidemiological study through the from more direct exposure measurements by enriching the sparse PM2.5 following: a) A historical reconstruction (2000-2014) of climate-ocean data landscape. and anthropogenic conditions associated with HABs events to identify potential triggers, b) an assessment of health practitioners’ knowledge 1792 and risk perception to explore local health effects of HABs, and c) an ecological study of the ocean-biological conditions that favor the presence CHALLENGES FOR WOMEN IN ACCESSING WATER AND and/or dominance of algae associated with toxins through an analysis of SANITATION FACILITIES IN PERI-URBAN SLUMS OF KENYA remotely sensed imagery and prospective field data collections. This study is being conducted in partnership with Ministry of Health, as establishing Poulomy Chakraborty, Alyson Young, John D. Anderson, a collaborative partnership with public health staff and key local Richard D. Rheingans stakeholders from the outset will ensure a participatory process to identify University of Florida, Gainesville, FL, United States potential interventions and public health priorities surrounding this largely The vulnerability surrounding insecurity and threat experienced by women unexplored public health issue. when they seek to meet their and their family’s daily water and sanitation needs, are not much researched and addressed. A high proportion of 1794 women in the developing world are subjected to violence, assault and POLLUTION STUDIES ON THE LOWER MISSISSIPPI threat on their daily commutes to fulfill water and sanitary requirements, most of which remain undocumented. This analysis uses quantitative and MISSISSIPPI RIVER IN PORT GIBSON AREA, MISSISSIPPI qualitative data from a larger cross-sectional study on water, sanitation and DURING THE FALL OF 2013 hygiene (WASH) disparities in peri-urban slums of Kisumu, Kenya during Alex D. Acholonu, Amber Tatum 2014-15. Of the 734 interviewed women, more than 94% had access to Alcorn State University, Alcorn State, MS, United States toilets. However, more than one-third reported that they felt insecure to access their toilets at night and approximately 11% said they had faced Water is critical for the survival of living things including man. It is some form of attack, threat or assault on their way to access toilets at the driver of life. Its quality is closely associated with the surrounding astmh.org 549 environment and the use made of it. It may also depend on whether the 1796 water body is lentic or lotic. The purpose of this study was to determine if the Mississippi River in the area of Port Gibson,MS was polluted and UNDERNUTRITION, DIARRHEA AND BREASTFEEDING IN compare the result with the Mississippi Water Quality Criteria (MSWQC) UNDER-FIVE - BENGO PROVINCE, ANGOLA and/or the Environmental Protection Agency(EPA) Standard. Water 1 2 2 3 samples were collected from the Mississippi River in Port Gibson Area in Miguel Brito , Ânia Soares , Cláudia Fançony , António Martins the Fall of 2013 for three consecutive times and tested with the LaMotte 1CISA - Health Research Centre in Angola/ESTeSL, Caxito, Angola, 2CISA - water pollution test kits. The physical characteristics of the river were Health Research Centre in Angola, Caxito, Angola, 3Diretor Provincial de taken including the temperature and recorded. The following chemical Saude, Caxito, Angola parameters were tested and analyzed: total alkalinity, ammonia-nitrogen, New interventions to reduce undernutrition should be design taking into calcium, carbon dioxide, chlorine, cooper, dissolved oxygen, magnesium, account their basic, underlying and immediate causes, since nutrition nitrate, hardness, pH, phosphate, and salinity. The parameters tested is capable of maximize health and minimize morbidity and mortality met the Mississippi Water Quality Criteria (MSWQC) with the exception in early childhood. This study aims to identify factors associated with of total alkalinity, hardness, and phosphate which exceeded the criteria. undernutrition (wasting, stunting and underweight) among children Coliform bacteria were present in the river water showing evidence of aged less than 5 in Bengo province, Angola. A total of 803 children aged bacteria contamination and the fact that the water was not potable or was 0 to 59 months were surveyed. Logistic regression analysis was used to unsanitary for human domestic use. examine undernutrition against a set of variables associated with health and water. Children nutritional status was classified as underweight, 1795 stunted and wasted if their Z-scores for weight-for-age (WAZ), height-for- ANTIBIOTIC RESISTANCE OF ENTEROBACTERIA IN TWO age (HAZ) and weight-for-height (WHZ) were less than -2.0 SD of WHO (2006) standards. Children in this study aged mainly 0-23 months (43%), WASTEWATER TREATMENT PLANTS OF TWO PERI URBAN 50.8% were males, 36% were currently breastfeeding, 34% had diarrhea COMMUNITIES OF LIMA, PERU in the last two weeks and 53.4% of the mothers does not treat water. Francesca Schiaffino1, Noelia Angulo1, Alejandro Florentini1, The prevalence of wasting was 5,6%, stunting 30.7 % and underweight Josmel Sevillano1, Cusi Ferradas1, Margot Faustino1, Lilia Cabrera2, 29.0%. The most significant factors for wasting were age (OR 4.5, 2.1-9.3 Martiza Calderón1, Pablo Tsukayama3, Gautam Dantas3, Robert H. risk for 0-23 age), being breastfeed (OR 4.0, 2.0-7.7) and having diarrhea Gilman4 episodes (OR 2.0, 1.0-3.7). The most significant factors for stunting were mother´s education (OR 0.5, 0.2-0.9 for mother with secondary or higher 1Universidad Peruana Cayetano Heredia, Lima, Peru, 2Biomedical Research education), age (OR 0.5, 0.4-0.8 risk for 0-23 age) and being breastfeed Unit, A.B. PRISMA, Lima, Peru, 3Dantas Lab, Washington University in St. (OR 0.4, 0.3-0.6). The most significant factors for underweight were age Louis, St. Louis, MO, United States, 4Department of International Health, (OR 1.7, 1.1-2.6 risk for 0-23 age class), being breastfeed (OR 1.7, 1.1- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United 2.7) and having diarrhea episodes (OR 1.9, 1.3-3.1).The high frequency States of reported untreated drinking water in this study may be related to the The increased use of antibiotics in human medicine and agriculture in occurrence of enteric pathogens, and consequently to the occurrence recent decades has introduced significant selective pressures on bacterial of the diarrhea episodes reported here. On the other hand, our results populations in virtually all human-associated environments and lead to suggest that breastfeeding may have a protective effect on the occurrence the evolution of multidrug-resistant bacteria that compromise our ability of stunting. Despite the need further investigation, our results suggest to treat infectious disease. Build environments, such as wastewater the existence of preventable morbidity triggered by undernutrition. treatment plants (WWTP) have already been identified as reservoirs of Community-based education intervention could represent good strategies antibiotic resistance genes with high potential for introduction into natural to reduce undernutrition. environments. Previous studies regarding the presence of antibiotic resistance bacteria have not been performed in sewage and WWTP in 1797 the peri urban shantytowns of Lima, Peru. This is the first report of the isolation and antibiotic resistance of specific Enterobacteria from two LABORATORY SURVEY FOR THE PREVALENCE OF ENTERIC WWTP of the districts of San Juan de Miraflores (SJM) and Villa El Salvador BACTERIA IN RESTAURANTS IN THE PERUVIAN AMAZON (VES), Lima, Peru. A longitudinal sampling was performed from September (IQUITOS, PERU) 2014 until February 2015 in the WWTP of SJM and VES, Lima, Peru. 1 1 1 Influent and effluent water samples were taken during each sampling date Colin R. Andrews , Mona Lotfipour , Andrew Rogers , Melita 2 2 2 2 from each WWTP. Total coliforms, strain isolation and antibiotic resistance Pizango , Ricardo Abadie , Rosa Burga , Claudio Rocha , Hamilton 3 1 to 12 different antibiotics was determined. Antibiotic resistance ranged Tilley , David Craft as follows: 10 to 80% for affluent VES samples, 80 to 100% for VES 1Pennsylvania State University College of Medicine, Hershey, PA, United effluent samples, 30 to 100% for affluent SJM samples and 70 to 80% for States, 2Navy Medical Research Unit No. 6, Lima, Peru, 3Navy Medical effluent samples. Regarding individual antibiotic resistance, SJM affluent Research Unit 6, Lima, Peru and effluent samples were 100% resistant to CF and SXT while effluent Food and water-borne pathogens are a common and preventable source samples where 66.6% resistant to CTR. Affluent and effluent samples of diarrheal illness and death worldwide, especially in countries with from VES where 100% resistant to CIP and effluent samples had high limited public health infrastructure. A contributing factor to diarrheal resistance percentages to CXM (85.7%), NIF (85.7%) and SXT (87.5%). illness may be the hygiene and sanitation practices of restaurants. This Isolated bacterial strains included E. coli, Enterobacter spp., Citrobacter study investigates the prevalence of pathogenic and commensal enteric spp., Serratia spp., Klebsiella pneumonie, and Salmonella spp. In bacteria in restaurants in Iquitos, Peru. A total of 17 restaurants were conclusion, results show that effluent waters do carry rasistant bacterial asked to consider participating in the study. Sixteen gave permission to strains into the environment, including pathogenic bacteria. Further studies team members to collect an average of 9 food and food preparation are needed to evaluate bacterial resistance genes and their behavior in contact surface sites for microbiological analysis. Samples were collected WWTP and their re-entrance into the community’s environment. by swab in transport media and delivered that day to the microbiology laboratory. A total of 1,280 restaurant samples were cultured for enteric bacterial pathogens (Salmonella, Shigella, Campylobacter and Aeromonas) and also for the presence of normal enteric flora using standard culture techniques. Culture results were then stratified by average cost per meal at the restaurants. Water was also collected astmh.org 550 from each restaurant for fecal coliform analysis. Salmonella, Shigella, 1799 Campylobacter, and Aeromonas spp. were isolated from 16 samples (0, 3, 0, and 13, respectively) at 10 of 16 (63%) restaurants. Other fecal IN FIELD ASSESSMENT OF MALARIA RAPID DIAGNOSTIC flora, most commonly E. coli, Proteus, Enterobacter, or Klebsiella, were TEST PERFORMANCE BY COMMUNITY HEALTHCARE isolated from 30 foods/juices and 35 surface sites at 15 of 16 (94%) WORKERS restaurants. Five of 16 (31%) restaurants yielded positive coliform counts from their water sources including at least one restaurant in each cost Nora Zwingerman1, Marcela Cancino2, Santiago Ferro2 stratified group (1 low, 1 medium, 1 high, and 2 very high cost). Our study 1University of Toronto, Toronto, ON, Canada, 2Fio Corporation, Toronto, demonstrates the presence of enteric pathogens and normal human fecal ON, Canada flora in the food, water, and preparation surfaces in restaurants in Iquitos, Under ideal conditions, the accuracy of malaria rapid diagnostic tests Peru. While this study does not clarify the relationship between enteric (RDTs) is considered equivalent to routine microscopy. However, in the contamination in restaurants and community diarrheal disease, there was field inaccurate test results may occur because of defective RDTs, human no significant correlation between average cost of meal and the presence processing errors and/or errors reading test results. Data ascertained of enteric bacteria. Future studies include observational and laboratory from 9 implementation studies of Fionet system was used to evaluate the assessments longitudinally and development of public health based frequency of these errors during routine use of malaria RDTs by healthcare intervention and education strategies. workers. In each study, healthcare workers received training on processing RDTs and integrated an automated RDT reader into their point-of-care 1798 case management. The reader features in-process quality control and FLIPPING THE SWITCH TO ACCURATELY DIAGNOSE automated test interpretation for malaria RDTs. In 4 of the 9 studies the MALARIA: A COMPARISON OF CLINICAL DIAGNOSIS, RAPID workers were blinded to device results allowing an evaluation of in field reading of test results. In these four studies, a total of 19,212 malaria RDTs DIAGNOSTIC TEST (RDT), MICROSCOPY AND PCR IN THE were processed and had overall agreement of 91.76% (kappa=84.45%). DIAGNOSIS OF MALARIA IN CAMEROON A stronger agreement (96.39%; kappa=92.45%) was observed when the Kenji O. Mfuh1, Olivia A. Achonduh-Atijegbe2, Rose G. Leke3, device had a positive or negative test result, consistent across all studies. Diane W. Taylor1, Vivek R. Nerurkar1 The discordant results predominantly occurred when the device indicated a quality control warning and the user interpreted that RDT. All nine studies 1Department of Tropical Medicine Medical Microbiology and Pharmacology were used to evaluate the proportion of RDTs with quality control warning. University of Hawaii, Honolulu, HI, United States, 2Northern Pacific The quality control issues were categorized into two main groups: faulty Global Health Program, University of Hawaii, Honolulu, HI, United States, RDTs (e.g. no control line, smearing) and human processing errors (e.g. 3Biotechnology Center-University of Yaounde I, Yaounde, Cameroon incorrect volume or placement of solutions, delayed reading, interpreting Accurate diagnosis of malaria is vital for effective disease management the wrong RDT). A total of 31,705 tests conducted by 151 healthcare and control. In Cameroon, presumptive diagnosis, RDT and microscopy workers were analyzed. There were approximately twice as many (~2200) are commonly used in malaria diagnosis. However, these methods lack human processing errors compared to any other error type. A random- sensitivity to detect low grade asymptomatic infections. PCR on the other effects meta-analysis, using Freeman-Tukey transformation, was used to hand permits the detection of sub-microscopic parasitemia that could be a estimate the average proportion of errors across users and studies. The potential roadblock as malaria endemic countries progress towards malaria meta-analyses estimated 7.61% (95% CI: 6.57%, 8.76%) errors due to elimination. In this study we compared the diagnostic test performance human processing across. RDT brand was associated with the proportion of clinical diagnosis, microscopy and RDT against PCR in the diagnosis of defective RDTs. These errors can jeopardize the accuracy of the results. of malaria. Blood samples were collected from 380 febrile children from Quality assurance devices would help prevent the use of compromised test Yaoundé and Maroua, Cameroon between February 2014 and October results. 2014 and their files were reviewed at the end of their hospital visit for clinical diagnosis of malaria. Microscopy, RDT and PCR based prevalence 1800 of malaria was 40% (151/380), 56% (213/380) and 63% (239/380), respectively. However, 95% (361/380) participants were presumed to EFFECTS OF INTRODUCING MALARIA RAPID DIAGNOSTIC have malaria based on fever, of which 34% (122/361) were negative by TESTS IN DRUG SHOPS: FINDINGS FROM THE EVALUATION PCR and 85% were prescribed quinine. PCR detected 88 and 26 more OF A CLUSTER RANDOMIZED TRIAL IN UGANDA malaria infections than microscopy and RDT, respectively. As compared to 1 2 3 PCR, the sensitivity of microscopy, RDT and clinical diagnosis was 51%, Anthony K. Mbonye , Pascal Magnussen , Eleanor Hutchinson , 3 3 4 72% and 99%, respectively; however the specificity was 93%, 62%, Kristian S. Hansen , Sham Lal , Sian E. Clarke and 3.3%, respectively; positive predictive value was 94%, 88% and 1Ministry of Health/Makerere University School of Public Health, Kampala, 63%, respectively; negative predictive value was 55%, 38% and 70%, Uganda, 2Centre for Medical Parasitology, University of Copenhagen, respectively. Thus, 34% of cases diagnosed as malaria were actually fever Copenhagen, Denmark, 3ACT Consortium, London School of Hygiene & cases caused by other pathogens. Eighty-eight (88) sub-microscopic Tropical Medicine, London, United Kingdom, 4London School of Hygiene & infections were identified by PCR in the study population, suggesting Tropical Medicine, London, United Kingdom that PCR may be the best tool for accurate diagnosis and control of WHO recommends universal access to malaria diagnosis, encompassing malaria since the presence of sub-microscopic malaria infections may be all treatment providers, including the private sector. Rapid diagnostic tests a potential hindrance towards malaria elimination. The development of a (mRDTs) provide a feasible means of confirming malaria diagnosis in drug rapid PCR based test to diagnose malaria could flip the switch to accurate shops. As yet, there is limited evidence of the effect of diagnostic testing diagnosis, control and elimination agenda of malaria. on antimalarial sales and referral practices by drug shops in Africa. A cluster-randomised trial to evaluate the impact and cost-effectiveness of using mRDTs, compared with presumptive treatment, undertaken in 65 registered drug shops in Mukono District, Uganda in 2010-12, was one of the first investigations of the impact of introducing mRDTs in the private retail sector. Analysis of data routinely recorded by drug shop vendors (DSVs) during the trial found use of mRDTs in drug shops was highly acceptable to both vendors and clients; a finding confirmed by household interviews in a random sample of patients. Adherence to mRDT test results

astmh.org 551 by DSVs was high with over 95% of treatment decisions consistent with Due to low specificity which could lead to enrolment of patients without mRDT result, reducing sales of ACTs by 40% compared to drug shops malaria parasites, mRDTs should only be used for initial screening and all using presumptive diagnosis. Validation of DSV treatment decisions by positive cases must be confirmed with microscopy. expert microscopy demonstrated that mRDT testing substantially improved the targeting of ACTs to patients with malaria parasites (72.9% of ACT 1802 treatments in shops using mRDTs were correctly targeted vs 33.7% in shops using presumptive diagnosis, P<0.001). Qualitative and economic A NON-AMPLIFICATION, OLIGONUCLEOTIDE-BASED evaluations amongst drug shop vendors, patients and local health staff, SANDWICH HYBRIDIZATION ASSAY FOR THE DETECTION OF conducted alongside the trial, revealed how pre-existing relationships PATHOGENS IN BLOOD between DSVs and their clients, and between DSVs and the wider health system shaped the response of drug vendors to the intervention and may Bryan Grabias, Sanjai Kumar have contributed to the high adherence to mRDT results. Potential for less Food and Drug Administration, Silver Spring, MD, United States desirous unintended consequences was also revealed. A synthesis of the Novel technologies for the sensitive and reliable detection of infectious insights generated by this early ground breaking trial in the retail sector agents in blood are still needed. While the standard method of nucleic will be presented, drawing evidence from across the epidemiological, acid-based pathogen detection generally relies on PCR amplification ethnographic and economic investigations conducted as part of the study, of target DNA or RNA, complex genome sequences can be resistant to illustrate the potential benefits and pitfalls of introducing mRDTs into to amplification, due to factors such as secondary or tertiary structure, drug shops. and the potential for nonspecific amplification or sample interference could result in false positive or false negative results. Here, we describe 1801 a novel nanoparticle-based sandwich hybridization assay (SHA) for the detection of Plasmodium falciparum and Babesia microti parasites PERFORMANCE OF MALARIA RAPID DIAGNOSTIC TESTS without the need for amplification of target sequences in genomic DNA. FOR SCREENING OF PATIENTS TO BE ENROLLED IN CLINICAL A uniquely identifiable “barcoded” magnetic microbead and biotinylated TRIALS AND RELATED STUDIES silica nanoparticle are conjugated to either P. falciparum- or B. microti- Deus S. Ishengoma1, Alex Shayo2, Celine Mandara1, Vito Baraka1, specific 30-mer oligonucleotides corresponding to sequences of the 18S Rashid Madebe1, Deogratias Ngatunga2, Erasmus Kamugisha3, ribosomal gene. For each parasite, the magnetic microbead and silica Samuel Gesase1, Esther Ngadaya4, Janneth Mghamba5, Ritha nanoparticle bead sets hybridize to a unique but adjacent region in the Njau6, Renatha Mandike7, Sigsbert Mkude7, Ally Mohamed7, Joram genome. Parasite burden can then be quantified and analyzed upon the Buza2, Martha Lemnge1 binding of an Avidin-PE fluorophore to the target capture complexes via a Bio-Plex 200 instrument. Determination of the analytical sensitivity of 1National Institute for Medical Research, Tanga, United Republic of the SHA for short complementary oligonucleotide sequences revealed a Tanzania, 2The Nelson Mandela African Institution of Science and limit of detection of 10-10 M for both P. falciparum and B. microti probe Technology, Arusha, United Republic of Tanzania, 3Catholic University sets. Analytical sensitivity studies conducted by spiking human blood of Health and Allied Sciences, Mwanza, United Republic of Tanzania, with known counts of parasites revealed that SHA can reliably detect up 4National Institute for Medical Research, Dar es Salaam, United Republic to 10 P. falciparum- or B. microti-infected red cells per mL of blood. of Tanzania, 5Ministry of Health and Social Welfare, Dar es Salaam, For comparison, in our hands PCR can detect 100 P. falciparum- or United Republic of Tanzania, 6World Health Organization Country Office, 1000 B. microti-infected red cells per mL of spiked blood. Thus, SHA Dar es Salaam, United Republic of Tanzania, 7National Malaria Control offers a 10-100 fold enhanced sensitivity for the detection of these two Programme, Dar es Salaam, United Republic of Tanzania intraerythrocytic parasites of global public health significance. Studies Malaria rapid diagnostic tests (mRDTs) are widely used for malaria to determine the clinical sensitivity of SHA for these pathogens are in diagnosis, but their applicability in clinical trials for patients screening progress. Details of the method development and sensitivity and specificity and management has not been well assessed. This study assessed the data will be presented. performance of mRDTs when used for screening of patients to be enrolled in clinical trials and other studies, particularly in areas with progressively 1803 declining malaria burden. The data was obtained from studies conducted at five health facilities (HFs) of Mkuzi and Muheza, Nachingwea, Rubya AUTOMATED DETECTION OF MALARIAL RETINOPATHY FOR and Ujiji in four districts of Muheza, Nachingwea, Muleba and Kigoma, HIGHLY SPECIFIC DIAGNOSIS OF CEREBRAL MALARIA respectively. Patients aged ≥6 months were screened with mRDTs Vinayak Joshi1, Carla Agurto1, Sheila Nemeth1, Eduardo Simon followed by microscopy for possible inclusion in clinical trials and other Barriga1, Peter Soliz1, Ian MacCormick2, Terrie Taylor3, Susan studies. The performance of mRDTs was compared with microscopy Lewallen4, Simon Harding2 as a gold standard, and factors affecting their accuracy were explored using multivariate logistic regression models. Of the 1,914 participants 1VisionQuest Biomedical LLC, Albuquerque, NM, United States, 2University screened; 1,188 (62.1%) and 1,019 (53.2%) were positive by mRDTs and of Liverpool, Liverpool, United Kingdom, 3Michigan State University, microscopy, respectively. Parasite positivity rates (by microscopy) were East Lansing, MI, United States, 4Kilimanjaro Centre for Community higher at all sites (>50.0%) except Nachingwea (with 35.8%). mRDTs Ophthalmology, Cape Town, South Africa had high sensitivity (>97% at all sites) while the specificity was relatively Cerebral malaria (CM) is a lethal clinical syndrome that claims the lives of lower (64.9% - 88.7%). After adjusting for age of patients, fever status about 584,000 people annually, 75% of whom are African children. As , site and the study type, the sensitivity of mRDT was significantly higher many as 23% of these cases are misclassified when the standard clinical in patients with parasite density ≥4000 asexual parasites/ul (OR=6.30, case definition for CM is used. When malarial retinopathy (MR) detection p=0.003). The specificity of mRDT was lower (64.9 - 87.7% ) and similar is included in the case definition, the specificity and positive predictive at all sites even after adjusting for the effects of fever status and age of value (PPV) of the CM diagnosis is greatly increased, and other causes of participants (p≥0.525), except at Muleba and Ujiji where the specificity coma can be sought in patients who are retinopathy-negative. Detection was significantly lower (p≤0.007) due to high rates of false positive mRDT of MR currently requires expensive equipment and well-trained personnel results. In conclusion, the high sensitivity of mRDTs indicate that they can and is thus limited only to research settings in malaria-endemic areas in be useful for screening to exclude majority of the patients without malaria Africa. We used retinal images from 175 Malawian pediatric patients with and save time and other resources which would be used for microscopy. MR, captured using a Topcon 50-EX camera to develop and test software algorithms for detecting the presence of MR, and of its associated retinal lesions. Performance assessment was made against manual image grading astmh.org 552 as the reference standard. The software achieved specificity of 100% 1805 and sensitivity of 95% for MR detection. The individual specificities for detecting retinal abnormalities associated with MR were 91% for retinal CONDITIONS THAT LEAD TO POLYANDROUS BEHAVIOR IN whitening, 100% for vessel discoloration, and 96% for white-centered THE YELLOW FEVER MOSQUITO AEDES AEGYPTI retinal hemorrhages. The system also detects papilledema, a condition associated with death due to raised intracranial pressure, with 100% Ethan C. Degner, Laura C. Harrington sensitivity and 81% specificity. The proposed MR detection system can Cornell University, Ithaca, NY, United States improve the PPV for diagnosis of CM from 68% (using current clinical Upon insemination, Aedes aegypti females receive seminal fluid proteins standard) to 98%. Our MR detection system integrates a low-cost and from males that render them refractory to subsequent mating. This portable retinal imaging camera with software developed to detect MR. response is often assumed to be immediate, complete, and lifelong. This system is designed to be used by non-ophthalmic personnel with Nonetheless, several studies have found that polyandry can occur in Ae. minimal training in low-resource clinical environments. aegypti, but little attention has been paid to the circumstances that result in polyandry. This promiscuity could have far-reaching implications. For 1804 example, polyandrous behavior could hinder inundative release strategies, LOT TESTING OF MALARIA RAPID DIAGNOSTIC TESTS: which often rely on the assumption of monandry. To our knowledge, no study has determined the timing of the onset of refractoriness, and the ACHIEVEMENTS AND LESSONS LEARNED FROM A SEVEN degree to which monandry is maintained over time remains unresolved. YEARS-LONG EXPERIENCE By using males with fluorescently labeled sperm to identify polyandrous Sandra Incardona1, Jennifer Luchavez2, Sina Nhem3, John females, we determined how soon females become refractory to Barnwell4, Nora Champouillon1, Peter Chiodini5, Christian Anthony additional inseminations and how this refractoriness wanes as females Luna2, Didier Ménard3, Rathana Meth3, Roxanne Rees-Channer5, age. We also determined the reproductive success of first and second Johanna Beulah Sornillo2, David Richard Bell6, Jane Cunningham7, males under these circumstances. This study clarifies the role of polyandry Iveth Jimena Gonzalez1 in the mating system of this important vector and will ultimately guide vector control strategies, predictive models, and experimental design. 1Foundation for Innovative New Diagnostics, Geneva, Switzerland, 2Research Institute for Tropical Medicine, Manila, Philippines, 3Institute Pasteur of Cambodia, Phnom Penh, Cambodia, 4Centers for Disease 1806 5 Control and Prevention, Atlanta, GA, United States, Hospital for Tropical HUMAN ADAPTATION TO CLIMATE CONTRIBUTES TO AEDES Diseases, London, United Kingdom, 6Intellectual Ventures, Seattle, WA, AEGYPTI ABUNDANCE IN THE SOUTHERN MARGINS OF ITS United States, 7World Health Organization, Geneva, Switzerland AUSTRALIAN DISTRIBUTION Malaria Rapid Diagnostic Tests (RDTs) have played a key role in fever case 1 2 3 management since the 2010 WHO recommendation that every suspected Brendan Trewin , Jonathan Darbro , Myron Zalucki , Greg 2 4 1 malaria case should be confirmed by parasitological diagnosis before Devine , Cassie Jansen , Nancy Schellhorn treatment. Sales of RDTs have increased from 46 million in 2008 to 319 1CSIRO, Brisbane, Australia, 2QIMR Berghofer, Brisbane, Australia, million in 2013. The wide range of commercially available products, 3University of Queensland, Brisbane, Australia, 4Queensland Health, with variable quality reported in field studies, led to the creation of the Brisbane, Australia WHO-FIND Malaria RDT Evaluation Programme that aims at providing The dengue vector Aedes aegypti has been identified in new areas south independent comparative performance data to guide procurement of the species’ core Australian distribution. It has been hypothesized (Product Testing) and comprehensive lot verification prior to deployment that an expansion by Ae. aegypti into these regions would require in countries (Lot Testing). The Lot Testing Programme specifically, with large water bodies that buffer extremes in temperature and humidity. As its two reference laboratories in Cambodia and the Philippines, has part of the human response to drought in the early 2000s, government provided quality data for more than 3600 RDT lots since 2007. RDTs are rebates were offered on large water storage containers such as rainwater tested against frozen blood samples collected from malaria patients, tanks (RWT). The installation of over 200,000 RWT has resulted in new standardized at 200 parasites per microliter of blood. The observed mean habitats for container-breeding mosquitoes throughout the region. Surveys failure rate of 1.85% is notably low, reflecting the fact that Lot Testing is have demonstrated that RWT are key containers for mosquito breeding, mainly requested by large funding/procurement agencies selecting only however little is known about the role RWT play in vector abundance in products meeting the WHO recommended minimum performance criteria cool and dry range margins. The current study was designed to investigate for procurement. The number of lots tested annually has increased from how RWT can contribute to a localized population of Ae. aegypti. To 59 to 927 in the last 7 years, with the 2014 testing volume covering an do this we divided the urban landscape into three categories: premises estimated 210 million RDTs, equivalent to 66% of the RDT market. Lot- with an exposed RWT, those with a sealed RWT and those with no RWT. tested RDTs were distributed in 48 countries, with 88% of RDTs destined Ovitraps and Gravid Aedes Traps (GAT) were used to measure adult for sub-Saharan Africa. Lot Testing informs not only parasite detection population abundance. Traps were retrieved and reset fortnightly for ten but also may reveal RDT anomalies, such as red background, incomplete weeks, and eggs were counted and reared to fourth instar for counting clearing, or problems with kit accessories. The reporting of issues observed and identification after each collection. Inspections of study site and on single-use buffer vials in particular has triggered the release of an surrounding premises documented characteristics of house construction Information Note to Users by the WHO and field corrective actions by RDT and surrounding urban environment. A multivariate time-series analysis manufacturers. The Lot Testing Programme plays a key role in encouraging will be performed to examine the effect of the predictor variables on each manufacturers to maintain the required level of quality from lot to lot. of the response variables at the scale of the study premises and the study Work is now underway to transition to a decentralized self-funding premises plus their neighbours. Results will be presented. Our results show system, and build local capacity in 12 pilot countries for lot testing in the effect that exposed RWT have on the abundance of Ae. aegypti national reference laboratories. when compared with a sealed RWT or no RWT present. The current trend of water storage in Australia is similar to a century ago, when Ae. aegypti was present and dengue epidemics occurred. Likewise, similar rebate schemes and drought conditions in the United States are increasing the number of large water containers in urban environments, and could provide a potential new habitat for the establishment of Ae. aegypti and other disease vectors.

astmh.org 553 1807 enhancement and suppression is critical for identifying systems where Wolbachia-based control is likely to succeed, for identifying potential EXPLORING HOST ORIENTED FLIGHT AND SPATIAL ASPECTS points where Wolbachia-based control is likely to break down and fail OF INDOOR MOVEMENT OF ANOPHELES GAMBIAE USING in the field, and for planning risk mitigation strategies in the case of INFRA-RED VIDEO TRACKING unforeseen harmful outcomes. Josephine E. Parker1, Natalia Angarita-Jaimes2, Matthew Hall2, 1809 Maurane Riesen1, Fabian Mashauri3, Jackline Martine3, Catherine E. Towers2, David Towers2, Philip J. McCall1 A CROSS-OVER STUDY TO EVALUATE THE DIVERSION OF 1Liverpool School of Tropical Medicine, Liverpool, United Kingdom, MALARIA VECTORS IN A COMMUNITY WITH INCOMPLETE 2Optical Engineering Group, School of Engineering, University of Warwick, COVERAGE OF SPATIAL REPELLENTS IN THE KILOMBERO Coventry, United Kingdom, 3National Institute for Medical Research, VALLEY, TANZANIA Mwanza, United Republic of Tanzania Marta F. Maia1, Katharina Kreppel2, Deogratius Roman3, Valeliana Fundamental to security and shelter, the human home is exploited by Mayagaya3, Emanuel Simfukwe3, Neil Lobo4, Amanda Ross1, Sarah many parasitic arthropods, including many vectors of malaria that spend Moore1 the majority of their adult life bloodfeeding or resting in this environment. 1Swiss Tropical and Public Health Institute, Basel, Switzerland, 2University Successful vector control methods like indoor residual spraying (IRS) of Glasgow, Glasgow, United Kingdom, 3Ifakara Health Institute, and long-lasting insecticide-treated bednets (LLINs) exploit this behavior. Bagamoyo, United Republic of Tanzania, 4University of Notre Dame, Notre Though central to malaria reduction and elimination plans worldwide, Dame, IN, United States they have limitations with a further serious threat presented by rapidly emerging insecticide resistance. Identifying possible routes to improve Malaria elimination is unlikely to occur if vector control campaigns rely control of nocturnal indoor transmitted malaria is a recognized priority. entirely on treated bed-nets and indoor residual spraying. There is a need We investigated spatial activity of African Anopheles sp. during nocturnal for vector control tools that address vectors that bite outside sleeping host orientation to human subjects, within or without LLINs, using a video hours. Spatial repellents may be able to fill this gap. However it is unclear system to track flight activity of multiple mosquitoes at high resolution if malaria vectors will be diverted from households that use spatial over periods of 60 minutes or more. In tests exploring responses to repellents to those that do not. The present study was performed for human-occupied LLINs carried out in a hut in rural Tanzania, behavior of a period of 24 weeks in rural Tanzania. A total of 90 households were local An. arabiensis populations was remarkably similar to An gambiae recruited and a cross-over design was used to measure the density of s.s. Kisumu strain mosquitoes tested in the same environment and as resting and blood-engorged mosquitoes in 3 coverage scenarios using previously reported in our laboratory tests. In the absence of a bed net, 0.03% transfluthrin coils: 1) no coverage; 2) complete coverage and; approach, landing and biting activity of An. gambiae s.s. at unprotected 3) incomplete coverage. Human blood index of each malaria vector human hosts revealed consistent spatial behaviors during approach species was calculated for each scenario. Human landing collections were and departure from the host, most likely in response to thermal and performed and vector biting times were recorded. The main vectors were odor cues emanating from the supine human host. We used a different found to be Anopheles arabiensis and Anopheles funestus s.s.. Both video-tracking system incorporating retro-reflective screens to obtain 3D species fed outdoors, outside sleeping hours and on humans as well as flight tracks of An. gambiae as they approached and entered through animals. Data from human landing catches showed that the repellent a ‘window’ in response to a human host, in the laboratory. Analysis of coils reduced the number of An arabiensis by 80% but did not reduce flight trajectories provided evidence that trajectories passing through the the number of host seeking An. funestus, this may be due to potential window showed consistent patterns in flight elevation change during development of pyrethroid resistance which has been documented in room entry and exit. The value of these and related studies on the spatial the area. The repellent coils did not reduce indoor and outdoor resting aspects of mosquito behavior in the domestic environment is considered in densities of Anophelines nor cause a shift in the human blood index. terms of its contribution to basic knowledge of vector biology and to the No diversion of malaria vectors was measured. On the other hand, the search for new vector control tools and strategies. spatial repellent coils reduced the household densities of Culex spp. by 26%, and contributed to 19% diversion of Culex spp. to non-repellent 1808 users. There is strong evidence that large proportion of malaria exposure is not controlled by the current vector control strategy in the Kilombero POSITIVE AND NEGATIVE EFFECTS OF WOLBACHIA Valley. The use of 0.03% transfluthrin coils in this area is unlikely to result INFECTION ON ARBOPATHOGEN TRANSMISSION in malaria reduction since much biting occurred in the morning after coils had gone out. The behavioural responses of pyrethroid resistant 1 1 2 Jason Rasgon , Brittany Dodson , Laura Kramer , Grant L. mosquitoes and Anopheles funestus to spatial repellents needs to be 3 Hughes further investigated given the increasing importance of this vector in the 1Pennsylvania State University, University Park, PA, United States, area. 2Wadsworth Center, Albany, NY, United States, 3University of Texas Medical Branch, Galveston, TX, United States 1810 In field trials across the globe, a revolutionary experiment in vector-borne INSECTICIDES AND POLLUTION EXERT STRONG SELECTION disease control is underway. Artificial Wolbachia infections have been shown to render mosquitoes resistant to transmission of many human ON NEW CRYPTIC SUBGROUPS OF ANOPHELES GAMBIAE pathogens. Wolbachia-infected mosquitoes are currently being released in Colince Kamdem, Caroline Fouet, Stephanie Gamez, Bradley J. multiple countries in an attempt to control dengue virus. However, it has White become clear that Wolbachia infection does not always lead to pathogen University of California Riverside, Riverside, CA, United States suppression in insects. Multiple studies in a wide variety of vector and non-vector insect species suggest that Wolbachia can enhance certain Ongoing ecological adaptation and lineage splitting within the Afrotropical parasites and viruses in arthropods; a sobering reminder that the pathogen malaria vector Anopheles gambiae s.l. has the potential to mitigate inhibitory effects resulting from Wolbachia infection in some insects the effectiveness of both traditional and novel vector control tools. cannot and should not be generalized across vector-pathogen systems. We explored the population structure and identified targets of natural I will present mechanistic data demonstrating how Wolbachia can act selection in 888 individuals of this species complex collected from directly or indirectly to cause enhancement or suppression of vector-borne contrasting environments. We provide evidence for clear subdivisions pathogens. Understanding the specific mechanisms leading to pathogen within the two sister taxa An. coluzzii and An. gambiae sensu stricto. astmh.org 554 Genome scans of all the new cryptic subgroups reveal pervasive signatures prevelances and infection intensities of (co)-infections with Loa loa of strong selection around genes involved in metabolic or target-site (Ll), Mansonella perstans (Mp), Wuchereria bancrofti (Wb) and resistance to insecticides. Notably, a selective sweep containing at least Plasmodium falciparum (Pf) in 8 villages of eastern Cameroon using eight detoxification enzymes contributes to local adaptation of urban highly sensitive and specific quantitative PCR (qPCR) for multiple parasites subgroups that thrive in polluted breeding sites. Our results show that on archived dried blood spots (20 ul whole blood equivalent per 6mm human-induced selection can play a prominent role in driving mosquito spot per individual). Resident populations (n=1,144; age range: 2-90 population differentiation during the early stages of adaptive evolution years old) were parasitized with Mp (76%), Ll (38%) and Pf (33%), with potentially dire consequence for malaria control. but not with Wb. Co-infections (49%) were more common than single infections (40%), with 21% having Ll and Mp, 3% with Ll and Pf, 15% 1811 with Mp and Pf, and 10 % with Ll, Mp and Pf. Interestingly, those with all three infections (Ll/Mp/Pf) had significantly higher Ll microfilariae (mf) DIRECT, HOUSEHOLD-LEVEL EFFECTS OF SPATIAL counts than either single Ll (P=0.01) or double Ll/Mp (P=0.03) and Ll/ REPELLENTS FOR DENGUE CONTROL - A MODELING Pf (P=0.05) infected individuals. The estimated counts of Ll mf were ASSESSMENT positively correlated with the intensities of Mp mf (Regression coefficient =1.43; P<0.0001). Population assessments at the community level showed 1 1 1 Quirine A. ten Bosch , Nicole L. Achee , John P. Grieco , Neil F. that despite Mp and Ll both having overdispersed distributions -typical 1 2 3 2 Lobo , Amy C. Morrison , Robert C. Reiner Jr. , Thomas W. Scott , of most filarial infections - the population dynamics of Ll showed much 2 1 Steven T. Stoddard , Alex P. Perkins greater overdispersion than did Mp. These data suggest a possible shared 1University of Notre Dame, Notre Dame, IN, United States, 2University host susceptibly to Ll and Mp infection and also provide a method we of California, Davis, CA, United States, 3Indiana University Bloomington, are terming “reverse molecular epidemiology” that should be broadly Bloomington, IN, United States applicable to many environmental niches containing infectious organisms In the absence of effective drugs or vaccines, efforts to control and prevent for which molecular targets are defined. dengue currently rely on interventions acting on the mosquito vector, Aedes aegypti. Thus, there is need for the development of new, broadly 1813 applicable vector control tools to augment the currently available options. THE PREVALENCE OF LYMPHATIC FILARIASIS RELATED Studies to date have shown that spatial repellents (SR) have the potential to reduce malaria transmission, but their impact on other vector-borne HYDROCELE, LYMPHEDEMA AND INFECTION IN MANDALAY diseases, such as dengue, is uncertain. To make accurate quantitative REGION, MYANMAR projections of its epidemiological impact, a crucial need is to enhance the Benjamin F. Dickson1, Patricia M. Graves1, Ni Ni Aye2, Thet Wai understanding of the mechanisms of action underlying its epidemiological Nwe2, San San Win3, Janet Douglass1, William J. McBride1 impact. SR products could potentially impact multiple components of 1James Cook University, Cairns, Australia, 2Ministry of Health, Naypyitaw, vectorial capacity (VC), a classical metric that relates different aspects Myanmar, 3World Health Organization, Yangon, Myanmar of mosquito life history to transmission potential. VC however, relies on the assumption that each individual has an equal probability of being Lymphatic filariasis (LF) is highly endemic within Myanmar. Despite the bitten. The effects of SR on mosquito movement and biting behavior establishment of an elimination programme in 2004, little remains known explicitly violate this assumption by potentially causing a reduction as well about the prevalence of LF related morbidity in the country. We therefore as a redistribution of bites. This impedes the use of VC in this context. conducted a cross-sectional survey to determine the prevalence of LF Individual-based models (IBM) are free from key simplifying assumptions infection and morbidity and their associated risk factors in 24 randomly of the classical formulation of VC and thus offer an opportunity to selected villages in four endemic townships within the Mandalay region explore the epidemiological impact of SR on dengue transmission in a of Myanmar - Amarapura, Patheingyi, Tada-U and Wundwin - between more realistic way. We present a novel adaptation of an IBM for dengue February and March 2015. Within each village, twenty households were transmission in Iquitos, Peru, to simulate fine-scale heterogeneities in randomly chosen for inclusion. Household members one year and older transmission, as informed by extensive entomological and epidemiological were tested for antigenemia with rapid immunochromatographic card data. SR effects on movement, biting behavior, blood feeding and tests (ICT). A night-blood slide was done for those with positive ICT results oviposition are incorporated in the model using probabilistic descriptions to quantify microfilaremia. Ultrasound assisted clinical examination was fit to data from laboratory experiments and experimental hut studies under done on household members 15 years and older for signs of LF-related natural field conditions in disease-endemic settings. We highlight the key morbidity. Household questionnaires and GPS mapping were completed factors that underlie the discrepancy between projections from the IBM for risk factor analysis. Of those tested with ICT in 414 households, 45 of and VC and demonstrate a positive effect of SR on reducing transmission 1018 individuals (4.4%, 95% confidence interval (CI) 3.2 to 5.9%) were at the household level. The results from this simulation study warrant positive. ICT antigenemia was highest in Amarapura (32/294, 10.9%, further testing and assessment of SR products on a population level. 95% CI 7.6 to 15.0%) followed by Tada-U (8/267, 3.0%, 95% CI 1.3 to 5.8%), Wundwin (4/343, 1.2% 95% CI 0.3 to 3.0%) and Patheingyi 1812 (1/114, 0.9%, 95% CI 0.02 to 4.8%). Eighteen of the 289 males (99% of those eligible for scrotal examination) had hydroceles (6.2%, 95% REVERSE MOLECULAR EPIDEMIOLOGY: INSIGHTS INTO CI 3.7 to 9.7%). Thirteen were unilateral and five were bilateral. Of the THE INFECTION DYNAMICS OF BLOOD-BORNE HUMAN 23 hydroceles, 14 were stage one, seven were stage two and two were PARASITES IN A LOA LOA-, MANSONELLA PERSTANS- stage three. No cases of limb lymphedema or elephantiasis were found AND PLASMODIUM FALCIPARUM-ENDEMIC REGION OF in the 827 individuals examined (0%, 97.5% one-sided CI 0 to 0.4%). CAMEROON The results of this study indicate a high prevalence of LF infection and hydrocele with low levels of limb lymphedema in the Mandalay Region Papa M. Drame1, Celine Montavon2, Sebastien Pion2, Michael of Myanmar. These results highlight the strong need for further rounds Fay1, Joseph Kubofick1, Thomas B. Nutman1 of mass drug administration as well as targeted surgery and morbidity 1National Institute of Allergy and Infectious Diseases, Bethesda, MD, alleviation programmes in the region. Further LF morbidity prevalence United States, 2Institut de Recherche pour le Developpement, Montpellier, studies are needed to elucidate the burden in the remainder of the France country. Interactions among co-infecting parasites can modify the epidemiology of parasitic infections. We conducted an epidemiologic assessment of

astmh.org 555 1814 presenting results from 24 months, and the final 36 month results will be presented at the meeting. Therapeutic coverage for the population aged PROGRESS TOWARD ELIMINATION OF LYMPHATIC >2 years was >80% in all four treatment rounds. Baseline results from 773 FILARIASIS IN HAITI: PRE-TRANSMISSION ASSESSMENT subjects aged ≥5 years old revealed a filarial antigenaemia rate of 17.3% SURVEY ACTIVITIES and a Mf rate of 5.3%. Evaluation at 24 months (697 tested) showed dramatic reductions in ICT and Mf rates (6.3% and 1.4%, respectively). Abdel Direny1, Luccene Desir2, Franck Monestime3, Carl Fayette3, Mf counts were reduced by 86.3% from baseline values (geometric Jean Frantz Lemoine4 mean decrease from 202.2 to 27.7 mf/ml, P = 0.01), and total clearance 1IMA World Health, Washington, DC, United States, 2University of Notre of microfilaraemia was achieved in 71% of those individuals who were Dame/Hospital St. Croix, Leogane, Haiti, 3IMA World Health, Port au microfilaraemic in 2012. We are currently conducting a parallel trial in Prince, Haiti, 4Programme National de Malaria et de Filariose Lymphatique an area with higher baseline infection rates (31.6% for antigenemia and (PNCM), MSPP, Port au Prince, Haiti 11.8% for microfilaremia) in the Democratic Republic of Congo, and 12 month results from that study will be presented at the meeting. These Lymphatic filariasis (LF) is one of the world’s most debilitating parasitic studies will provide strong evidence regarding the use of semiannual MDA diseases; worldwide 120 million people are believed be infected with with Alb for elimination of LF in central Africa. LF. In Haiti, 11 million people are at risk for LF and the disease remains a serious public health problem. The Ministry of Health aims to eliminate LF by 2020, through annual MDA with albendazole and diethylcarbamazine citrate (DEC). MDA started initially in the areas of highest endemicity 1816 called “red zones,” where Immunochromatographic (ICT) test positivity among school children was 10-45% when mapped in 2000. Despite a HIGHLIGHTING HIGH LYMPHATIC FILARIASIS TRANSMISSION number of critical challenges, including the low level of public health AREAS USING AN SMS REPORTING TOOL: A MORBIDITY infrastructure, loss of donor funding, and the 2010 earthquake, which MAPPING SURVEY IN DAR ES SALAAM disrupted health services throughout the country, the Haiti NTD Program 1 1 1 has scaled up progressively. Since 2012, the program has achieved 100% Upendo Mwingira , Maria Chikawe , Cecelia Uisso , Irene 1 1 1 2 geographic coverage, with reported and surveyed coverage well above Mremi , Wilfred Lazarus , Alpha Malishee , Mwelecele Macelela , 3 3 3 the 65% target for disease elimination. In order to assess the program’s Charles Mackenzie , Hayley Mableson , Louise A. Kelly-Hope , 3 readiness for transmission assessment surveys (TAS), blood specimens were Michelle C. Stanton collected to detect W. bancrofti infection among persons aged ≥2 years. 1Ministry of Health and Social Welfare, Dar es Salaam, United Republic of Twenty sentinel and spot check sites were chosen to represent 52 endemic Tanzania, 2National Institute of Medical Research, Dar es Salaam, United districts; all sampled districts had completed at least 5 consecutive MDA Republic of Tanzania, 3Liverpool School of Tropical Medicine, Liverpool, rounds. At each site, approximately 500 samples were taken and tested United Kingdom using ICT. Results showed a significant reduction of filarial infection: 40% The Tanzania Lymphatic Filariasis (LF) Elimination program was launched of the “red zones” had ICT prevalence of <2% and 48 endemic districts in 2000 with the aim of distributing Ivermectin and Albendazole to qualified for TAS to determine if transmission has been interrupted. The LF endemic populations. The program, which is now integrated with remaining 4 districts, which had ICT positivity between 31-39% when other neglected tropical diseases (NTDs), covers 107 districts, and LF mapped, now have ICT positivity of 2.35-6.5%. While not yet eligible prevalence is now showing signs of decreasing. There is however limited for TAS, these districts demonstrate a significant reduction in LF infection information on the number of people with clinical symptoms of LF after 6 rounds of MDA. The Haiti NTD Program is optimistic that these i.e. lymphedema and hydrocele cases in Tanzania. This information is districts will be eligible for TAS after two more MDA rounds. The program required for better planning of morbidity management in the country. has made tremendous progress towards LF elimination in spite of multiple The national NTD control program, in collaboration with Liverpool School challenges. Haiti expects to reach the 2020 goal to eliminate LF; one of the of Tropical Medicine, conducted a morbidity survey in March 2015, in greatest achievements for the poorest country in the Caribbean. Temeke municipality, Dar es Salaam (population 1.5 million). The survey was conducted using a bespoke SMS reporting tool, MeasureSMS, which 1815 enabled survey data summaries to be viewed instantaneously through a web browser, and downloaded for further analysis. During the survey, A COMMUNITY STUDY OF THE IMPACT OF SEMIANNUAL community drug distributors visited every house in their designated ALBENDAZOLE ON LYMPHATIC FILARIASIS IN CENTRAL catchment area, and recorded information on each lymphedema and AFRICA hydrocele case identified using a paper form. These forms were collated by Sebastien D. Pion1, Cédric B. Chesnais1, François Missamou2, supervising front line health workers, who then reported the information Gary J. Weil3, Michel Boussinesq1 by SMS to the local phone number allocated to the MeasureSMS tool. Progress was monitored by the national NTD control program throughout 1Institut de recherche pour le Développement, Montpellier, France, the survey using a webpage, and by directly downloading the reported 2Ministère de la santé et de la population, Brazzaville, Republic of the SMS messages to check for missing reports. For data quality assurance, a Congo, 3Washington University School of Medicine, Saint Louis, MO, random subset of reported cases were visited, and their conditions verified. United States A total of 2547 patients were identified; 987 of patients had lymphedema Implementation of mass drug administration (MDA) with ivermectin plus cases, 1743 had hydrocele, of these 183 had both conditions. Verification albendazole (Alb) for lymphatic filariasis (LF) has been delayed in Central is ongoing and will be completed in May 2015. To date, 28 reported Africa, because ivermectin can induce serious adverse events in people hydrocele cases have been verified, of which 88% (25/28) were confirmed with very high Loa loa microfilaremia . Albendazole has activity against to have the condition. Given the high reported morbidity burden in Wuchereria bancrofti, and it is safe for use in patients with loiasis. In this area, it is now vital that services such as hydrocele surgery and 2012, the WHO recommended use of Alb MDA together with vector lymphedema management are made accessible to the affected population. control to combat LF in areas with co-endemic loiasis. In September 2012, we started a 3-year community trial of semi-annual Alb alone on LF in a village with a population of 1055 in Madingou District in the Republic of Congo. Infection with W. bancrofti was diagnosed using the Binax Now Filariasis card test (ICT) for antigenaemia; persons with positive card tests were tested for microfilaraemia (Mf) by night blood smears. We are now

astmh.org 556 1817 effect on the female adult worms (macrofilariae). Multiple doses of ivermectin are thought to cause a cumulative effect on macrofilariae MICRO-MAPPING DISTRIBUTION POINTS, RISK POPULATIONS manifesting either as permanent reductions in fecundity or a shortened TO TREATMENT NUMBERS TO MAXIMIZE COVERAGE TO life-span. These assumptions have been incorporated into mathematical IMPACT OF MASS DRUG ADMINISTRATION FOR LYMPHATIC models to support elimination efforts. Yet, for decades the nature of FILARIASIS IN URBAN DAR ES SALAAM, TANZANIA this presumed cumulative action has avoided rigorous investigation because scarce longitudinal data on macrofilariae have not been Upendo Mwingira1, Maria Chikawe1, Cecilia Uisso2, Irene interrogated with suitably powerful analytical techniques. Here, we Mremi2, Wilfred Lazarus2, Alpha Malishee2, Mwelecele Malecela3, analyse data on the fecundity and vitality of female worms from the most Joan Fahy4, Michelle Stanton4, Hayley Mableson4, Louise Kelly- comprehensive clinical trial of multiple doses of ivermectin treatment Hope4 (comparing 3-monthly with annual treatment rounds administered during 1Neglected Tropical Diseases Control Programme - National Institute for three years in Cameroon) using a recently developed state-of-the-art Medical Research, Dar es Salaam, United Republic of Tanzania, 2Neglected modelling framework. We demonstrate that multiple doses of ivermectin Tropical Diseases Control Programme, Dar es Salaam, United Republic of treatment have a substantial macrofilaricidal effect, even at the doses Tanzania, 3National Institute of Medical Research, Dar es Salaam, United and frequencies used for routine MDA. We find no evidence that the Republic of Tanzania, 4Liverpool School of Tropical Medicine, Liverpool, anti-fecundity activity of ivermectin is enhanced by multiple treatments. United Kingdom We discuss our results in the context of the feasibility to eliminate onchocerciasis in the timeframes set by the global health community. The large rapidly growing urban centre of Dar-es-Salaam in Tanzania has a significant risk of lymphatic filariasis (LF), which is transmitted by Culex spp. mosquitoes that thrive in human domestic environments. Prior 1819 to the recent scale up of mass drug administration (MDA) to interrupt MODELING EFFECTIVENESS OF DRUG ADMINISTRATION ON transmission, the overall LF infection rate was estimated to be 10%, with A POPULATION INFECTED WITH SCHISTOSOMA MANSONI young adult males, and informal and peri-urban areas at a significantly higher risk of infection than other sub-groups and areas. In order to Roberta O. Prado1, Sonia P. Carvalho2, Sylvie M. Kamphorst2, improve MDA coverage rates to those at greatest risk, this study aimed Rodrigo C. Oliveira3, Andréa Gazzinelli1 to map and examine the spatial patterns of the MDA distribution points, 1Escola de Enfermagem UFMG, Belo Horizonte, Brazil, 2Universidade risk populations, and treatments numbers across the three districts of Federal de Minas Gerais, Belo Horizonte, Brazil, 3Centro de Pesquisas René the city with an estimated 4.4 million population at risk. Environmental Rachou, Belo Horizonte, Brazil assessments were also conducted to identify characteristics of low coverage areas, and the specific factors that may place sub-groups at Schistosomiasis is one of the most important public health problems that higher risk of infection, including potential breeding sites of Culex spp.. affect human populations, especially those living in poorer regions, with In Temeke district 73 distribution points reported an average coverage of low socioeconomic environment, without adequate sanitation and clean 149%, in Kinondoni district 105 distribution points reported an average water. WHO recommends treatment without prior diagnosis of the most coverage of 105% and in Ilala district 63 distribution points reported vulnerable individuals such as school children and adults in endemic areas. an average coverage of 101%. Coverage throughout the three districts In Brazil treatment is based on the infection prevalence. In areas of low ranged from 9% (~10 times under) to over 1000% (~10 times over) and medium prevalence treatment is given only for positive individuals at specific locations. These excessive coverage values are indicative of and in situations where the prevalence is greater than 50% treatment is population movement both within and into the city. The great variation directed to the entire population. The objective is to develop a non-linear and distinct spatial patterns found at a micro level suggest that urban mathematical model to evaluate the effectiveness of mass treatment of populations move dramatically within small geographical areas, as well as a population infected with S. mansoni. The evolution of infected and at different rates across the different areas of the city, thus making MDA non-infected persons with time was studied by building a 2-dimensional implementation and reaching high coverage challenging. This study takes system of differential equations. We consider that a) children born without one important step forward to better understanding and being able to infection, b) the population is growing with a growth of logistical type, predict the problem areas in a highly dynamic and densely populated city. without having reached its maximum growth and c) once treated an This is critical and will help the LF Programme to specifically target and individual will be free of infection unless it re-infects. The population increase human resources, training, social mobilisation to where they are was divided into two strata: P0 (t), which corresponds to the number of needed most. uninfected persons in year (t) and P1 (t) and those corresponding to the number of infected people during the year (t). It was possible to develop 1818 a mathematical model, consisting of a system of differential equations that has in its domain, single global attractor. The 2-dimensional system MULTIPLE IVERMECTIN DOSES ARE MACROFILARICIDAL: has a unique global attractor where the number of infected persons is IMPLICATIONS FOR THE ELIMINATION OF ONCHOCERCIASIS non-zero, due to the re-infection effect. It is proved that the model got its equilibrium. The modeling results suggest that if the treatment is the only Martin Walker1, Sébastien D. Pion2, Hanwei Fang3, Thomas intervention in the population, that is, without additional Investments in S. Churcher1, Jacques Gardon4, Joseph Kamgno5, Maria-Gloria better sanitation and health education programs, even treating the whole Basáñez1, Michel Boussinesq2 population or just those infected, the prevalence always will be around 1Imperial College London, London, United Kingdom, 2Université de 10%. The model also suggests that in this way overtime prevalence tends Montpellier, Montpellier, France, 3University of Oxford, Oxford, United to always keep this level with few possibilities of over spreading disease in Kingdom, 4IRD, La Paz, Plurinational State of Bolivia, 5University of the area. Yaounde, Yaounde, Cameroon The predominant strategy for achieving the World Health Organization’s control and elimination goals for human onchocerciasis is based on mass drug administration (MDA) with ivermectin. The feasibility of achieving these goals crucially depends on the long-term effects of multiple doses of ivermectin on the long-lived Onchocerca volvulus filarial nematode, which causes onchocerciasis. A single dose of ivermectin rapidly kills the microfilariae while also exerting a temporary sterilization (embryostatic)

astmh.org 557 1820 intensities of infection and corresponding transmission parameters. Treatment costs for SAC and pre-SAC/adults were estimated at US$ 0.74 MODELLING EGG COUNTS TO COMPARE EGG REDUCTION and US$ 1.74, respectively. The incremental cost-effectiveness ratio (ICER) RATES IN RANDOMIZED COMPARATIVE TRIALS OF was calculated in 2015 US$ per disability-adjusted life year (DALY) averted, TREATMENTS OF INTESTINAL SCHISTOSOMIASIS comparing treatment strategies against current WHO recommendations of no treatment. We defined strategies as highly cost-effective if the ICER Michel T. Vaillant1, Anna Schritz1, Piero L. Olliaro2 was less than the World Bank classification for a low-income country 1Luxembourg Institute of Health, Strassen, Luxembourg, 2UNICEF/UNDP/ (GDP per capita: US$ 1,035). An integrated MDA program against WB/World Health Organization Special Programme for Research and schistosomiasis and STH was highly cost-effective in treating SAC alone at Training in Tropical Diseases, Geneva, Switzerland a prevalence of 5% (ICER: US$ 396/DALY averted), 10% (ICER: US$ 297/ DALY averted), and 15% (ICER: US$ 285/DALY averted) compared to no Treatment efficacy for schistosomiasis and soil-transmitted nematodes is treatment. Expanded community-wide coverage was highly cost-effective customarily assessed as egg reduction rate (ERR) based on the difference at a prevalence of 10% (ICER: US$ 902/DALY averted) and 15% (ICER: in grouped means between pre- and post-treatment egg counts. This US$ 796/DALY averted) compared to treatment of SAC alone. Integrated however does not allow comparison of treatment effects in controlled annual MDA programs against schistosomiasis and STH may be highly trials. Here, we assess whether Poisson-type modelling could be used cost-effective at prevalence thresholds lower than WHO guidelines. to compare efficacy between treatments using a database from 24 These results support re-evaluating global guidelines to consider lowered trial enrolling 4,740 individuals infected with Schistosoma mansoni, prevalence thresholds for integrated treatment. S. haematobium, or S. japonicum, and treated with 40-80 mg/ kg praziquantel. Sensitivity analysis used a subset of 856 subjects in a trial comparing 40 vs 60 mg/kg praziquantel. Gender, age, treatment, 1822 species, follow-up duration and baseline egg counts were entered in all IMPROVING TREATMENT COVERAGE - MASS DRUG models as factors. The number of Kato-Katz smears (differences across ADMINISTRATION AS SEEN FROM THE COMMUNITY HEALTH studies) was used as a proportionality constant (offset) in the models to WORKERS’ PERSPECTIVE analyse the sum of counts. Alternative models (quasi-Poisson, negative binomial & zero-inflated Poisson) were fitted and compared. Random Sarah Nogaro1, Michelle Clements1, Alexandra Weldon1, Abou variation in risk between individuals and random variation between slides N’dri2, Esther Comoe2, Sei Adou2, Elvis Allo2, Alain Toh2, Fiona were also allowed for in a multi-level model with the same distributions. Fleming1 1050 patients with 3577 measurements were analysed. 92% of the 1SCI, Imperial College, London, United Kingdom, 2University Felix observed post-treatment data were zero. The Poisson model of the sum Houphouet-Boigny, Abidjan, Côte D’Ivoire of egg counts and the quasi-Poisson model proved unsuited due to over- dispersion. The negative binomial and the zero-inflated model showed a National-scale schistosomiasis control programmes have now been better fit and predicted 92.07% and 91.98% of zeros. With the multilevel implemented in many endemic countries using mass drug administration modelling strategy, the Poisson model performed best (95.05% of zero with praziquantel. Results from a validated treatment coverage survey counts predicted). Praziquantel at 40mg/kg, 60mg/kg or 80mg/kg reduced after the first mass drug administration in Cote d’Ivoire (CDI) in 2013, the egg counts with no significant difference between treatments. highlighted that some districts were under-performing and below the Baseline counts were significant predictors of post-treatments counts. The World Health Organization target of treating at least 75% of school aged sensitivity analysis showed similar results. This study shows that adequate children. To understand the reasons behind this low coverage, structured modelling of the sum of post-treatment egg counts or raw egg counts interviews were conducted with community health workers (CHWs) in 12 could be useful for comparing treatment effects of anthelmintic treatment. villages in CDI (1 per village). Accounts given by the CHW were captured both on paper and on a digital audio recorder. Transcripts were then 1821 translated into English and the data analysed using NVIVO software. To ensure that the information portrayed by the CHW was a true reflection of COST-EFFECTIVENESS OF CHANGING PREVALENCE their thoughts, the interviews were done on a one-to-one basis following THRESHOLDS FOR MASS DRUG ADMINISTRATION AGAINST free and informed consent. The interviews were led by an independent SCHISTOSOMIASIS TO SOIL-TRANSMITTED HELMINTHIASIS social scientist and allowed for privacy. Across all interviewees, four themes were repeatedly reported: negative perception by the communities of Nathan C. Lo1, Isaac I. Bogoch2, Giovanna Raso3, Jean T. free medication; limited time for drug distribution due to insufficient Coulibaly4, Jürg Utzinger3, Jason R. Andrews1 human resources; loss of income during campaigns, and inadequate 1Stanford University School of Medicine, Stanford, CA, United States, social mobilisation. Other issues were raised but are considered to be 2University of Toronto, Toronto, ON, Canada, 3Swiss Tropical and Public country-specific. Results from this survey highlight potential issues which, Health Institute and University of Basel, Basel, Switzerland, 4Université Félix if addressed, can improve preventive chemotherapy (PCT) coverage. The Houphouët-Boigny, Centre Suisse de Recherches Scientifiques en Côte presenter will discuss the sustainability, the cost and efficiency of proposed d’Ivoire, Swiss Tropical and Public Health Institute, and University of Basel, solutions. With the emphasis now being on eliminating schistosomiasis, Abidjan, Côte D’Ivoire findings from this study are applicable to many PCT control programmes, which will inform national guidelines to fine tune their strategy to ensure Current WHO guidelines on mass drug administration (MDA) against that the 2020 targets are met. helminth infections do not recommend MDA for schistosomiasis and soil-transmitted helminthiasis (STH) below a prevalence of 10% and 20%, respectively, and use separate treatment guidelines for these two helminthiases. We evaluated the cost-effectiveness of changing prevalence thresholds for integrated, annual MDA to school-age children (SAC) and the entire community. We developed a dynamic, age-structured transmission and cost-effectiveness model that simulates integrated MDA programs for schistosomiasis and STH. We simulated a 5-year treatment program with praziquantel plus albendazole at 75% coverage among: (i) SAC alone or (ii) entire community (pre-SAC, SAC, and adults). We tested prevalence values of 1%, 5%, 10%, and 15%. We simulated settings of 10,000 pre-SAC, SAC, and adults with a range of helminth-specific

astmh.org 558 1823 praziquantel from 2004, 2005, 2006, and 2013 were 94.5%, 97.8%, 97.1%, and 95.0% respectively and cure rates 72.3%, 75.7%, 80.7% THE USE OF A MARKOV TRANSITION PROBABILITY MODEL and 87.2%. Cure rates by POC-CCA in 2004 and 2013 were however AS A PROGRAMMATIC TOOL FOR THE CONTROL OF significantly lower at 47.8% and 9.4% respectively. Infection prevalence SCHISTOSOMIASIS and intensities in 2013 and 2014 were higher than at baseline. We indicate that drug efficacy measured by Kato-Katz has not reduced with Arminder K. Deol1, Maria-Gloria Basäñez2, Martin Walker2, MDA, but that cure rates measured by POC-CCA are lower. Although cure Antonio Montresor3, Michael French1 rates are often considered to be a less important criteria for morbidity 1Schistosomiasis Control Initiative, London, United Kingdom, 2Imperial than a reduction in egg output, it is imperative that the causes for the College London, London, United Kingdom, 3World Health Organization, significant differences between Kato-Katz and POC-CCA results, and the Geneva, Switzerland higher infection intensities after ten years MDA, are elucidated so we can understand any risks of MDA strategies as well as measure their benefits. The World Health Organization (WHO), in partnership with the global Results presented will include model outputs to predict if higher infection community, have set ambitious targets for the control and/or elimination intensities observed ten years into the MDA programme are due to high of schistosomiasis by 2020. To be able to achieve this it is essential that transmission, reduced drug efficacy, or reductions in the development of control programme managers can monitor the impact of treatment and protective immunity, as control programmes progress. identify areas that are not responding as expected. This will allow suitable adjustments to be made to maximise the impact of the intervention. With this objective, in 2014 a programme-friendly Markov transmission 1825 model was developed at the Schistosomiasis Control Initiative (SCI) CONQUERING SCHISTOSOMIASIS IN CHINA: THE FINAL in collaboration with the WHO to model the changes in the levels of CHAPTER schistosomiasis infection following successive rounds of treatment. The model was parameterized using data obtained from the monitoring and Donald P. McManus1, Darren Gray2, Yue-Sheng Li1, Gail M. evaluation components of the large-scale deworming programmes in Williams3, Catherine Gordon1, Donald Harn4, Zeng Feng5, Remigio Uganda and Mali. This model is an extension of an earlier Markov model Olveda6, Allen Ross7 developed for soil-transmitted helminth infection by WHO. Results showed 1QIMR Berghofer Medical Research Institute, Brisbane, Australia, that the transition probabilities derived from baseline and year 1 data 2Australian National University, Canberra, Australia, 3University of can be used to predict the prevalence of each infection intensity group Queensland, Brisbane, Australia, 4University of Georgia, Athens, GA, in the following year. The capacity of the model to predict changes in United States, 5National Institute of Parasitic Diseases, Chinese Centre for infection prevalence following successive rounds of treatment was then Disease Control and Prevention, Shanghai, China, 6Research Institute for tested on various data sets from 2 countries in sub-Saharan Africa. These Tropical Medicine, Manila, Philippines, 7Griffith University, Gold Coast, data were not used to develop and validate the model, so that only new Australia scenarios could be tested. The model was tested to observe whether it could provide an early warning of the treatment campaigns that failed to Major control efforts over many decades have resulted in a substantial meet their targets. The performance of the model was also tested against reduction in the prevalence of schistosomiasis japonica in the People’s different parasite species (S. mansoni and S. haematobium), location Republic of China, although pockets of new infection continue to arise, and underlying endemicity as well as host age. The outputs of the model particularly in the mountainous areas of the south. As well, the completion post-validation will be discussed as well as its suitability as a user-friendly of the Three Gorges Dam, which crosses the Yangtze River and other programmatic tool to facilitate the monitoring of schistosomiasis control large irrigation projects underway, may have significant environmental programmes. and ecological impacts likely resulting in expansion of the habitats for the intermediate snail host Oncomelania hupensis in some areas, thereby 1824 increasing the risk of human and bovine infection, and resulting in potentially new challenging consequences for control. The epidemiological HOTSPOTS OF SCHISTOSOMA MANSONI TRANSMISSION picture for China will be briefly summarised and the current effective TEN YEARS INTO A MASS DRUG ADMINISTRATION control strategies highlighted. The situation in the Philippines will also be PROGRAM briefly outlined but the picture is far less encouraging as there is limited national funding for schistosomiasis control; since the termination of Poppy H. Lamberton1, Kate Mitchell1, Charlotte M. Gower1, the World Bank Loan program for schistosomiasis control in the late Moses Adriko2, Moses Arinaitwe2, Annet Enzaru2, Annet 1990’s, both schistosome prevalence and the associated morbidity have Namukuta2, Thomas Crellen1, Edridah M. Tukahebwa2, Narcis B. rebounded to former levels. Some results of recent surveillance studies we Kabatereine3, Alan Fenwick1, Joanne P. Webster4 have undertaken in the Philippines will be described which indicate that 1Imperial College London, London, United Kingdom, 2Vector Control schistosomiasis japonica is now far more prevalent, both in humans and Division, Ministry of Health, Kampala, Uganda, 3Schistosomiasis Control bovines, than has been appreciated. Results of a large intervention trial Initiative at Vector Control Division, Ministry of Health, Kampala, Uganda, we have completed in China - in the highly endemic Dongting Lake area 4Royal Veterinary College, London, United Kingdom downstream of the Three Gorges Dam, aimed at field-testing integrated strategies, including the use of a bovine transmission blocking vaccine, for The Schistosomiasis Control Initiative began mass drug administration schistosomiasis control, will be presented. The results of the trial in China (MDA) with praziquantel in Uganda in 2003 with great reductions in will provide parameters for mathematical modelling of future control infection prevalence, intensities and associated morbidity. However, methods so as to define the long-term impact and cost-effectiveness of possible treatment failures have been recorded. In addition, theoretical integrated control measures for both China and the Philippines. We believe models have indicated that cessation of MDA may result in higher egg that such an integrated approach, incorporating bovine vaccination, can counts than pre-intervention levels in certain individuals. Prevalence lead to the future elimination of schistosomiasis from China. and intensity of infection by Kato-Katz were recorded for Schistosoma mansoni in children from three primary schools in Mayuge District, Uganda. Data were collected pre-, one-week-post- and four-weeks-post- praziquantel in 2004, 2005 and 2006, and pre-, one-week-post- and three-weeks-post-praziquantel in 2013 and pre-praziquantel in 2014. In 2004 and 2013 point-of-care circulating-cathodic-antigen tests (POC-CCA) were also performed. Mean egg reduction rates by three/four-weeks-post-

astmh.org 559 1826 CRISPR/CAS9 system to validate several genes, including PfCARL, in which mutations convey resistance. In addition, we showed that these same PLASMODIUM FALCIPARUM GENETIC CROSSES WITHOUT mutations protected P. falciparum gametocytes from IZP activity and that CHIMPANZEES PfCARL protein is localized to the endoplasmic reticulum/Golgi apparatus. Finally, we utilized Saccharomyces cerevisiae as a model to identify several 1 2 3 Richard S. Pinapati , Ashley M. Vaughan , Ian H. Cheeseman , pathways affected by IZP exposure, which were then functionally validated 1 1 2 Lisa A. Checkley , Carolyn A. Hutyra , Nelly Camargo , Matthew in P. falciparum. By determining the mechanism of action of the IZPs, this 2 3 4 Fishbaugher , Shalini Nair , Francois H. Nosten , Timothy J. study will significantly advance efforts against malaria, both by improving 3 2 1 Anderson , Stefan H. Kappe , Michael T. Ferdig the utility of a promising new class of antimalarials and by identifying new 1University of Notre Dame, Notre Dame, IN, United States, 2Seattle targets for antimalarial intervention. Biomedical Research Institute, Seattle, WA, United States, 3Texas Biomedical Research Institute, San Antonio, TX, United States, 4Mahidol 1828 University, Mae Sot, Thailand DEEP SEQUENCING OF ANOPHELES GAMBIAE FROM Experimental genetic crosses in Plasmodium falciparum have played NATURAL POPULATIONS SPANNING SUB-SAHARAN AFRICA - a pivotal role in the discovery of genes underlying several important phenotypic traits including drug resistance and host specificity. Previously, A RESOURCE FOR VECTOR CONTROL RESEARCH P. falciparum genetic crosses were carried out in splenectomized Alistair Miles1, Dominic Kwiatkowski2, The Anopheles gambiae chimpanzees and in spite of the fact that three successful experimental 1000 Genomes Consortium3 crosses were generated, ethical and logistical concerns have now 1University of Oxford, Oxford, United Kingdom, 2Wellcome Trust Sanger rendered this technology obsolete. Here we demonstrate a new model Institute, Cambridge, United Kingdom, 3Institutional affiliations are listed for P. falciparum experimental genetic crosses: a human hepatocyte- at http://www.malariagen.net/ag1000g, United Kingdom liver chimeric mouse (FRG huHep mouse) injected with human red blood cells (huRBCs) that allows for complete P. falciparum liver stage The Anopheles gambiae 1000 genomes project (Ag1000G) is using development and the transition of exo-erythrocytic merozoites to asexual whole-genome sequencing to study genome variation in wild-caught blood stage development. Using this novel and versatile model, we have mosquitoes from populations across Africa. In phase 1 of the project high rapidly generated and analyzed three experimental crosses, including throughput sequence data from 765 specimens from 8 countries have the identification of unique recombinant progeny from each cross. A been generated. The sequence data have been used to discover over 52 chloroquine (CQ) sensitive transgenic strain, NF54HT-GFP–luc, was used million single nucleotide polymorphisms - on average 1 SNP every ~2 as a parent in all three of our new experimental crosses and was crossed accessible bases - providing the first genome-wide view of the spectacular with three different strains: GB4 and 7G8, two strains used in a previous natural diversity within and between natural populations. These data have chimpanzee experimental cross, and NHP*, a recent field isolate from been publicly released and comprise the largest open access genomic Southeast Asia. We characterized all crosses using microsatellite markers resource available for any vector species. Here we provide an overview and further characterized progeny from the NF54HT-GFP–luc × NHP* cross of the Ag1000G phase 1 data resource and initial results of population using thousands of single nucleotide polymorphisms (SNPs) from next- genetic analyses, focusing on applications to malaria epidemiology and generation sequence data and custom genotyping microarrays. These data vector control. First, analyses of population structure in the Ag1000G were used to generate genetic maps and compute recombination rates cohort reveal a complex mosaic, with incomplete speciation, geography, across the genome. The high-density SNP-based linkage map will be used ecology and demography all influencing gene flow across the species’ in conjunction with quantitative trait loci (QTL) mapping to assay a wide range. These data could be integrated into models informing vector variety of quantifiable phenotypes such as drug responses, thus facilitating control strategy, and we discuss steps towards this goal. Second, these the study of complex genetic traits in P. falciparum. data enable high-resolution analyses of loci under strong recent selection, including discovery of novel insecticide resistance mutations. We illustrate 1827 this with data from the voltage-gated sodium channel gene, and show that multiple independent haplotypes within both West and East African DETERMINING THE MECHANISM OF ACTION OF populations have been involved in selective sweeps, cutting across species THE IMIDAZOLOPIPERAZINES, A NOVEL CLASS OF barriers and major geographic features. We also present preliminary ANTIMALARIALS evidence for novel resistance mutations, and discuss how haplotype data from Ag1000G could be used to diagnose the origin and track the spread Gregory LaMonte, Melanie Wree, Marie Nachon, Greg Goldgof, of insecticide resistance. Finally, we present data from the Ag1000G Victoria Corey, David Plouffe, Edgar Vigil, Elizabeth Winzeler coastal Kenyan population, where all individuals exhibit long runs of University of California, San Diego, La Jolla, CA, United States homozygosity consistent with a severe recent population bottleneck. These data demonstrate that demographic events leave a strong genetic signal, Malaria, despite ongoing public health intervention worldwide, remains and we discuss how genomic data could be used to provide feedback a tremendous burden globally. While progress has been made recently about the impact of vector control interventions. against malaria, the emergence of artemisinin resistance in Plasmodium falciparum has accelerated the search for both new and more effective antimalarial drug candidates. One of the most promising new compound classes in clinical development are the Imidazolopiperazines (IZPs), which are not only effective against all stages of Plasmodium infection, but also prevent transmission and dramatically reduce the rate of future infection. The lead compound of the IZPs, GNF156, is currently in phase IIb clinical trials. Unfortunately, the development of this class of compounds is hampered by a limited understanding of their mechanism of action. Previous in vitro evolution studies identified a previously uncharacterized gene, designated the P. falciparum cyclic amine resistance locus, as a potential target for the IZPs. More recent studies, however, have implicated several additional genes/pathways as potential targets of the IZPs. Given this ambiguity about the target and activity of the IZPs, this study will therefore first validate putative drug targets, then go on to examine both the localization and function of those validated targets. We have used the astmh.org 560 1829 be a useful criterion for selecting new vaccines and drugs for further development and testing. (Additional authors will be listed in the LARGE-SCALE SCANS FOR GENOMIC REGIONS UNDER presentation). POSITIVE SELECTION IN SOUTHEAST ASIAN PLASMODIUM FALCIPARUM REVEAL GENES OF PUBLIC HEALTH 1830 IMPORTANCE EXPLORING UNKNOWN GENES IN MALARIA PARASITES BY A Christopher G. Jacob1, Cesar Arze2, David L. Saunders3, Charlotte ROBUST GENE REGULATORY SYSTEM Lanteri3, Rick Fairhurst4, Chanaki Amaratunga4, John C. Tan5, Becky A. Miller6, Olivo Miotto7, Bronwyn MacInnis8, Pharath Lim4, Suresh Maddur Ganesan, Alejandra Falla, Sebastian Nasamu, Seila Suon9, Poravuth Yi9, Sokunthea Sreng9, Podjanee Jittamala10, Jacquin C. Niles Kesinee Chotivanich7, Mallika Imwong7, Kitipumi Chutasmit11, Massachusetts Institute of Technology, Cambridge, MA, United States 12 13 Chaiyaporn Suchatsoonthorn , Ratchadaporn Runcharoen , Tran Malaria is a major health problem in tropical and subtropical countries. 14 15 16 16 Tihn Hien , Myat P. Kyaw , Mayfong Mayxay , Paul Newton , The most severe form of malaria is caused by the parasite, Plasmodium 17 17 Maniphone Khanthavong , Bouasy Hongvanthong , Aung falciparum. A limited set of antimalarial drugs is used to treat the disease, 18 18 19 Pyae Phyo , Francois Nosten , Md. Abul Faiz , Md. Ridwanur but drug resistance is spreading at alarming rate. Hence, there is an urgent 19 20 21 22 Rahman , Akhterul Islam , Harald Noedl , Chanthap Lon , need for identification of novel anti-malarial drugs. A major challenge in 23 8 1 24 Wasif Khan , Susana Campino , Jason Bailey , Mehul Dhorda , new antimalarial drug development is identification and prioritization of 1 6 7 Shannon Takala-Harrison , Michael Ferdig , Elizabeth Ashley , potential targets for drug discovery. This is mainly due to lack of reliable 7 7 7 25 Arjen Dondorp , Nicholas Day , Nicholas White , Pascal Ringwald , functional genetics tools for investigating parasite genes. To address this 8 1 Dominic Kwiatkowski , Christopher V. Plowe need, we have developed a RNA-protein interaction system that facilitates 1Center for Malaria Research, Institute for Global Health, University of robust and inducible regulation of target gene translation in eukaryotic Maryland School of Medicine, Baltimore, MD, United States, 2Institute organisms, including Plasmodium. Here, we present the application of for Genome Sciences, University of Maryland School of Medicine, protein engineering approaches to integrate our synthetic control system Baltimore, MD, United States, 3Armed Forces Research Institute of with native Plasmodium translational regulatory mechanisms. In so doing, Medical Sciences, Bangkok, Thailand, 4Laboratory of Malaria and we have achieved substantially increased regulatory dynamic ranges (up Vector Research, National Institute of Allergy and Infectious Diseases, to 200-fold) compared to a 5-10 fold range of the original system. As National Institutes of Health, Rockville, MD, United States, 5Research and a proof-of-concept, we have successfully used this system to generate Development, Roche NimbleGen, Inc, Madison, WI, United States, 6Eck parasite lines in which various proteins of interest can be knocked down Institute for Global Health, Department of Biological Sciences, University to reveal clear growth phenotypes. In addition, we have successfully of Notre Dame, South Bend, IN, United States, 7Mahidol-Oxford Tropical combined this approach with CRISPR/Cas9 genome editing technology to Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, rapidly validate essential genes. We are currently applying these genetic Bangkok, Thailand, 8Wellcome Trust Sanger Institute, Hinxton, United tools to broadly study parasite genes of unknown function. Since ~60% Kingdom, 9National Center for Parasitology, Entomology and Malaria of the encoded P. falciparum genes have no known homologs in other Control, Phnom Penh, Cambodia, 10Faculty of Tropical Medicine, Mahidol eukaryotes, we believe that understanding their functions will aid in University, Bangkok, Thailand, 11Phusing Hospital, Srisaket Province, identifying potential targets for novel antimalarial drug development. Thailand, 12Kraburi Hospital, Ranong Province, Thailand, 13Khunhan hospital, Srisaket province, Thailand, 14Hospital for Tropical Diseases, 1831 Ho Chi Minh City, Vietnam, 15Department of Medical Research, Lower Myanmar, Yangon, Myanmar, 16University of Health Sciences, Vientiane, PARTICIPATION OF INNATE IMMUNE CELLS IN MODULATING Lao People’s Democratic Republic, 17Center of Malariology, Parasitology, BLOOD FLUKE DEVELOPMENT and Entomology, Vientiane, Lao People’s Democratic Republic Ellen C. Fox, Stephen J. Davies As artemisinin resistance in Plasmodium falciparum continues to Uniformed Serivces University, Bethesda, MD, United States simultaneously spread and emerge in new areas throughout Southeast Asia, plans are underway for targeted malaria elimination. Achieving Schistosomes develop in the blood stream of their hosts, where they regional elimination will require effective antimalarial drugs, an efficacious feed on blood cells and produce eggs that cause severe pathology. vaccine, or both; however, few drugs remain effective in Southeast Previous work has demonstrated that host immune function is required Asia and currently there is no vaccine. The discovery of new drugs for normal schistosome development, as parasite development is and vaccines is necessary if elimination is to be successful. To identify dramatically impaired in some immunodeficient settings. Recently, we candidate drug and immune targets, we used three methods - two presented evidence that regulation of innate inflammatory responses is a long-haplotype tests and population differentiation using FST - to locate requirement for schistosome development to proceed as administration regions of the P. falciparum genome that are potentially under positive of innate immune stimuli such as LPS, MSU and IL-4 restored parasite directional selection among Southeast Asian parasites. Literature review development in RAG-1-/ animals. - Here we review our recent progress of the previous use of these methods in malaria parasite genomic toward identifying the innate immune cells that are implicated in these studies showed little overlap among genes, and differing sampling and host-schistosome interactions. Following administration of various genotyping methods prohibit meta-analyses. We genotyped approximately innate immune stimuli to RAG-1-/- mice, splenic neutrophils, monocytes, 30,000 loci in over 2,000 samples from 19 geographic sites across the macrophages and non-classical macrophages were assessed for changes Greater Mekong Subregion using a DNA microarray and whole-genome in expression of activation markers and Relm-α by flow cytometry. sequencing. Regions under selection within each geographic site were Administration of pro-inflammatory stimuli LPS and MSU resulted in identified, and meta-analyses identified the most highly-selected genomic significant decreases in surface expression of CD204 and CD206 in all regions shared across all sites. Across all analyses there are 245 genes cell populations, while treatment with IL-4 cytokine complex resulted in within the most highly-selected regions, including genes associated significant increase in CD204 and CD206. Poly I:C, a TLR 3 agonist that with drug resistance and encoding current vaccine antigens. Many did not rescue parasite development, resulted in no significant changes genes with potential impact in public health are present including genes in CD204 and CD206 expression. Taken together, these data suggest involved in drug export, vesicle transport, and red blood cell binding. The that while innate immune cells are likely important environmental factors genes identified in our scans could be under selection for many reasons for parasite development, we are unable to identify changes in innate including association with drug resistance as well as human, vector, or cell phenotype that correlate with successful completion of the parasite’s environmental factors. Evidence of positive directional selection may astmh.org 561 developmental cycle. Ongoing studies are assessing changes in innate dose), hepatitis B (doses at 0, 1 and 6 months), and meningococcus immune cell metabolism as a possible mechanism facilitating schistosome A+C (doses at 0 and 2 months) vaccines were administered. Helminth infection. infections were treated a week after the second hepatitis B immunization. Participants were bled at baseline, 2 months after the start of 1832 immunizations and 2 months after the final hepatitis B immunization to evaluate humoral and cellular immune responses to the vaccine antigens THE ADIPOSE TISSUE DERIVED STEM CELLS (ASC) SHOWS using both antibody and cytokine ELISAs. CD3+/CD4+/CD25high T IMMUNOREGULATION FUNCTIONS IN SCHISTOSOMIASIS regulatory (Treg) cell levels were also determined at each time point to INFLAMMATION ENVIRONMENT assess their relationship to vaccine responses. As we have previously reported participants with schistosomiasis had significantly higher 1 1 1 Adriana Bozzi Melo , Dirli Emmerick Eller , Lorena Cassia Ferraz , proportions of circulating Treg cells than uninfected controls at baseline. 2 1 Talita Rocha Gomes , Vitor Hugo Miranda , Carlos Eduardo These levels increased 1 week after praziquantel treatment, but decreased 1 2 1 Calzavara-Silva , Alfredo Miranda Goes , Rodrigo Correa-Oliveira to uninfected control levels by 7 months after treatment. Anti-TT antibody 1Centro de Pesquisas René Rachou/FIOCRUZ-MG, Belo Horizonte, Brazil, levels in both infected and uninfected groups were comparable at all 2Instituto de Ciências Biológicas da UFMG, Belo Horizonte, Brazil measured time-points indicating that schistosome infection did not alter Numerous reports have shown that mesenchymal stem cells (MSC) appears IgG recall responses to this immunization. Preliminary analyses of antibody to be important in therapeutics to regulate immune response invoked in responses to hepatitis B surface antigen indicate a somewhat lower settings such as tissue injury, transplantation and autoimmunity. In this responsiveness to the primary and booster immunizations in those with S. study we investigated the effect of these cells on the immunoregulation mansoni infection. Further analyses are ongoing. activities of adipose tissue derived stem cells (ASC) in a Schistosoma mansoni experimental model. The ASC were isolated from C57BL/6 1834 mice, expanded in vitro and phenotypic and functionally characterized. TARGETING THE BURDEN OF SCHISTOSOMIASIS IN These cells were injected via the tail vein into C57BL/6 mice (n=6) two weeks after S. mansoni infection. The splenocytes were obtained and MADAGASCAR: GYNAECOLOGICAL MANIFESTATIONS OF the in vitro proliferative response was determined after six days of SCHISTOSOMIASIS IN AN AREA SCALING UP MASS DRUG culture of splenocytes in the presence or not of ASC, and stimulated ADMINISTRATION OF PRAZIQUANTEL with Schistosoma egg crude antigens (SEA) or adult worms (SWAP) or Bodo S. Randrianasolo1, Peter M. Jourdan1, Pascaline concanavalin A. After thirty days of ASC injection, in vitro stimulation Ravoniarimbinina2, Charles E. Ramarokoto2, Fanjasoa of splenocytes in the presence of ASC led to a significant increase on Rakotomanana2, Vololomboahangy E. Ravaoalimalala2, Svein G. proliferation. On the other hand, the addition of ASC to spleen cell Gundersen3, Hermann Feldmeier4, Birgitte J. Vennervald5, Lisette cultures from infected mice that did not receive ASC in vivo showed van Lieshout6, Borghild Roald7, Peter Leutscher8, Alan Fenwick1, a decreased proliferative response. Interestingly, a decrease in in vitro Eyrun F. Kjetland9 splenocyte proliferation was also observed after sixty days post-ASC 1Schistosomiasis Control Initiative, Imperial College London, London, injection, even in the presence of fresh ASC. CD4+ T cell activation was United Kingdom, 2Institut Pasteur de Madagascar, Antananarivo, analyzed (CD25, CD69, CD28 and CTLA-4) after fifteen, thirty and sixty Madagascar, 3University of Agder, Kristiansand, Norway, 4Charité University days post-ASC injection. We observed a decrease in activation of T CD4+ Medicine, Berlin, Germany, 5University of Copenhagen, Copenhagen, subpopulation, mainly after fifteen and thirty days post-ASC injection. Denmark, 6Leiden University Medical Center, Leiden, Netherlands, 7Oslo In conclusion, in mice infected with S. mansoni, the ASC were able to University Hospital, Oslo, Norway, 8Aarhus University Hospital, Aarhus, modulate the immune response during the early inflammatory process, Denmark, 9University of KwaZulu-Natal, Durban, South Africa in a time-dependent manner. These data emphasize the putative role of these cells as candidates for cellular therapy, including the control of Schistosoma haematobium infection frequently causes morbidity in the inflammation caused by parasitic diseases. genital tract, and the disease may increase the risk of HIV transmission. Genital schistosomiasis in women of reproductive age living in endemic 1833 areas is under-diagnosed, and efforts are needed to better understand the pathophysiology and to provide control measures for the disease. A LOW TO MODERATE INTENSITY SCHISTOSOMA study was undertaken in order to determine the female genital morbidity MANSONI INFECTIONS DO NOT ALTER PROTECTIVE caused by schistosomiasis, and to describe its histopathological correlates ANTIBODY RESPONSES TO TETANUS TOXOID BOOSTER in an area of Madagascar prior to mass drug administration (MDA) of IMMUNIZATIONS praziquantel. Women aged 15-35 years living in an S. haematobium- endemic area in Madagascar underwent pelvic and colposcopic 1 2 1 Diana K. Riner , Eric M. Ndombi , Jennifer M. Carter , Nupur examinations. Women were grouped according to intensity of urinary 1 2 2 2 Kittur , Emmy Kavere , Harrison K. Korir , Amos Omondi , W. Evan S. haematobium infection, and small biopsies were taken from genital 3 2 1 Secor , Diana Karanja , Daniel G. Colley lesions and examined microscopically using standard haematoxylin and 1University of Georgia, Athens, GA, United States, 2Kenya Medical eosin stain. Updated mapping data of schistosomiasis was collected for Research Institute, Kisumu, Kenya, 3Centers for Disease Control and the strategic planning, implementation and review of MDA of praziquantel Prevention, Atlanta, GA, United States in the same region of Madagascar. Genital lesions named sandy patches Helminths such as schistosomes are remarkable in their ability to modulate and rubbery papules were found in 41 of 118 women (35%). Rubbery host immune responses, which promotes their survival. Immunoregulation papules only reported and described in this study contained an intense begins early in schistosome infection and has been characterized by cellular immune reaction dominated by eosinophils, epithelial erosion, and hyporesponsiveness to parasite antigens and bystander antigens, viable ova. There was a significant decrease in the prevalence of rubbery suggesting schistosome infection at the time of immunizations could papules with age, even after adjustment for urinary ova excretion. The lower the protective response to vaccines. To investigate the impact that sandy patches with grains showed moderate cellular immune reaction concurrent helminth infection might have on an individual’s responses and ova (viable and/or calcified), and were most prevalent in women with to vaccine antigens, we recruited participants from Kisumu Polytechnic low-intensity urinary S. haematobium infection. These findings in women College in western Kenya. Participants were enrolled, consented and living in an endemic area of Madagascar indicate a dynamic evolution of screened for schistosomiasis and soil transmitted helminths (STHs) and inflammatory genital lesions caused by S. haematobium and a clear need assigned to groups based on helminth status. Tetanus toxoid (TT; single for preventive chemotherapy in school-age children as recommended by the World Health Organization. The authors present the results in light of

astmh.org 562 the current scale-up of MDA of praziquantel in Madagascar put in place by 1837 the Ministry of Health and the Ministry of Education, and supported by the Schistosomiasis Control Initiative (SCI). AN ULTRA-SENSITIVE URINE-BASED ASSAY TARGETING THE CIRCULATING ANODIC ANTIGEN (CAA) FOR DIAGNOSIS OF 1835 UROGENITAL TO INTESTINAL SCHISTOSOMIASIS IN LOW- ENDEMIC AREAS LENTIVIRUS HIV-1 INTEGRATES WIDELY THROUGHOUT THE GENOME OF THE HUMAN BLOOD FLUKE SCHISTOSOMA Govert J. van Dam, Claudia J. de Dood, Dieuwke Kornelis, MANSONI Lisette van Lieshout, Paul L. Corstjens LUMC, Leiden, Netherlands Paul J. Brindley1, Sutas Suttiprapa1, Gabriel Rinaldi1, Isheng J. Tsai2, Sergei Iordanskiy1, Victoria H. Mann1, Larisa Dubrovsky1, The recent renewed interest in mapping, intensified control and Hong-bin Yan1, Nancy Holroyd2, Tatiana Pushansky1, Matthew elimination of schistosomiasis has put the need for highly accurate Berriman2, Michael I. Bukrinsky1 diagnostic assays high on the agenda. The well-studied schistosome 1George Washington University, Washington, DC, United States, antigen detection assays CCA- and CAA-ELISA have now been 2Wellcome Trust Sanger Institute, Hinxton, United Kingdom transformed into a Point-of-Care rapid test (POC-CCA) and an ultra- sensitive UCP lateral flow based strip assay (UCP-CAA), resp. The simple Lentivirus-mediated gene expression manipulation offers advantages for field applicable POC-CCA test may replace the Kato-Katz testing for functional genomics of the schistosome, allowing to establish informative prevalence mapping of community-level Schistosoma mansoni infections lines of transgenic schistosomes and to elucidate gene functions of these using a single drop of urine as well as evaluate quickly (within days) pathogens. To investigate the ability of lentiviral vectors to integrate into the efficacy of treatment. However this test shows variable sensitivity in the schistosomal genome, blood stream forms of the human schistosome, the diagnosis of S. haematobium. The recently developed UCP-CAA Schistosoma mansoni, including schistosomules and adult female and assay detects antigen in serum or urine of all schistosome species at male parasites were exposed to vesicular stomatitis virus glycoprotein sub-pg levels, a sensitivity allowing detection of single worm infections. pseudotyped virions of HIV-1. Reverse transcription of the lentiviral The assay has been transformed into a robust, dry-reagent based RNA genome proceeded, as confirmed by the presence of strong-stop test, and is currently used in several low-resource settings in Africa. In and positive strand cDNAs, in turn confirming the internalization of the combination with optimized sampling schedules involving pooled urines lentiviral nucleocapsid into the cytoplasm of schistosome cells. Integration this would allow rapid identification of foci of low prevalence/intensity S. of HIV provirus into chromosomes of the schistosomes followed, as haematobium and S. mansoni infections. Recent studies using the 2 ml established by anchored PCR targeting integrated provirus in the vicinity urine dry reagent UCP-CAA format performed in low prevalence (<2%), S. of endogenous mobile elements, by high throughput sequencing of haematobium settings (near elimination) show an over 10-fold increase lentivirus-anchored PCR products, and by whole genome sequences of in the prevalence of active schistosome infections. Similar results have the schistosomes. On a population scale, integrations of lentiviral provirus been shown for S. japonicum settings in China and S. mansoni settings were widely distributed throughout the eight pairs of chromosomes of in Brasil and Africa. The UCP-CAA strip assay therefore is a valuable highly the schistosomes. Density of integrations was frequently > 10 events per sensitive diagnostic tool, applicable for screening and case finding in very 100 kilobase pair windows. Integration site preference was biased to non- low prevalence areas, including pre-elimination settings. coding regions of the schistosome genome, a preference dissimilar to that of HIV in human T cells. Integrations into exons and introns of protein- 1838 encoding loci were also seen. The ability of HIV-1 to complete biochemical processes essential for lentivirus replication was notable and unexpected EVALUATING THE IMPACT OF PULSE OXIMETRY ON given that schistosomes are phylogenetically far distant from primates and PNEUMONIA MORTALITY IN CHILDREN UNDER FIVE IN other mammals naturally infected by the genus Lentivirus. RESOURCE-POOR SETTINGS 1836 Jessica Floyd1, Lindsey Wu2, Rasa Izadnegahdar3, Deborah Burgess3, David Mukanga3, Azra Ghani1 DEVELOPMENT OF A BIOSENSOR-BASED RAPID URINE TEST 1Imperial College London, London, United Kingdom, 2London School FOR DETECTION OF UROGENITAL SCHISTOSOMIASIS of Hygiene & Tropical Medicine, London, United Kingdom, 3The Bill & Melinda Gates Foundation, Seattle, WA, United States Kathleen Mach1, Ruchika Mohan1, Shailja Patel1, Pak K. Wong2, Michael Hsieh3, Joseph C. Liao1 Despite available interventions, pneumonia is still responsible for an 1Stanford University, Stanford, CA, United States, 2University of Arizona, estimated 15% of childhood deaths worldwide. Recent research has Tucson, AZ, United States, 3Biomedical Research Institute, Rockville, MD, shown that hypoxia and malnutrition are strong predictors of mortality in United States children hospitalized for pneumonia. This has led to increasing support for the use of oxygen therapy and monitoring oxygen saturation in the Schistosomiasis affects up to 300 million people with serious and diverse management of severe cases. It is estimated that 15% of children under sequelae arising from infection. Diagnosis of urogenital schistosomiasis five hospitalised for pneumonia have hypoxemia and that approximately (Schistosoma haematobium infection) relies on microscopic identification 1.5 million children with severe pneumonia require oxygen treatment and enumeration of parasite eggs in urine, however this is time consuming each year. We present a deterministic compartmental model to assess and requires technical skill. A point-of care device for detection of S. the impact of introducing pulse oximetry as a prognostic to distinguish haematobium would significantly reduce the time-to-result with the severe from non-severe pneumonia in under-fives across 15 of the potential to improve patient care. In this work, we demonstrate the highest-burden countries. Incidence of pneumonia in each country was use of our established biosensor platform for bacterial identification for fitted to data on the mortality rates in each country. The impact of this the detection of S. haematobium in urine. We developed capture and improved prognostic was compared to the current mortality rates under detector probes targeting S. haematobium rRNA, a robust egg lysis Integrated Management of Childhood Illness (IMCI) guidelines. We found protocol and integration into our established platform. Using the biosensor that, assuming access to supplemental oxygen, pulse oximetry has the assay, we demonstrated direct detection of S. haematobium eggs spiked potential to avert an estimated 200,000 deaths if implemented across in human urine at clinically relevant ranges with detection of as few as 30 the 15 countries, whereas IMCI was found to have a relatively small eggs/ ml urine. impact on mortality. Pulse oximetry can significantly increase the incidence of correctly-treated cases as well as reduce the incidence of incorrect

astmh.org 563 treatment with antibiotics. We also found pulse oximetry to be highly 1840 cost-effective, with median estimates ranging from $2.46 to $9.43 per DALY averted in 14 of the 15 countries analysed (US$). This combination RESPIRATORY VIRAL DETECTIONS DURING SYMPTOMATIC of significant burden reduction and high cost-effectiveness makes pulse TO ASYMPTOMATIC PERIODS IN YOUNG ANDEAN CHILDREN oximetry a promising candidate for an intervention against pneumonia in 1 1 2 resource-poor settings. Leigh M. Howard , Monika Johnson , John V. Williams , Yuwei Zhu3, Ana I. Gil4, Kathryn M. Edwards1, Marie R. Griffin5, Claudio 1839 F. Lanata4, Carlos G. Grijalva6 1Division of Infectious Diseases, Department of Pediatrics, Vanderbilt HOUSEHOLD-LEVEL RISK FACTORS FOR SECONDARY University, Nashville, TN, United States, 2Department of Pathology, INFLUENZA-LIKE ILLNESS IN A RURAL AREA OF Microbiology, and Immunology, Vanderbilt University, Nashville, TN, United BANGLADESH States, 3Department of Biostatistics, Vanderbilt University, Nashville, TN, United States, 4Instituto de Investigacion Nutricional, Lima, Peru, 1 2 2 Anne M. Weaver , Manoshi Islam , Kaniz Khatun-e-Jannat , 5Department of Pediatrics, Vanderbilt University, Nashville, TN, United 3 4 3 Emily Cercone , Margaret A. DiVita , Kimberly Krytus , Badrul States, 6Department of Health Policy, Vanderbilt University, Nashville, TN, 2 2 2 Munir Sohel , Makhdum Ahmed , Abid Mahmud Rahman , United States Mustafizur Rahman2, W. Abdullah Brooks5, Eduardo Azziz- Baumgartner6, Jihnhee Yu3, Alicia M. Fry6, Stephen P. Luby7, Pavani Viruses are commonly detected in children with acute respiratory K. Ram3 illnesses (ARI) and in asymptomatic children. Longitudinal studies of viral detections during asymptomatic periods surrounding ARI could facilitate 1Indiana University, Indianapolis, IN, United States, 2International Centre interpretation of viral detections but are currently scant. Methods. We for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh, used reverse transcription-polymerase chain reaction (RT-PCR) to analyze 3University of Buffalo, Buffalo, NY, United States, 4State University of New respiratory samples from young Andean children for viruses during York, Cortland, Cortland, NY, United States, 5Johns Hopkins Bloomberg asymptomatic periods within 8-120 days of index ARI (cough or fever). School of Public Health, Baltimore, MD, United States, 6Centers for Disease We compared viral detections over time within children and explored RT- Control and Prevention, Atlanta, GA, United States, 7Stanford University, PCR cycle thresholds (CT) as surrogates for viral loads. Results. At least Stanford, CA, United States one respiratory virus was detected in 367 (43%) of 859 samples collected Influenza-like illness (ILI) is an important public health concern in during asymptomatic periods, with more frequent detections in periods Bangladesh. Individuals with ILI are likely to transmit their illness to close with rhinorrhea (49%) than those without (34%, p<0.001). Relative to contacts, including household members. Household-level risk factors index ARI with human rhinovirus (HRV), adenovirus (AdV), respiratory for secondary ILI in a low-income, vulnerable population have not been syncytial virus (RSV), and parainfluenza virus (PIV) detected, the same virus characterized. We conducted secondary data analysis from participants was also detected during 32%, 22%, 10%, and 3% of asymptomatic in the control arm of a randomized controlled trial of handwashing and periods, respectively. RSV was only detected 8-30 days after index RSV ARI, secondary ILI. We recruited index case-patients with ILI--fever (<5 years), whereas HRV and AdV were detected throughout asymptomatic periods. fever, cough or sore throat (≥5years)--from health facilities, collected Human metapneumovirus (MPV) and influenza were rarely detected during information on household factors, and conducted syndromic surveillance asymptomatic periods (<3%). No significant differences were observed in on all household contacts for ten days after resolution of index case- the CT for HRV or AdV during asymptomatic periods relative to ARI. For patients’ symptoms. We conducted multivariable negative binomial RSV, CT were significantly lower during ARI relative to the asymptomatic regression to evaluate the effects of household factors on risk of secondary period (p=0.03). Conclusions. These findings indicate that influenza, ILI among household contacts and accounting for clustering by household. MPV, PIV, and RSV detections in children with ARI usually indicate a A wealth index was created using principal components analysis of causal relationship. When HRV or AdV is detected during ARI, the causal household assets. We analyzed data from 1491 household contacts of relationship is less certain. 184 index case-patients. Mean age was 26 years. Most (71%) reported that smoking occurred in their home, 27% shared a latrine with 1 other 1841 household, and 36% shared a latrine with >1 other household. A total of 114 participants had symptoms of ILI during follow-up. Smoking in DESCRIPTION OF THE POPULATION STRUCTURE TO GENETIC the home (RRadj 1.91, 95% CI 1.23-2.96), and sharing a latrine with 1 DIVERSITY OF MYCOBACTERIUM TUBERCULOSIS AMONG other household (RRadj 2.07, 95% CI 1.18, 3.64) or >1 household (RRadj PATIENTS OF HAITIAN ORIGIN LIVING IN FLORIDA 3.08, 95% CI 1.81-5.23) compared to not sharing, were independently 1 1 2 associated with increased risk of secondary ILI, even after adjustment for Marie N. Seraphin , Alice M. Abernathy , Richard T. Doggett , J. 1 1 wealth. These results suggest that efforts to reduce tobacco use in homes Glenn Morris , Michael Lauzardo could reduce respiratory illness in Bangladesh. The association between 1University of Florida, Gainesville, FL, United States, 2Florida Department of use of shared latrines and household ILI transmission had not previously Health, Tallahassee, FL, United States been demonstrated. It is possible that certain respiratory pathogens could Individuals of Haitian origin have one of the highest tuberculosis (TB) be transmitted effectively through contact with feces or contaminated case rates in Florida. However, literature on the propensity of certain fomites present in shared latrines; future research could investigate these M. tuberculosis strains to transmit faster than background rate in this mechanisms in more depth. population is limited. We investigated the genetic diversity, occurrence of strain emergence, and determinants of emergent strains among Haitians living in Florida. All culture confirmed TB cases reported to the Florida Department of Health (FDOH) are genotyped using spoligotyping and MIRU. We analyzed data on 482 TB cases of Haitian origin reported to FDOH from 2002 to 2014. We used the web application MIRU-VNTRplus for strain family and shared international types (SIT) assignment. We used SpolTools and the program DESTUS to asses strain emergence, recent transmission index and genetic diversity. In multivariate regression, we measured the socio-demographic and clinical determinants of strain emergence. Of the 482 strains, 136 (28.2%) belonged to the Haarlem lineage, 130 (27.0%) to the LAM lineage and 91 (18.8%) to the T lineage. SIT50, H3 sub-lineage, was the most common spolygotype with 59 astmh.org 564 strains (12.2%). Sixty two spoligotypes were identified as orphans. The 1843 different isolates were characterized into 114 genotypes with average cluster size of 4.2, recent transmission index and clustering rate of 0.76 INCIDENCE TO RISK FACTORS FOR RESPIRATORY SYNCYTIAL and 0.24 respectively, and a virtual heterozygosity of 0.040. Adjusting VIRUS TO HUMAN METAPNEUMOVIRUS INFECTIONS for false discovery rate, The H3 sub-lineage, was identified as emergent AMONG CHILDREN IN THE REMOTE HIGHLANDS OF PERU (θ=46.84, p=2.44×10-04, q=0.02785), i.e. spreading faster than background transmission rate. A history of incarceration (AOR=7.63, CI: Andrew Wu1, Philip J. Budge2, John V. Williams3, Marie R. Griffin4, 1.17, 49.79; p=0.0337) was the strongest predictor of strain emergence Kathryn M. Edwards5, Monika Johnson6, Yuwei Zhu7, Stella after controlling for age, gender, years in the US, HIV status, initial drug Hartinger8, Hector A. Verastegui9, Ana I. Gil9, Claudio F. Lanata9, resistance, site of disease, illicit drug and alcohol use, and homelessness. Carlos G. Grijalva4 The H3 sub-lineage seems to be emerging in Haitian communities in 1School of Medicine, Vanderbilt University, Nashville, TN, United States, Florida, largely driven by exogenous infection among individuals with a 2Division of Infectious Diseases, Washington University School of Medicine, history of incarceration. Renewed efforts to track and treat TB patients of St. Louis, MO, United States, 3Department of Pathology, Microbiology, Haitian origin are warranted to curtail the spread of this Mtb clone. and Immunology, Vanderbilt University, Nashville, TN, United States, 4Department of Health Policy, Vanderbilt University, Nashville, TN, United 1842 States, 5Vanderbilt Vaccine Research Program, Division of Infectious Diseases, Department of Pediatrics, Vanderbilt University, Nashville, TN, EXPANSION OF TYPE 1 CYTOKINE PRODUCING CD4+T United States, 6Department of Pediatrics, Vanderbilt University, Nashville, CELLS OCCURING IN DISTINCT MEMORY COMPARTMENTS TN, United States, 7Department of Biostatistics, Vanderbilt University, DELINEATES LATENT VS. ACTIVE TUBERCULOUS DISEASE Nashville, TN, United States, 8Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland, 9Instituto de Investigacion 1 2 2 Soumya Chatterjee , Pavan Kumar , Subash Babu , Thomas B. Nutricional, Lima, Peru Nutman1 1National Institutes of Health/National Institute of Allergy and Infectious The disease burden and risk factors for respiratory syncytial virus (RSV) Diseases, Bethesda, MD, United States, 2NIH-ICER/NIRT, Chennai, India and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. Methods: We conducted a prospective, Optimal CD4+ responses in the control of tuberculosis (TB) caused by household-based cohort study of children aged <3 years living in remote Mycobacterium tuberculosis (Mtb) depends on antigen-specific, protective rural highland communities in San Marcos, Cajamarca, Peru. Acute type 1 cytokine producing stable precursor memory pool. The quality respiratory illnesses (ARI), including lower respiratory tract infection (LRTI), of these responses in active pulmonary (PTB) versus latent TB (LTBI) is, were monitored through weekly household visits from March 2009 however, poorly understood. We used multiparameter flow cytometry on through September 2011. Nasal swabs collected during ARI/LRTI were whole blood from 9 LTBI and 10 PTB subjects to assess the nature of Mtb tested for RSV, MPV, and other respiratory viruses using real-time RT-PCR. antigen (Ag) (ESAT6 and CFP10, E6/C10)-specific memory T cell responses. Incidence rates and rate ratios were calculated using mixed effects Poisson At baseline, PTB subjects compared to LTBI had increased frequencies of regression. Results: Among 892 enrolled children, incidence rates of RSV total CD4+IFN-γ+ cells (median frequency 0.4 % vs. 0.11, p= 0.01) as well and MPV ARI were 30 and 17 episodes per 100 child-years, respectively. as CD4+IFN-γ+TNF-α- (median frequency 0.35 % 0.1%, p= 0.004) and The proportions of RSV and MPV ARI that presented as LRTI were 12.5% CD4+IFN-γ+IL-2- cells (median frequency 0.05 % 0.23%, p= 0.04). No and 8.9%, respectively. Clinic visits for ARI and hospitalizations were differences were seen in the absolute frequencies of total CD4+TNF-α+ significantly more frequent (all p values <0.05) among children with RSV or CD4+IL-2+ cells. Interestingly, within CD4+IFN-γ+ cells, PTB subjects (clinic 41% and hospital 5.3%) and MPV ARI (38% and 3.5%) when showed increased frequencies of cells with a naïve-like phenotype compared with other viral infections (23% and 0.7%) and infections (CD45RA+CCR7+, NV, median frequency 9.2% vs. 2.7%, p=0.05) as well without virus detected (24% and 0.6%). In multivariable analysis, risk as stem cell like memory cells (CD45RA+CCR7+CD27+CD95+, TSCM) factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00- (median frequency 1.5% vs. 0.001%, p=0.02). The PTB group showed 1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12- increased CD4+IFN-γ+TNF-α- cells frequencies in the TSCM compartment 2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd (median frequency 0.6% vs.% 0.001%,p=0.03) while increased CD4+ compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd IFN-γ+IL-2- cells were seen in the TEMRAs (CD54RA+CCR7-) (median compared to 1st quartile residents). Having an unemployed household frequency 8.3% vs. 2.2 %, p= 0.01). On E6/C10 stimulation, however, LTBI head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12- subjects showed an increased net frequency of CD4+IFN-γ+ cells in Central 4.01). Conclusion: In rural high altitude communities in Peru, childhood memory (CD45RA-CCR7+, TCM) (median net frequency 8.5 % vs. -3.3%, ARI due to RSV or MPV were common and associated with higher p=0.05) and TSCM cells (median net frequency 0.01 % vs. -0.4%, p=0.03) morbidity than ARI due to other viruses or with no viral detections. The compared to PTB. Finally, the LTBI group showed E6/C10-specific increased risk factors identified in this study may be considered for interventional net frequencies of CD4+IL-2+ cells in the NV compartment (median studies to control infections by these viruses among young children from net frequency 3.09% vs. 0.8% PTB, p=0.05). These data suggest that developing countries. although increased baseline CD4+ IFN-γ+ responses in are seen in subjects with PTB, Mtb- antigen specific increased IFN-γ and IL-2 within precursor 1844 CD4+ memory cells (TCM and TSCM) as seen in LTBI subjects might be associated with infection containment. PNEUMONIA FORGOTTEN NO MORE: PNEUMONIA.ORG.AU Brian Greenwood London School of Hygiene &Tropical Medicine, London, United Kingdom In 1992, pneumonia was described as the “forgotten pandemic” and remains the most common cause of childhood mortality in the developing world. In 2006 at ISPPD5 in Alice Springs, Australia, a declaration was issued for the development of a global action plan against childhood pneumonia. In 2009, at a Tri-Nation (Indonesia, Papua New Guinea and Australia) meeting held in Sydney, Australia, it was resolved to establish a journal dedicated to pneumonia. The pneumonia journal (www. pneumonia.org.au) was launched in 2012. Since that time, pneumonia has strived to be internationally recognised as the premier, open access, astmh.org 565 peer-reviewed Journal for publishing on the topic of pneumonia. In role of memory T cells present in peripheral tissues has not been explored. December 2014, a Gates Foundation Grant was awarded to the Journal We have identified a population of Leishmania-specific memory CD4+ to assist with the development of a sustainable business platform. The T cells present in the skin of mice that have resolved a primary infection esteemed Editorial Board currently has over 40 international members with L. major. These cells are present in skin distant from the primary and regional Deputy Editor-in-Chiefs appointed in Australiasia, North infection, and produce IFNγ in response to L. major stimulation. Using skin and South America, Asia, Africa and Europe. pneumonia is indexed grafts we show that they are resident in the skin, rather than recirculating. by Google Scholar and the Directory of Open Access Journals. An Following Leishmania challenge, these cells enhance the early recruitment application has been made for Scopus listing and systems are in place of circulating T cells to the skin in a CXCR3 dependent manner, resulting for an application to MEDLINE and PubMed. Recognising the importance in better control of the parasites. Our findings indicate that protective of rapid dissemination of research, a continuous publication model is immunity to Leishmania, and thus the success of a vaccine, may depend used. To date over 20 manuscripts have been published with as many in on generating both circulating and skin-resident memory T cells. the pipeline. The Journal site has been accessed from over 150 countries across all continents and has had over 80,000 page views with greater 1847 than 65% of these visits being from new visitors. pneumonia is currently partnered with the Lung Foundation Australia, the Influenza Specialist LEISHMANIA MAJOR INFECTION INDUCES TRANSMISSIBLE Group (Australia) and the World Pneumonia Day Coalition to advocate for ALTERATIONS IN THE SKIN MICROBIOME and increase the awareness of pneumonia appropriate to a broad range of Ciara Gimblet, Michael A. Loesche, Elizabeth A. Grice, Phillip communities globally. pneumonia is published by Griffith University ePress Scott and is supported by the University and philanthropic sources. pneumonia has a major commitment to becoming the international forum for the University of Pennsylvania, Philadelphia, PA, United States distribution of quality, peer-reviewed content on pneumonia and raising Cutaneous leishmaniasis is a disease characterized by ulcerating skin the global profile of the disease - to be forgotten no more!! lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent 1845 tissue damage. Studies have shown that skin commensals enhance the immune response to L. major, but how the microbiome changes during THE ROLE OF VASCULAR REMODELING IN THE infection has not been characterized. Using analysis of the 16S ribosomal IMMUNOPATHOLOGY OF LEISHMANIA INFECTION RNA gene, we found that infection with L. major causes a loss in bacterial Tiffany S. Weinkopff, Christoph Konradt, David Christian, Phillip diversity during the peak of infection, resulting in a dominance of the Scott genus Staphylococcus. However once the lesions resolved, bacterial diversity returned to pre-infection levels. Alternatively, when mice University of Pennsylvania, Philadelphia, PA, United States developed more severely ulcerated lesions, the proportion of Streptococcus Cutaneous leishmaniasis is caused by intracellular protozoan parasites, significantly increased on the lesions, demonstrating that L. major induced and has a wide spectrum of clinical presentations mediated in large part alterations in the skin microbiome can vary depending on the severity by an exaggerated inflammatory response. Since vascular remodeling of disease. Strikingly, we observed similar changes in the microbiome contributes to the magnitude of the inflammatory response, we on non-inflamed skin distant from the infection site, as well as in skin hypothesized that manipulation of the cellular and molecular mediators from cohoused naïve mice. These results indicate that the altered skin promoting vascular remodeling might provide a novel approach to limit microbiome present at the site of infection is transmissible to uninfected pathology in leishmaniasis. To address this, we first characterized the skin despite having different immune responses at these sites. Current vascular remodeling that occurs in mice infected with Leishmania major. studies are directed at defining what factors mediate the changes in the We found dramatic changes in vessel morphology, structure, and number skin microbiome during L. major infection and how this transmissible within leishmanial lesions, and using intravital imaging we visualized microbiome influences disease. a significant increase in vascular permeability that is a consequence of vascular remodeling in leishmaniasis. At the peak of infection, VEGF-A and 1848 VEGFR-2 expression were upregulated and correspondingly endothelial cells were proliferating at the site of infection. To determine if these VEGF- FACTORS ASSOCIATED WITH PROTECTION OR mediated responses contributed to the magnitude of the pathology in the SUSCEPTIBILITY TO DEVELOPMENTS OF DISEASE IN disease, we treated L. major infected mice with neutralizing antibodies HOUSEHOLD CONTACTS OF CUTANEOUS LEISHMANIASIS directed against VEGFR-2. This treatment led to a decrease in the PATIENTS pathology seen in L. major infected mice compared with control animals. 1 1 1 Taken together these data suggest that VEGF-A-mediated vascular Edgar M. Carvalho , Aline Muniz , Ednaldo Lago , Luiz Henrique 1 1 1 1 remodeling occurs in leishmaniasis and that blockade of this remodeling Guimarães , Lucas Carvalho , Paulo Machado , Augusto Carvalho , 1 2 can lessen the magnitude of the immunopathology associated with this Olívia Bacellar , Marshall Glesby disease. 1Federal University of Bahia, Salvador, Brazil, 2Cornell University, New York, NY, United States 1846 The majority of infected subjects in an area of L.braziliensis transmission SKIN RESIDENT MEMORY CD4+ T CELLS ENHANCE have an asymptomatic or subclinical (SC) infection. While the Th1 response is important for Leishmania killing, in patients with cutaneous PROTECTION AGAINST LEISHMANIA MAJOR INFECTION leishmaniasis (CL) T cell activation and production of pro-inflammatory Nelson D. Glennie1, Venkata A. Yeramilli1, Daniel P. Beiting1, cytokines are associated with pathology. To better determine factors Susan W. Volk1, Casey T. Weaver2, Phillip Scott1 related to susceptibility and resistance to disease we have established a 1University of Pennsylvania, Philadelphia, PA, United States, 2University of cohort of 308 household contacts (HC) of CL patients without previous Alabama at Birmingham, Birmingham, AL, United States or current evidence of CL in the endemic area of Corte de Pedra, Bahia, Brazil. Chemokine and cytokine levels and Leishmania skin test (LST) were Leishmania-infected patients become refractory to reinfection following performed at entry and in the years 2 and 4, and the association of the disease resolution, and following a primary infection with Leishmania immune response with clinical outcome was analyzed. The immunologic major C57BL/6 mice are highly resistant to reinfection, yet effective response of HC who develop disease with those who remained disease immune protection has not been achieved by vaccines. While circulating free was also compared. Based on LST and, or in vitro IFN-γ production in Leishmania-specific T cells are known to play a critical role in immunity, the cultures stimulated with SLA 114 (37%) subjects had evidence of exposure astmh.org 566 to L.braziliensis. In 55 (17,8%) of them the LST was positive but in these, 1850 IFN-γ was only detected in 36 (65,4%). Moreover in 59 HC only IFN-γ production was observed. After 4 years of follow up CL was documented DEVELOPMENT OF A CANDIDATE LEISHMANIASIS VACCINE in 44 (14,2%) of 308 HC. The incidence of CL per 100 persons-years was LEISH-F3 + GLA-SE 0,92 in those who only produce IFN-γ and 4.2 in those with positive LST. 1 1 1 The major source of IFN-γ were NK and CD4+ T cells. Monocytes from Rhea N. Coler , Malcolm S. Duthie , Kimberly A. Hofmeyer , 1 1 1 subjects with SC infection produce less oxidative burst than cells of CL Lakshmi Jayashankar , Jill Ashman , Randall F. Howard , Anna 1 2 1 patients upon L. braziliensis infection, but they had great ability to kill Marie Beckmann , Dinesh Mondal , Steven G. Reed Leishmania independent of ROS and NO production. Our data indicate 1Infectious Disease Research Institute, Seattle, WA, United States, that a positive LST do not protect against CL due to L. braziliensis. Control 2International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, of the infection was associated with IFN-γ production and negative LST Bangladesh and greater ability of monocytes to kill leishmaniasis. Key antigens of Leishmania species identified in the context of host responses in Leishmania-exposed individuals were prioritized for the 1849 development of a subunit vaccine against visceral leishmaniasis (VL). DYNAMICS OF ANTIGEN SPECIFIC CD4+ MEMORY T CELL Two Leishmania proteins – nucleoside hydrolase (NH) and a sterol 24-c-methyltransferase (SMT), each of which are protective in animal RESPONSE DURING ACTIVE CUTANEOUS LEISHMANIASIS TO models of VL when properly adjuvanted – were produced as a single SIX MONTHS AFTER TREATMENT recombinant fusion protein NS (LEISH-F3) for ease of antigen production Kenneth J. Gollob1, Tatjana S. Keesen2, Erica Vieira3, Paulo and broad coverage of a heterogeneous MHC population. When Machado4, Luis Guimarães4, Edgar Carvalho4, Walderez O. Dutra3 formulated with GLA-SE, a TLR4 TH1-promoting adjuvant, the LEISH-F3 polyprotein induced potent protection against both L. donovani and L. 1Hospital Santa Casa-BH, Belo Horizonte, MG, Brazil, 2Federal University infantum in mice. A robust immune response to each component of of Paraiba, Paraiba, Brazil, 3UFMG, Belo Horizonte, MG, Brazil, 4UFBA, the vaccine with polyfunctional CD4 TH1 cell responses, characterized Salvador, Bahia, Brazil by production of antigen-specific IFN, TNF, and IL-2, and low levels of Human cutaneous leishmaniasis is a devastating tropical disease that IL-5 and IL-10, was induced in immunized mice. Based on the sum of affects millions globally and for which no effective vaccine exists. While pre-clinical data, we prepared GMP materials and performed a Phase 1 there are effective treatments, problems with toxicity, compliance and clinical study with LEISH-F3 + GLA-SE in healthy, uninfected adults in the resistance are serious issues that point to the need for the development United States. The vaccine candidate was shown to be safe and induced of new treatments and vaccines. The immunoregulatory environment in a strong antigen-specific immune response, as evidenced by cytokine and individuals actively infected with L. braziliensis is a key factor associated immunoglobulin subclass data. These data provide a strong rationale for with development or resolution of disease. Our understanding of the additional trials in Leishmania-endemic countries. balance between memory cell compartments in active disease and following cure is not well understood. Thus, we undertook studies 1851 designed to investigate the balance between antigen specific CD4+ T cell memory subpopulations during active disease and six months after EVALUATION OF TRYPANOSOMA CRUZI-SPECIFIC treatment. We report findings of CD4+ T cells from three compartments: HUMORAL TO T CELL RESPONSES AFTER THERAPY WITH central memory (CM (CD45RA-,CCR7+)), effector memory (EM (CD45RA- BENZNIDAZOLE IN CHILDREN IN THE EARLY CHRONIC PHASE ,CCR7-)) and naïve (CD45RA+,CCR7+) as defined using multiparameter OF CHAGAS DISEASE flow cytometry in a group of 13 CL patients following overnight cultures in media, with Soluble Leishmania Antigen (SLA) or polyclonal stimuli Maria C. Albareda1, Ana María De Rissio1, Marisa Fernandez1, (anti-CD3/CD28). Our results indicate that in active disease and 6 months Alicia Serjan2, Gretchen Colley3, Maria G. Alvarez4, Laura Fichera1, following treatment, the distribution of CD4+ subpopulations did not Rodolfo Viotti4, Rick L. Tarleton3, Susana A. Laucella1 change and was on average; 30% CM, 45% EM and 20% naïve. We 1Instituto Nacional de Parasitologia Dr M Fatala Chaben, Buenos Aires, demonstrated significant increases in the frequency of cells expressing Argentina, 2Hospital Fernandez, Buenos Aires, Argentina, 3University CD69, and the inflammatory cytokines; IFN-gamma and TNF-alpha, of Georgia, Athens, GA, United States, 4Hospital General Interzonal de within the EM cell population following SLA stimulation. Interestingly, Agudos Eva Peron, Buenos Aires, Argentina IL-10 producing cells where were not biased to the EM population and We have previously shown that children in the indeterminate phase of distributed between EM and CM. Six months post treatment, cultures Chagas disease have polifunctional T cells specific for T. cruzi, while the stimulated with SLA showed a decrease in EM cells expressing CD69, IL-17 overall T cell compartment already shows signs of persistent antigen and IL-10, while IFN-gamma, TNF-alpha and granzyme A producing EM T stimulation. In this study, the effect of treatment with benznidazole on cells were maintained at similar levels or increased to that seen in active humoral and cellular T cell responses specific for T. cruzi, as well as on the disease. There was a striking maintenance of the overall subpopulation phenotype of the overall T cell compartment was evaluated in 21 T. cruzi- balance during active disease and six months following treatment. infected children. Treatment with benznidazole induced an early decline These findings could help understand the balance between CD4+ T cell in the total frequencies of activated (HLA-DR+) and highly differentiated subpopulations and their maintenance over time after disease resolution. memory (CD45RA-CD27-CD28-) and effector (CD45RA+CCR7-CD62L-) T cells along with a decrease in T. cruzi-specific IFN-γ- and IL-2-producing T cells. A significant fall in antibody levels specific for T. cruzi, as measured by the conventional serological tests, ELISA, immunofluorescence and hemagglutination, after 36 months following treatment with benznidazole was found. The non-conventional multiplex assay also detected a significant impact on humoral responses by 6 months post-treatment. The early decline in antibody levels found in children is in contrast with that observed in adults in which the fall in antibody levels is very slow. Our results show a significant impact on humoral and T cell responses after treatment with benznidazole which might be indicative of a reduction in parasite load.

astmh.org 567 1852 responses are robust. However, in vitro WNV infectivity assays in cells overexpressing avian IFIT genes show that the avian IFIT homolog does SMALL RNA SIGNATURES OF A MIDGUT ESCAPE BARRIER not restrict the NS5-E218A mutant virus. Further studies of infected birds, IN CULEX QUINQUEFASCIATUS MOSQUITOES INFECTED BY including sequencing of the avian transcriptome, will help to define the WEST NILE VIRUS passerine innate immune response to WNV infection. Abhishek Prasad1, Doug Brackney1, Claudia Rueckert1, Darci 1854 Smith1, Selene Garcia-Luna1, Corey Campbell1, Jennifer Beane2, Gregory D. Ebel1 DECONSTRUCTING THE NEUTRALIZING ANTIBODY 1Colorado State University, Fort Collins, CO, United States, 2Boston RESPONSE ELICITED BY A WEST NILE VIRUS VACCINE University, Boston, MA, United States CANDIDATE Small RNA regulatory pathways (SRRPs) are important regulators of Leslie Goo, Julie E. Ledgerwood, Ted C. Pierson endogenous pre- and post-transcriptional control in metazoans. The role National Institutes of Health, Bethesda, MD, United States of SRRPs such as the exogenous small-interfering RNA (exo-siRNA), PIWI- interacting RNA (piRNA) and microRNA (miRNA) pathways in controlling There is no licensed vaccine or therapy to protect humans against West arbovirus infection in insects has been the subject of intense study in Nile virus (WNV), a mosquito-borne encephalitic flavivirus. Although recent years. The role of any of these pathways in vector competence, neutralizing antibodies (NAbs) are a correlate of protection for existing however, is poorly understood. To evaluate how SRRPs may contribute to flavivirus vaccines, the epitopes recognized by anti-WNV NAbs are vector competence, we identified Cx. quinquefasciatus mosquitoes that unknown. The main target of flavivirus NAbs is the E protein, which were susceptible to WNV but did not permit virus escape from the midgut contains three structural domains (DI, DII, DIII). Two recent studies showed into peripheral compartments after 14 days of extrinsic incubation. We that, despite low sequence conservation, a flexible hinge between DI then compared sRNA expression from these “elite controllers” of WNV to and DII is a primary target of NAbs against multiple DENV serotypes, those that permitted virus dissemination. In particular we compared the raising the possibility that this region is a functionally important target intensity of sRNA targeting of the WNV genome, differential production of flavivirus NAbs. To explore the role of the hinge as a target of WNV of virus-derived small interfering RNAs (viRNAs) reads, and miRNA NAbs, we created a library of E variants containing 31 mutations in expression among these two groups of mosquitoes. We found that viRNAs surface-accessible hinge residues. Reporter virus particles incorporating differentially target 1,519 positions of the WNV genome, and that 177 each variant were tested for infectivity and characterized using a panel of reads are differentially produced between groups. The most significantly well-characterized monoclonal antibodies (mAbs) to identify confounding differentially targeted positions and expressed viRNA reads targeted changes in virion conformational integrity. An unexpectedly large fraction conserved structures in the 3’utr of the WNV genome. Similar results (18/31) of the hinge region variants displayed altered sensitivity to mAbs were obtained from analysis of sRNA reads corresponding to a larger size targeting poorly accessible distal epitopes. Preliminary characterization class (24-30nt in length). 1076 WNV genome positions were differentially of one of these variants suggests that the overall changes in antigenicity targeted, but only 3 sRNA reads were differentially produced. These reads were due to altered virion conformational dynamics, which allows the also tended to target conserved structures in the WNV 3’utr. A miRNA transient exposure of otherwise inaccessible epitopes. The remaining signature associated with the elite controller phenotype was also detected. hinge mutations that did not alter overall antigenicity were tested for These results indicate that SRRPs contribute to the formation of a midgut neutralization sensitivity to sera from recipients of a candidate WNV escape barrier in Cx. quinquefasciatus mosquitoes and provide novel vaccine. We identified a combination of two mutations at proximal insights into the molecular mechanisms that underpin vector competence residues on the E protein that reduced neutralization potency of sera from in the Culex-WNV system. multiple donors, suggesting a significant contribution of NAbs against the hinge to the overall neutralizing activity of polyclonal sera. Overall, these 1853 results will provide insight into the importance of DI-DII hinge in eliciting protective NAb responses against flaviviruses, and in regulating virion AVIAN INNATE IMMUNE RESPONSES TO WEST NILE VIRUS conformational changes. INFECTION 1855 Nisha Duggal, Aaron C. Brault Centers for Disease Control and Prevention, Fort Collins, CO, United States INFECTION, DISSEMINATION TO TRANSMISSION OF JAPANESE ENCEPHALITIS VIRUS IN NORTH AMERICAN Since the first reports of West Nile virus (WNV) in the U.S. in 1999, WNV has been maintained in North America in an enzootic cycle between CULEX MOSQUITOES highly susceptible passerine birds and mosquitoes. However, the mortality Yan-Jang S. Huang1, Susan M. Hettenbach1, Julie N. Harbin1, of passerine birds in response to WNV infection and the capacity for viral Stephen Higgs1, Alan D. Barrett2, Elin Maki3, Lee W. Cohnstaedt3, replication vary dramatically between viral strains and avian species. For Dana L. Vanlandingham1 example, American crows (AMCRs) inoculated with the North American 1Kansas State University, Manhattan, KS, United States, 2University of Texas strain of WNV (NY99) manifest high viremias with concomitantly high Medical Branch, Galveston, TX, United States, 3United States Department mortality rates. However, AMCRs inoculated with an African strain of of Agriculture, Manhattan, KS, United States WNV (KEN98) exhibit significantly lower viremias and mortality rates. In contrast, the viremias and mortality rates of NY99 and KEN98 are not Japanese encephalitis virus (JEV) is a flavivirus transmitted by Culex significantly different in inoculated house sparrows (HOSPs). In order to species mosquitoes in Asia and sporadically Australia and Western Pacific. understand these viral- and host-specific differences in WNV replication Because of the variation in surveillance and diagnostic methods, the true and mortality, the expression levels of avian interferon genes and other global incidence of Japanese encephalitis virus remains unknown with innate immune factors potentially involved in regulating WNV replication an estimated annual case number greater than 55,000. The geographic were measured by qRT-PCR in samples taken from AMCRs inoculated distribution of JEV has changed significantly in the last 30 years as JEV with NY99 or KEN98. To further probe the avian interferon response to has expanded its geographic range. More recently, the detection of JEV WNV infection, AMCRs and HOSPs were inoculated with a WNV mutant viral nucleic acids was reported in Cx. pipiensin Italy and subsequently lacking 2’-methyltransferase activity (NS5-E218A) that has been shown raised the concern of the emergence of JEV in Europe. With the to be susceptible to restriction by the interferon-stimulated gene family presence of several species of Culex mosquitoes that are vectors in JEV IFIT in mammals. Replication of the NS5-E218A mutant virus was severely endemic areas, susceptible vertebrate hosts present and no vaccination retarded in both avian species, suggesting that AMCR and HOSP antiviral program implemented, the continuous threat of introduction of JEV into astmh.org 568 North America remains a human and veterinary public health concern. affected by YF virus infection, in vivo and in vitro, and could play a role Studies to determine the vector competence of North American Culex in infection control. We have used a cell-spheroid liver model (InSphero™) populations for the transmission of JEV are currently lacking. In this study, including major human liver primary cells (hepatocytes, Kupffer and liver selected Culex species mosquitoes were orally challenged with JEV and endothelial cells) to study transcriptional regulations following infection characterized for viral infection and dissemination by the detection of with YF viruses. Spheroids composed of primary hepatocytes only were infectious virions of JEV. Transmission of JEV was also evaluated by RT-PCR used as controls. About 400 genes related to innate immunity and of viral nucleic acids in mosquito saliva. hepatic metabolism were analyzed by PCR array at different times post- infection. No difference in transcriptional regulation of apoptosis-related 1856 genes (TNF-α, FASL, TRADD) was seen between the 2 viruses. YF17D-204 infection was shown to induce earlier and stronger activation than YFAsibi POTENTIAL FOR CO-INFECTION OF A NOVEL MOSQUITO- infection (p-value<0.05) of type III (IFNλ1 and IFNλ2) and type I β (but SPECIFIC FLAVIVIRUS TO BLOCK HUMAN FLAVIVIRAL not α) interferons, as well as a larger panel of ISGs. YF17D-204 infection DISEASE AGENT INFECTION AND/OR TRANSMISSION IN also generated distinct JAK/STAT pathway regulations in liver spheroids MOSQUITOES and in hepatospheroids, suggesting that liver spheroids may respond hierarchically to infection, the non-parenchymal cells response shaping 1 2 2 1 Silvina Goenaga , Joan L. Kenney , Nisha K. Duggal , S. Levis , the hepatocytes one. Whole transcriptome analysis was also carried out 1 2 Delia Enria , Aaron C. Brault by RNA-Seq at 11h post-infection. Analysis of upstream transcription 1Instituto Nacional de Enfermedades Virales Humanas, Pergamino, regulators (Ingenuity® Pathway Analysis) confirmed the establishment of a Argentina, 2Centers for Disease Control and Prevention, Fort Collins, CO, strong, early antiviral profile after YF17D-204 infection (z-scores: 2.7-5.0, United States p-values<10-10) and predicted transcription regulation of liver metabolism- related genes after YFAsibi infection(|z-score|≥2.3, p-value<10-3). Ongoing Nhumirim virus (NHUV) represents an example of a unique subset of RNA-Seq studies at later infection times will provide more information on apparently insect-specific viruses that phylogenetically affiliate with the ability of this liver model to mimic metabolic changes following wt dual-host mosquito-borne flaviviruses. Previous in vitro co-infection Asibi infection in vivo. experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a 10,000-fold reduction in viral production of West Nile virus (WNV). In order to assess the potential for in vivo 1858 blockage of medically important flaviviruses in mosquitoes by NHUV, Cx. COMPREHENSIVE MUTAGENESIS OF HCV E1/E2 ENVELOPE quinquefasciatus mosquitoes were intrathoracically inoculated with TO EPITOPE MAP ANTI-ENV ANTIBODIES TO FUNCTIONAL approximately 1,000 PFU of NHUV and 100 PFU of WNV or solely with WNV as a control. Mosquitoes were allowed to extrinsically incubate the RESIDUES CRITICAL FOR HCV INFECTIVITY viruses for 3, 5, 7 or 9 days prior to saliva collection by capillary tubes and Jennifer M. Pfaff, Trevor Barnes, Edgar Davidson, Benjamin J. subsequent trituration of the bodies for assessment of transmissibility and Doranz relative replication of the viruses, respectively. Results demonstrated 100% Integral Molecular, Inc., Philadelphia, PA, United States WNV infection of mosquitoes at all four time points in the control groups. Similarly, NHUV and WNV experimental co-infection groups exhibited To obtain epitope maps for anti-HCV Envelope (E1/E2) monoclonal 100% WNV infection at dpi 5,7 and 9 with 90% infection rates in the co- antibodies (MAbs), we individually mutated 552 residues of HCV (H77 inoculated group at dpi 3. No significant differences in the mean viral titer strain) E1/E2 to alanine. Each mutant was expressed in human cells and from triturated bodies were observed at any time point between the dual analyzed for its effects on MAb reactivity. This ‘Shotgun Mutagenesis’ and control WNV inoculation groups. Although there was an observed approach offers the capability of mapping both linear and conformational trend for the WNV titers in saliva to be higher in the control group epitopes, even for structurally complex proteins such as the oligomeric compared to the dual infection group, this difference was not significant. and glycosylated HCV Envelope protein. This approach identified critical Nevertheless, the proportion of mosquitoes (≥ 21 mosquitoes/ sampling) amino acids required for the binding of dozens of MAbs, and has also that were capable of transmitting WNV was significantly lower for the been used to propose E2 disulfide bond cysteine pairs that are not resolved WNV/NHUV group than the WNV control at dpi 3, 7 and 9. By dpi 9, a by the available E2 crystal structures. This approach has helped define the 40% reduction in transmissibility in mosquitoes from the dual inoculation range of immunodominant structures on HCV E1/E2 and identify novel group was observed compared to the WNV control. These data indicate neutralizing antibody epitopes that can be used for the development of the potential that infection of Culex vectors with NHUV could serve as a improved therapeutics, diagnostics, and vaccine candidates. In addition, barrier for efficient transmissibility of flaviviruses associated with human to identify residues important for HCV infectivity we produced infectious morbidity/mortality. HCV pseudoviruses from each mutant Env clone in the library. These pseudoviruses were used to evaluate each Env clone for infectivity on 1857 target cells. This allowed us to identify critical E1/E2 residues whose mutation eliminated HCV infectivity, identifying crucial HCV E1/E2 A THREE-DIMENSIONAL, MULTICELLULAR LIVER MODEL structural components that enable HCV infectivity. TO STUDY TRANSCRIPTIONAL ACTIVATION OF INNATE IMMUNE RESPONSE TO HEPATIC METABOLISM FOLLOWING 1859 INFECTION WITH WILD-TYPE OR ATTENUATED YELLOW FEVER VIRUS UNDERSTANDING THE DISTRIBUTION OF CHOLERA BURDEN TO RISK IN AFRICA: SPATIAL MODELING TO GUIDE Nicolas Masse-Deragon1, Nathalie Mantel2, Catherine Legras- PREVENTION TO CONTROL EFFORTS Lachuer1, Veronique Barban2 Sean M. Moore, Andrew A. Azman, Justin Lessler 1Université Lyon 1, Lyon, France, 2Sanofi Pasteur, Marcy-L’Etoile, France Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United Most commercial Yellow Fever (YF) vaccines are based on the attenuated States YF17D-204 strain derived by serial cultivation of wild-type YF Asibi virus. YF virus is highly hepatotropic in vivo and can replicate in vitro in human There are an estimated 2.8 million cholera cases per year globally, but hepatocytes. No restriction of YF17D-204 replication, compared to YF the majority of these cases are not detected or reported. Because of Asibi, was observed in these cells. However, other liver cells populations inadequate surveillance and reporting the global distribution of cholera like endothelial and macrophage cells were previously shown to be risk and its public health burden are poorly known. Previous attempts to determine the burden of cholera globally, and specifically in Africa, have astmh.org 569 relied on a limited number of case studies that do not capture the broad 1861 range of settings and environmental conditions where cholera occurs. Here we assemble a large database of cholera surveillance and incidence ‘O ANTIGENIC’ POLYSACCHARIDE SPECIFIC MEMORY B CELL reports from a variety of government, scientific, and non-governmental RESPONSES IN YOUNG CHILDREN, OLDER CHILDREN TO agency sources, with a particular focus on sub-Saharan Africa where a ADULTS INFECTED WITH VIBRIO CHOLERAE O1 OGAWA IN majority of cholera cases have been reported in the past several decades BANGLADESH but where the distribution of risk and burden is still poorly understood. We develop a hierarchical Bayesian modelling framework to estimate Amena Aktar1, M. Arifur Rahman1, Sadia Afrin1, Aklima Akter1, the cholera incidence and risk at a 5km scale across the entire African Taher Uddin1, Omar Faruk1, Israk Nur Sami1, Tahirah Yasmin1, Continent. Our method allows us to synthesize environmental and Fahima Chowdhury1, Ashraful I. Khan1, Daniel T. Leung2, Pavol socioeconomic variables with cholera incidence reports at different spatial Kovac3, Peng Xu3, Stephen B. Calderwood2, Jason B. Harris2, and temporal scales and estimate cholera incidence at a high spatial Firdausi Qadri1, Edward T. Ryan2 resolution. Preliminary results for 10 countries in West Africa indicate a 1International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, cumulative cholera incidence rate of 3.3 per 100,000 since 2009 with local Bangladesh, 2Massachusetts General Hospital, Harvard Medical School, incidence rates as high as nearly 8,000 per 100,000. Over four million Boston, MA, United States, 3National Institutes of Health, Bethesda, MD, people in these countries live in area with an annual incidence rate >100 United States per 100,000. The resulting maps can be used to identify areas of high Infection with Vibrio cholerae O1 causes the cholera, which can be life or low incidence (and risk) at finer spatial scales than the country-level, threatening if quick and proper treatment is not given especially in severe such as the province, district, or city-level. Work is ongoing to expand the dehydrating cases. It has been considered that long term protection model globally and incorporate additional explanatory variables. Improving against cholera may be mediated by anamnestic memory B cell responses our understanding of the spatial distribution of cholera and associating after natural infection with V. cholerae O1. Protection against cholera incidence with climate, environmental and socioeconomic factors will is serogroup specific, and serogrouping is defined by the O-specific provide a basis for planning public health preventions to reduce cholera polysaccharide (OSP) of lipopolysaccharide (LPS). We determined Ogawa transmission. O-specific polysaccharide (OSP) and Lipopolysaccharide (LPS) specific memory B cell responses as well as other immune responses in Bangladesh 1860 in patients with cholera. They included young children (2 to 5 years of LABORATORY EVALUATION OF age; n= 11), older children (6 to 17 years of age; n=21) and adults (18 to IMMUNOCHROMATOGRAPHIC RAPID DIAGNOSTIC TESTS 55 years of age; n=28). Patients were studied after hospitalization (day FOR CHOLERA IN HAITI 2) as well as at convalescence at day 7, day 30, day 90 and day 180. We observed vibriocidal antibody responses that lasted up to the follow Wilfredo R. Matias1, Abelard Cademil2, Fabrice E. Julceus2, Leslie up periods (P<0.05) in both older children and adults while responses M. Mayo-Smith3, Molly F. Franke1, Jason B. Harris3, Louise C. Ivers4 decreased to the baseline levels by 3 months in younger children. Patients 1Harvard Medical School, Boston, MA, United States, 2Zanmi Lasante, Saint of all age groups developed OSP and LPS specific plasma IgA, IgG and Marc, Haiti, 3Massachusetts General Hospital, Boston, MA, United States, IgM antibody responses within 7 days (P<0.01) of onset of disease which 4Brigham & Women’s Hospital, Boston, MA, United States decreased to baseline values at convalescence at 6 months; adults showed higher OSP and LPS specific antibody responses than children. We also Rapid diagnostic tests (RDTs) for cholera play a key role in responding found that in all age groups OSP specific IgA and IgG memory B cell to cholera epidemics. Because microbiological culture capacity is often responses developed within 30 days of illness, which persisted throughout non-existent in resource-poor settings where most cholera epidemics the follow-up period. In addition, they also developed LPS specific IgA occurs, RDTs can allow early identification of Vibrio cholerae as the memory B cell by day 30 (P <0.02). All age groups had comparable causative agent in outbreaks, facilitating the deployment of rapid public memory B cell responses to OSP and LPS while children had higher OSP health measures. Despite their importance, evidence on the performance IgA memory B cell responses than adults (P <0.05) on days 30 and 180. characteristics of the many available RDTs for cholera is scarce. This study We describe for the first time OSP-specific memory B cell responses in all evaluated the performance characteristics of two cholera RDTs: Span age groups of cholera patients and show that the responses persist over Diagnostic’s Crystal VC O1/O139 RDT, and Standard Diagnostic’s SD Bioline the study period, which suggest that OSP-specific memory B cell may play Cholera O1/O139 RDT, in a regional laboratory in Haiti, where a protracted a role in mediating long term immunity against cholera. cholera epidemic is now in its fifth year. We retrospectively reviewed de- identified records from May 2014 to January 2015 of a laboratory-based 1862 surveillance program for Vibrio cholerae at Hôpital Saint-Nicolas in Saint- Marc, Haiti. We analyzed 189 Crystal VC RDT results and 233 SD Bioline CHARACTERIZATION OF DUODENAL MUCOSAL ASSOCIATED RDT results and compared these to culture results as the gold standard. Of INVARIANT T (MAIT) CELLS IN VIBRIO CHOLERAE INFECTION 236 cultures, 125 were positive for O1, 15 were positive for non-O1, and 96 were negative for V. cholerae. Crystal VC demonstrated a sensitivity of M. Arif Rahman1, Taufiq R. Bhuiyan1, Mohammad Rubel Hoq1, 98.8% (95% CI: 96.5%-100%) and specificity of 72.1% (95% CI: 63.5%- Rasheduzzaman Rashu1, Mohammad Ikhtear Uddin1, Amena 80.7%). Notably, we documented a high percentage of V. cholerae O139 Aktar1, Ashraful I. Khan1, Fahima Chowdhury1, Jason B. Harris2, positive results, with 39% of all tests showing positive results for O139. Stephen B. Calderwood2, Edward T. Ryan2, Firdausi Qadri1, Daniel Given the absence of V. cholerae O139 in Haiti, these are likely a result T. Leung3 of cross-reactivity. SD Bioline demonstrated a sensitivity of 77.7% (95% 1Centre for Vaccine Science, International Centre for Diarrhoeal Disease CI: 70.3%-85.1%) and specificity of 93.7% (95% CI: 89.2%-98.2%). SD Research, Bangladesh, Dhaka, Bangladesh, 2Division of Infectious Diseases, Bioline did not demonstrate the O139 cross-reactivity seen with Crystal Massachusetts General Hospital, Boston, MA, United States, 3Division of VC, as no O139 positive results were documented. This study highlights Infectious Diseases, University of Utah, Salt Lake City, UT, United States the suboptimal specificity of Crystal VC, and brings attention to a high Cholera is an acute dehydrating diarrheal disease caused by Vibrio rate of O139 cross reactivity, a characteristic that may adversely impact cholerae O1 infection. The mechanisms of protection against cholera are its interpretation in the field. Additionally, it is the first study to document not well known. MAIT cells are recently described innate-like T cells with the performance characteristics of the SD Bioline RDT that unlike other adaptive capacity. We have previously shown that circulating MAIT cells available cholera RDTs, shows high specificity but low sensitivity. are activated during cholera and associated with V. cholerae LPS-specific antibody responses. The objective of this study was to characterize MAIT

astmh.org 570 cells in the intestinal mucosa during cholera. We collected peripheral blood 1864 and duodenal biopsy specimens by endoscopy from adults with confirmed V. cholerae O1 infection at days 2 and 30 after onset of disease. A COMPARISON OF DIARRHEAL SEVERITY SCORES IN A Preliminary data using multispectral fluorescence microscopy suggest that MULTISITE COMMUNITY BASED STUDY MAIT cells are mostly present in the crypt of the duodenal lamina propria 1 2 3 and are more abundant at day 2 post illness compared with day 30. Gwenyth Lee , Stephanie Richard , Gagandeep Kang , Eric 4 2 5 4 Using flow cytometry, we found that a greater percentage of duodenal Houpt , Jessica Seidman , Laura Pendergast , Richard L. Guerrant , 1 1 1 MAIT cells are activated (CD38+) than those in the periphery at both time Laura E. Caulfield , Robert E. Black , Margaret Kosek points. Stool alpha-1-antitrypsin, a marker of intestinal permeability, was 1Johns Hopkins School of Public Health, Baltimore, MD, United States, correlated with a decrease in % of activated MAITs between days 2 and 2Fogarty International Center, National Institutes of Health, Bethesda, MD, 30. More complete results, including analysis of corresponding LPS-specific United States, 3Christian Medical College, Vellore, India, 4University of antibody responses, will be available at time of presentation. Virginia, Charlottesville, VA, United States, 5Temple University, Philadelphia, PA, United States 1863 There is a lack of consensus on how best to measure diarrheal severity. SMALL INTESTINE BACTERIAL OVERGROWTH IN Several severity scores based on caregiver-reported symptoms have been published, but the performance of these in relation to child health BANGLADESHI TWO YEAR OLDS outcomes is unclear. The MAL-ED study is a multi-site, prospective birth Jeffrey Donowitz1, Rashidul Haque2, Beth Kirkpatrick3, Jennie cohort. In this report, we describe a modified Vesikari score (MAL-ED Ma4, Masud Alam2, Miao Lu4, Ross Colgate3, William Petri4 score), as well as two previously published severity scores, one by Clark 1Virginia Commonwealth University, Richmond, VA, United States, and colleagues, and one derived from a Peruvian cohort study (Community 2International Centre for Diarrhoeal Disease Research, Bangladesh, Diarrheal Severity (CODA) score). The association between these scores Dhaka, Bangladesh, 3University of Vermont, Burlington, VT, United States, and the risk of hospitalization was tested by means of receiver operating 4University of Virginia, Charlottesville, VA, United States characteristic analysis, and each score was also related to short-term weight gain, illness etiology, and moderate-to-severe diarrhea (MSD) Small intestine bacterial overgrowth (SIBO) has been associated with as defined by dysentery, health-care worker diagnosed dehydration, adverse nutritional outcomes, intestinal inflammation, and increased or hospitalization. A total of 9,803 episodes of non-persistent diarrhea intestinal permeability when overgrowth is secondary to preexisting from 1681 unique children were considered. There were 135 cases of intestinal pathology. Children living in unsanitary conditions have hospitalization and 1,147 episodes (11.7%) met the definition of MSD. high rates of SIBO despite having no predisposing condition. Limited The area under the curve of each score as a predictor of hospitalization information is known about the detrimental effects of SIBO when was 0.82 (Clark), 0.84 (MAL-ED), and 0.87 (CODA). Agreement with overgrowth develops in the setting of poor sanitation. We tested for SIBO MSD diarrhea was lower (AUC= 0.65, 0.68, 0.70 for Clark, MAL-ED, and via glucose hydrogen breath testing at 2 years of age in a cohort of 90 CODA respectively). Relative to enteropathogen-negative episodes, mean Bangladeshi infants. Children had C-reactive protein (CRP), endotoxin scores were higher during rotavirus- and adenovirus-positive diarrhea and core- antibody (endocab), fecal Reg 1β, Lactulose:Mannitol ratio (L:M), and lower during campylobacter- and giardia-positive diarrhea; and the mean anthropometric indices measured. All children were previously enrolled in MAL-ED or CODA scores were also significantly higher during astrovirus-, the PROVIDE study, a longitudinal birth cohort designed to investigate oral ETEC-, norovirus- and cryptosporidium-positive illness. Although families vaccination failure and environmental enteropathy. As part of PROVIDE, an were more likely to seek care for severe diarrhea across all sites, our results extensive collection of biomarkers for enteropathy as was available. This also suggest that a large percentage of these cases never reached the data was analyzed via multivariate logistic regression and smoothly clipped health care system. Diarrhea severity scores based on maternal report are absolute deviation (SCAD) to identify possible predictors of SIBO from a set able to predict relevant child health related outcomes. They may therefore of 50 biomarkers collected during the first 24 weeks of life. The incidence be useful in estimating the burden of disease, and the impact of disease of SIBO was 16.7% (15/90). Children with SIBO had a greater mean loss control interventions, in community-based studies where not all episodes in height-for-age Z score from birth to 2 years than those without (-.86 will necessarily reach the health care system. versus -.35, p value 0.03). Mean Reg 1β was higher in the children with overgrowth (116.75 µg/ml versus 65.62 µg/ml, p value .022). CRP, L:M, 1865 and endocab, were not statistically different in children with SIBO. Serum zinc level and fecal calprotectin were identified via both logistic regression ASSOCIATION BETWEEN ENTEROPATHOGENS TO and SCAD as possible predictors of SIBO. This data shows that SIBO due MODERATE-TO-SEVERE MALNUTRITION IN CHILDREN AGED to unsanitary living conditions is associated with intestinal epithelial cell 6-24 MONTHS IN DHAKA, BANGLADESH (MAL-ED): A CASE- damage but not increased systemic inflammation. An increased rate of CONTROL STUDY stunting in the first 2 years is associated with the development of SIBO which, along with increased fecal calprotectin and serum zinc levels in James A. Platts-Mills1, Mami Taniuchi1, Md. Jashim Uddin2, infancy, may represent a phenotypic predisposition to development of SIBO Shihab U. Sobuz2, Mustafa Mahfuz2, Md. Abdul Gaffar2, Dinesh in the developing world setting. Mondal2, Md. Iqbal Hossain2, Munirul Islam2, William A. Petri1, Rashidul Haque2, Eric R. Houpt1, Tahmeed Ahmed2 1University of Virginia, Charlottesville, VA, United States, 2International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh The association between individual enteropathogens or cumulative pathogen burden and malnutrition in the absence of diarrheal disease remains poorly understood. As part of the MAL-ED study, we sought to identify pathogens associated with malnutrition by performing a case-control study of children presenting to a nutrition clinic in Dhaka, Bangladesh. Moderate to severely underweight children [weight for age Z score (WAZ) <-2] aged 6-24 months were enrolled as cases, and better nourished children aged 6-24 months (WAZ > -1) were enrolled as controls. All stools (500 cases and 480 controls) were tested using conventional bacterial culture as well as PCR for diarrheagenic E. coli

astmh.org 571 subtypes and by enzyme immunoassay (EIA) for rotavirus, adenovirus, 1867 astrovirus, Entamoeba histolytica, Giardia, and Cryptosporidium. A random subset of 202 cases and controls were also tested for a broader CHARACTERIZING THE SPATIAL DISTRIBUTION OF MALARIA range of pathogens with arrayed, singleplex quantitative PCR using VECTORS IN AN AREA OF HIGH TRANSMISSION IN TaqMan Array Cards (TAC). The association between pathogens and NORTHERN ZAMBIA: EVIDENCE OF SPATIAL-TEMPORAL malnutrition was estimated using age- and sex-adjusted logistic regression. VARIATION IN THE DISTRIBUTION OF ANOPHELES FUNESTUS By conventional culture, only detection in stool of Campylobacter TO ANOPHELES GAMBIAE TO IMPLICATIONS FOR TARGETED was associated with malnutrition. In the subset tested by TAC, INTERVENTIONS Campylobacter, LT-ETEC, Aar-negative EAEC, Shigella, Norovirus GII and Giardia detection were associated with malnutrition. This set of pathogens Jessie Pinchoff1, Jennifer Stevenson1, Douglas E. Norris1, Mbanga was used to define a pathogen burden score. In a multivariate model, age, Muleba2, Mike Chaponda2, Modest Mulenga2, William J. Moss1, drinking water outside of the home and pathogen burden were associated Frank C. Curriero1 with malnutrition, and higher income was associated with better 1Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United nourished children. In this exploratory analysis, a subset of pathogens were States, 2Tropical Disease Research Centre, Ndola, Zambia identified for incorporation into a metric of pathogen burden, which could be validated in other studies of early childhood growth. Pathogen burden Characterizing the spatial distribution of malaria vectors is critical was an independent risk factor for malnutrition. to understanding transmission dynamics, with implications for the effectiveness of targeted control interventions. Active entomological 1866 surveillance was conducted at randomly selected households in Nchelenge District in Zambia from April 2012 to December 2014. At each visit, a URBAN MALARIA RISK CHARACTERISTICS FROM MULTIPLE questionnaire was administered and a CDC light trap left overnight for METRICS OF THE URBAN-TO-RURAL CONTINUUM: indoor mosquito collections. A total of 4,591 Anopheles funestus s.s. RELATIONSHIPS WITH ANOPHELES VECTOR ABUNDANCES and 548 An. gambiae s.s. were captured at 461 households. Counts IN BLANTYRE, MALAWI of An. funestus and An. gambiae were modeled using zero-inflated Poisson regression models as a function of environmental variables. Both Mark L. Wilson1, Nicole F. Dear1, Themba Mzilahowa2, Don P. species were significantly associated with closer proximity to category 1, Mathanga3, Terrie E. Taylor4, Edward D. Walker4 2, and 3 streams and with increasing degree of topographical slope. Both 1University of Michigan School of Public Health, Ann Arbor, MI, United species had higher abundances inland compared to along the banks of States, 2Malaria Alert Centre, College of Medicine, University of Malawi, Lake Mweru. Overall, An. funestus did not display seasonal variation, but Blantyre, Malawi, 3College of Medicine, University of Malawi, Blantyre, the abundance of An. gambiae was four times higher in the rainy season Malawi, 4Michigan State University, East Lansing, MI, United States as compared with the dry season (RR=4.1; 95% confidence intervals: 2.9, 6.0). In the rainy season, An. funestus abundance increased 10% Malaria risk in urban, peri-urban, and urban slum settings is becoming in proximity to category 2 streams (RR=1.1; 95% CI: 1.0, 1.1) and 10% a major concern as urbanization swells in malaria endemic countries. per increased degree of topographical slope (RR=1.1; 95% CI: 1.0, 1.3). Analysis of such malaria risk is complicated by multiple definitions of While An. funestus abundance was higher in proximity to roads in the dry what is “urban,” but also by uncertainty in where transmission occurs. season, this association reversed in the rainy season when An. funestus We analyzed household-level Anopheles mosquito abundance patterns abundance decreased 50% with proximity to roads (RR=0.5; 95% CI: 0.4, across an urban-to-rural continuum in and around the city of Blantyre, 0.6). An. gambiae abundance was not associated with proximity to roads Malawi. As the country’s “commercial capital,” Blantyre (~1.1M pop.) has but decreased in proximity to roads in the rainy season (RR=0.3; 95% CI: highly diverse land use/land cover (LU/LC) inside its ~225 sq km city limits. 0.2, 0.5). These findings suggest differences in breeding site preferences Mosquito abundance was sampled during the rainy and dry seasons of between these species. Regression models expressing the significant 2015 with light-traps and aspiration at 320 houses in 64 locations situated spatial and seasonal variation in the abundance of An. funestus and An. ~2.5km equidistant along 8 transects radiating outward from the city gambiae mosquitoes, modeled as a function of identified environmental center. Using household geolocations, GIS-based data on geographical features, were used to generate maps of species-specific predictive features, and satellite-image derived LU/LC, the urban-rural status of each abundance. These maps can be used to maximize the impact of targeted household was classified by various metrics, including census population, vector control interventions such as IRS or larviciding. house density, peri-domestic vegetation/agriculture, proximity to roads/ infrastructure and a PCA-derived “urbanicity score.” Multi-level statistics 1868 (e.g. households, locations, census areas) and spatial statistics (e.g. clustering, autocorrelation, interaction) were used to evaluate mosquito SPATIO-TEMPORAL VARIATION IN MALARIA TRANSMISSION abundance in relation to traditional and derived urban-rural classifications. INTENSITY IN RWANDA Results indicated that Anopheles indoor abundance generally increased with distance from the city center, but this explained less than one-third Corine K. Karema1, Emmanuel Hakizimana1, Dunia of the variation, making this designation of urban-rural was not strongly Munyakanage1, Alphonse Mutabazi1, Alphonse Rukundo1, Jean predictive of Anopheles abundance. LU/LC classifications that accounted Baptiste Mazarati2, Agnes Binagwaho3 for urban agriculture and topography improved predictability, regardless 1Malaria and Other Parasitic Diseases Division, Kigali, Rwanda, 2National of geographic location. This association remained after controlling for Reference Laboratory, Biomedical Services Department-RBC, Kigali, clustering. Our findings have important implications for understanding Rwanda, 3Ministry of Health, Kigali, Rwanda household- and community-level “urban” malaria risk, and for identifying Knowledge of vector distribution and bionomics is critical for vector borne locations where malaria prevention and control efforts might be most diseases control program strategy. Rwanda made steady progress in the effective. control of malaria over the past decade by scaling up malaria control prevention, treatment, community case management, and behavior change communication. The use of long-lasting insecticidal nets (LLINs) and insecticide indoor residual spraying (IRS) has altered vector bionomics in Africa. This is the first report from Rwanda that determined the abundance, species composition, and infectivity of mosquitoes collected from entomological monitoring in seven sentinel sites by pyrethrum spray collection (PSC) and human landing catches (HLC). The monthly collections

astmh.org 572 between 2010 and 2013 identified 340,684 mosquitoes to species 1870 level using morphological characteristics and grouped into anophelines (26.2%) and culicines (73.8%). The species composition comprised of An. EVALUATION OF A NOVEL LONG LASTING INSECTICIDAL gambiae s.l, and An. funestus as the major malaria vectors and six other NET TO INDOOR RESIDUAL SPRAY PRODUCT, SEPARATELY anophelines. The culicines comprised of Culex, Mansonia, Coquellittidia TO TOGETHER, AGAINST MALARIA TRANSMITTED BY and Aedes mosquitoes. For Anopheles gambiae s.l. (n = 84,189), the PYRETHROID RESISTANT MOSQUITOES IN NORTHWEST proportion of mosquitoes host-seeking indoors and outdoors was assessed TANZANIA: A CLUSTER RANDOMIZED CONTROLLED TRIAL as well as infection the rates. The mosquitoes collected indoors dropped from an average of 51.3% (95% CI = 44.7, 51.0) in 2010 to 44.9% (95% Natacha Protopopoff1, Derek Charlwood1, Jacklin Mosha2, CI = 43.1, 49.8) in 2013 (p < 0.005). We also calculated mean densities Alexandra Wright1, William Kisinza3, Franklin Mosha4, Immo and entomological inoculation rates (EIR). The mean resting density for Kleinschmidt1, Mark Rowland1 An. gambiae s.l was 0.3 mosquitoes/house/night with the highest resting 1London School of Hygiene & Tropical Medicine, London, United Kingdom, density reported in Mashesha (1.0 An. gambiae /h/n). The average annual 2NIMR Mwanza, Mwanza, United Republic of Tanzania, 3NIMR Amani, EIR 99.5 (range 1.0 - 329.8) with Mashesha showing the highest EIR of Muheza, United Republic of Tanzania, 4KCM College, Moshi, United 329.8 (a rice growing area) followed by Busoro and Kicukiro with 107.5 Republic of Tanzania and 103.6 infective bites per person per year respectively. We plan to collect and analyze mosquitoes from additional sentinel sites to provide The scaling up of the primary malaria vector control interventions - long a comprehensive database on vector bionomics which will be the critical lasting insecticidal nets (LLIN) and indoor residual spraying (IRS) - are data informing vector borne diseases control policies in Rwanda. responsible for the major reduction in malaria burden in Africa. We need to develop a more rational approach to deployment of chemical control, 1869 one which reduces selection pressure for resistance but continues the present gains in malaria control. To help define future strategy of LLIN IMPROVED MONITORING OF IRS COVERAGE ON BIOKO and IRS deployment in East Africa we are conducting a 4 arm cluster ISLAND THROUGH THE USE OF A GIS-BASED CAMPAIGN randomised controlled trial (CRT) in North-West Tanzania where the initial INFORMATION MANAGEMENT SYSTEM prevalence of malaria infection was 65% and resistance to pyrethroids in the predominant vector Anopheles gambiae exceeded 90% and Wonder Philip Phiri1, Guillermo Garcia1, Liberato Motobe consisted of at least two resistance mechanisms. The base arm of the trial Vaz1, Lucas Ondo Nze Nchama1, Diosdado Olo Motu1, Jose Osa is universal coverage of Olyset LN, the pyrethroid LLIN which constitutes Osa Nfumu1, Telesforo Eyegue Abuy1, Restituto Mangue Avue1, the current standard of care. The second arm is universal coverage with Jeremias Nzamio Mba Eyono1, Teobaldo Babo1, Marcos Mbulito Olyset Plus, a LLIN which combines pyrethroid and the synergist PBO Ivanga1, Rosa Patricia Richard Ateme1, John Bradley2, Immo that in bioassay can overcome pyrethroid resistance mediated by mixed Kleinshmidt2, Christopher Schwabe3, Dianna B. Hergott1 function oxidases; this intervention is a potential future standard of care. 1Medical Care Development International, Malabo, Equatorial Guinea, The third arm combines Olyset LLIN and IRS with Actellic CS, a long lasting 2London School of Hygiene & Tropical Medicine, London, United Kingdom, organophosphate insecticide for IRS. The fourth arm combines the LLIN 3Medical Care Development International, Silver Spring, MD, United States with the synergist PBO and the IRS with the long lasting OP - and is the combination intervention most likely to control malaria transmitted by Starting in 2014, the Bioko Island Malaria Control Project (BIMCP) has used highly pyrethroid resistant vector populations. The study area comprises a GIS-based Campaign Information Management System (CIMS) to plan, 48 clusters and population 150,000 inhabitants, allocated into 12 clusters implement and monitor Indoor Residual Spraying (IRS). The CIMS uniquely per arm using restricted randomisation to ensure balance between study identifies each household based on geographical location. The maps can arms. The interventions were rolled out in January 2015 and achieved be easily updated to reflect changes due to new houses, or destroyed or the required coverage to achieve community impact ahead of the long burnt down houses, thus enhancing the accuracy of the house count that transmission season. Analysis of mosquito population surveillance and is used as the denominator for IRS coverage rates, and eliminating the malaria infection prevalence in children in the four arms will be presented. ability of Spray Operators to report fictitious houses. High resolution maps The findings will help to define context-specific interventions and their that clearly identify households, enable Supervisors to track and verify that potential to maintain or accelerate present progress and prevent further spraying has occurred in houses reported by Spray Operators. This has selection of insecticide resistance. virtually eliminated the ability of Spray Operators to falsify spray records, thus inflating the numerator in IRS coverage rates. The CIMS also permits 1871 identification of non-compliant households, thus enabling focalized intervention where Spray Operators and community leaders return to low- IMPACT OF SEASONAL PATTERNS TO PARASITE ASEXUAL compliance areas for mobilization in an effort to increase spray coverage. STAGE ON ANOPHELES GAMBIAE SUSCEPTIBILITY TO Prior to 2014, Spray Operator data obtained from SP1 cards suggested PLASMODIUM FALCIPARUM INFECTION IN BURKINA FASO that spray coverage was consistently at least 80%, while retrospective 6-month recall data from annual Malaria Indicator Surveys (MIS) suggested Awa Gneme1, Wamdaogo M. Guelbeogo2, Michelle M. Riehle3, that IRS coverage was no higher than 65% (95% CI = 61-69%) in 2010 Gustave B. Kabre1, N’Falé Sagnon2, Kenneth D. Vernick4 and as low as 47% (95% CI = 41%-54%) in 2013. Without the CIMS it 1Université de Ouagadougou, Ouagadougou, Burkina Faso, 2Centre was impossible to discern whether the discrepancy was due to errors in National de Recherche et de Formation sur le Paludisme, Ouagadougou, the housing count and/or falsification of IRS spray data or to poor recall Burkina Faso, 3Department of Microbiology, University of Minnesota, by MIS respondents. In 2014, using the CIMS, the spray data revealed Minnesota, MN, United States, 4Unit of Insect Vector Genetics and 57% coverage during the spray round, while the MIS reported that 60% Genomics, Department of Parasites and Insect Vectors, Institut Pasteur, (95% CI= 51- 68%) of surveyed households were sprayed in the previous CNRS Unit of Hosts, Vectors and Pathogens (URA3012), Paris, France 6 months. By linking the CIMS and MIS data it was determined that MIS data were 85% accurate compared to CIMS spray data, confirming a Transmission reduction is a key component of global efforts to control and high level of sprayer falsification and under reporting of the number of eliminate malaria. A wide range of novel transmission-reducing drugs and houses to be sprayed in previous years. The CIMS has improved coverage vaccines are currently under development. Currently, it is unclear how the monitoring for IRS and confirmed that a high refusal rate exists in Bioko densities of the parasite stages or the season influence the infection rate Island,undermining coverage and program performance. and its intensity. Here, we highlighted the importance of the Plasmodium falciparum stages seasonal pattern in Anopheles gambiae infections success. Parasitological data were obtained by blood slide processing from

astmh.org 573 child volunteers with parental consent. Larvae were sampled from natural 1873 pools, reared to adulthood before experiment. Gametocytes carriers’ infectiousness to mosquitoes was determined at the peak and end of wet TARGETING THE CELL STRESS RESPONSE OF PLASMODIUM season and dry season via membrane feeding assay. Infection prevalence FALCIPARUM TO OVERCOME ARTEMISININ RESISTANCE and intensity were determined one week after feeding by midgut 1 1 1 1 dissection. About 28062 mosquitoes offered blood meal and 29.6% fed Leann Tilley , Stanley C. Xie , Con Dogovski , Shannon Kenny , 1 2 2 3 and survived until dissection, seven days later. The average number of Jess Bridgford , Gaetan Burgio , Simon Foote , David A. Fidock , 4 4 5 1 dissected mosquitoes 75 (range 18 - 207) was quite the same according to Sachel Mok , Zbynek Bozdech , Kesinee Chotivanich , Nick Klonis , 6 the assays period. In 71.8% (79/110) of feeding experiments, at least one Arjen M. Dondorp mosquito was infected. The median percentage of infected mosquitoes 1University of Melbourne, Parkville, Australia, 2Australian National per infectious experiment was 15.7% (IQR: 07.3- 89.2 %) with a median University, A.C.T., Australia, 3Columbia University Medical Center, New oocyst number of 2 (range 1 - 101). The prevalence of infected blood York, NY, United States, 4Nanyang Technological University, Singapore, meal was similar across season (70.0%, 72.7% to 70.1% at the dry, the Singapore, 5Mahidol University, Bangkok, Thailand, 6Mahidol-Oxford peak, and the end of the wet season. Mosquitoes’ infection rate also did Research Unit, Bangkok, Thailand not show any significant variation within season. The infection success Artemisinin derivatives (ARTs) are recommended, in combination was higher for asexual parasites carriers (91%) than non carriers (9%). regimens, as first line antimalarials in most countries where malaria is However, mosquitoes’ infection rate and oocyst load did not significantly endemic. However their mechanism of action is poorly understood and vary according to the asexual forms carriage. This highlights the need to their usefulness is threatened by the emergence of drug resistance. carefully interpret evaluations, regarding asexual parasites and transmission We undertook a detailed kinetic analysis of the drug responses of K13 season for malaria control program. wildtype (sensitive) and mutant (resistant) isolates of Plasmodium falciparum sourced from a region in Cambodia (Pailin). We demonstrate 1872 that ART treatment induces growth retardation and an accumulation of QUANTIFYING BIAS TO OVERESTIMATION IN SELF- ubiquitinated proteins, indicative of a cellular stress response that engages the ubiquitin/ proteasome system. We show that resistant parasites exhibit REPORTED ITN USE: A SYSTEMATIC REVIEW TO META- lower levels of ubiquitinated proteins and delayed on-set of cell death, ANALYSIS indicating an enhanced cell stress response. We found that the stress Paul Joseph Krezanoski response can be targeted by inhibiting the proteasome. Accordingly, clinically-used proteasome inhibitors strongly synergize ART activity against Massachusetts General Hospital, Cambridge, MA, United States both sensitive and resistant parasites, including isogenic lines expressing Insecticide-treated bednets (ITNs) are one of the most cost effective mutant or wildtype K13. Synergy is also observed against P. berghei in malaria prevention measures. In 2013, the WHO recommended universal vivo. Our work provides a rationale for improving the detection of ART coverage with ITNs for all 3 billion individuals at risk of malaria world- resistance in the field and for treatment strategies that can be employed in wide. Evidence for this recommendation is based on robust evidence of areas with ART resistance. an 18-23% reduction in child mortality among households using ITNs. However, these studies used self-reported ITN use as a proxy for actual 1874 ITN use. We hypothesized that self-reports would overestimate actual ITN use, because self-reported ITN use may be subject to recall and social ROLE OF CELL CYCLE REGULATORS IN ARTEMISININ desirability bias. We performed a systematic review of the literature INDUCED DORMANCY IN PLASMODIUM FALCIPARUM IN to identify studies which included both self-reports and another more VITRO objective measure of ITN use (surprise sleeping visits, visual confirmation 1 1 1 of mounted ITNs, etc) in the same population in order to determine the Karen-Ann Gray , Karryn J. Gresty , Nanhua Chen , Christopher 1 2 1 3 magnitude of overestimation. We searched for relevant terms in Pubmed Peatey , Veronica Zhang , Marina Chavchich , Norman C. Waters , 1 and Embase, reviewing 464 titles and abstracts. We performed full article Qin Cheng reviews of 193 studies and eventually included 19 studies for analysis. 1Australian Army Malaria Institute, Brisbane, Australia, 2University of The studies examined were published from 1989 through 2013, including Queensland, Brisbane, Australia, 3Walter Reed Army Institute of Research, countries from Southeast Asia and sub-Saharan Africa. Six of 19 studies Silver Spring, MD, United States used surprise night visits to confirm self-reported use, while the rest used Artemisinin-induced dormancy provides a plausible explanation for the visual confirmation of a mounted ITN. Self-reported ITN use over-estimated variable rates of recrudescence reported in the field following artemisinin actual ITN use ranging from -2.9% to 32.1%, with a mean of 9.1%. monotherapy. This phenomenon is reminiscent of cell cycle arrest in This 9.1% mean difference between self-reported and observed ITN use mammalian cells where cell cycle regulators, such as cyclin dependent represents a 23.5% overestimation of actual ITN use. The significant and kinases (CDKs) and cyclins play an important role. We investigated the consistent overestimation of ITN use reported by self-reports suggests that transcription dynamics of 6 P. falciparum CDKs and 4 cyclins as well as 1) ITNs may be more effective than currently thought, i.e. the accepted protein expression and kinase activity of selected CDKs before and after relationship between ITN use and malaria outcomes may be based on dihydroartemisinin (DHA) treatment. The role of CDKs in dormancy was an overestimate of their actual use, and 2) self-reported ITN use may further investigated by evaluating the effect of 3 CDK inhibitors on the not be an appropriate measure of actual ITN use, indicating the need to induction of and parasite recovery from dormancy. Transcription analysis shift from self-reports towards more valid measures of ITN use in malaria revealed an up-regulation of two plasmodial CDKs throughout the prevention studies, most especially related to adherence behaviors and dormancy period, and a down-regulation of genes encoding the remaining cost-effectiveness modeling. 4 CDKs and cyclins. The 3 inhibitors demonstrated different effect on parasite recovery from dormancy, one of these inhibitors completely blocked the parasite recovery from dormancy when it was added at the early stage of dormancy. The results suggest that plasmodial CDKs play an essential role in artemisinin induced dormancy, most likely control of parasite entry into S phase and mitosis. These findings provide new insights of cell cycle regulation in P. falciparum and in artemisinin induced dormancy.

astmh.org 574 1875 1876 ARTESUNATE/AMODIAQUINE VERSUS ARTEMETHER/ PARASITE CLEARANCE IN CHILDREN UNDER FIVE YEARS OF LUMEFANTRINE FOR THE TREATMENT OF UNCOMPLICATED AGE WITH UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN UGANDA: CHANGING EFFICACY PATTERNS MALARIA AFTER TREATMENT WITH ARTEMETHER- CONSISTENT WITH CHANGES IN TREATMENT PRACTICES TO LUMEFANTRINE IN NCHELENGE DISTRICT, ZAMBIA DRUG SENSITIVITIES Mwiche Siame1, Mike Chaponda2, Geoffrey Chansa3, Danver Melissa D. Conrad1, Adoke Yeka2, Ruth Kigozi3, Myers Hamayobe4, Natasha Laban1, Philip E. Thuma1 Lugemwa4, Peter Okui4, Charles Katureebe5, Kassahun Belay6, 1Macha Research Trust, Choma, Zambia, 2Tropical Diseases Research B.K. Kapella6, Michelle A. Chang7, Moses R. Kamya8, Sarah G. Centre, Ndola, Zambia, 3Kabuta Rural Health Centre, Nchelenge, Zambia, Staedke9, Grant Dorsey1, Philip J. Rosenthal1 4St. Paul’s Mission Hospital, Nchelenge, Zambia 1University of California San Francisco, San Francisco, CA, United States, Artemether-lumefantrine (AL) has been used in Zambia as first line 2Makerere University School of Public Health, College of Health Sciences, treatment since 2002. The World Health Organization (WHO) reported a Kampala, Uganda, 3Infectious Diseases Research Collaboration, Kampala, decline in malaria prevalence of over 60% in Zambia and this has been Uganda, 4National Malaria Control Program, Ministry of Health, Kampala, partly attributed to prompt and effective treatment with AL. While efficacy Uganda, 5World Health Organzation, Kampala, Uganda, 6US President’s of AL remains high, there have anecdotal reports of delayed clearance of Malaria Initiative, Malaria Branch, Centers for Disease Control and parasites after treatment with the drug combination. Countries in South- Prevention, Atlanta, GA, United States, 7Malaria Branch, Division of east Asia, including Thailand, Cambodia and Myanmar, have reported Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, artemisinin drug resistance, manifested by delayed parasite clearance and Atlanta, GA, United States, 8Department of Medicine, Makerere University rare cases of treatment failure. Therefore, there is need to examine the College of Health Sciences, Kampala, Uganda, 9London School of Hygiene efficacy of AL in Zambia and document whether or not some patients & Tropical Medicine, London, United Kingdom experience delayed parasite clearance despite adequate treatment with the With older therapies limited by widespread drug resistance, standard drug. This study aimed to examine the efficacy of AL and delayed parasite treatment for uncomplicated falciparum malaria is now artemisinin- clearance in children in Nchelenge District, Zambia. Febrile children based combination therapy, with nearly all endemic countries in sub- aged 6 to 59 months, with uncomplicated Plasmodium falciparum Saharan Africa recommending either artemether/lumefantrine (AL) or infection, were enrolled into the study beginning in December 2014. The artesunate/amodiaquine (AS/AQ). In Uganda, AL has shown superior children were treated for three days with directly observed therapy of AL efficacy compared to AS/AQ and is the first-line regimen. However, recent based on weight according to the WHO protocol and followed-up 35 changes in treatment practices and evidence of shifting drug sensitivities days to evaluate drug efficacy by monitoring clinical and parasitological prompted a reassessment of the relative efficacies of these regimens. We parameters with Giemsa-stained blood smears and PCR. The study results enrolled 602 patients aged 6-59 months from health centers in the Apac, showing parasite clearance times, parasite slope half-life (using the Mubende, and Kanungu Districts of Uganda in 2013-14. Children with WWARN Parasite Clearance Estimator) and associated clinical parameters, uncomplicated falciparum malaria were randomly assigned treatment with as well as the presence of K13 propeller mutations, will be presented. AL or AS/AQ, and 594 (98.7%) of those enrolled were followed for 28 Preliminary analysis of the first 20 participants who have complete data days. Recurrent infections were genotyped to distinguish recrudescence sets (of a planned total of 100), revealed that all study participants cleared from new infection, and Plasmodium falciparum resistance-mediating parasites within 48 hours, with 60% of the children having a lag phase polymorphisms were characterized for all infections. At each site the before parasite clearance began, and a subsequent median clearance half- risk of recurrent parasitemia was lower in children treated with AS/AQ life of 2.69 hrs (IQR 1.64, 3.13). compared to those treated with AL (overall 28.6% vs. 44.6%; p <0.001). Recrudescences were uncommon, but all occurred in the AL treatment 1877 arm (0% vs. 2.5%; p = 0.006). Recovery in hemoglobin was greater in the AS/AQ arm (1.73 vs. 1.39 g/dl, p = 0.04). Both regimens were well EFFICACY OF CHLOROQUINE TO PRIMAQUINE IN THE tolerated; serious adverse events were uncommon (1.7% for AS/AQ and TREATMENT OF UNCOMPLICATED PLASMODIUM VIVAX 1.0% for AL). In new infections after therapy the two regimens selected MALARIA, CRUZEIRO DO SUL, ACRE, BRAZIL, 2014 for opposite polymorphisms in pfcrt and pfmdr1, with each selecting Suiane Negreiros1, Samela Farias1, Thayna M. Souza1, Giselle R. for polymorphisms associated with decreased sensitivity to the partner Vianna2, Sheila Akinyi-Okoth3, Paola Marchesini4, Venkatachalam drug. Polymorphisms in the K13 propeller domain, which have been Udhayakumar3, Marinete M. Povoa2, Ana Carolina Santelli4, associated with artemisinin resistance in Asia, were uncommon (1/76) Alexandre Macedo de Oliveira3 and not associated with recurrent parasitemia. Although both regimens were highly efficacious, AS/AQ showed superior efficacy, contrasting with 1Secretaria de Saude do Acre, Cruzeiro do Sul, Brazil, 2Instituto Evandro older data, and consistent with recent changes in parasite drug sensitivity. Chagas, Belem, Brazil, 3Centers for Disease Control and Prevention, Malaria treatment guidelines should consider multiple or rotating regimens Atlanta, GA, United States, 4Ministerio da Saude, Brasilia, Brazil to maintain the efficacies of leading treatments. The World Health Organization recommends the regular monitoring of antimalarial treatment policies. We evaluated the in vivo efficacy of chloroquine and primaquine for the treatment of uncomplicated P. vivax malaria in Brazil. The study was conducted in Cruzeiro do Sul from February to December 2014. We enrolled patients ≥5 years of age with parasitologically confirmed P. vivax monoinfection (parasitemia between 250 and 100,000 parasites/uL) and no evidence of severe disease. Patients were treated under direct observation with chloroquine for 3 days (daily dose of 25 mg/Kg). After laboratory confirmation of normal glucose-6- phosphate dehydrogenase (G6PD) activity levels, primaquine (daily dose of 0.5mg/Kg) was administered, also under direct observation, for 7 days. We monitored patients clinically and parasitologically on Days 1, 2, 3, 7, 14, 21, 28 and then every 4 weeks until Day 168. Seven neutral microsatellites were used to differentiate genetic profile of parasites detected at the time

astmh.org 575 of enrollment and recurrent infection. We enrolled 132 patients, 13 were 1879 excluded (nine with G6PD deficiency, and four with either low-density parasitemia or P. falciparum infection). Among the 119 valid patients, MUTATION OF THE MU-SUBUNIT OF THE PLASMODIUM 65 (54.6%) were male and the median age was 24 years. The geometric FALCIPARUM CLATHRIN-ASSOCIATED AP2 ADAPTOR mean of asexual parasitemia at admission was 3,373 per uL. At Day 28, PROTEIN COMPLEX (PFAP2-MU) TO ITS EFFECT ON PARASITE no patient, among 110 patients to reach this time point, presented with SUSCEPTIBILITY TO ANTIMALARIAL AGENTS recurrent P. vivax parasitemia; while at Day 168, 28 (30.1%; 95% CI: 21.0-40.5%) presented with recurrent P. vivax infection. Microsatellite Donelly A. van Schalkwyk1, Gisela Henriques1, Christian Flueck2, typing demonstrated that 13 of those infections were due to a different David A. Baker2, David A. Fidock3, Colin J. Sutherland1 strain (i.e., reinfection), while 15 were caused by a genetically identical 1Department of Immunology and Infection, Faculty of Infectious and strain compared to Day 0 and were most likely relapses. This finding brings Tropical Diseases, London School of Hygiene & Tropical Medicine, London, the corrected rate of relapse to 18.8% (95% CI: 10.2-27.3%). Treatment United Kingdom, 2Department of Pathogen Molecular Biology, Faculty with chloroquine and primaquine appears to remain efficacious to treat of Infectious and Tropical Diseases, London School of Hygiene & Tropical P. vivax malaria and prevent recrudescence, but it is likely associated Medicine, London, United Kingdom, 3Department of Microbiology and with relapses 6 months after acute disease. Revision of the primaquine Immunology, Columbia University Medical Center, New York, NY, United regimen with possible increase in total dose or use over 14 days should be States considered. Reports of Plasmodium falciparum infections with reduced susceptibility to artemisinin are now widespread throughout the Greater Mekong 1878 sub-region and threaten to undermine Artemisinin-based Combination DISSECTING THE MUTATIONAL ACQUISITION OF PFCRT- Therapies (ACTs), currently the first-line WHO recommendation for malaria MEDIATED ANTIMALARIAL DRUG RESISTANCE treatment. While the genetic basis for this reduced sensitivity to artemisinin in Asia has been associated with mutations in kelch13 (PF3D7_1343700), Stanislaw J. Gabryszewski1, Thanat Chookajorn2, David A. other candidate genes are thought to be involved in resistance developing Fidock1 independently elsewhere. Selection for parasites surviving artemisinin 1Department of Microbiology and Immunology, Columbia University exposure in the murine malaria P. chabaudi uncovered a novel locus College of Physicians and Surgeons, New York, NY, United States, associated with antimalarial resistance, pcap2-mu. This gene encodes 2Department of Biochemistry and Center for Excellence in Malaria, the mu chain of an adaptor protein complex that functions in clathrin- Mahidol University, Bangkok, Thailand mediated endocytosis. Sequencing of submicroscopic parasites surviving ACT treatment in Kenyan children revealed an increased survival of Named for its primary role in mediating resistance to chloroquine (CQ), parasites harbouring the Ser160Asn polymorphisms in the P. falciparum the Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) homologue, pfap2-mu. We have recently reported that the episomal is increasingly recognized as a multi-drug resistance transporter with expression of the mutant form of pfap2-mu (160Asn) in Dd2 parasites pleiotropic effects on parasite susceptibility to our present arsenal of resulted in a significantly reduced susceptibility to dihydroartemisinin antimalarials. Field studies of drug selective forces on the pfcrt locus have using the standard 48 hour in vitro growth inhibition assay. Furthermore, historically centered on the single-nucleotide polymorphism (SNP) K76T, expression of the mutant pfap2-mu also resulted in reduced susceptibility a critical determinant of CQ resistance that is always accompanied by to quinine. No differences in susceptibility to dihydroartemisinin were at least three mutations in all CQ-resistant isolates. The impact of these observed when comparing wild type with mutant parasites using the ring mutations on parasite drug resistance, fitness, and the mutational paths stage assay (RSA0-6h). We seek to expand on our previous findings by accessible to parasites as they acquire resistance remains unclear. To using gene editing CRISPR-Cas9 and Zinc Finger Nuclease approaches to explore this, we used pfcrt-specific Zinc-Finger Nucleases (ZFNs) to dissect replace the endogenous wild type Ser160 pfap2-mu gene with the mutant the mutational trajectories leading to the evolution of the Ecuadorian pfcrt 160Asn gene associated with residual parasitemia after ACT treatment in allele Ecu1110, which harbors the fewest polymorphisms in a CQ-resistant Kenya. We will report the effects of this mutation on the in vitro parasite parasite (namely K76T, A220S, N326D, I356L). We generated a collection drug sensitivity to a range of antimalarial agents assessed with growth of otherwise isogenic asexual blood-stage parasites expressing the wild- inhibition assays employing both the standard 48 hour exposure and type (CQ-sensitive) PfCRT haplotype as well as each possible single-, newer 6 hour pulse assays. double-, triple-, and quadruple-SNP combination of the four SNPs that comprise Ecu1110 PfCRT. We also generated isogenic parasites expressing 1880 the related quintuple-SNP 7G8 PfCRT variant (C72S, K76T, A220S, N326D, I356L) that is highly prevalent throughout South America and the Western IMMUNOMODULATION BY LITOMOSOIDES SIGMODONTIS Pacific. Parasite susceptibility to a panel of clinically employed antimalarials INFECTION TO FILARIAL ANTIGEN ADMINISTRATION was determined via standard IC50 assays and was complemented with IMPROVES GLUCOSE TOLERANCE IN DIET-INDUCED OBESITY data from flow cytometry-based in vitro growth competition assays MICE to model the mutational paths of PfCRT-mediated drug resistance. Our studies indicate that multiple PfCRT SNPs have a direct impact on parasite Afiat Berbudi, Jesuthas Ajendra, David Schmidt, Fabian Gondorf, susceptibility to various antimalarial compounds, define mutational Anna-Lena Neumann, Achim Hoerauf, Marc P. Hübner pathways that likely led to CQ resistance, and delineate growth rate University Hospital of Bonn, Bonn, Germany constraints imposed on parasites as they evolve resistance. Adipocyte necrosis in obesity causes pro-inflammatory macrophages to infiltrate into the adipose tissue and results in chronic inflammation and insulin resistance. Since filariae induce a regulatory immune response in their hosts and trigger type 2 immune responses that counter regulate type 1 immune responses, we investigated whether immunomodulation by Litomosoides sigmodontis (L.s.) improves glucose tolerance in diet- induced obesity (DIO) mice. After 10 and 16 weeks on high fat diet, respectively, L.s.-infected and L.s. antigen (LsAg)-treated mice were tested for glucose tolerance and immunological analysis was performed. Both L.s. infection and LsAg administration in DIO mice increased eosinophil and alternatively activated macrophage frequencies within the epididymal

astmh.org 576 adipose tissue and improved glucose tolerance, suggesting enhanced 1882 insulin sensitivity. This improved glucose tolerance by L.s. infection was dependent on eosinophils, as was shown with eosinophil deficient TISSUE-SPECIFIC TRANSCRIPTOMICS TO PROTEOMICS OF dblGATA mice. Total epididymal adipose tissue B-cell numbers were DIROFILARIA IMMITIS TO ITS WOLBACHIA ENDOSYMBIONT further reduced in L.s.-infected DIO mice and consisted substantially of 1 2 1 B1-cells, whereas uninfected DIO controls had increased numbers of B2- Ashley N. Luck , Kathryn G. Anderson , Colleen M. McClung , 1 1 2 cells. Consistently, L.s.-infected DIO-animals produced less IgG2a, which Nathan C. VerBerkmoes , Jeremy M. Foster , Shelly Michalski , 1 was previously shown to contribute to insulin resistance. qPCR arrays of Barton E. Slatko epididymal adipose tissue further suggested a suppressed adipogenesis 1New England Biolabs, Ipswich, MA, United States, 2University of in L.s.-infected DIO mice. Accordingly, the differentiation of 3T3-L1 Wisconsin Oshkosh, Oshkosh, WI, United States preadipose cells to mature adipocytes was suppressed by LsAg treatment Recent evidence for the development of drug resistance among parasitic in vitro. However, two weeks of LsAg treatment did not suffice to reduce nematodes has accentuated the need for development of new treatment adipose tissue weight and adipocyte size in DIO mice. In conclusion our modalities. Although transcriptomic and proteomic characterization of investigation indicates that L.s. infection and LsAg treatment restores filarial nematode life cycles using whole worms have greatly enhanced our a cellular composition within the adipose tissue of DIO mice that is knowledge of the biology of these organisms, it is clear that tissue-level dominated by eosinophils and alternatively activated macrophages and approaches are needed to provide spatial resolution of gene expression improves glucose tolerance in an eosinophil dependent manner. Additional that can aid drug discovery and vaccine studies. Here, we describe the protective mechanisms may include a suppressed adipogenesis and the first concurrent tissue-specific transcriptomic and proteomic profiling of induction of regulatory responses and are currently further investigated. a filarial nematode (D. immitis) and its Wolbachia endosymbiont (wDi) in order to better understand tissue functions and identify tissue-specific 1881 antigens that may be used for the development of new diagnostic CHEMOKINES TO THE REGULATION OF EOSINOPHILIA IN and therapeutic tools. Hierarchical clustering of the D. immitis tissue transcriptomes, along with the recently published whole-worm adult LOIASIS male and female D. immitis transcriptomes, revealed that the whole- Senbagavalli Prakash Babu, Pryscilla Yoon, Michelle Makiya, worm transcriptome is typically dominated by transcripts originating Joseph Kubofcik, Thomas B. Nutman, Amy D. Klion from the gonads (testis and uterus). The uterus appears to have the National Institutes of Health, Bethesda, MD, United States most variable transcriptome, and may reflect variance in worm age and fecundity. Although many functions are shared between the reproductive Although eosinophilia is considered a hallmark of human helminth tissues, the most significant differences in gene expression were observed infection, the degree of blood eosinophilia varies considerably among between the uterus and testis. Interestingly, wDi gene expression in the infected individuals. Whereas some of this variation is likely due to male and female body wall is fairly similar, yet slightly different to that of differences in parasite burden, the host immune response to parasite Wolbachia gene expression in the uterus. Proteomic methods verified 32% antigens clearly plays an important role. To explore the role of chemokines of the predicted D. immitis proteome, including over 700 hypothetical in the regulation of blood eosinophilia in patients with microfilaremic proteins of D. immitis. Of note, hypothetical proteins were among some loiasis, patients with loiasis were divided into low and high eosinophil of the most abundant Wolbachia proteins identified, which may fulfill groups based on the median absolute eosinophil count (AEC). Chemokines some important yet still uncharacterized biological function. The spatial were measured by multiparameter immunoassays in antigen (Brugia resolution gained from this parallel transcriptomic and proteomic analysis malayi antigen [BMA)])- or mitogen (PMA/ionomycin ([PI])-sitmulated adds to our understanding of filarial biology and serves as a resource with PBMC supernatants from 11 patients with loiasis. Chemokine levels in which to develop future therapeutic strategies against filarial nematodes unstimulated supernatants were comparable between the two groups and their Wolbachia endosymbionts. with the exception of IL-8, that was significantly increased in the low eosinophil group (GM 9.4 vs. 3.8 mcg/ml in the high eosinophil group, 1883 p<0.01) and showed a negative correlation with AEC overall (r = -0.75, p = 0.001). No significant differences were detected in BMA-stimulated GENETIC VARIATION IN ONCHOCERCA VOLVULUS TO chemokine levels between the two groups, although eotaxin 1, RANTES WOLBACHIA ENDOSYMBIONT REVEALS STRUCTURED and MCP-4 showed significant negative correlations with AEC overall PHYLOGEOGRAPHY IN RELATION TO PHENOTYPIC (r= -0.77, p=0.007 for eotaxin-1 and r= -0.65, p=0.37 for RANTES and DIVERGENCE OF PATHOGENICITY MCP-4). TARC levels were increased in PI stimulated supernatants in the high eosinophil group (p=0.056). Microarray analysis was performed using Young-Jun Choi1, Samantha N. McNulty1, Rahul Tyagi1, Philip PBMC from a separate group of 24 patients with loiasis divided into high Ozersky1, Thomas R. Unnasch2, Carmelle T. Norice3, Thomas B. and low eosinophil groups. Preliminary analysis of chemokine expression Nutman3, Gary J. Weil1, Peter U. Fischer1, Makedonka Mitreva1 reveals upregulation of TARC and eotaxin-2 in the high eosinophil group 1Washington University in St. Louis, St. Louis, MO, United States, and upregulation of RANTES in the low eosinophil group. Although IL-5 2University of South Florida, Tampa, FL, United States, 3National Institute of expression is comparable between the two groups, genes associated with Allergy and Infectious Diseases, Bethesda, MD, United States Th1 and inflammatory responses appear to be upregulated in the low Onchocerca volvulus, the filarial nematode that causes onchocerciasis, eosinophil group. Taken together these data suggest that differences in is widely endemic in sub-Saharan Africa and in parts of Latin America. chemokine secretion by PBMC may contribute to the regulation of blood The pathology ranges from sub-clinical symptoms to dermatitis and eosinophilia in loiasis. ocular disease, and epidemiological studies have shown that blinding onchocerciasis is much more common in dry savannah regions than in rain forest regions of West Africa. To develop a comprehensive understanding of the population genetics and structure of O. volvulus, we investigated the genomic diversity within and between O. volvulus populations by analyzing whole-genome (nuclear, mitochondrial and Wolbachia) sequences of >30 clinical parasite samples. Of these, 20 were collected from seven countries in Africa (forest or savanna) and 10 from Ecuador in South America. At a mean depth of 60x coverage per sample, we identified and annotated ~1 million segregating SNPs and small indels

astmh.org 577 (including 65k missense and 1k nonsense variants, together affecting 9k Africa and parts of Latin America. Large-scale public health programs genes), as well as ~300 genomic regions (with a combined total length based on mass distribution of ivermectin have reduced Onchocerca of >5Mb) displaying copy number variations. Admixture analysis of volvulus infection rates in many areas, and plans are being developed to the inter- and intra-continental patterns of nuclear, mitochondrial and scale up activities to eliminate the disease. Improved diagnostic methods Wolbachia sequence variations provided genetic insights regarding the are needed for identifying hypoendemic areas that were excluded phylogeography of the parasite at an unprecedented resolution. Signatures from prior control programs and for determining when transmission of differential selection, identified through genomic markers of both has been interrupted. The recently introduced Ov-16 antibody test is the nuclear genome of the parasite and the Wolbachia endosymbiont, a major step forward, but it has only moderate sensitivity in subjects provided evidence of local adaption underpinning the phenotypic with microfiladermia. We have used a multi-omics approach to identify divergence of pathogenicity between the forest and the savanna strains. novel diagnostic antigens with high levels of sensitivity and specificity The study also provides new information on the genetic variability of that may be useful for immunoassays to support the onchocerciasis potential vaccine, drug, and diagnostic targets. elimination program. The approach included: i) development of a relational database that includes the annotated genome, developmental 1884 transcriptome (including MF, L3, adult male and adult female), and adult female proteome of O. volvulus; ii) affinity purification O. volvulus HELMINTH PARASITES TO CANCER-CAUSING TUMORS antigens using IgG from onchocerciasis patients for identification via CONDITION HUMAN MONOCYTES SIMILARLY: INSIGHTS mass spectrometry. A total of 180 immundominant proteins showed INTO PARALLEL MECHANISMS OF IMMUNE EVASION favorable interactions with patient and control sera. These included many of the major diagnostic antigens that have been identified over the 1 1 2 Prakash Babu Narasimhan , Naureen Huda , Helen Sabzevari , past 25 years (e.g., Ov16, Ov3.6, Ov7) plus many new candidates. The 2 1 Robert Hofmeister , Thomas B Nutman , Roshanak Tolouei immunodominant proteins were characterized based on their conservation 1 Semnani with orthologs in relevant species, expression pattern across the life 1National Institute of Allergy and Infectious Diseases, Bethesda, MD, cycle, and expression among eight individual female worms, and 19 United States, 2EMD Serono Research and Development Institute, Billerica, candidates were prioritized for recombinant expression and laboratory MA, United States testing in serodiagnostic assays. These candidate proteins, as well as our A number of features of the host-parasite interface are reminiscent of extensive genomic, transcriptomic, and proteomic datasets, are offered those that are also observed at the host-cancer interface. In particular, to the community (http://nematode.net) to further basic and translational both cancer cells and parasites establish a tissue microenvironment that onchocerciasis research in diagnostics and other areas. leads to immune evasion and likely reflects an alteration of the function of various antigen-presenting cells. The present study investigated how 1886 the phenotype and function of circulating human monocytes is altered by FURTHER CHARACTERIZATION OF A CARBOHYDRATE-RICH exposure to live filarial parasites and if these functional and phenotypic alterations parallel those induced by exposure to tumors. Thus, human CIRCULATING WUCHERERIA BANCROFTI ANTIGEN AS A monocytes were exposed either to live microfilariae (mf) of Brugia malayi MEMBER OF THE JUV-P120 GENE FAMILY - a causative agent of lymphatic filariasis - or to three different cancer Philip J. Budge, Jeanne Rumsey, Samantha McNulty, Reid cell lines MDA-MB-231 (breast cancer), OVCAR (ovarian cancer), or U-87 Townsend, Peter U. Fischer, Gary J. Weil (glioblastoma). After 2 to 7 days of culture, cells were harvested, flow- Washington University in St. Louis, St. Louis, MO, United States sorted and assessed for mRNA expression, phenotype and function. To our great interest, following exposure to either mf or any of the 3 cell lines, Rapid diagnostic tests (RDTs) used in the Global Programme to Eliminate the cell surface expression of the inhibitory ligands PDL1 and PDL2 were Lymphatic Filariasis detect a 200 kD circulating filarial antigen (Wb-CFA) in highly induced. Furthermore, monocytes exposed to tumor cell lines for blood and serum samples from humans infected with W. bancrofti. Prior even 2 days showed markedly upregulated expression of M1-associated studies have shown that Wb-CFA is an adult worm excretory-secretory (TNF-α, PDL1; > 6-fold), M2-associated (PDL2, MRC1; >5 fold) and Mreg- (E-S) product that is recognized by monoclonal antibodies AD12.1 and associated (IL-10, IDO, TGF-β; > 4−10−fold) genes, as well the expression DH6.5. These antibodies bind to a single repeated epitope that is not of MMP-9 and VEGF, both known to be pro-angiogenic. The expression specific to W. bancrofti and is likely responsible for false positive RDT of these markers was also elevated in mf-exposed monocytes but most results seen in some persons with loiasis. The exact nature of the epitope profoundly only after 7 days of exposure. Conditioning the human is unknown, but its immunoreactivity is destroyed by metaperiodate and monocytes with either mf or tumor cell lines clearly altered their function is not affected by pronase B. In the present study, the Consortium for as shown by a diminution of production of IP10, TNF-α, CCL22, and IL-10 Functional Glycomics (Emory University) assessed the binding specificity in response to TLR3 and TLR7 agonists. Collectively, our data suggest that of AD12.1. The antibody bound strongly to only 2 of 609 targets in helminth parasites and tumor cell lines share similar abilities to alter the their mammalian glycan array (GlcAß1-3GlcNAc and GlcAß1-3Gal). phenotype and function of human monocytes and may provide common These disaccharides have been detected in O-linked carbohydrate side insights into immune evasion. chains in glycoproteins from other nematodes including C. elegans. To identify the protein associated with the glycan moiety, we used tandem 1885 mass spectroscopy to analyze a tryptic digest of Wb-CFA that had been immunoaffinity-purified from pooled patient sera using antibody DH6.5. A MULTI-OMICS APPROACH FOR DEVELOPING IMPROVED Three peptide sequences were identified in sequences encoded by two DIAGNOSTIC TOOLS FOR ONCHOCERCIASIS predicted ORFs situated adjacent to each other on a single 5,762 base pair contig in the W. bancrofti draft genome assembly (GenBank accession Samantha N. McNulty1, Bruce A. Rosa1, Peter U. Fischer2, LM003610.1). These peptide sequences were not observed in human or Reid Townsend2, Kurt C. Curtis2, Sabine Specht3, Gary J. Weil2, common contaminant proteins. Although there is some ambiguity in the Makedonka Mitreva1 contig assembly in the vicinity of these ORFs, comparisons with Brugia 1The Genome Institute, St. Louis, MO, United States, 2Washington sequences suggest that the two predicted ORFs actually combine to form University School of Medicine, St. Louis, MO, United States, 3Institute for a single ORF encoding protein of ~550 amino acids with high homology Medical Microbiology, Immunology and Pathology, University Hospital of (66% identity, E score 1e-164) to a B. malayi protein (GenBank accession Bonn, Bonn, Germany AHB87099.1) that is an orthologue of the L. sigmodontis E-S protein Onchocerciasis is a neglected tropical disease that is responsible for significant morbidity (blindness and severe skin disease) in sub-Saharan astmh.org 578 Juv-p120 (GenBank accession AAS92593.1). Work in progress may provide per week and all mosquitoes collected were identified and numerated. insights regarding the function of Wb-CFA and lead to a more specific Cx. quinquefasciatus and Ae. albopictus were pooled and tested for assay for the antigen. West Nile virus (WNV) by RT-PCR or tested by stable isotope analysis. In total, 720 trap nights were completed from July to August 2013 yielding 1887 a total of 32,140 Cx. quinquefasciatus and 7,722 Ae. albopictus. Overall, 69 marked female mosquitoes (n=2,758) and 24 marked male NEW EVIDENCE THAT ANOPHELES GAMBIAE SENSU LATO mosquitoes (n=350) were captured throughout the study period. Mean DISCRIMINATE AQUATIC HABITATS FOR OVIPOSITION: distance traveled (MDT) was calculated by sex and species. Female Cx. COULD THIS LIFE TRAIT BE EXPLOITED TO CONTROL quinquefasciatus have a MDT of 0.94km, female Ae. albopictus of RESIDUAL MALARIA TRANSMISSION? 0.38km, male Cx. quinquefasciatus of 1.16km, and male Ae. albopictus of 1.04km. This study provides a greater understanding of the dispersal of 1 1 2 Manuela Herrera , Michael N. Okal , Steve W. Lindsay , Ulrike two important mosquito vectors capable of transmitting diseases in urban 1 Fillinger environments. We also confirm the ability to use stable isotope enrichment 1International Centre of Insect Physiology and Ecology/London School as a means to study the biology of mosquitoes. of Hygiene & Tropical Medicine, Mbita, Kenya, 2School of Biological and Biomedical Sciences, Durham University, Durham, United Kingdom 1889 Residual malaria transmission in Africa is sustained by vector populations MINIMUM INFECTIOUS TIME 50: A METRIC NOVEL FOR that resist insecticides and bite outdoors. These could be conceivably STANDARDIZED COMPARISONS OF VECTOR COMPETENCE controlled by targeting gravid Anopheles gambiae s.l. searching for oviposition sites. Thus the aim of this study was to investigate if An. Rebecca Christofferson1, Helen Wearing2, Christopher Mores1 gambiae s.l. make informed choices when selecting egg-laying sites 1Louisiana State University, Baton Rouge, LA, United States, 2University of and to identify physical, chemical and biological parameters associated New Mexico, Albuquerque, NM, United States with this choices. Egg-count bioassays were used to evaluate oviposition responses to habitat water and test if bacterial volatiles affect the selection Chikungunya (CHIKV) virus has seen an increase in its transmission of the aquatic habitat. A cross-sectional case–control study of aquatic intensity and geographic range. Two particular events - the Indian Ocean habitats was done on Rusinga Island in Lake Victoria, Western Kenya and the ongoing outbreak in the Caribbean, each resulting in hundreds to compare the characteristics of habitats colonised and not colonized of thousands of cases - have been caused by different lineages of the by early instar Anopheles larvae. Factors evaluated included biological virus. It has been reported that phenotypic differences between lineages characteristics of the sites, zooplankton, invertebrate fauna, physical of CHIKV are critical to understanding the scope of outbreaks. After parameters, nutrients, bacteria communities and volatile chemicals the emergence of East Central South African sublineage in the Indian released from the water. Experiments showed that wild and caged An. Ocean (ECSA-V), laboratory studies indicated increased efficiency of this gambiae s.l. discriminate between potential aquatic habitats using viral type in a historically secondary vector, Ae. albopictus. Since then, chemical cues. In the field no evidence was found that bacteria from this combination of lineage-vector has been the focus of most of the natural habitat water influence habitat selection. Although chemical cues CHIKV vector competence studies. However, the ongoing outbreak in were highly diverse analysis suggests that cases and control habitats differ the Caribbean has been attributed to a strain belonging to the Southeast in the headspace volatile profiles. High turbidity >200 NTU was the only Asian genotype and Ae. aegypti, suggesting that this focus might be environmental factor strongly associated with cases. Other risk factors short-sighted. There is a paucity of data directly comparing the vector were higher grass coverage (positive association), and the abundance competence of these two lineages in Ae. aegypti. Further, mathematical of creeping water bugs of the family Naucoridae and fish (negative models of transmission, used often to predict and forecast outbreak associations). This study demonstrates that gravid An. gambiae choose trajectories, rely on vector competence studies to parameterize their suitable habitats for oviposition using a complex system of chemical models by extrapolating the extrinsic incubation period (EIP) of the virus and visual cues from water bodies. Habitats preferred by An. gambiae within the mosquito vector(s). These two measures- vector competence exhibited distinct and measurable characteristics that can be potentially and EIP- are parts of a single process, but are rarely considered together exploited to attract and kill gravid mosquitoes. Such strategies would either for the design of experimental investigations or for interpretation additionally target insecticide resistant and outdoor vector improving of vector competence to parameterize models. To bridge these gaps, we vector monitoring and control. directly compare experimental vector competence results of these two lineages and subsequently propose the MIT50, the mosquito infectious 1888 time 50 (the time it takes post-exposure for 50% of exposed mosquitoes to become infectious). We show that the phenotypic differences detected QUANTIFYING DISPERSAL BEHAVIOR FOR CULEX between the two lineages are more directly comparable and more likely to QUINQUEFASCIATUS TO AEDES ALBOPICTUS IN COLLEGE be appropriately interpreted for model parameterization with the MIT50. STATION, TEXAS We demonstrate the effect of mosquito mortality on transmission by calculating the mortality reduced transmission rate as the probability that a Emily Boothe1, Mark Johnsen2, Brendan Roark1, Gabriel L. mosquito survives to transmit at MIT50. Hamer1 1Texas A&M University, College Station, TX, United States, 2Brazos County 1890 Health Department, Bryan, TX, United States NATURAL WOLBACHIA INFECTIONS IN ANOPHELES To better control populations of mosquitoes and break the transmission GAMBIAE SENSU LATO cycle of vector-borne diseases, it is crucial to understand the dispersal of adult mosquitoes. We performed a stable isotope mark-capture Robert Shaw1, Perrine Marcenac1, Abdoulaye Diabaté2, Flaminia study, focusing on Culex quinquefasciatus and Aedes albopictus, to Catteruccia1 characterize dispersal distance and behavior. We enriched (i.e. marked) 1Harvard T.H. Chan School of Public Health, Boston, MA, United States, 13 naturally occurring larval mosquitoes in container habitats with C-glucose 2Institut de Recherche en Sciences de la Santé/Centre Muraz, Bobo- 15 or N-potassium nitrate at two different locations (~0.5km apart) in Dioulasso, Burkina Faso College Station, Texas in 2013. We used 32 CDC light trap, 32 gravid trap, and 16 BG Sentinel at different trap locations within a two-kilometer Wolbachia is an intracellular bacterial endosymbiont that infects the radius of the enriched larval habitats. Each location was trapped once germlines of many arthropod species. It has been proposed as a tool to control malaria transmission in Anopheles mosquitoes for two key astmh.org 579 properties. First, Wolbachia can spread through natural populations due to throughput sequencing to explore the genomic patterns of divergence reproductive phenotypes induced in the host insect, principally cytoplasmic and local adaptation in wild-caught An. funestus from Cameroon. incompatibility (CI). In CI, Wolbachia-uninfected females produce no fertile Genotyping of 6605 SNPs across 101 individuals confirmed the presence progeny with Wolbachia-infected males, while Wolbachia-infected females of cryptic ecotypes differentially adapted to the savannah and rainforest. produce fertile progeny with any male, thus driving the infection into Genomic regions of high differentiation between the two ecotypes are the population. Second, Wolbachia infection can block human pathogen clustered on the 3R chromosome, particularly within the 3Ra and 3Rb development in several insects, recently extended to include the inhibition chromosomal inversions. Comparative mapping of chromosomal arms of Plasmodium development in female Anopheles mosquitoes. Central showed that several outlier regions of genetic differentiation within the to the future of using Wolbachia in malaria control, our laboratory has 3Rb inversion of An. funestus map to the 2La inversion of An. gambiae, identified for the first time strong evidence of natural Wolbachia infections which is also associated with adaptation to aridity. Despite 50 million years in field populations of An. gambiae sensu lato in Burkina Faso, Africa. of divergence, it appears that An. funestus and An. gambiae utilize the Whole-genome shotgun metagenomic sequencing has placed this strain in same repertoire of genes to adapt to contrasting environment - a truly a novel phylogenetic group – wAnga – distinct from, but related to, other remarkable case of convergent evolution. Further functional analyses dipteran Wolbachia strains. Infection persisted at low frequency (20-40%) of genes within the overlapping chromosomal regions of An. funestus over four years despite imperfect vertical transmission to progeny. We and An. gambiae will provide a deeper understanding of the direct have successfully colonized mosquitoes harboring this infection and have mechanisms underlying parallel adaptation in these two rapidly evolving examined whether these bacteria affect the reproductive success of their species. mosquito host. Moreover, fluorescent in situ hybridization targeting 16S rRNA sequences localizes wAnga within the female germline, consistent 1893 with vertical transmission. Our results suggest a role for Wolbachia in modulating aspects of mosquito biology that are highly relevant to EFFICACY OF SISAL STRIPS IMPREGNATED WITH vectorial capacity. TRANSFLUTHRIN SPATIAL REPELLENT DISPENSED AT ROOM TEMPERATURE TO PROTECT AGAINST OUTDOOR BITING 1891 MALARIA VECTORS REGULATION OF THE MOSQUITO MIDGUT BACTERIA BY THE Sheila O. Barasa, Arnold Mmbando, Johnson Kyeba, Hasan STEROID HORMONE 20-HYDROXYECDYSONE Ngonyani, Mohammed Kitumbukile, Gerald F. Killeen Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania Sarah D. Sneed, Letitia K. Thompson, Michael Povelones Department of Pathobiology, School of Veterinary Medicine, University of In most African settings, people spend time outside houses in the early Pennsylvania, Philadelphia, PA, United States evening before they are under the protection of long lasting insecticide treated nets thus are exposed to infectious mosquito bites. An ideal spatial Anopheles gambiae and Aedes aegypti are mosquito species that repellent is likely to provide long range repellency outdoors and reduce cause high morbidity and mortality by spreading pathogens such as mosquito bites. The objectives of this study were to determine protective Plasmodium parasites and arboviruses. As the midgut of the mosquito efficacy of sisal strips treated with Transfluthrin and to determine is the main barrier to dissemination of pathogens from a bloodmeal into protection to non-users, as well as degree of diversion of mosquitoes the hemolymph, understanding midgut immune mechanisms and their from users of Transfluthrin sisal strips to the non-users. Experiments were regulation is critical. Blood feeding triggers signaling pathways required conducted in a rural village, southeastern Tanzania. The main malaria for successful egg development. We hypothesized that these pathways vectors are Anopheles arabiensis mosquitoes that bite both indoors may play additional roles in modulating immunity. The steroid hormone and outdoors. Efficacy of Transfluthrin sisal strips was determined by 20-hydroxyecdysone (20E) signaling cascade plays an important role in measuring the biting rate of mosquitoes of human landing catchers egg development. 20E is rapidly produced in the ovaries in response to with treated Transfluthrin sisal compared to untreated sisal. Durability of blood feeding and is released into the hemolymph where it can signal to efficacy of treated sisal was determined as well as protection of treated peripheral organs. Previously, studies of the relationship between 20E and to non-user at different distances (10m, 20m, 30m, 40m and 60m) from mosquito immunity have been focused on 20E’s effect on the fat body. To the user of treated sisal. Over 8000 persons hours of human catches were date, no studies have examined the midgut as a potential target of 20E conducted. Treated strips prevented more than 80% bites for a period of signaling. We found that directly injecting 20E into non-blood fed Ae. 30 weeks and at least 50% bites were prevented 90 weeks after the strips aegypti and An. gambiae resulted in a significant increase in midgut had been treated. Treated strips provided 40% relative protection to non- bacteria measured by colony counting and 16S qPCR. The increase in users at 5m and no evidence of increased risk to non-users beyond that bacteria parallels what is observed after blood feeding. Metagenomic, distance was obvious. Analysis of all 4032 person hours of human landing transcriptomic, and functional analyses of 20E treated mosquitoes are catches from the dose-response reveal that; 0.01ml Transfluthrin provided underway to explore mechanisms leading to expansion of midgut bacteria. 80% protection against mosquito bites, 1ml Transfluthrin provided 70% Our work provides evidence that 20E signaling influences midgut bacteria protection, 2ml provided 70% protection and 5ml Transfluthrin provided levels and that this mechanism is conserved across diverse mosquito 70% protection. Sisal fibers are excellent substrates for dispensing vapour species. Understanding regulation of the mosquito commensal population active spatial repellents, including Transfluthrin without the need of is crucial as their abundance and species composition have been external sources of heat. This study shows that treated sisal strips reduced implicated in disease transmission. bites of outdoor biting An. arabiensis hence are likely to protect against malaria occurring outdoors LLINs may not be sufficient. 1892 1894 GENOMIC DIVERGENCE TO LOCAL ADAPTATION IN CRYPTIC SUBGROUPS OF ANOPHELES FUNESTUS NORTH AMERICAN PARAGONIMIASIS: IDENTIFICATION OF A Caroline Fouet, Colince Kamdem, Stephanie Gamez, Bradley J. NOVEL INTERMEDIATE SNAIL HOST FROM MISSOURI White Melanie Lloyd1, Stephen E. McMurray2, Peter U. Fischer1 University of California Riverside, Riverside, CA, United States 1Washington University School of Medicine, St. Louis, MO, United States, 2 Anopheles funestus, the second most important vector of human Missouri Department of Conservation, Columbia, MO, United States malaria in Sub-Saharan Africa, is splitting into multiple cryptic species Paragonimiasis is a foodborne trematode infection that affects 23 million and subgroups, which have yet to be fully delineated. We used high- people mainly in Asia. The infection is locally of great public health astmh.org 580 importance and can cause a serious lung disease that is often misdiagnosed model which showed that proximity from a person’s home to the nearest as tuberculosis or cancer. In North America, paragonimiasis is caused by water contact site and concentration of human fecal contamination at Paragonimus kellicotti. Infection is rarely seen in humans but is common this point explained ~50% of the risk of infection. This result was for data is the animal definitive host in some states. After a small outbreak of obtained during a community survey prior to treatment when prevalence human paragonimiasis in southern Missouri, the second intermediate of infection was 45%. We also observed that human fecal contamination host and source of human infection was identified as common crayfish increased considerably in the downstream portion of the village. Human species Orconectes punctimanus, O. luteus and O. virilis. Although fecal contamination was assessed by determination of a widely used the infection rates in crayfish were locally very high (>60%), the first Lachnospiraceae marker, which we validated by pyrosequencing and qPCR intermediate host remained unknown. Only the walker snails Pomatiopsis of local stool samples. In this opportunity, we used QGIS to test our model lapidaria and P. cincinnatiensis (family Hydrobiidae) have been reported in this same village following treatment. All individuals who tested positive as first intermediate hosts for P. kellicotti. These snail species have not were treated in 2009 and at follow up in 2012, prevalence had declined been observed in areas with high infection rates in crayfish. In order to by 48% and intensity by 44%. Those infected were again treated in 2012 identify the snail host of P. kellicotti in our study area, we collected more and the village was re examined in 2013 when prevalence declined by 32% than 2,000 snails of the three most common species and screened them and intensity by 30%. Re infection rates were 33.7 and 18.4% in 2012 and by light exposure/cercariae shedding and dissection for developmental 2013, respectively. Incidence was 22.0 and 12.9%. Our model explained stages of P. kellicotti. We detected cerariae and rediae of P. kellicotti in 73% and 81% of the risk of infection in 2012 and 2013, respectively. the endemic species Elimia potosiensis (family Pleuroceridae). Trematode Improvement in identification of risk by the model over time can be identity was confirmed by PCR and DNA sequencing. E. potosiensis is also explained by the effect of treatment. People who live closer to water with the first intermediate host to at least two undescribed trematode species. high human fecal contamination are more likely to be re infected and According to ITS-2 sequence, these appear similar to Lecithodendrium people who live in proximity to water with low contamination are likely to spathulatum, a parasite of bats, and Collyriclum faba, a parasite of birds. remain infection free. This is further supported by spatial analysis which Our findings indicate that P. kellicotti has a wider first intermediate host showed that over time, new infections clustered downstream. Our findings range than previously assumed, and can use high abundance snail species give more insight into the importance of human fecal water contamination of different families for development. The flexibility of the host range of all for schistosome transmission. Models of schistosome transmission and developmental stages of P. kellicotti may explain why this parasite species spatial analysis may aid in identifying areas at risk of re infection in can be locally so abundant. communities with high prevalence of infection undergoing treatment. 1895 1897 ASSESSING THE EFFECT OF WATER QUALITY MARKERS ON DETERMINANTS OF SCHISTOSOMA JAPONICUM THE VIABILITY OF SCHISTOSOME-BEARING SNAILS INTERMEDIATE HOST MIGRATION IN SICHUAN, CHINA Amsul Khanal, Yi-Ju Hsieh, Margaret Mentink-Kane, Grace Jennifer R. Head1, Howard H. Chang2, Justin V. Remais1 Cheung, Michael H. Hsieh 1Department of Environmental Health, Rollins School of Public Health, Biomedical Research Institute, Rockville, MD, United States Emory University, Atlanta, GA, United States, 2Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Schistosomiasis, infection by Schistosoma worms, is a disease that Atlanta, GA, United States affects over 200 million people worldwide, mostly in developing areas in Africa and Asia. Biomphalaria, Bulinus, and Oncomelania snails are Schistosomiasis is targeted for elimination in China, and monitoring for the intermediate hosts for Schistosoma, which emerge from these snails re-emergence in previously controlled areas in this country has become as cercaria, the larval stage which infects humans. At the Biomedical a major public health priority. Host and vector dispersal can facilitate Research Institute (BRI), we maintain the life cycle for multiple species of the spread and re-emergence of infectious diseases, but little is known schistosomes and provide these parasites for researchers around the world. about the movement of Oncomelania hupensis, the intermediate host Given the importance of optimizing viability of lab-cultivated snails to for Schistosoma japonicum. This study characterized intermediate our mission, we are investigating the effects of water quality markers on host snail movement between villages in Western China and examined the growth and viability of Biomphalaria, Bulinus, and Oncomelania environmental factors that affect host dispersal in this setting. Snail snails. We have determined the baseline values for various water quality migration rates between 32 sites in Sichuan Province, China, were markers such as pH, chlorine content, conductivity, total dissolved solids, estimated using Bayesian assignment tests conducted on genotypes of salinity, hardness and surface tension. Adjustment of multiple water 833 O. hupensis snails. Bi-directional effective geographic distances (EGD) quality markers affects the viability of schistosome-bearing snails. Our between each site pair were estimated based on geographic weightings work has implications for not only optimal laboratory cultivation of snails, representing nine environmental models: Euclidean, topography, incline, but may also help identify novel means by which water properties can be wetness, land use, distance from watershed, stream use, streams and manipulated in order to reduce infestation by schistosome-bearing snails. channels, and stream velocity. Median, first quartile and minimum EGD values were analyzed as to their ability to explain estimated paired 1896 migration rates using mixed effects models. Among sites, 7.8% to 32.7% of sampled snails were identified as migrants, with 20 sites containing SPATIAL ANALYSIS TO HUMAN FECAL WATER over 20% migrants. Migration rates were generally low between sites; CONTAMINATION BY MICROBIAL SOURCE TRACKING: however, for 12 sites, as much as 80% of the migrant population and ASSOCIATION WITH RISK OF SCHISTOSOMIASIS FOLLOWING over 10% of the overall snail population originated from a proximal TREATMENT IN BRAZIL site. EGD was found to be a significant predictor of migration rate, with the log of the minimum EGD emerging as the best predictor across all 1 2 3 Rafael Ponce-Terashima , Ronald Blanton , Mitermayer G. Reis environmental models. Odds of migration decreased as EGD increased (OR 1Mercer University, Macon, GA, United States, 2Center for Global Health from Euclidean model: 0.70, 95% CI: 0.63, 0.78). Models accounting for and Diseases, Case Western Reserve University, Cleveland, OH, United topography and wetness explained a significantly larger proportion of the States, 3Laboratory of Pathology and Molecular Biology, Gonçalo Moniz variance in migration between sites as compared to the Euclidean model. Research Center, Oswaldo Cruz Foundation, Salvador, Brazil Random intercept models suggest nearly 50% of the variation in migration rate can be attributed to site-specific factors, and roughly 10% can be Schistosomiasis is to a degree a disease of contact with fecally attributed to EGD. Our findings have important implications for controlling contaminated surface waters, rather than ingestion. In a community in the geographic spread of schistosomiasis in China. rural Bahia, Brazil that straddles a shallow river, we previously developed a astmh.org 581 1898 death. CYP450s are targets of many antifungal and cancer therapies. Antifungal azoles target 14α-demethylase (CYP51A1), a vital CYP450 DOES FLOODING DETERMINE THE DISTRIBUTION OF enzyme for sterol metabolism and cell membrane stability in fungi. We SCHISTOSOME-TRANSMITTING SNAILS IN MIDDLE TO found that imidazole antifungal agents related to miconazole targeted LOWER REACHES OF THE YANGTZE RIVER, CHINA? CYP450 and resulted in larval and adult worm death at low micromolar concentrations. In addition, combined sub-lethal concentrations of both Sheng-Bang Zheng1, Song Liang2, Yi-Biao Zhou1, Jin-Yi Wu1, CYP450-specific dsRNA and miconazole showed an additive effect on Jian-Chuan Gao1, Lin-Han Li1, Guang-Hui Ren3, Xiu-Xia Song1, larval worm death indicating that the effect of miconazole is CYP450 Zhong He4, Qing-Wu Jiang1 specific. Our results indicate that the schistosome CYP450 is essential for 1Fudan University, Shanghai, China, 2University of Florida, Gainesville, FL, worm survival and could be an ideal drug target. United States, 3Hunan Station for Schistosomiasis Control, Changsha, China, 4Junshan Office of Leading Group for Schistosomiasis Control, 1900 Yueyang, China SCHISTOSOME ABC TRANSPORTERS: ROLES IN DRUG Schistosomiasis, caused by blood fluke genus Schistosoma, is one of SUSCEPTIBILITY TO PARASITE PHYSIOLOGY the most devastating tropical diseases in the world. Oncomelania hupensis is the only intermediate host of schistosoma and its growth Swarna Bais, Yue Ning, Ravi S. Kasinathan, Robert M. Greenberg and development are sensitive to environmental factors. In China, these University of Pennsylvania, Philadelphia, PA, United States snails are only found in the 12 Provinces located along the Yangtze River and south of it. Hunan Province, located in the southeastern hinterland Praziquantel (PZQ) is essentially the only drug available for the treatment of China, along the middle and lower reaches of the Yangtze River, is of schistosomiasis, a disease affecting hundreds of millions. Although one of the schistosomiasis endemic areas in China, and Oncomelania invaluable, PZQ has significant limitations. It is largely ineffective against snails are mainly distributed in the vast floodplains of Dongting Lake juvenile schistosomes, and there are several reports of treatment failures in region, the northeastern part of Hunan Province, while no snail is found the field. Clearly, there is an urgent need for new therapeutics. ATP binding in the southwestern part of Hunan Province, where the altitude is much cassette (ABC) transporters such as P-glycoprotein (Pgp) mediate efflux of higher. In this study, we focused on the influence of extreme low air toxins and xenobiotics from cells and are associated with drug resistance in temperature, annual precipitation and time of flooding on the distribution many organisms, including parasitic helminths. They show broad substrate of Oncomelania snails in Hunan Province, China. The distribution areas of specificity and are inhibited by several drugs currently in clinical use. ABC snails in Hunan Province were marked and the data of annual extreme low transporters are also implicated in a variety of normal physiological activities air temperature, annual precipitation and the time of flooding from 1995 and transport many potent signaling molecules with high affinity, including to 2002 was collected or calculated. Nonparametric tests suggest that in several with immunomodulatory activity. We hypothesize that schistosome Hunan Province, the extreme low air temperature and precipitation are ABC transporters offer attractive candidate targets for new or repurposed not the main factors that impact the distribution of Oncomelania snails, drugs that act either as antischistosomals on their own or as adjuncts that while the time of flooding is a crucial factor that influences the distribution enhance parasite susceptibility to PZQ. Schistosomes with reduced PZQ of Oncomelania snails in Hunan Province, and the favorable time for the sensitivity show higher basal expression of ABC transporters such as Pgp snail’s survival ranges from about 2 to 7 months. (SMDR2) and multidrug resistance associated protein (SmMRP1). ABC transporters are also upregulated in response to sub-lethal concentrations 1899 of PZQ. PZQ is both an inhibitor and likely substrate of schistosome Pgp. Disruption of transporter function (by inhibition) or expression (by THE SCHISTOSOMA MANSONI CYTOCHROME P450 (CYP450) RNAi) increases the activity of PZQ against adult parasites, and results in IS ESSENTIAL FOR WORM SURVIVAL PZQ-refractory juvenile worms becoming susceptible to the drug. ABC transporters also appear to play a role in parasite egg production. We are Peter D. Ziniel1, Ethan Fisher2, Andrew Barnard1, Larissa M. currently investigating the role of schistosome ABC transporters in PZQ Podust3, David Williams1 susceptibility of the parasite within the host. We are also assessing the 1Rush University Medical Center, Chicago, IL, United States, 2Illinois role of these transporters in the parasite’s modulation of host immune Mathematics and Science Academy, Aurora, IL, United States, 3Skaggs responses. These studies should provide important insights into the role of School of Pharmacy and Pharmaceutical Sciences, University of California ABC transporters in PZQ susceptibility and parasite physiology, and may San Diego, La Jolla, CA, United States offer targets for novel or repurposed therapeutics. Schistosomiasis affects millions of people in developing countries and is responsible for over 200,000 deaths annually. There is only one drug, 1901 praziquantel, available for its treatment. Recent data suggest that drug EBOLA EPIDEMIC IMPEDES MALARIA CARE DELIVERY IN resistance could soon be a problem. There is therefore the need to identify GUINEA new drug targets and develop drugs for the treatment of schistosomiasis. Unlike many other organisms, e.g., humans have 57 CYP450 genes and Mateusz Plucinski1, Timothée Guilavogui2, Sidibe Sidikiba3, C. elegans has 83 CYP450 genes, Schistosoma mansoni has only one Nouman Diakité2, Souleymane Diakité2, Mohamed Dioubaté2, CYP450 gene encoded in its genome. Analysis shows that the predicted Ibrahima Bah4, Ian Hennessee5, Jessica K. Butts1, Eric S. Halsey1, 1452 bp open reading frame encodes a characteristic heme-binding Peter D. McElroy1, S. Patrick Kachur1, Jamila Aboulhab1, Richard region in its catalytic domain and a hydrophobic sequence that is usually James6, Moussa Keita2 present as the membrane interacting region in other CYP450s. The highest 1Centers for Disease Control and Prevention, Atlanta, GA, United States, identity to human CYP450s is 22%. Using 5’ RACE and analysis of cDNAs 2National Malaria Control Program, Conakry, Guinea, 3Mafèrinyah Rural from worm populations and different developmental stages, we found no Health Research Center, Mafèrinyah, Guinea, 4Catholic Relief Services, evidence that the schistosome CYP450 mRNA is differentially spliced or Conakry, Guinea, 5Emory Rollins School of Public Health, Atlanta, GA, processed, suggesting that a single CYP450 protein is present in worms. United States, 6Division of Prevention and Disease Control, Ministry of Analysis of CYP450 mRNA abundance indicates that it is differentially Health, Conakry, Guinea regulated with the egg and schistosomula having the highest levels. Additionally, adult female worms have higher message levels than adult The current Ebola epidemic has had significant impact on the overall male worms. We used reverse genetic and chemical tools in order to functioning of the healthcare system in affected countries. Due to the determine if the CYP450 is essential for parasite survival. RNA interference overlap of symptoms of Ebola virus disease and malaria, and malaria’s caused large reductions in CYP450 mRNA and resulted in schistosomula position as the leading cause of health facility visits, malaria care delivery is astmh.org 582 particularly sensitive to healthcare system perturbations due to the Ebola 1903 epidemic. A survey of 60 randomly-selected health facilities in prefectures highly affected by Ebola and 60 randomly-selected health facilities in CLUSTERING OF IMPORTED MALARIA CASES IN A SETTING Ebola-unaffected prefectures was performed in Guinea in December OF VERY-LOW MALARIA INCIDENCE IN NORTHERN SENEGAL 2014. Study teams abstracted malaria case management indicators from 1 1 1 2 registers for January-November for 2013 and 2014 and interviewed Yakou Dieye , Adama Tall , Gnagna Dieng Sow , Algaye Ngom , 3 1 1 4 healthcare workers and community health workers. Nationwide weekly Mady Ba , Badara Cisse , Farba Faye , Balla M. Mboup , Michael 5 1 6 5 surveillance data on suspected malaria cases reported for 2011-2014 Hainsworth , Philippe Guinot , Duncan Earle , Rick W. Steketee were also analyzed. The expected number of cases in 2014, estimated 1PATH MACEPA, Dakar, Senegal, 2Richard-Toll District Medical Office, from the trends in 2011-2013, was compared to the observed surveillance Richard-Toll, Senegal, 3Senegal National Malaria Program (NMCP), Dakar, data for 2014. There were substantial reductions in all-cause patient visits Senegal, 4Saint-Louis Regional Medical Office, Saint-Louis, Senegal,5 PATH (-42%), fever cases (-46%), and patients treated with oral and injectable MACEPA, Seattle, WA, United States, 6PATH MACEPA, Lusaka, Zambia antimalarials (-58% and -69%) in adults and children >5 in Ebola-affected Richard-Toll district (pop. 157,915) in northern Senegal is home to prefectures, with smaller but still substantial reductions in other age industrial activities among which are sugar cane harvesting and refining, groups and in Ebola-unaffected prefectures. In Ebola-affected prefectures, with about 2,000 seasonal and 3,000 permanent workers. Recognizing only 74% of community health workers were operational, and only 48% very low transmission and numbers of infected residents in the district, of those working reported actively treating malaria cases, compared to a malaria case investigation strategy was initiated in Richard-Toll by the 66% before the Ebola epidemic (p-value <0.01). Nationwide, the Ebola NMCP in 2012 and has continued as a routine district-wide intervention. epidemic was estimated to have resulted in 74,000 (95% CI: 71,000- RDT or microscopy-confirmed cases presenting to health facilities are 77,000) fewer malaria cases seen at health facilities from the start of the followed to their homes and all members of the index case household Ebola epidemic to the end of 2014. The decrease in malaria care delivery and the 5 nearest households are tested for malaria and given treatment at the health facility and community level due to the Ebola epidemic if positive. In 2013, 234 passively detected cases of malaria were threatens malaria control in Guinea. Untreated and inappropriately treated investigated and 10,071 contacts were tested, with 42 positive secondary malaria cases lead to excess malaria morbidity and mortality, and thus cases. Of the 276 total positive cases, 175 (63%) had recent travel history. more fever cases in the community. This makes identification of suspect In 2014, 134 passively detected cases of malaria were investigated and Ebola cases more difficult, potentially hampering an effective Ebola 5,751 contacts were tested, with 14 positive secondary cases. Of the 148 outbreak response. total positive cases, 104 (70%) had recent travel history. Travel appears to play an important role in malaria transmission and there appears to be 1902 clustering of travel-related cases around Richard-Toll city during October- DEATHS DUE TO PLASMODIUM KNOWLESI MALARIA IN November: in 2013 and 2014, 79% and 80% of cases had recent travel (53% and 62% of total imported cases in district) and 51% and 57% SABAH, MALAYSIA, 2012-2014: REDUCED FATALITY RATE occurred in October and November. In 2014, 82% of cases with recent WITH IMPROVED USE OF INTRAVENOUS ARTESUNATE travel were concentrated in 4 neighborhoods. This period coincides with Giri Rajahram1, Bridget E. Barber2, Timothy William1, Matthew J. the beginning of the school year and the sugar cane harvest, as well as a Grigg2, Jenarun Jelip3, Jayaram Menon4, Tsin W. Yeo2, Nicholas M. major religious holiday in 2014. These results suggest that opportunities Anstey2 exist to improve targeting of malaria elimination strategies within the district, including focused screening of higher-risk populations such as 1Department of Infectious Diseases, Queen Elizabeth Hospital, Kota seasonal workers, pupils and travelers. During 2012-2014, 478 cases were Kinabalu, Malaysia, 2Menzies School of Health Research, Darwin, Northern passively identified in health facilities and 72% were associated with travel Territory, Australia, 3Sabah Department of Health, Kota Kinabalu, Malaysia, and likely imported, suggesting that local transmission within the district 4Department of Medicine, Queen Elizabeth Hospital, Kota Kinabalu, is extremely low (average of 0.28/1000 pop./year) and with attention to Malaysia reducing the risk of imported infections, the district could rapidly become Plasmodium knowlesi is the most common cause of malaria in Malaysia, malaria-free. and an important cause of fatal malaria in Sabah. In a review of malaria deaths in Sabah during 2010-2011, fatal outcomes were associated with 1904 misdiagnosis of knowlesi malaria as P. malariae and consequent delayed initiation of parenteral therapy. In Malaysia intravenous artesunate is now TOLERABILITY TO SAFETY OF WEEKLY PRIMAQUINE the recommended firstline treatment of severe malaria of any species. AGAINST RELAPSE OF PLASMODIUM VIVAX IN GLUCOSE- We reviewed malaria notification data and case notes of mandatorily- 6-PHOSPHATE DEHYDROGENASE DEFICIENT TO NORMAL reported malaria deaths in Sabah 2012-2014, to describe clinical details CAMBODIANS of P. knowlesi deaths and to assess for trends in P. knowlesi case fatality. Sixteen malaria deaths were reported: 7 P. knowlesi, 7 P. falciparum, Walter R. Taylor1, Sim Kheng2, Muth Sinoun2, Narann Tops3, and 1 P. vivax (all PCR-confirmed), and one microscopy-diagnosed “P. Khem Kosal4, Khon Sothea4, Phum Souy5, Saorin Kim6, Chuor malariae”. Median age of fatal P. knowlesi cases was 61 years, and four Char2, Chan Vanna7, Po Ly2, Pascal Ringwald8, Virak Khieu2, were female. Complications of PCR-confirmed P. knowlesi cases included Alexandra Kerleguer6, Pety Tor6, John K. Baird9, Steven Bjorge3, jaundice (N=5), metabolic acidosis (N=5), acute kidney injury (N=3), shock Didier Menard6, Eva Christophel10 (N=6), and respiratory distress (N=7). Four P. knowlesi cases were diagnosed 1MORU, Bangkok, Thailand, 2CNM, Phnom Penh, Cambodia, 3World by microscopy as P. malariae, 1 as P. falciparum, 1 as P. vivax and 1 as Health Organization, Phnom Penh, Cambodia, 4Pailin Referral Hospital, P. knowlesi. All recognised to have severe malaria on admission received Pailin, Cambodia, 5Aning Venh Referral Hospital, Oddar Meanchey, intravenous artesunate. A total of 3138 cases of microscopy-diagnosed P. Cambodia, 6Pasteur Institute, Phnom Penh, Cambodia, 7Pramong malariae/P. knowlesi were notified in Sabah during 2012-2014, giving a Health Centre, Pursat, Cambodia, 8World Health Organization, Geneva, fatality rate of 2.23 per 1000 notifications, compared to a fatality rate of Switzerland, 9Eijkman Oxford Clinical Research Unit, Jakarta, Indonesia, 5.5 per 1000 notifications during 2010-2011 (1087 notifications with 6 P. 10WHO WPRO, Manila, Philippines knowlesi deaths). Despite ongoing microscopic misdiagnosis of P. knowlesi, Primaquine (PQ) is not implemented in many malaria endemic countries, management of severe malaria in Sabah appears to have improved. Although including Cambodia, to prevent Plasmodium vivax relapse for fear of the study demonstrates the ability of P. knowlesi to cause fatal disease precipitating PQ-induced acute haemolytic anaemia (AHA) in patients with despite optimal therapy, increased use of artesunate has been associated glucose-6-phosphate dehydrogenase deficient (G6PDd). Reluctance to with a reduction in P. knowlesi fatality-rates.

astmh.org 583 use primaquine is reinforced by a lack of quality safety data. From January levels to inform evidence-based programmatic decisions. The challenges 2013-January 2014, Cambodians with acute vivax malaria were treated appear to be behavioral and organizational, relating to how staff value with dihydroartemisinin-piperaquine on Days (D) 0, 1 and 2 plus weekly and use data in their everyday work. primaquine 0.75 mg/kg x 8 doses (D0, 7, 14 to D49) and follow to Day 56. G6PD genotype and measured G6PD activity confirmed G6PD status. The 1906 primary outcome was treatment completion without primaquine toxicity defined as any one of: (i) severe anaemia (Hb<7 g/dL), (ii) a fractional fall SEASONAL MALARIA CHEMOPREVENTION, THREE YEARS OF in Hb >25% vs. D0, (iii) blood transfusion, (iv) haemoglobinuria, (v) acute IMPLEMENTATION kidney injury (AKI, an increase in baseline serum creatinine > 50%), or Estrella Lasry1, Matthew Coldiron2, Alena Koscalova3, Francesco (vi) methaemoglobinaemia (metHb) > 20%. The Trial registration number Grandesso2, Paul Milligan4, Ma Angeles Lima5, Jorgen Stassjins6, is ACTRN12613000003774. 75 patients were enrolled with a median Esther Sterk3, Greg Elder7, Martin de Smet6 (range) age of 24 (5-63) years; 63 (84%) patients were males. D0 G6PD activity ranged from 0.1-1.5 U/g Hb (median 0.85 U/g Hb) in 18 G6PDd 1Medecins Sans Frontieres/Doctors Without Borders, New York, NY, patients (17/18 had the Viangchan variant) and 6.9-18.5 U/g Hb (12 U/g United States, 2Epicentre, Paris, France, 3Medecins Sans Frontieres/Doctors Hb) in 57 G6PD normals (G6PDn). Median (range) D0 Hb concentrations Without Borders, Geneva, Switzerland, 4London School of Hygiene & were similar (p=0.46) between G6PDd vs. G6PDn: 13 g/dL (9.6-16) vs. Tropical Medicine, London, United Kingdom, 5Medecins Sans Frontieres/ 13.5 g/dL (9-16.3) and nadired on D2 in both groups: 10.8 g/dL (8.2- Doctors Without Borders, Barcelona, Spain, 6Medecins Sans Frontieres/ 15.3) vs. 12.4 (8.8-15.2) g/dL (p=0.006), respectively. By D7, five G6PDd Doctors Without Borders, Brussels, Belgium, 7Medecins Sans Frontieres/ patients (27.7%) had > 25% fall in Hb vs. 0/57 in G6PDn (p=0.00049), Doctors Without Borders, Paris, France including one G6PDd male who required a blood transfusion (D0-D5 Hb In 2012, Médecins Sans Frontières (MSF) started implementing seasonal 10.0-7.2 g/dL). No patient developed severe anaemia, haemoglobinuria, malaria chemoprevention (SMC), following WHO recommendation for metHb concentration > 4.9% or AKI. In conclusion, vivax infected, G6PDd children in areas with high seasonal transmission using sulphadoxine- patients suffered significant, mostly transient, falls in Hb and one was pyrimethamine and amodiaquine. MSF works in southern Mali, Chad and transfused. Weekly primaquine in G6PDd patients mandates medical Niger where children suffer 2-3 episodes of malaria/year and where the supervision and pretreatment screening for G6PD status. The feasibility malaria season is accompanied by a malnutrition peak causing an increase of implementing a package of G6PDd testing and supervised primaquine in admissions. SMC started in 2012 in MSF projects in Mali and Chad, should be explored. and in 2013 in Niger. Monthly contacts with families at SMC delivery, give opportunities to provide other health interventions. In 2013 SMC 1905 was combined with screening for malnutrition, and in 2014, in Chad, with Pentavalent vaccination for children under 2. In Niger we included IMPROVING MALARIA DATA QUALITY TO USE IN HEALTH SMC in a preventive package (PP) which includes nutrition screening MANAGEMENT INFORMATION SYSTEM, TANZANIA and prevention and EPI. Programs were evaluated through surveys to Ritha A. Willilo1, Franky Chacky2, Renata Mandike2, Enock determine coverage, adherence and acceptability of SMC. We assessed Mhehe3, Naomi Kaspar4, George Greer4, Ramsan Mahdi1, Jeremiah the impact of the programs on incidence of simple and severe malaria, Ngondi1 hospital mortality, all-cause hospitalizations and admissions with severe malarial anaemia, using program data. Estimates of SMC efficacy were 1RTI International, Dar es Salaam, United Republic of Tanzania, 2National made from the proportion of malaria cases who had received SMC and Malaria Control Program, Dar es Salaam, United Republic of Tanzania, SMC coverage, using the screening method. Side-effects where monitored 3Ministry of Health and Social Welfare, Dar es Salaam, United Republic of through re-inforced national pharmacovigilance systems. The prevalence Tanzania, 4United States Agency for International Development, Dar es of molecular markers of resistance to SMC drugs was assessed through Salaam, United Republic of Tanzania surveys before and after SMC implementation. There has been a high Malaria data is an important aspect for monitoring malaria burden and level of acceptability of SMC in the communities. Monthly coverage of intervention coverage to inform evidence-based programmatic decisions. SMC exceeded 85% in rural areas but was lower in an urban area. When Anecdotal evidence suggests that the quality of malaria data from routine combined with a PP and delivered at the health center, coverage was health management information system (HMIS) is poor which made similar to SMC alone. Pentavalent vaccine coverage increaased when it difficult to analyze, interpret and ultimately the use of these data is combined with SMC in Chad. SMC led to substantial reductions of both limited. The situation analysis was conducted to assess, identify gaps, and simple and severe malaria cases in Mali, Chad and Niger. We observed setting up priorities of malaria data quality and use in Tanzania’s HMIS. a reduction in cases of severe malarial anaemia, but no reduction in the Desk reviews and field-based data collection was conducted to gather number of cases of cerebral malaria. Integration with other interventions is information that describes current practice, barriers and needs for malaria feasible and can prevent missed opportunities in the child health package. data quality improvement. A stakeholder’s workshop was convened to triangulate data, identify gaps, propose solutions, prioritize activities and 1907 develop a work plan to improve data quality and use. The findings suggest that malaria data quality in Tanzania is poor. The main issues reported at MALARIA INDICATORS IN THE DEMOCRATIC REPUBLIC OF the facility level were data inconsistencies (in the registers, tally sheets THE CONGO, 2014 and summary forms), data collection tools not being available and not Filiberto Hernandez being filled out. The findings also showed that most of health facilities do not complete the tally sheets. At the district and regional levels, the main Centers for Disease Control and Prevention, Atlanta, GA, United States challenge encountered was unreliable internet connectivity that hindered Malaria continues to be a major health problem in DRC, accounting for an timely processing of data into the DHIS2 system. The stakeholders estimated 40% of outpatient visits by children under five and 19% of the proposed priorities for improving data quality and use, including: 1) data overall mortality in the same age group. The implementation of large scale quality and use of data to be introduced as permanent agenda item malaria interventions in the country continues to face serious challenges. in Health Management teams at district and regional level; 2) develop The USG funding for malaria activities in the Democratic Republic of guidelines on data quality and use; and 3) supporting CHMTs to conduct Congo (DRC) has increased from $18 million in FY 2010, to 50 million in regular, comprehensive and effective supportive supervision and, including FY 2014, a substantial increase which has allowed the DRC to obtain the data quality assessments. HMIS that produce complete, timely, reliable, successful results seen in the last Demographic and Health Survey (2013). and valid data are needed by national malaria control programs to monitor Results have shown: a) the increase in the use of mosquito nets by children malaria burden and intervention coverage at national and sub-national under five, from 38% to 56%; b) the increase in their use by pregnant astmh.org 584 women, from 43% to 60%; and c) the malaria prevalence in children genome of Leptomonas is much smaller but contains in contrast more under five, with a rate of 30.8% obtained by RTDs, and 22.6% obtained protein coding genes. It was seen that this genome expansion is mostly through microscopy tests. The aim of this study is to review malaria cases due to larger number of repetitive sequences and analysis of SNPs showed throughout ten years, and describe the different malaria interventions that the core genome was more variable in this isolate. Aneuploidy carried out during those same years and their impact. The NMCP is indicated there is significant opportunity for generation of SNPs that reviewing this data to define its new country malaria strategy 2015-2020. may have many applications in molecular epidemiology. Transposable Additionally, data will be presented from the 5 provinces supported by elements (TEs) provided a source of genetic variation in Leptomonas. PMI to show the impact of five years of interventions in those provinces. Variation in the Ras protein superfamily between Leishmania donovani The US President’s Malaria Initiative in the Democratic Republic of Congo and Leptomonas was observed. Absence of urea cycle in Leptomonas has been supporting the majority of interventions in five provinces, and was found to be an ancestral feature. Our whole-genome sequence together, with the support of the Global Fund, the World Bank, and the data reveals genetic structural differences between Leishmania and Department for International Development of the British Government it’s ancestral species Leptomonas, which cannot be identified by using (DFID), the coverage of the country has reached all the health zones, even multilocus typing alone. Our research finding has immense potential for those with very difficult access. creating renewed impact of the parasite genome on biomedical research, contributing to a paradigm shift in research activities that will lead to new 1908 diagnosis and treatment. DEVELOPMENT OF EFFECTOR MOLECULES TO 1910 BLOCK LEISHMANIA TRANSMISSION UTILIZING THE PARATRANSGENIC APPROACH ELECTRONIC VOLUMETRIC ASSESSMENT DURING SODIUM STIBOGLUCONATE THERAPY IN PATIENTS WITH CUTANEOUS Ivy Hurwitz, Annabeth Fieck, Ravi Durvasula LEISHMANIASIS: A PROMISING TECHNIQUE USING DIGITAL University of New Mexico, Albuquerque, NM, United States 3D MODELS Leishmaniasis is a neglected tropical disease that affects 13 million people Braulio M. Valencia1, Fernando Zvietcovich2, Roberto J. worldwide. This disease is caused by the protozoan parasite Leishmania, Lavarello2, Andrea K. Boggild3, Benjamin Castañeda2, Alejandro and is transmitted by the bite of an infected female phlebotomine sand Llanos-Cuentas1 fly. Our laboratory utilizes the paratransgenic approach to control parasite 1Institute of Tropical Medicine Alexander von Humboldt, Lima, Peru, transmission by host vectors. In this approach, symbiotic or commensal 2Pontificia Universidad Católica del Peru, Lima, Peru,3 University of Toronto, bacteria residing within the gut of the vector are genetically modified Toronto, ON, Canada to express molecules that target the parasite. In previous work, we had reported on the toxicity of honey bee melittin against Leishmania Cutaneous Leishmaniasis (CL) is susceptible to bias and subjectivity during spp. Leishmaniacidal activities of human histones H2A and H2B has assessment of treatment response and follow-up. As a part of standard been shown by others. In this study, we are examining the combined of care, methods to estimate the extent of lesions are usually performed toxicity of these two antimicrobial peptides (AMP’s) on Leishmania through manual or visual methods which are non-uniform and difficult to major promastigotes in an effort to develop a broader panel of effector standardize in low-income settings. This work shows a novel, non-invasive molecules for use in the paratransgenic strategy. In experiments measuring method to obtain metrics of depth and volume by creating digital models live/dead ratios of cultured promastigotes by flow cytometry and of CL lesions. Digital models of CL lesions were created by acquisition fluorescent plate assays, the IC100 for melittin and H2B are observed at of point-clouds with a commercial 3D scanner. The data were exported 5 uM and 7 uM, respectively. Synergistic toxicity is observed when the using the .XYZ file format that provided the point coordinates to recreate AMP’s are used in combination treatments, decreasing the calculated 3D mesh models. After IRB approval, patients with CL were enrolled, and IC100 values by more than half. There results were further verified by lesions were digitalized: twenty-six before treatment, and 8 at the end of con-focal microscopy. Similar experiments are underway to characterize treatment. Two volumes were considered from each lesion: inflammatory the activity of these two AMP’s against other strains of Leishmania as volume (IV, a volume between an imaginary line following normal skin well as Trypanosoma cruzi, the causative agent of Chagas disease. The surface and an imaginary surface located at the top of raised edges) and addition of a second AMP to paratransgenic systems that result in more an ulcerative volume (UV, a volume between an imaginary line following efficient parasite killing has multiple advantages. Specifically, it decreases normal skin surface and the deepest point of the ulcer). Three metrics (in the absolute expression levels required from the transformed commensal mm3) and one coefficient were obtained for each lesion: global volume bacteria within the gut of the sand fly. Additionally, the use of multiple (GV: IV+UV), IV, UV, and the volume coefficient (VC: IV/UV proportion). AMP’s drastically reduces the incidence of acquired resistance by the Mean duration of disease was 2.2 ± 0.89 months. 12 of 26 (46%) parasite were classified as ulcer-predominant (if UV was higher than IV), and 14 (54%) as inflammatory-predominant (if IV was higher than UV). Median 1909 metrics at baseline evaluation were: 221.6 for GV, 143.14 for IV, 36.6 for UV, and 1.66 for VC. According treatment outcome, there were no EVOLUTIONARY COMPARISON OF THE GENOME OF significant differences in these metrics at baseline evaluation. In patients LEISHMANIA DONOVANI CLINICAL ISOLATES FROM INDIA with volumetric evaluations after treatment, GV was higher in those WITH ITS ANCESTOR LEPTOMONAS classified as treatment failure compared to those classified as cured after 1-3 months of follow-up (2218.5 vs. 224, p=0.04). As a proof of concept, Neeloo Singh1, Surendra Chikara2 this study represents initial evidence to support the utility of electronic 1CSIR Central Drug Research Institute, Lucknow, India, 2Xcelris Genomics, volumetric assessment of treatment response and follow-up of CL, with Ahmedabad, India future possible extension to other transmissible and non-transmissible Flagellates of the family Trypanosomatidae fall into two natural groups. dermal diseases. The ancestral genera is Leptomonas which is confined to invertebrates, the more evolved genera is Leishmania which uses both vertebrate and invertebrate hosts. Utilizing next generation sequencing technology we explore the genomes of the two clinical isolates, Leishmania and Leptomonas to answer a wide range of evolutionary and pathological questions. We find that the genome of Leishmania donovani was similar to size and coding capacity with other Leishmania genomes. However, astmh.org 585 1911 could benefit from early treatment strategies. The objective of this study was to evaluate if Gal-3 level in plasma is associate with the development THE DILEMMAS OF CONGENITAL CHAGAS DISEASE of the severe form of CC and prognosis. We have used samples collected SCREENING IN AN ENDEMIC SETTING in a previous retrospective cohort that enrolled T cruzi seropositive, and seronegative blood donors (BD) in São Paulo and Montes Claros, Brazil. 1 2 Louisa A. Messenger , Gerson Galdos-Cardenas , Victoria This cohort was supplemented with CC patients from a tertiary hospital 3 4 5 6 R. Rendell , Malasa Jois , Vishal Shah , Edward Valencia , Leny (Heart Institute). All subjects underwent a health clinical evaluation, ECG, 6 6 6 6 Sanchez , Janet Acosta , Manuela Verastegui , Herado Sanchez , and echocardiogram (Echo). ECG and Echo were reviewed blindly by 6 2 7 Remo Gonza , Robert H. Gilman , Caryn Bern centralized reading centers. The subjects were classified as with or without 1London School of Hygiene & Tropical Medicine, London, United Kingdom, signs of CC by a blinded panel of 3 cardiologists. Gal-3 (VIDAS® galectin 3 2Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United France - bioMerieux Inc.) was available to test 441 samples: 101 negative States, 3Duke University, Durham, NC, United States, 4Brown University, controls, 190 BD without CC, 60 BD with CC, and 90 patients with CC. Providence, RI, United States, 5St. Louis University School of Medicine, St. The median level of GAL-3 was 13.1ng/mL for negative controls, 12.ng/mL Louis, MO, United States, 6Universidad Peruana Cayetano Heredia, Lima, for BD without CC, 13.1ng/mL for BD and 15.4ng/mL for CC patients. The Peru, 7University of California San Francisco, San Francisco, CA, United proportion of individuals with Gal-3 level > 17.8 was significantly higher States (p<0.0001) among the CC patients (37.8%) as compared to negative controls (14.8%), BD without CC(11.1%) and BD with CC (16.7%). Concomitant with successful trans-national disease control programs Ejection fraction <50 was also associated with higher levels of Gal3 across Latin America, Chagas disease has shifted from a neglected, (p=0.0001). The Gal3 showed correlation with lCAM-1, MPO, PAI-1, CRP, endemic parasitic infection of the rural poor to an urbanized chronic IL6, TNFα, IL8, VEGF, Troponin and NT-proBNP, with p values <0,01. Follow disease and now a potentially emergent global health problem. Congenital up date on mortality was available for the CC patients. In this group, we transmission has become proportionately more important, estimated to could detect an association of Gal-3 level and subsequent death in the account for 22% of new Trypanosoma cruzi infections in 2015. Treatment follow up 5 years. (p=0.0004). In conclusion, our data suggest that Gal-3 during infancy is significantly more efficacious and better tolerated than is associated with the more severe form of CC and risk of death. later, but current diagnostic methods, even when optimally executed, fail to detect over half of infected neonates and <20% of infants complete 9-months of follow-up. We recruited pregnant women presenting for 1913 delivery in two urban hospitals in Santa Cruz department, Bolivia and A FIELD-APPLICABLE MOLECULAR TOOL TO DIAGNOSE monitored infants of infected women at birth, 1, 6 and 9 months to AMERICAN CUTANEOUS LEISHMANIASIS evaluate the performance of quantitative PCR (qPCR), IgM Western blots (using trypomastigote excreted-secreted antigen; TESA-blots) and Bruno L. Travi1, Omar A. Saldarriaga1, Alejandro Castellanos1, micromethod (microscopic observation of trypomastigotes) for newborn Gerald C. Baldeviano2, Maxy De los Santos2, Peter C. Melby1, screening for congenital Chagas disease. Of 518 at-risk infants from 507 Andres G. Lescano2 seropositive women, unequivocal congenital transmission was identified 1University of Texas Medical Branch, Galveston, TX, United States, 2US in 32 infants of 29 mothers, including 3 sets of concordantly infected Naval Medical Research Unit - 6, Lima, Peru twins (5.7% transmission rate); 6 additional neonates were diagnosed at 6 months or later and vectorial or intrapartum transmission could not Dermal and mucosal leishmaniasis is widely distributed in Central and be excluded. In cord blood, qPCR, TESA-blot and micromethod displayed South America affecting an estimated 190,000- 300,000 people annually. sensitivity/specificity of 82.8%/97.3% (median of 7143.6 parasites/ Microscopy is the most common diagnostic method used in endemic ml; interquartile range of 5.0-187788.9 parasites/ml), 71.4%/99.5% regions but its sensitivity is low (≤70%) and tends to decrease further with and 20.7%/100%, respectively. When birth and 1 month results were disease chronicity. Serology is variable and does not distinguish between combined, cumulative sensitivity reached 96.9%, 89.7% and 38.7% for current and past infections. Conventional or quantitative PCR from qPCR, TESA-blot and micromethod, respectively. qPCR has the potential to dermal or mucosal samples have high sensitivity (≈87-98%) and specificity facilitate earlier diagnosis and circumvent loss to follow-up. We critically (≥87%) but require expensive equipment, trained personnel and lab discuss the technical, logistical and economic obstacles of implementing facilities beyond the possibilities of resource-limited health infrastructure routine molecular screening for congenital Chagas disease in resource- of endemic areas. We developed a novel point of care molecular test to limited settings and describe the future prospects for improvement. diagnose dermal and mucosal leishmaniasis produced by Leishmania Viannia spp., which are responsible for the majority of cases. We designed 1912 primers and probes that targeted the kinetoplast DNA minicircles. Leishmania DNA was extracted using the Qiagen® kit and detected by GALECTIN 3 IS ASSOCIATED WITH THE MORE SEVERE FORM isothermal Recombinase Polymerase Amplification coupled with a lateral OF CHAGAS CARDIOMYOPATHY flow immunochromatographic strip (RPA-LF). The test has sensitivity similar to real time PCR (gold standard) detecting as few as 0.1 parasites 1 2 3 Fabio Fernandes , Carlos H. Moreira , Léa C. Oliveira , Marcela per reaction. It does not require expensive equipment and the results 4 1 1 4 Souza , Charles Mady , Barbara M. Ianni , Erika Manuli , Ester C. are read with the naked eye in < 1 hour. The RPA-LF specificity for the L. 4 Sabino Viannia subgenus was confirmed by the amplification of L. braziliensis, 1Heart Institute, Hospital das Clínicas de São Paulo, School of Medicine, L. panamensis, L. guyanensis, L. peruviana and L. lainsoni. There University of São Paulo, São Paulo, Brazil, 2Institute of Infectology Emilio was no cross amplification with L. chagasi, L. major, L. mexicana, L. Ribas; Laboratory of Parasitology (LIM46), Tropical Medicine Institute amazonensis or T. cruzi. Preliminary data indicated that RPA-LF has an of São Paulo, University of São Paulo, São Paulo, Brazil, 3Laboratory of excellent agreement with PCR as determined in patient samples from Medicine Laboratorial (LIM03), Hospital das Clínicas de São Paulo, School endemic areas of Peru. We are evaluating additional primer sets capable of Medicine, University of São Paulo, São Paulo, Brazil, 4Laboratory of of amplifying the Leishmania subgenus with the goal of developing an Parasitology (LIM46), Tropical Medicine Institute of São Paulo, University of RPA- multiplex lateral flow test that encompasses all species that produce São Paulo, São Paulo, Brazil cutaneous leishmaniasis. This novel method could fill the need for a field applicable diagnostic tool critical to cutaneous and mucosal leishmaniasis Chagas Chronic Cardiomyopathy (CC) is characterized by a diffuse management and control. myocarditis with intense myocardial remodeling, fibrosis, cardiomyocyte hypertrophy and damage. Gal-3 is involved into two pathophysiological mechanisms (fibrosis and inflammation), hence GAL-3 levels maybe a good biomarker to stratify Chagas Disease patients and identify those who astmh.org 586 1914 1916 ACTIVATION OF BICYCLIC NITRO DRUGS BY A NOVEL EXPORTED EPOXIDE HYDROLASES MODULATE NITROREDUCTASE (NTR2) IN LEISHMANIA ERYTHROCYTE SIGNALLING LIPIDS DURING PLASMODIUM FALCIPARUM INFECTION Susan Wyllie, Adam Roberts, Suzanne Norval, Stephen Patterson, Alan Fairlamb Natalie J. Spillman, Daniel E. Goldberg University of Dundee, Dundee, United Kingdom Department of Internal Medicine (Infectious Diseases), Washington University School of Medicine, St. Louis, MO, United States The novel nitroimidazopyran agent, (S)-PA-824, has potent antibacterial activity against Mycobacterium tuberculosis in vitro and in vivo and Erythrocytes are storage reservoirs for epoxide-containing lipid signalling is currently in Phase II clinical trials for TB. In contrast to M. tuberculosis, molecules, including epoxyeicosatrienoic acids (EETs) and epoxy​ where the (R) enantiomer is inactive, our previous studies demonstrated octadecenoic acids (EpOMEs). EETs/EpOMEs function as vasodilators that (R)-PA-824 shows potent cidal acitivity against Leishmania and anti-inflammatory modulators in the blood stream. These bioactive donovani, the causative agent of visceral leishmaniasis (VL). In the epoxides are hydrolysed by epoxide hydrolases, converting them into less murine model of VL, (R)-PA-824 led to >99% suppression of parasite active diols. We have identified and characterized two epoxide hydrolases burden when administered orally at 100 mg kg-1, twice daily for 5 days. (EH) of Plasmodium falciparum, PfEH1 and PfEH2. Both proteins Defining the mechanism of action of this promising anti-leishmanial has are exported to the periphery of infected erythrocytes. Recombinantly now become the focus of our current studies. In general, nitro drugs are expressed PfEH1 can hydrolyze a non-physiological reporter epoxide, and believed to function as pro drugs requiring enzyme mediated reduction both enzymes convert several EET regioisomers to the corresponding before becoming cytotoxic. In trypanosomatids, a type I nitroreductase diols. Overexpression of PfEH1 or PfEH2 in parasites results in a significant (NTR) has been demonstrated as catalysing the bio-activation of the alteration in the epoxide fatty acids stored in the infected erythrocyte bicyclic nitro drugs nifurtimox, benznidazole and fexinidazole. However, phospholipids. Although we were able to knock out PfEH1 and 2 in vitro, transgenic L. donovani promastigotes overexpressing L. major NTR we propose they may have an increased importance in vivo. P. berghei do not show an increased sensitivity to (R)-PA-824 suggesting that this ANKA has no predicted exported EHs, but chemical inhibition of the nitroimidazopyran is not activated by NTR. (R)-des-nitro-PA-824 is inactive host EH enzyme reduced the percentage of mice that developed severe, against L. donovani in vitro, confirming that the nitro group is important cerebral malaria, without reducing parasitemia. We hypothesize that the for the anti-leishmanial activity of PA-824. Thus, if the mechanism of parasite disruption of EETs/EpOMEs leads to perturbed vascular function, action of PA-824 does involve bio-activation, then this putative reduction and favorable conditions for binding and sequestration of infected is mediated by an as-yet unidentified enzyme(s). Here, we describe our erythrocytes to the microvascular endothelium. use of genome-wide sequencing, proteomics and genetic approaches to identify NTR2, a novel nitroreductase involved in the bio-activation of (R)- 1917 PA-824 and several other bicyclic nitro drugs. A PLASMODIUM SPECIFIC KINASE IS AN ESSENTIAL S PHASE 1915 PROMOTING FACTOR DURING BLOOD-STAGE SCHIZOGONY METABOLIC REGULATION OF MACROPHAGE FATE: THE ROLE Markus Ganter1, Jonathan M. Goldberg1, Jeffrey D. Dvorin2, Joao 3 4 1 4 OF MTORC2 SIGNALING IN ALTERNATIVELY ACTIVATED A. Paulo , Jonas King , Aditya S. Paul , Isabelle Coppens , Rays 5 1 6 3 MACROPHAGES H. Jiang , Jing Yang , David A. Baker , Steven P. Gygi , Rhoel R. Dinglasan4, Manoj T. Duraisingh1 Stanley Ching-Cheng Huang, Amber M. Smith, Bart Everts, 1Harvard T.H. Chan School of Public Health, Boston, MA, United States, Erika L. Pearce, Joel D. Schilling, Edward J. Pearce 2Boston Children’s Hospital, Boston, MA, United States, 3Harvard Medical Washington University School of Medicine, Department of Pathology and School, Boston, MA, United States, 4Johns Hopkins Malaria Research Immunology, St. Louis, MO, United States Institute, Baltimore, MD, United States, 5University of South Florida, Tampa, FL, United States, 6London School of Hygiene & Tropical Medicine, The mammalian target of rapamycin complexes, mTORC1 and mTORC2 London, United Kingdom have emerged as important regulators of environmental cues for development of immune cells. mTORC1, the most well studied mTOR Like invasion and host cell remodeling, Plasmodium schizogony is a complex whose activity is highly responsive to changes in cellular glucose parasite specific process, offering an attractive route for intervention. and amino acid levels. Intriguingly, however, it has been shown that the During schizogony a multinucleated cell is formed after which daughter constitutive activation of mTORC1 negatively regulates the alternative parasites bud off the mother cell. In search of potential new drug targets, (M2) macrophage activation. In contrast, it is still unknown that the we assessed all schizont-stage kinases for their essentiality in Plasmodium role of mTORC2 in macrophage activation. Here we report that myeloid falciparum, employing the inducible destabilization domain system in lineage specific deletion of Rictor, a critical adaptor protein of mTORC2 a loss-of-function knockdown screen. We identified the P. falciparum in macrophages, they failed to fully become M2 macrophages during the cdc2-related protein kinase (CRK) 4 as essential for proliferation in the Heligmosomoides polygyrus infection and have protective immunity to blood-stage and for transmission to anopheline mosquitoes. Knockdown the parasite. Also, importantly, we observed that level of IRF4 expression of P. falciparum CRK4 led to a complete block of DNA replication at the and glycolytic/mitochondrial metabolism was markedly decreased from onset of schizogony. Organellar development, however, was not impaired Rictor-deficient M2 cells during the infection. Since IRF4 is required in mutant parasites. This suggests that the regulation of nuclear and for aerobic glycolysis and development of CD8 T cells, we found that organellar development is independent. By quantitative phosphoproteomic expression of IRF4 was elevated in IL-4 stimulated macrophages, and profiling, we identified key effects for P. falciparum CRK4 on pathways conditional IRF4 deletion in macrophages affected neither mTORC2 activity that co-ordinate cell cycle events including the initiation of DNA nor the phosphorylation of Stat6, but led to a significant reduction of replication, histone modifications, and regulation of gene transcription. P. glucose metabolism and polarization of M2 macrophages. Taken together, falciparum CRK4 was also found to be required for subsequent rounds of our finding suggests that mTORC2-IRF4 signaling links to metabolic DNA replication, which characterize schizogony. Together our data indicate reprogramming and activation of macrophages. that chemotherapeutic targeting of P. falciparum CRK4 would be possible throughout schizogony, which in addition to blocking transmission, are attractive features for drug development.

astmh.org 587 1918 1920 SCHISTOSOMA MANSONI INFECTION INDUCES ANTI- GENETIC MODIFICATION OF THE DIARRHEAL PATHOGEN ATHEROGENIC TRANSCRIPTIONAL CHANGES IN HEPATIC CRYPTOSPORIDIUM PARVUM MACROPHAGES Sumiti Vinayak, Mattie C. Pawlowic, Adam Sateriale, Carrie F. Keke C. Fairfax1, Andrew Elvington3, Andrew Ready2, Edward J. Brooks, Caleb J. Studstill, Yael Bar-Peled, Michael Cipriano, Boris Pearce3, Gwendalyn J. Randolph3 Striepen 1Purdue University, West Lafayette, IN, United States, 2Washington Center for Tropical and Emerging Global Diseases, University of Georgia, University, St. Louis, MO, United States Athens, GA, United States Hepatic macrophages play an essential role in the granulomatous response Cryptosporidium is the second most important pathogen after rotavirus to infection with the parasitic helminth Schistosoma Mansoni, but to cause diarrhea in young children. Cryptosporidium is also an the transcriptional changes that underlie this participation are poorly opportunistic pathogen and causes severe disease in HIV/AIDS patients and understood. To explore this, we sorted the two previously recognized organ transplant recipients. Currently, there are no fully effective drugs hepatic macrophage populations (perivascular and Kupffer) from naïve or vaccines to treat or prevent cryptosporidiosis. The main roadblock in and S. mansoni infected mice and performed microarray analysis as part the development of drugs and vaccines is the overall poor tractability of of the Immunological Genome Project. Consistent with the pattern of Cryptosporidium due to lack of continuous culture system, poor animal great diversity identified in other organ macrophages, the two hepatic models, and lack of genetic tools. We report here a robust approach to macrophage populations displayed signatures distinct from all other genetically modify this important human pathogen. We demonstrate the macrophages, with the two populations exhibiting remarkable differences transfection of Cryptosporidium parvum sporozoites in tissue culture between them. However, this diversity was greatly reduced following and optimization of regulatory sequences and electroporation conditions infection with S. mansoni, and in fact, many of the transcripts identified to drive expression of a luciferase reporter gene. We developed a mouse as uniquely perivascular or Kupffer cell specific were lost following model for C. parvum infection to inject electroporated sporozoites directly infection, raising the possibility that both populations may be replenished into the small intestine of IFN-γ knockout mice. We used the CRISPR/ by monocytes following infection. Our analysis showed a profound Cas9 system to knockout the parasite’s thymidine kinase (tk) gene and alteration in phospholipid and cholesterol metabolic pathways, including replaced it with a cassette expressing the luciferase reporter fused to a prostaglandin signaling, in addition to alterations in M2 markers. These neomycin resistance gene that conferred paromomycin resistance in vivo. changes suggested a possible mechanism for the previously reported Quantitative PCR and luminescence measurements were used to monitor atheroprotective effects of S. mansoni infection. Indeed we find that infection in mice, and development of paromomycin-resistant transgenic ApoE null mice fed a high fat diet in combination with S. mansoni parasites. We confirmed loss of tk gene in the stable transgenics, and infection have reduced body mass and increased glucose tolerance in evaluated the use of transgenic oocysts for performing drug assays. Using addition to reduced plaque area as compared to control mice. this powerful approach, we have generated stable transgenic parasite lines that express other reporters such as fluorescent protein and red-shifted 1919 luciferase. We used the red-shifted luciferase transgenic to monitor and quantify the real-time dynamics of C. parvum infection in mice using A GENOME-WIDE CRISPR/CAS9 SCREEN REVEALS GENES in vivo bioluminescence imaging. Ongoing efforts are directed towards THAT ARE CRITICAL FOR TOXOPLASMA GONDII GROWTH IN testing the efficacy of potential anti-cryptosporidial compounds in mice HUMAN FIBROBLASTS using this transgenic parasite. Our ability to genetically engineer C. parvum will help to answer key questions related to parasite biology and Diego Huet, Saima Sidik, Sebastian Lourido accelerate the development of novel therapeutics for disease intervention. Whitehead Institute for Biomedical Research, Cambridge, MA, United States 1921 Despite recent advances in apicomplexan genetics, the available tools have TRYPANOSOMA BRUCEI INFECTION ACCELERATES THE remained low-throughput. Although RNAi can be used to elucidate gene MOUSE CIRCADIAN CLOCK function in Trypanosoma brucei, differences in the underlying machinery have precluded its use in apicomplexans. Recently, we and others used Filipa Rijo-Ferreira1, Joseph S. Takahashi2, Luisa M. Figueiredo1 CRISPR/Cas9 to generate double-stranded DNA breaks and efficiently 1Instituto de Medicina Molecular, Biology of Parasitism Lab, Lisbon, induce precise mutations in Toxoplasma. We have now used CRISPR/Cas9 Portugal, 2UT Southwestern, Department of Neuroscience, Howard to perform pooled genetic screens. By transfecting a Toxoplasma strain Hughes Medical Institute, Dallas, TX, United States that constitutively expresses Cas9 with a library comprised of ten different sgRNAs against each gene, we mutated every gene in the Toxoplasma By living in a 24-hour world, organisms are subjected to daily genome, in multiple ways, in seven days. Quantifying the fold-change in environmental changes. Many organisms have evolved molecular abundance of each sgRNA over the course of this experiment using next- mechanisms to anticipate such changes. In humans, the internal circadian generation sequencing allowed us to identify genes that contribute to the clock regulates many physiological functions, including sleep/wake cycle fitness of Toxoplasma when grown in human fibroblasts. The power of and metabolism. Although the internal clock is controlled by the brain, having ten independent mutations per gene allowed us to identify a set all cells have an intrinsic clock. Patients with sleeping sickness show of genes that we can confidently say are critical under these conditions. In alterations of sleep/wake cycle, body temperature and endocrine secretion, a CRISPR/Cas9 screen performed in the presence of a toxic uracil analog, which have led to the hypothesis that sleeping sickness may be a circadian sgRNAs against a component of the uracil scavenging pathway were rhythm disorder. We first infected mice with T. brucei and we recorded enriched by approximately 1000-fold, demonstrating that our platform the circadian behavior using a running-wheel assay. We observed that yields expected results and holds potential for identifying mechanisms infected animals run 2-fold less during the active phase and are 7-fold of drug resistance. These results give us insight into Toxoplasma’s large more active in the rest phase than healthy mice, confirming the changes set of uncharacterized genes on an unprecedented scale. Our work in circadian behavior observed in patients. When we infected circadian now focuses on characterizing a set of 58 hypothetical genes that are reporter mice and measured the circadian parameters of several organs conserved within Apicomplexa and confer significant fitness defects when ex vivo, we observed that, although all organs have a robust circadian mutated. rhythm, those with higher parasite load have an internal clock that runs two hours faster than non-infected organs. These alterations were reproduced in vitro, when parasites were directly co-cultured with isolated astmh.org 588 fibroblasts, suggesting that parasites may have a direct effect on the host of the encoded P. falciparum genes have no known homologs in other cell circadian clock. Finally we observed that expression of clock genes in eukaryotes, we believe that understanding their functions will aid in vivo is significantly affected in peripheral tissues, especially in those with identifying potential targets for novel antimalarial drug development. the highest parasite load. These results show that (i) T. brucei mouse infection reproduces circadian behavior changes observed in humans; (ii) T. 1924 brucei infection accelerates the mouse circadian rhythm by two hours; (iii) this effect may be partly caused by a direct interaction with the parasite. A NETWORK OF PROTEIN INTERACTIONS REQUIRED FOR TRAFFICKING OF PFEMP1 IN P. FALCIPARUM-INFECTED 1922 ERYTHROCYTES THE INOSITOL PHOSPHATE PATHWAY CONTROLS Steven Batinovic1, Emma McHugh1, Aishwarya Kulkarni1, Joseph 2 1 1 TRANSCRIPTION OF TELOMERIC EXPRESSION SITES IN D. Smith , Matthew W. Dixon , Leann Tilley TRYPANOSOMES 1Department of Biochemistry and Molecular Biology, Bio21 Institute, The University of Melbourne, Parkville, VIC, Australia, 2Center for Infectious Igor Cestari, Kenneth Stuart Disease Research, Seattle, WA, United States Center for Infectious Disease Research, Seattle, WA, United States Plasmodium falciparum is the most virulent human malaria parasite. African trypanosomes evade host antibody clearance by periodically Parasites invade red blood cells (RBCs) and extensively modify the structure changing their variant surface glycoprotein (VSG) coat. They transcribe and morphology of their host cell - including the generation of virulence only one VSG gene at a time from one of about 20 telomeric expression complexes on the surface of the erythrocyte. These complexes comprise sites (ESs), and they undergo antigenic variation either by switching of a collection of exported parasite proteins that assemble at knob-like transcription between telomeric ESs or by recombination of the VSG gene structures under the surface of the erythrocyte membrane and allow expressed. We found that the inositol phosphate/phosphatidylinositol infected RBCs to cytoadhere and sequester within the microvasculature of (IP) pathway controls both transcription of telomeric ESs and VSG the host. One key parasite protein, P. falciparum Erythrocyte Membrane antigenic switching in Trypanosoma brucei. Conditional knockdown of Protein-1 (PfEMP1), is largely responsible for this adhesion. It is becoming phosphatidylinositol 5-kinase (PIP5K), phosphatidylinositol 5-phosphatase clear that PfEMP1 is trafficked with the aid of a complement of host and (PIP5Pase) or overexpression of phospholipase C (PLC) derepresses parasite-structures and compartments that are generated de novo during numerous silent telomeric ESs in T. brucei bloodstream forms. This the approximate 48-hour lifecycle of the parasite inside its host RBC. derepression is specific to telomeric ESs and coincides with an increase in In this work, we have made use of mini-PfEMP1 constructs to examine the number of telomeric and RNA polymerase I foci that colocalize outside this complex export process. We have delineated discrete trafficking of the nucleolus. Monoallelic VSG transcription resumes after re-expression compartments that these virulence proteins associate with during export of PIP5K; however, most of the resultant cells switch the VSG gene and used immunoprecipitation followed by mass spectrometry to identify expressed. PIP5K, PLC, their metabolic substrates and products localize to the ‘interactome’ of virulence proteins in these compartments. Known the plasma membrane, whereas PIP5Pase localizes in the nucleus proximal and novel interacting-proteins were identified across multiple parasite to telomeres. PIP5Pase associates with repressor/activator protein 1 (RAP1), and host compartments, consistent with our current knowledge of the and their telomeric silencing function is altered by PIP5K knockdown. The PfEMP1 trafficking pathway. This includes parasite proteins localized to the results show that the IP pathway controls ES transcription and antigenic parasite secretory pathway, parasitophorous vacuole (such as PTEX) and switching in T. brucei by epigenetic regulation of telomere silencing, exported proteins found in the host RBC compartment. We also present which likely involve a signal transduction process. the identification of a number of human chaperone-type proteins that may represent a mechanism for parasite recruitment of host factors in the 1923 export of parasite proteins such as PfEMP1. Using inducible knockdown systems we show that depletion of these identified proteins results in EXPLORING UNKNOWN GENES IN MALARIA PARASITES BY A the reduction of PfEMP1 export to the surface of the RBC. Ultimately, ROBUST GENE REGULATORY SYSTEM understanding and targeting the export of parasite virulence proteins may ultimately allow us to ablate parasite virulence in vivo. Suresh Maddur Ganesan, Alejandra Falla, Sebastian Nasamu, Jacquin C. Niles 1925 Massachusetts Institute of Technology, Cambridge, MA, United States Malaria is a major health problem in tropical and subtropical countries. PROGRAMMATIC USE OF MOLECULAR XENOMONITORING The most severe form of malaria is caused by the parasite, Plasmodium AT THE LEVEL OF EVALUATION UNITS TO ASSESS falciparum. A limited set of antimalarial drugs is used to treat the disease, PERSISTENCE OF LYMPHATIC FILARIASIS IN SRI LANKA but drug resistance is spreading at alarming rate. Hence, there is an urgent Ramakrishna U. Rao1, Sandhya D. Samarasekera2, Kumara C. need for identification of novel anti-malarial drugs. A major challenge in Nagodavithana2, Udaya S. Ranasinghe2, Manjula W. Punchihewa3, new antimalarial drug development is identification and prioritization of Ralph H. Henderson4, Gary J. Weil1 potential targets for drug discovery. This is mainly due to lack of reliable 1Washington University School of Medicine, St. Louis, MO, United States, functional genetics tools for investigating parasite genes. To address this 2Ministry of Health, Anti-Filariasis Campaign, Colombo, Sri Lanka, 3Ministry need, we have developed a RNA-protein interaction system that facilitates of Health, Regional Anti-Filariasis Unit, Galle, Sri Lanka, 4The Task Force for robust and inducible regulation of target gene translation in eukaryotic Global Health, Decatur, GA, United States organisms, including Plasmodium. Here, we present the application of protein engineering approaches to integrate our synthetic control system Sri Lanka’s Anti Filariasis Campaign (AFC) distributed 5 annual rounds with native Plasmodium translational regulatory mechanisms. In so doing, of MDA with DEC plus Alb. to all LF endemic regions in the country we have achieved substantially increased regulatory dynamic ranges (up from 2002-2006. Post-MDA surveillance has consistently documented to 200-fold) compared to a 5-10 fold range of the original system. As microfilaremia rates <1% in all sentinel and spot check sites, and all a proof-of-concept, we have successfully used this system to generate implementation units easily satisfied WHO TAS targets in 2013. However, parasite lines in which various proteins of interest can be knocked down recent studies have shown that Sri Lanka has low level persistence of LF in to reveal clear growth phenotypes. In addition, we have successfully some areas based on several criteria, especially molecular xenomonitoring combined this approach with CRISPR/Cas9 genome editing technology to (MX, detection of filarial DNA in mosquitoes). Some of the highest signals rapidly validate essential genes. We are currently applying these genetic for persistence of LF were observed in sentinel sites in Galle district. The tools to broadly study parasite genes of unknown function. Since ~60% purpose of this study was to demonstrate the use of MX at the program astmh.org 589 level and to field test different sampling methods. Galle district (population 205 (41%) people. Among those with at least one positive snip, the mean 1.1 million) was divided into two evaluation units (EUs). These included a MF load per snip, determined by averaging the number in both snips, was coastal EU with persistent LF and a low risk inland EU. Mosquitoes were 27.5 (range: 0.5-341.5). On-site tests for other filariae showed 273 (55%) systematically sampled from ~300 trap sites in 30 randomly selected people were infected with M. perstans, 108 (22%) with L. loa, and 25 clusters (lower health administrative units) per EU. Approximately 28,000 (5%) with LF. Six (1%) people were infected with all four filarial parasites, blood fed, gravid or semigravid Culex quinquefasciatus mosquitoes were 51 (10%) with three, and 135 (27%) with two. The OV-16 antibody test collected with CDC gravid traps, sorted into pools, and tested for filarial for O. volvulus was positive in 333 (67%) people. Additional laboratory DNA by qPCR. 92/620 pools (14.8%) from the coastal EU and 8/583 pools testing is pending to define OV-16 test sensitivity and specificity in this (1.4%) from the inland EU were positive for filarial DNA. 16/30 clusters setting. A better understanding of the performance of the OV-16 antibody in the coastal EU had one or more positive pools compared to 3/30 in test in the African context, particularly in the setting of co-endemic filarial the inland EU. Maximum likelihood estimates (MLE) for filarial DNA rates infections, is needed to ensure proper usage by elimination programs. calculated by Poolscreen2 were essentially the same when the same number of pools were collected and tested from 75, 150, or 300 trap 1927 sites. The range of filarial DNA rates calculated in the coastal EU with the different samples was 0.61-0.72%, and the range in the inland EU was TOWARDS THE ELIMINATION OF LYMPHATIC FILARIASIS IN 0.04-0.06%. The ability to use a smaller number of trap sites reduces the MALAWI: CESSATION OF MASS DRUG ADMINISTRATION cost and time required for mosquito sampling. The MX results suggest NATIONWIDE AFTER TRANSMISSION ASSESSMENT SURVEYS there is widespread, low-level persistence of LF in coastal Galle district 8 1 2 3 3 years after the last round of MDA. This study has shown MX can be used Square Mkwanda , Bagrey Ngwira , Brent Thomas , Joan Fahy , 4 3 3 by national programs to assess and map the persistence of LF at the level Maria Rebollo , Louise Kelly-Hope , Moses Bockarie of large EUs in regions with Culex transmission. 1Ministry of Health, Lilongwe, Malawi, 2College of Medicine, Lilongwe, Malawi, 3Liverpool School of Tropical Medicine, Liverpool, United 1926 Kingdom, 4NTD Support Center, Task Force for Global Health, Atlanta, GA, United States EPIDEMIOLOGICAL, CLINICAL, AND LABORATORY Malawi, a small land-locked country in south-eastern Africa was shown EVALUATION OF ONCHOCERCIASIS IN AN AREA OF HIGH to be highly endemic for lymphatic filariasis (LF) when disease mapping PREVALENCE -TSHOPO PROJECT AREA, DEMOCRATIC at national scale was completed in 2008. LF is a debilitating mosquito- REPUBLIC OF THE CONGO, 2014 borne parasitic infection that is endemic in 34 countries in Africa. Mapping Nana Wilson1, Paul T. Cantey2, Josias Likwela3, Karla Feeser4, delineated 26 LF endemic districts out of 28 and mass drug administration Nestor Ndakala Gyamba5, Jacques Muzinga wa Muzinga5, (MDA) to eliminate the disease started in 9 districts in 2008. In 2009, MDA Nicholas Ayebazibwe6, Yassa D. Ndjakani7, Naomi Awaca was scaled up to 100% geographic coverage for the target population of Pitchouna8, Dieudonné Mumba Ngoyi9, Antoinette K. Tshefu10, 13 million people at risk. Between 2008 and 2014, treatment coverage Vitaliano Cama1 surpassed 80% for each MDA round. In 2014, after 6 consecutive rounds of MDA, Malawi met all the criteria to conduct transmission assessment 1Division of Parasitic Diseases and Malaria and Epidemic Intelligence surveys (TAS) to determine if transmission of LF has been interrupted. Pre- Service, Centers for Disease Control and Prevention, Atlanta, GA, United TAS sentinel site surveys involving >300 parsons, five years or older, per States, 2Division of Parasitic Diseases and Malaria, Centers for Disease site were conducted at 48 sites. None of the sentinel sites was shown to Control and Prevention, Atlanta, GA, United States, 3Programme National have a microfilaria (MF) prevalence rate of 1% or greater. In 2014, TAS de la Lutte contre l’Onchocercose, Kisangani, Democratic Republic of was conducted in 11 evaluation units (EUs) following WHO guidelines and the Congo, 4Oak Ridge Institute for Science and Education, Oak Ridge, infection status determined using a point of care ICT method. The survey TN, United States, 5Field Epidemiology and Laboratory Training Program, was conducted in 30 randomly selected schools per EU and altogether Kinshasa, Democratic Republic of the Congo, 6African Field Epidemiology 18,337 children, about 6 and 7 years old were enrolled from 330 schools. Network, Kampala, Uganda, 7Division of Global Health Protection, Centers A total of 34 (0.19%) children from all 11 EUs were found to be ICT for Disease Control and Prevention, Kinshasa, Democratic Republic of positive. The LF infection rate for each EU was below the critical cut- the Congo, 8Programme Nationale de la Lutte contre l’Onchocercose, off level suggesting that all EUs met the criteria to stop MDA. The NTD Kinshasa, Democratic Republic of the Congo, 9Institut National de Regional Programme Review Group (RPRG) for the WHO African Region Recherche Biomédicale, Kinshasa, Congo, Democratic Republic of the, reviewed and approved the TAS results in 2015 indicating that MDA 10Ecole de Santé Publique, Kinshasa, Democratic Republic of the Congo, could be stopped in Malawi. However Malawi is endemic for two other Onchocerciasis, a neglected parasitic disease caused by Onchocerca debilitating neglected tropical diseases targeted with the same drugs as LF: volvulus, affects at least 37 million people globally. Efforts to eliminate onchocerciasis and soil transmitted helminthiasis. The endemicity status of this disease are based on mass drug administration of ivermectin (IVM these two diseases should be taken in to consideration before any decision MDA). As part of a study to evaluate tools for measuring the impact to stop distribution of ivermectin and albendazole can be made. The RPRG of elimination efforts, we evaluated different diagnostic tests for O. report singled out Malawi for a special commendation as a success story. volvulus. We performed convenience sampling in Tshopo Project area Stopping MDA in Malawi represents a big step forward for the global LF in the Democratic Republic of Congo, where there was a baseline elimination programme as we approach the 2020 target. nodule prevalence of 50-70%, and IVM MDA had been ongoing for 1-5 years before the study. Risk factor and clinical data were collected for 500 people. Blood smears for Loa loa and Mansonella perstans, immunochromatographic card tests for lymphatic filariasis (LF), and skin snips for onchocerciasis were evaluated on-site. Plasma, serum, blood smears, dried blood spots, and preserved skin snips were sent to CDC- Atlanta for further testing. Median participant age was 50 years (range: 6-88 years); 193 (39%) were female. Past-year ivermectin use was reported by 60 (12%), though 117 (34%) reported having taken it at least once before. At least one nodule was present in 253 (51%) people, with a median of three (range 1-11) nodules. Onchocercal eye disease was present in five (1%) people; one (0.2%) had microfilaria (MF) in the anterior chamber of the eye. The skin snip was positive for O. volvulus in

astmh.org 590 1928 were truly due to Wb and not a cross reaction due to Loa infection, we collected dried blood spots (DBS) to perform multiplex assays for Wb123 SUCCESSFUL FINAL TRANSMISSION ASSESSMENT SURVEY and Bm14, two antigens for filarial parasites. Antibody based assays to FOR LYMPHATIC FILARIASIS USING ICT AND STRIP TEST SIX detect Wb123 has been shown to be sensitive and specific for LF infection YEARS AFTER STOPPING MDA IN TOGO while Bm14 has lower specificity and is recognized by a proportion of individual with other filarial infections. DNA was extracted from each DBS 1 2 1 Améyo M. Dorkenoo , Rachel N. Bronzan , Kossi G. Yakpa , and amplified by PCR and qPCR using pan filarial primers. Only one sample 1 1 1 3 Efoé Sossou , Poukpessi Adjeloh , Menssah Teko , Anders Seim , had borderline positive responses to Wb123, but 13 had positive serology 4 Yao Sodahlon to Bm14, suggesting that ICT positivity was related to Loa and not Wb. 1Ministry of Health, Lomé, Togo, 2HDI, Seattle, WA, United States, 3HDI, All 28 samples had positive results for Loa by both PCR approaches. Our Oslo, Norway, 4Mectizan Donation Program, Atlanta, GA, United States inability to confirm that ICT positivity was related to Wb suggests that LF is no longer present and therefore no intervention is required against LF. Lymphatic filariasis (LF) was once endemic in 8 of the 40 districts in Togo. More robust epidemiological methods may be required to confirm that From 2000 to 2009, the National Lymphatic Filariasis Control Program transmission of LF has been interrupted. These results would represent a of Togo conducted between seven and nine rounds of mass drug tremendous step forward for the Global Program to Eliminate Lymphatic administration (MDA) with albendazole and ivermectin in these 8 districts. filariasis, shrinking the LF map by one more country and helping to cross In 2010, based on consistently high MDA coverage and low prevalence the bridge towards the achievement of the ultimate goal of worldwide of nocturnal microfilaremia (<1%) at sentinel and spot-check sites, MDA elimination of LF by 2020. for LF was stopped following a successful Transmission Assessment Survey (TAS). According to World Health Organization (WHO) recommendations, two TAS should be conducted 2 to 3 and 5 to 6 years after stopping 1930 MDA. Togo conducted and passed its first post-MDA TAS in 2012, and its PROGRESS TOWARDS LYMPHATIC FILARIASIS ELIMINATION second, final post-MDA TAS in January 2015, to reconfirm that there is no IN SIERRA LEONE transmission of Wuchereria bancrofti. We report on this latter survey here. The survey was conducted according to WHO recommendations. The 8 Santigie Sesay1, Jusufu Paye2, Mohamed S. Bah2, Florence M. endemic districts were grouped into 4 evaluation units (EU); in the north, McCarthy1, Abdulai Conteh1, Mustapha Sonnie2, Mary H. Tone, Cinkassé and Kpendjal districts comprise EU1; in the northeast, Hodges2, Joseph B. Koroma3, Yaobi Zhang4 Binah and Doufelgou districts make EU2; Kozah district in central eastern 1Neglected Tropical Disease Program, Ministry of Health and Sanitation, Togo is EU3; and Amou and Haho districts in the south are EU4. School- Freetown, Sierra Leone, 2Helen Keller International - Sierra Leone, going children aged 6 to 7 years old were selected for testing using Freetown, Sierra Leone, 3Family Health International (FHI 360), Accra, cluster sampling. Children were tested for LF filarial antigen using both an Ghana, 4Helen Keller International Regional Office for Africa, Dakar, immunochromatographic test (ICT) and an LF test strip in EU1 and EU2, Senegal and ICT alone in EU3 and EU4. Test results were scored 0 for negative tests and 1 to 4 according to the intensity of a positive result. An EU was Lymphatic filariasis (LF) is endemic across Sierra Leone, and mass drug considered to have successfully passed the TAS when the number of administration (MDA) with ivermectin and albendazole started in positive cases found was inferior to a critical cut-off number, which varied 2007, reaching 100% geographical coverage in 2010 with effective from 18 to 20 among the EUs. Of the children tested – 1701 in EU1, epidemiological coverage. Baseline microfilaraemia (mf) level was assessed 1547 in EU2, 1542 in EU3, and 1564 in EU4 – there were, respectively, before the first MDA. Mid-term assessment (after the 3rd MDA) and 6 (0.35%), 0 (0%), 0 (0%) and 0 (0%) positive cases found, well below pre-TAS (after the 5th MDA) was conducted in 12 rural health districts the critical threshold in every EU. All six cases were positive by both test (HDs) at sentinel sites (SS) and spot check sites (SC), using midnight blood methods. The risk of recrudescence of LF remains very low in these 8 samples from at least 300 people at each site. Two HDs were paired into previously endemic districts more than six years after stopping MDA for each group (6 groups) according to population size and epidemiological LF in Togo. Togo is preparing a dossier to submit to WHO for validation of characteristics, sharing SS and SC. At baseline (14 sites), the mean mf elimination of LF. prevalence in 12 HDs was 2.6% (95% CI: 2.3-3.0%), ranging 0-6.9%. The mean mf density was 1.3mf/ml (95% CI: 1.0-1.7). Ten HDs had 1929 mf prevalence ≥1% at SS. At mid-term (6 SS and 6 SC), the mean mf prevalence was 0.3% (95% CI: 0.2-0.5%), ranging 0-1.6%. The mean SHRINKING THE LYMPHATIC FILARIASIS MAP: DOES GABON mf density was 0.1mf/ml (95% CI: 0.0-0.1). Eleven HDs showed mf NEED TREATMENT TO ELIMINATE LYMPHATIC FILARIASIS? prevalence <1% at SS and SC. In 2013 a pre-TAS was conducted in 6 SS and 7 SC. Overall mf prevalence was 0.5% (95% CI: 0.4%-0.8%), ranging 1 2 3 Maria Rebollo Polo , Julienne Atsame , Vitaliano Cama , Moses 0-2.7%. The mean mf density was 1.0mf/ml (95% CI: 0.30-1.8). Nine HDs 4 John Bockarie showed mf prevalence <1%, persistent from the mid-term. Compared to 1Task Force for Global Health, Decatur, GA, United States, 2Ministry baseline there was significant decrease in mf prevalence and mf density of Health Gabon, Libreville, Gabon, 3Centers for Disease Control and (p<0.001). Eight districts qualified for and will be subject to transmission Prevention, Atlanta, GA, United States, 4Liverpool School of Tropical assessment survey (TAS). Three HDs (Bombali, Kailahun, and Koinadugu) Medicine, Liverpool, United Kingdom that showed mf prevalence ≥1% had baseline mf prevalence 6.9%, 5.7% and 2.6% respectively, and, together with Kenema (though mf prevalence Historical records suggest that lymphatic filariasis (LF), was found in <1% at pre-TAS), share borders with Guinea and/or Liberia where 100% Gabon, but there is little information on its presence. MDA has never geographical coverage of MDA has not been reached. These 4 HDs will been conducted. Establishing the endemicity of LF is challenging using continue MDA for additional 2 years, while the cross border issues are traditional parasitological and serological methods because of the limited addressed. Significant increase in mf density from the mid-term was skills for microscopy and coendemicity with Loa loa (loa). Loa and Wb mainly due to a SC in hard to reach areas in Bombali. This highlights the microfilaria are difficult to distinguish microscopically and Loa antigens importance of SC in identifying hot spot of LF prior to TAS. have been shown to cross react with Wb antigens in individuals with high Loa microfilaria counts who are negative for Wb test positive by ICT. We conducted a nationwide integrated survey of LF, onchocerciasis and loiasis. For LF, 114 villages were surveyed across the 9 provinces. Individuals aged 15 years or above were tested using ICT cards. A total of 28 ICT positive individuals were found in 22 communities, from 18 different districts. To further investigate if the ICT positives found during the survey astmh.org Abstract Author Index A-591

The number(s) following author name refers to the abstract number.

Achonduh-Atijegbe, Olivia A. 1798 Affara, Muna 1215, 1399, 1582, Akala, Hoseah M. 207, 208, 850 A Acosta, Angela 384 213, 529, 625, 889, 92 Akame, Julie 1689 Aamir, Uzma Bashir 1772 Acosta, Belsy 181 Afolabi, Muhammed O. 363 Akanda, Shafqat 1790 Aarestrup, Frank M. 1500 Acosta, Janet 1911 Afonne, Chinenye 75 Akano, Kazeem 810 Aarons, Emma 1178 Acosta, Janeth 29 Afrane, Yaw 1391, 896 Akarachotpong, Thantapat 416 Aaskov, John 789 ACT Consortium - Drug Quality Afrin, Sadia 1861 Akbari, Masoud 330 Abadie, Ricardo 394, 1024, 1670, Team 819 Afriyie-Gyawu, Evans 413 Akerey-Diop, Daisy 854 1797 ACT Consortium RDTs in Context Afwamba, Isaac A. 1326 Akhund, Tauseef 1008 Abass, Ali K. 305, 657 Working Group 1522, 1699 Ag1000g Consortium 1384 Akila, Joel D. 1392 Abdala, Edson 474 The ACTwatch Group 817, 1524 Agaba, Bosco B. 1572, 243 Akindele, Samuel 1568 Abdalla, Marwah 1305 Acuna, Miguel 738 Agaba, Gad 65 Akintunde, Grace 1568 Abdel Aziz, Mustafa 1762 Adair, Linda S. 396 Agbenyega, Tsiri 371 Akinyede, Akinwumi A. 1492 Abdel-Rahman, B 421 Adakun, Susan 1050 Agbla, Schadrac 888 Akinyele, Olajumoke 1568 Abd El Wahed, Ahmed 189, 797 Adaku Nze, Chinwe 839 Agbo, Yao M. 506, 508 Akinyi Okoth, Sheila 226, 1877 Abdoun, Asim O. 1740 Adams, David 1040, 288, 64, 787 Agbowai, Carine 889 Akkoyunlu, Mustafa 338 Abdulai, Martha A. 842, 997 Adams, Emily 1739 Ager, Arba L. 262 Akogbeto, Martin 106, 119 Abdulla, Salim 1049, 123, 1633, Adams, John H. 1611, 1630, 1643, Agmas, Adem 1544, 1546, 1628 Akoko, Larry 1722 1637, 854 201, 557, 940, 1473, 49 Agnandji, Selidji T. 618 Akpan, Mfonobong E. 129 Abdybekova, Aida 1025 Adams, Matthew 1581, 1602, Agomo, Chimere 1568 Akparibo, Raymond 1049 Abe, Mayumi 724 1606, 1646, 835, 893, 921, 923, Agongo, Godfred 194, 216 Aksoy, Emre 101 Abebe, Almaz 1438 943, 978, 924 Agossa, Fiacre R. 106 Aksoy, Serap 101, 637 Abebe, Getachew 566 Adams, Nehkonti 1023, 1677 Agrawal, Sonia 923 Aktar, Amena 1861, 1862 Abebe, Yonas 989 Adanu, Richard 487 Agudelo, Ivony Y. 1463 Akter, Aklima 1861 Abedin, Jaynal 1163 Adapa, Swamy Rakesh 587 Aguiar, Anna C. C. 252 Akter, Jasmin 886 Abel, Lucy 383, 719, 714 Addiss, David 1300, 469 Aguiar, Joao 1644 Akuamoah, Jacqueline 351 Abernathy, Alice M. 1841 Addissie, Adamu 70 Aguilar, Pablo 1188, 241 Akue, Adovi D. 44 Abernethy, Neil 685 Addo, Kwesi 1023, 1677 Aguilar, Patricia 1458 Akum, Aveika 1662 Abeyewickreme, Wimaladharma Addo, Phyllis 402 Aguilar, Ruth 1570 Alagesan, Kathirvel 16 1102 Addo, Phyllis G. A. 1322 Aguilar, Yojani 786 Alaii, Jane 379, 380 Abie, Getnet 1515 Adedire, Elizabeth B. 185 Aguirre, Sebastian 1257 Alam, Masud 1700, 1863, 408 Abiola, Annie W. K. 328, 1610 Adegnika, Ayola Akim 1651 Agurto, Carla 1803 Alam, Md. Murshid 397 Abla Geiser, Nada 83 Adejuwon, Adekunle O. 892 Agwanda, Bernard 703 Alam, Mohammad S. 886 Aboellail, Tawfik A. 40 Ademikpo, Liscovich 1002 Ahmad, Abdullahi 1582 Alam, Mohammad Murshid 392 Abolude, Olukemi O. 1294 Ademowo, George O. 1603, 825 Ahmed, Adem 1629, 974 Alam, Mohammad Shafiul 1411, Abongwa, Melanie 1072 Ademowo, Olusegun G. 1498 Ahmed, Hinda 1453 316 Aboriga, Raymond 216 Adeneye, Adeniyi 1568 Ahmed, Khalil 1772 Alam, Shafiul 768 Abot, Esteban 1275, 352 Adeneye, Kazeem 994 Ahmed, Makhdum 1839 Alami, R. 421 Abot, Steve 1634 Adenis, Antoine 308 Ahmed, Rafi 172 Al-Amin, Hasan Mohammad 316 Aboud, Said 429 Adeogun, Adedapo 1568, 1654, Ahmed, Sabeena 886 Alano, Pietro 1488 Aboulhab, Jamila 1901 994 Ahmed, Salwa F. 421 Alao, Manzidatou 1002 Abraham, David 608, 670 Aderoyeje, Temitope 810 Ahmed, Shahnawaz 27, 28, 576 Alarcon, Jorge O. 1011, 1667, 409 Abraham, Thomas 88 Adeusi, Oluwole 1516, 1517, 345 Ahmed, Shamsir 28 Alava, Freddy 125 Abrego, Feny 1345 Adewale, Bisi 438 Ahmed, Tahmeed 1865, 28 Alba, Sandra 679, 691 Abreha, Tesfay 14, 566 Adhikari, Shiva R. 1198 Ahorlu, Collins 907 Albareda, Maria C. 1851 Abreu, Cláudia B. 63 Adhin, Malti 226 Ahoua Alou, Ludovic 1370 Albers, Anna 1708, 1709 Abril, Marcelo 477 Adiamoh, Majidah H. 1399 Ahouidi, Ambroise D. 931 Alberti D’Amato, Anahí 1089 Abuaku, Benjamin 1480, 899, 907 Adibaku, Seraphine 243 Ahumada, Martha 1577 Albertini, Audrey 1739 Abubakar, Ismaela 1582 Adjei, Alex 1049 Aidoo, Michael 244 Albujar, Christian B. 661, 1110 Abudho, Bernard 1243, 1785 Adjei, Andrew A. 318, 487 Aierken, Amina 1026, 1027, 574 Alcaide, Maria 570 Abudo, Mamo U. 417 Adjei, George 240 Aïkpon, Rock 106 Alcorta, Yolanda 1275, 1634, 352 Abugri, James 194 Adjei Boakye, Daniel 130 Aina, Oluwagbemiga 1492, 1568 Aldaach, Haidar 1790 Abuom, David C. 703 Adjeloh, Poukpessi 1928 Ainslie, Rob 657 Alegría, Cindy 1584 Abuy, Telesforo Eyegue 1003, Adjogoua, Edgar 158 Aisiri, Adolor 1516, 1517 Alemayehu, Abreham T. A. 72 1660, 1869 Adjuik, Martin 1049 Aiyenigba, Bolatito 1516, 1517, Alemayehu, Bereket H. 14 Accrombessi, Manfred 854, 968 Adou, Sei 1822 345 Alembo, Desta A. 68 Achan, Jane 1337, 1615, 653, Adrien, Paul 1664 Ajayi, Ikeoluwapo O. 75, 1498 Alemu, Abebe 206 1399, 888, 889 Adriko, Moses 1824 Ajayi, Olapeju O. 892 Alera, Maria T. 739 Acheampong, Princess R. 803 Adu-Gyasi, Dennis 240 Ajendra, Jesuthas 1241, 1880 Alexander, Neal 1254, 1363, 738 Acheampong, Salomey 1682, 404 Adu-Sarkodie, Yaw 400 Ajibaye, Olusola 1568, 1586, 929 Alexander, Neal D. 684 Achee, Nicole L. 1368, 1403, Aebig, Joan 1649, 985 Akabanda, Fortune 130 Alexandre, Jean Semé Fils 897 1811, 96, 104, 729 Ae-Ngibise, Kenneth 1305 Akabas, Myles H. 258 Alfonso-Parra, Catalina 1414 Acholonu, Alex D. W. 1794 Affara, Dr Muna 888 Akadiri, Inoussa 241 Alger, Jackeline 909 Akala, Hosea 211, 347 Alhassan, Andy K. 1080 astmh.org A-592 Abstract Author Index The number(s) following author name refers to the abstract number.

Alhousseini, Mohamed L. 820 Ambayo, Denis 1658 Andrews, Colin R. 1797 Arca, Bruno 342 Ali, Abdullah S. 112, 1216, 1235, Amber, Dismer 1059 Andrews, Howard 1032 Arencibia, Amely 181 305, 268, 600, 657 Ambler, Gwen 1127 Andrews, Jason R. 1198, 1273, Arens, Theo 983 Ali, Ali 1049 Ambrose, Kelley 681 1821, 1200 Arévalo, Andrea 1571 Ali, Asad 1772 Ambroziak, John 83 Andrews, Ross 26, 541 Arévalo, Myriam 1571 Ali, Doreen 307, 358 Ambuel, Yuping 168 Andrianandrasana, Gilbert 241 Arévalo Cortés, Andrea 52, 649 Ali, Mohamed 268, 600 Amegbo, Komi I. 508 Andriandrasana, Gilbert 1188 Arévalo-Herrera, Myriam 1577, Ali, Shahnawaj 576 Amenga-Etego, Seeba 842, 997 Andújar-Pérez, Doris 1422 1584, 1632, 314, 320, 1569 Ali, Syed A. 1008 Amer, Said 1140 Anema, Aranka 1457 Arguin, Paul 808 Alifrangis, Michael 1489, 1500, Amin, Magdy A. 1133 Angarita-Jaimes, Natalia 1807, 724 Arias, Luzlexis 175, 756 319, 805 Amin, Nuhu 580 Angeles, Jose Ma. M. 531, 532 Arichábala Wilches, Anita L. 1052, Alilio, Martin 681 Amoa-Bosompem, Mildred 482 Angelo, Michael A. 761 1731, 500 Aliota, Matthew T. 743 Amoako, Nicholas 194, 240 Angov, Evelina 1278, 15, 1641, 19, Ariey, Frédéric 12 Aljayyoussi, Ghaith 1076 Amoako, Sabastina 240 372, 938 Arifeen, Shams E. 582 Al-Kamel, Mohamed A. N. 427 Amoako-Sakyi, Daniel 928 Angulo, Noelia 1038, 1751, 1795 Arik, Anam 638 Allen, Elizabeth 464 Amoo, George 1558, 833, 843, Angulo Surca, Noelia P. 1095 Arikpo, Iwara 837 Allen, Henrietta 912 900, 910 Angus, Brian J. 1201 Arinaitwe, Emmanuel 1261, 1486, Allen, James 1386 Amorim, Francianne M. 432 Aniebo, Ifeyinwa 1503, 325 1614, 283, 809, 811 Allen, Judith E. 1240 Amornpaisarnloet, Kittisak 56 Aniedobe, Maureen 1568 Arinaitwe, Moses 1824 Allen, Koya C. 1736 Ampofo, William 482 Aniemena, Chidozie 1683 Arinola, Ganiyu O. 1603 Allers, Claudia 963 Ampuero, Julia S. 1110, 1131, Anishchenko, Michael 1448 Arlian, Larry G. 98 Allman, Erik 1469 131, 439, 775, 785, 786, 792 Ankrah, Love 240 Armistead, Jennifer S. 1296, 1630, Allman, Windy 338 Amratia, Punam 238 Annan, Augustina 400 631 Allo, Elvis 1822 Amuzu, Hilaria E. 173 The Anopheles gambiae 1000 Armstrong, Janice 1041 Al-mafazy, Abdul-wahid 268, 305, Anantharaman, Vivek 1295 Genomes Consortium 1828, Armstrong, Margaret 647 600, 1216 Anash, Evelyn 1337 1389 Arndt, Michael 1141 Almeida, Mariana J. 1488 Anathan, Julie 682 Anova, Lalaine 1558, 833, 843, Arnold, Benjamin F. 579 Almeida, Rodrigo 1161 Anato, Simplice 31 891, 900, 910 Aroian, Raffi V. 473 Alonso, Pedro L. 1570, 1633, 938 Ancel Meyers, Lauren 160 Ansah, Deidra 507 Arora, Avish 258 Alonso, Sergi 1098 Andagalu, Ben 208, 211, 347, Anselmo, Rui 618 Arowolo, Tolu 994 Alonso-Harper, Nico 1660 850, 207 Anshebo, Gedeon Yohannes 1372 Arrasco, Juan 659 Alout, Haoues 880 Andargie, Zebene 70 Anstey, Nicholas M. 1902, 282, Arriens, Sandra 644 Alpers, Michael 770 Anders, Robin F. 937 355, 627, 1560, 865 Arrizabalaga, Gustavo 1150, 1293 Alphonse, Rukundo 315 Andersen, Gregers R. 1176 Ansumana, Rashid 1182 Arrospide, Nancy 565 Altieri, Lisa 79 Anderson, Charles 1635, 1648, Antão, Tiago 1384 Arruda, Sérgio 1083 Altmann, Sharon E. 1183 1649, 878, 939, 985, 991 Anthony, Penelope S. 1692 Arsanok, Montri 10, 15 Alum, Masud 1136 Anderson, Corey D. 1405 Antillon, Marina 1671 Artemisinin Collaboration (TRAC), Alusala, Dorcas 464 Anderson, Gorm 983 Antonio, Martin 1018, 1676, 411 On behalf of the Tracking Alvarado, Fernanda L. 1599 Anderson, Jennifer M. 1260, 127, Antwi, Gifty 803 Resistance to 11 Alvarado, Luisa I. 135, 1422 220 Antwi, Gifty D. 1691 Artemov, Gleb 1385 Alvarez, Carlos 775 Anderson, John D. 1792 Antwi, Maxwell 1682 Arterburn, Jeffrey B. 758 Alvarez, Gonzalo 1463 Anderson, John W. 262 Anusiem, Angela C. 1120 Arya, Ravi 734 Alvarez, Maria G. 1851 Anderson, Kathryn G. 1882 Anusiem, Chikere A. 1120 Arze, Cesar 1640, 1829 Alvarez-Antonio, Carlos 1131, Anderson, Margot 682 Anyanti, Jennifer 837 Asamene, Negga 1438 439, 786 Anderson, Olivia 1557 Anyanwu, Greg I. 1392 Asante, Kwaku P. 240, 1305 Alves, Dimes H. P. 1148 Anderson, Roy M. 461, 464, 53, Anyona, Samuel B. 1591 Aseffa, Abraham 1045, 70 Amadi, Agwu N. 1169, 354 54, 540 Anyorigiya, Thomas 216 Asghar, Muhammad 905 Amadi, Chinasa O. 1169 Anderson, Scott 371 Apaer, Shadike 1026, 1027, 574 Ashbaugh, Hayley 1684 Amado-Garavito, Andrés B. 1632 Anderson, Timothy J. C. 1158, Apenteng, Mark A. 404 Ashley, Elizabeth 11, 1829, 943 Amadou, Bio A. 1685 1589, 1781, 1782, 1826, 583, Apiwattanakul, Nopporn 162 Ashman, Jill 1850 Amalvict, Rémy 1532 669, 671, 1780 Aponte, John 1570, 854 Ashmony, Hossam 1453 Amambua-Ngwa, Alfred 1586, Andolina, Chiara 289 Appawu, Maxwel 130 Ashorn, Per 1006 213, 529 Andonova, Maya 740 Apperson, Charles 1311, 1394, Asiedu, Kingsley 82 Amarasinghe, Ananda 767 Andrade, Christy A. 758 543, 708 Asito, Stephen A. 331 Amaratunga, Chanaki 127, 1829, Andrade, Daniela V. 523 Appiah, Alfred A. 404 Assadou, Mahamadoun H. 1279, 220, 940 Andrade, Heitor F. Andrade. Junior. Appiah-Opong, Regina 402 1576, 990 Amato, Roberto 317 1145, 964 Arana, Byron 1094 Assefa, Ashenafi 1045, 14, 566 Amatya, Bibush 1198 Andrade, Luiza F. 1776 Arang, Nadia 1608 Assefa, Liya 51 Amaya, Moushimi 141, 747 Andrade, Marcia C. R. 942 Arango, Eliana 976 Astete, Helvio 131, 726 Amaya, Ramón 1632 Andrade Junior, Heitor F. 1142 Araujo, Fernanda F. 513 Astudillo, Osvaldo G. 477 Amaya-Burns, Alba 1329 André, Claudine 666 Araujo, Irene T. 1013 Astupina, Sofia 1751 Amaya-Larios, Irma Y. 1432 Andreadis, Theodore 543 Araujo, Joselito 752 Aswa, Daniel 719, 884 Ambagahawita, Anuradha 767 Andrew, Dean 16 Aravind, L. 1295 Asweto, Collins O. 87 astmh.org Abstract Author Index A-593

The number(s) following author name refers to the abstract number.

Atabe, Andrew 1514 Ayenew, Asmamaw 1546, 1628, Bah, Amat 625 Bangoura, NFaly 889 Ataide, Ricardo 11, 603 1629 Bah, Ibrahima 1901 Bangs, Derek J. 552, 761 Atcheson, Erwan 607 Ayi, Irene 431 Bah, Mamadou M. 625 Banic, Dalma M. 321 Ateba Ngoa, Ulysse 1651 Ayimele, Godfred A. 1072 Bah, Mohamed S. 1930 Banik, Soma S. R.. 38 Athmani, Mwaka 1049 Ayisi-Boateng, Nana K. 639 Bahlo, Melanie 317, 568 Bannister-Tyrrell, Melanie 1615, Athreya, Harihan 463 Ayode, Desta 495 Bahora, Yasmin 682 653 Atia, Ehab 1129 Ayodo, George 326 Bahrambegi, Ramine 1188, 241 Bansal, Geetha 361, 365 Atibu, Joseph L. 186 Ayoub, Ehab A. 1133, 1762 Bai, Xilian 1325 Bansil, Pooja 1628, 280 Atieli, Harrysone 1391, 896 Ayvar, Viterbo 1034, 475, 572 Baiden, Frank 842, 997 Bantuchai, Sirasate 199 Atkinson, Louise E. 607 Azam, Syed Iqbal 1772 Baiden, Rita 1049 Baptista, Barbara O. 321 Atkinson, Peter M. 662 Aziz, Ammar 355 Bailey, Jason A. 1602, 1606, 1646, Baragaña, Beatriz 815 Atsame, Julienne 1929 Aziz, Fatima 1772 943, 978, 1829 Baraka, Vito 1801, 212 Attaher, Oumar 1601 Aziz, Mustafa A. 1180 Bailey, Jeffrey A. 585, 916, 915, Baral, Stefan 31 Atting, Inyang A. 129 Azman, Andrew 139, 1666 543 Barasa, Sheila O. 1893 Atto, Ruth 1034 Azman, Andrew A. 1859 Bailey, Robin 1319 Barbachano-Guerro, Arturo 1423 Attupina Figueroa, Elisabeth S. Azman, Andrew S. 1460 Bailey, Trevor C. 147 Barban, Veronique 1857 1095 Azmi, Ishrat J. 27, 576 Bain, James 1006 Barber, Bridget E. 1902, 282, 355, Atwell, Jessica 1599 Azongo, Daniel 216 Baird, J. Kevin 617, 804, 864, 1904 1560 Atwine, Daniel 65 Azoulay, Laurent 1703 Bais, Swarna 1777, 1900 Barbosa, Lucio M. 1161 Auala, Joyce 563 Azumah, Bright K. 1322 Bakach, Iurii 389 Barbosa, Susana 925 Aubry, Maite 765 Azziz-Baumgartner, Eduardo 1839 Bakare, Omowumi 994 Barboza, Jose Luis 726 Auburn, Sarah 14, 355 Bakary, Maiga 928 Barbre, Kira A. 646 Audet, Carolyn M. 32 Baker, David A. 1879 Barbu, Corentin M. 95 Audi, Allan 1585 Baker, Julia M. 1772 Barcellos, Christovam 147 Auguste, Albert J. 1442 B Baker, Kelly 390 Bardaji, Azucena 1570 Auma, Ann 329, 332 Baker, Kevin 1774, 1775 Barfod, Lea 1176 Ba, El Hadj 1348 Auma, Mary 1050 Baker, Margaret 1231, 504 Baric, Ralph S. 1416, 1430, 550, Ba, Elhadji 270 Aung, Poe P. 1581 Baker, Mark 857 548 Ba, Elhadji Konco Ciré 272, 271, Avancena, Anton Lorenzo V. 1541 Baker, Stephen 392 Barillas-Mury, Carolina 636 1302 Avelar, Livia G. 1776 Bakker, Mirjam 679, 691 Barker, Christopher M. 1380, 1447 Ba, Fatou 353, 826 Avery, Vicky M. 1093, 1096 Bakker, Roel 1250, 55 Barker, Kevin R. 253 Ba, Mady 1501, 1626, 1652, 1903, Avila, Frank W. 1355 Balaich, Jared 993 Barnadas, Céline 568 242, 310, 311, 312, 353, 584, Aviles, Merita 262 Balakrishnan, N 7 Barnadas, Celine 831 826, 827, 975 Avilés, Paula A. 1478 Balam, Alasseini 966 Barnafo, Emma 991, 1648 Ba, Souleymane 1626, 975 Aviles, Ricardo 1663 Balassiano, Ilana 422 Barnard, Andrew 1899 Ba, Yamar 192 Avilés Monterrey, William 622 Balasubramanian, Sujata 10, 585, Barnes, Franz D. 1345 Baba, Ebenezer S. 229, 1498 Avramova, Larissa 1377 802 Barnes, Karen I. 851 Baba, Marycelin M. 665 Avril, Marion 626 Baldeviano, Gerald C. 1316, 1510, Barnes, Laura E. 1050 Babakhanyan, Anna 1597, 489 Avue, Restituto Mangue 1003, 1913, 1644 Barnes, Samantha 201, 49, 940 Babalola, Ayodele S. 287 1660, 1869 Baldwin, Amy 149 Barnes, Trevor 1, 1858, 38 Babatunde, Ahmed 345 Avula, Bharathi 1528, 1535 Baldwin, Susan L. 981 Barnett, Eric 103, 802, 585 Babayan, Simon A. 1240, 443 Awab, Ghulam R. 214 Balikagala, Betty 370, 374 Barney, Rebecca S. 274, 1538 Babcock, Gregory 551 Awaca, Naomi 456, 1716 Balilo, Marcel P. 1454, 1455, 791 Barnor, Jacob S. 482 Baber, Ibrahim 1208 Awaca Pitchouna, Naomi 1926 Ballard, Ron 1680 Barnwell, John W. 1212, 808, 895, Baber, Ibrahima 1279 Awandare, Gordon A. 194, 1322 Ballesteros, Cristina 1724, 668 1229, 1804, 226 Babiaka, Smith B. 1072 Awandu, Shehu S. 264 Ballou, W. Ripley 1277, 180, 182, Baro, Nicholas 584, 931, 875 Babo, Teobaldo 1003, 1660, 1869 Awano, Tesema 229 1462, 1276, 1278 Barratt, Michael 1006 Babtista, Rodrigo 1316 Awe, Aderonke O. 1637, 1638 Balmaseda, Angel 133, 136, 592, Barrera, Patricia 1458 Babu, Subash 1842 Aweeka, Francesca 812 761 Barreto, Ismael S. D. C. 831 Bacellar, Olívia 1848 Awine, Timothy 216 Balogun, Emmanuel O. 929 Barreto dos Santos, Flavia 752 Bachman, Victoria 1791 Awodele, Olufunsho 1492 Baloji, Sylvain 1103, 1743 Barrett, Alan D. T. 1441, 1855 Bachmann, Martin 986 Awolola, Bridget 994 Bamadio, Amadou 820 Barrett, Lynn K. 1292, 861, 281 Badanicova, Kristina 1733 Awolola, Samson T. 1392, 1654, Banahene, Alfred 698 Barrie, Umaru 1086 Badara Gueye, Alioune 1652 994, 1568, 1586 Banania, Jo Glenna 1275, 1634, Barriga, Eduardo Simon 1803 Badejo, Joseph A. 1498 Awor, Phyllis 1189 352 Barrios, Diana 938 Badgandi, Hemant 638 Awori, Patricia 1210 Banda, Cesar 393 Barro, Ahmed 776 Badiane, Aïda Sadikh 1610 Ayandipo, Esther O. 345 Banda, Clifford G. 847, 851 Barros, Lucas F. 1148 Badolo, Ousman 1655, 969 Aydin-Schmidt, Berit 657 Bandoh, Betty 1176 Barros, Ximena 1314 Ba Fall, Kadidiatou 824 Aye, Kyin H. 1581 Bandyopadhyay, Nabamita 920 Barry, Alyssa 317, 568 Bagagnan, Cheik 84 Aye, Ni Ni 1813 Banegas, Engels 1542 Barry, Amadou 1624 Bagiella, Emilia 1032 Ayebazibwe, Nicholas 1926 Banerjee, Antara 520 Barry, Amanda 1229, 458 Baguma, Emmanuella 1572 Ayede, Adejumoke 810 Bangert, Mathieu 744 Barry, Meagan A. 1747 Baguma, Lucia 1572 Ayele, Workenesh 1438 Bangirana, Paul 195 Bartelt, Luther 1290, 1674 astmh.org A-594 Abstract Author Index The number(s) following author name refers to the abstract number.

Bartholomeu, Daniella 1316 Becker, Stephan 1462, 180 Benton, Briana 1451 Bibby, Jaclyn 1718 Bartow McKenney, Casey 1754 Becker, Tim 1708 Berbudi, Afiat 1241, 1880 Bickersmith, Sara A. 102, 125 Bart-Plange, Constance 1561 Becker-Dreps, Sylvia 396 Berens-Riha, Nicole 1707 Bickham-Wright, Utibe 1779 Barud, Hernane 1092 Beckmann, Anna Marie 1850 Berger, Amanda 397 Bidaisee, Satesh 1054 Barzilay, Ezra 1059 Bedford, Trevor 371 Bergmann-Leitner, Elke S. 1641, Bidii, Ngalah 208 Basáñez, María-Gloria 1721, 1818, Beebe, Elyse 981 946, 1278, 372 Biedenkopf, Nadine 180 1823, 460, 537 Beeching, Nicholas 1178 Bergo, Eduardo S. 1435 Biéler, Sylvain 1103, 1249, 1742, Basaye, Seife 614 Beeson, James G. 16, 1614, 603, Bergren, Nicholas A. 1442 1743 Bashaye, Seife 269 831, 937, 11, 333 Berjohn, Catherine M. 887 Bienevente, Ernest D. 325 Basilico, Nicoletta 1530 Begum, Farzana 582 Berkowitz, Jillian 581, 867 Biey, Joseph 1443, 619 Basnyat, Buddha 423 Behene, Eric 1023, 1677 Bermúdez, J. Rafael 1793 Bigogo, Godfrey M. 1108, 1585 Basra, Arti 854 Behi, Fodjo K. 115 Bern, Caryn 1085, 1751, 1752, Bikorimana, Jean Paul 73 Basri, Herdiana H. 656, 865 Behme, Matthew 69 1911, 29 Bilgo, Etienne 1281 Bass, Jennifer 791 Behura, Susanta K. 1193 Bernabeu, Maria 626 Billig, Erica M. 1755 Bass, Judith K. 34 Bei, Amy K. 931 Bernal, Edson 1038 Billingsley, Peter F. 1633, 1637, Bassat, Quique 1269, 618 Beijnen, Jos H. 1090 Bernal-Rubio, Dabeiba 1257, 1258 1639, 561, 989, 1636, 938 Basta, Nicole 1323, 1325 Beiting, Daniel 521 Berne, Laura 224 Billman, Zachary P. 980 Bastien, Jessica 1527 Beiting, Daniel P. 1846 Bernson, Jeff 1544, 1629, 974 Binagwaho, Agnes 1340, 1379, Bastien, Patrick 1316 Bejar, Vilma 409 Berriman, Matthew 1835, 926 1578, 1868, 315 Batalaho, Jaco 249 Bekele, Abyot 1438 Berry, Alexander S. 711 Bing, Xiaoli 101 Batchelor, Joseph D. 557 Belais, Raphael 666 Berry, Andrea 943, 978 Bingham, Andrea 725 Batcho, Wilfrid 1685, 527 Belay, Haileeyesus Adamu 1140 Berry, Neil 1718 Bingham, Karen 946 Batengana, Bernard 718 Belay, Kassahum A. 947 Bertinaria, Massimo 1529 Binka, Fred 1049, 1701 Bates, Imelda 1691 Belay, Kassahun 1875 Bery, Renuka 498 Binkert, Christopher 1488 Bath, David 1523 Belemvire, Allison 1622, 720 Besançon, Marjorie 1240 Birame Diouf, Mame 1652 Bathily, Abdrahamane 902 Belenchia, Matthew 64 Besansky, Nora J. 1195, 1384 Birbeck, Gretchen L. 1051 Batista, Izabella C. A. 755 Bell, Aaron 643 Beshir, Khalid 834 Bird, Tom 612 Batsa, Linda 639 Bell, Cynthia 1729 Beshir, Khalid B. 821 Birger, Maxwell 277, 674 Batsa-Debrah, Linda 1708, 1709 Bell, David R. 1804 Bessell, Paul R. 1103, 1249, 1742, Biritwum, Nana-Kwadwo 458 Batt, Carl 372 Bell, Martin 967 1743 Birkett, Ashley J. 1276, 1277 Battle, Katherine E. 296, 913 Bella, Assumpta Lucienne 1689 Bessong, Pascal O. 784, 1004 Birkholtz, Lyn-Marie 264 Batty, Kevin T. 215 Belmonte, Arnel 1275, 1634, 352 Betancourt, Bryan 1155 Birrell, Geoffrey W. 262 Batzell, Kimberly 1536 Belmonte, Maria 1275, 1634, 352 Bethony, Jeffrey 471, 606 Birren, Bruce W. 371 Batzloff, Michael 60 Belofsky, Gil 478 Bett, Andrew J. 1222, 760 Biryukov, Sergei 19 Bau, Haim H. 1778 Beltrán, Cristian 1632 Bettis, Alison A. 53 Bisanzio, Donal 304 Bauer, Cici 573 Beltran, Davis A. 1410, 1461 Betuela, Inoni 1262, 317, 830 Biselli-Périco, Joice Matos M. 755 Bauleni, Andrew 841, 914, 307, Beltran-Alzate, Juan C. 1726 Bever, Caitlin A. 1548, 1551, 1760, Bishop, Danett K. 1021 599 Beltrán-Ayala, Efraín 1052, 1423, 957, 958 Bishop, Henry 808 Baurin, Nicolas 1437 1731, 500 Bever, Caitlin A 613 Bishop, Richard 1294 Baus, Esteban G. 1761, 509 Belvins, Meridith 32 Beverley, Stephen M. 1316 Biswas, Biswajit 1016, 1024, 57 Bausch, Daniel G. 1268, 132, Benavente, Luis 1002 Beyenbach, Klaus W. 715 Biswas, Shwapon 27, 576 1764, 183, 406, 661, 705, 792 Benavides, Victor 1034 Beyene, Belay 974, 1515 Biswas, Sumi 560, 982, 986, 987 Bausell, Loren 359 Benavides, Yoldy 314 Beyene, Berhane 1438 Bittar, Fadi 467 Bautista-Cerón, Arely 405 Benca, Juraj 1733, 493 Bezabih, Belay 1546, 1628 Bjorge, Steven 1904 Bax, Magdalena 1332 Bendezu, Jorge 828, 829 Bhalla, Nishank 138 Bjorkman, Anders 657 Bayih, Abebe Genetu 235, 206 Bendezu-Medina, Sandy 1766 Bhandari, Kalpana 1231, 504 Black, Robert E. 1864 Bayot, Bonny 1793 Benecky, Micheal 280 Bhat, Geeta 843, 891, 910 Black, IV, William C. 1196, 762 Bazan, Isabel 439, 1131 Benitez Ortiz, Washington 51 Bhatia, Sangeeta M. 1638 Blackmore, Mark S. 1405 Bazie, Thomas 224 Benjamin, John 215 Bhatnagar, Julu 37 Blacksell, Stuart D. 542 Bazone, Lindsey 176 Benjamin, Nygren L. 1203 Bhatnagar, Suyash 1205 Blackwell, Jerry 367 Bazzone, Lindsey 763 Benjamins, Laura 1729 Bhatt, Samir 296, 304 Blagborough, Andrew 1642 Beach, Ray 1369, 1379 Benkeser, David C. 371 Bhattacharjee, Souvik 1172 Blanas, Demetri A. 1725 Beach, Raymond 720 Ben Mamoun, Choukri 545 Bhattacharya, Antoinette 1301, Blanco, Pedro 1053, 1401, 143 Beane, Jennifer 1852 Bennett, Adam 1218, 1550, 1552, 823 Blanton, Laura V. 1006, 399 Beaso, Delma 1719 1579, 278, 305, 655 Bhattarai, Achuyt 305 Blanton, Ronald 1161, 1896 Beati, Lorenza 93 Bennett, Ashley 1544 Bhavnani, Darlene 1542, 876 Blasco, Teresa 510 Beati Ziegler, Lorenza 543 Bennett, Jason W. 1276, 1278 Bhengsri, Saithip 416 Blau, Dianna M. 37 Beattie, Lynette 512 Bennett, Shannon N. 766, 770 Bhoomiboonchoo, Piraya 184 Blay, Emmanuel A. 431 Beau De Rochars, Madsen 155 Bennuru, Sasisekhar 640, 643, 670 Bhuiyan, Taufiqur R. 397, 1862 Blazes, David 1704, 58, 132 Beau de Rochars, Valery Madsen Benoit, Joshua B. 637 Bhutta, Zulfiqar A. 618 Blazes, Elizabeth 1704 1059, 1229 Benoit, Nicolas 824 Bhuyian, Sazzadul I. 27, 576 Blok, David J. 1022, 1679 Beaumier, Coreen M. 461, 463 Bensch, Staffan 905 Bianco-Jr, Cesare 942 Blömker, Dominique 1241 Becker, Kira 1678 Ben-Shachar, Rotem 159 Bianco-Junior, Cesare 321 Boakye, Daniel A. 1322, 1715, 511 astmh.org Abstract Author Index A-595

The number(s) following author name refers to the abstract number.

Boamah, Daniel 404 Borum, Marie 471 Brazil, Reginaldo 100 Bruxvoort, Katia 1522 Boamah, Ellen 1305 Bosco-Lauth, Angela M. 793 Breiman, Robert F. 1203, 297, 417 Bryan, Christopher 1 Boatin, Boakye 1721 Bosire, Rodney 1769 Brelsford, Jill 471, 606 Bryan, Patricia 1289, 463 Bobanga, Thierry L. 1573, 290, Botchway, F 204 Brennan, Beth A. 309, 1622 Bryant, Juliet E. 660 344 Botchway, Felix A. 318 Brenya, Ruth C. 351 Bryson, Lindsay 1514 Bobbili, Naveen 245, 335, 932, Botta’, Giordano 1389 Brett-Major, David 1268 Buatiche, Jesus Nazareth 1662 933 Bottazzi, Maria Elena 1747, 463, Brevezosek, A 1659 Bucheton, Bruno 1317 Bobogare, Albino 750 1289 Brewster, Jessica 1262 Buchwald, Andrea G. 599 Boccia, Delia 1763 Bottomley, Christian 283 Brian, Iona 986, 987 Buchy, Philippe 1452, 590 Bock, Ronnie 236, 299 Bouckenooghe, Alain 774 Briand, Valérie 854 Buck, Amy H. 443 Bockarie, Moses 1927, 727, 1045 Boudet, Florence 553 Brichard, Julie 1509, 741 Buckee, Caroline 616, 951, 1395, Boddey, Justin A. 1296, 631, 946 Boudko, Dmitri Y. 1350 Brickley, Elizabeth B. 1264 931 Bodeau-Livinec, Florence 428 Boudova, Sarah 1265, 1602, 1646, Bridges, Daniel J. 1567, 867 Buckeridge, David L. 685 Boehm, Alexandria 25 927 Bridgford, Jess 1873 Buckley, Renata 1209 Boel, Machteld 333 Bougma, Windtaré R. 1227 Brieger, William R. 1181, 1655, Buckner, Frederick S. 1314 Boelaert, Marleen 1250, 1740 Bougouma, Edith C. 853 1656, 1657, 315, 969 Budge, Philip J. 1843, 1886 Boele- Van Hensbroek, Michael 51 Boukary, Rahamatou 1019 Brienen, Eric 51 Budke, Christine M. 1025 Boeykens, Peter 1720 Boulos, Marcos 1487 Brienen, Eric A. T. 468 Buehler, Charlotte 32 Bogan, Joseph A. 1183 Boum II, Yap 1575, 292 Briët, Olivier 1566, 614, 1239 Buekens, Pierre 1247 Bogard, Sherri 1738 Bouraima, Aziz 1239 Briggs, Melissa 307 Buerfent, Benedikt C. 1241 Boggild, Andrea K. 1910 Bousema, Teun 1208, 1215, 1574, Briggs, Neima 463 Bufano, Meagan K. 397 Bogoch, Isaac I. 1198, 1273, 1821 1598, 298, 559, 564, 588, 880, Brindley, Paul J. 1835 Buff, Ann M. 297, 683, 960 Bogus, Joshua 1226 982 Brinkerhoff, Jory 543 Buffet, Pierre A. 1470 Bohissou, Francis 889 Boussaroque, Agathe 824 Brissette, Catherine A. 701 Buitrago, Sonia M. 1726 Boivin, Michael J. 34, 428 Boussinesq, Michel 1079, 1715, Brito, Luana P. S. 1252 Bujard, Hermann 337 Bojang, Ebrima 1319 1716, 1717, 1721, 1815, 1818, Brito, Maria das Graças 1745 Bukrinsky, Michael I. 1835 Bojang, Kalifa 363, 889 459 Brito, Miguel 1067, 1796 Bulimo, Wallace 208 Boko, Pélagie 527 Bouyer, Donald H. 61 Brnova, Jaroslava 1733 Bun, Rathvicheth 15, 323 Bolay, Fatorma K. 1226, 737 Bowen, Richard A. 793 Brockley, Sarah 1648, 375, 985, Bunditvorapoom, Duangkamon Bolick, David 1290, 1674 Bowers, Levi J. 399 991 1481 Bolling, Bethany G. 1442 Bowie, Aleah C. 666 Brockschmidt, Felix 1708 Bunn, Patrick 518 Bollweg, Brigid 793 Bowman, Natalie M. 103, 1085, 29 Brockstedt, Dirk G. 1647 Buonomo, Erica L. 1291 Bolton, Birgit 1321 Bowyer, Georgina 1277, 1462, Brod, Florian 986 Burchell, Ann 1735 Bompangue, Didier 1666 180, 182 Broeckel, Rebecca 41 Burga, Rosa 1670, 1797, 393, 394 Bompard, Anaïs 560, 982 Boyce, Ross 231 Brogdon, William G. 1658 Burgess, Deborah 1838 Bona, Mariana D. 1668 Boyer, Sébastien 116, 1239, 1369 Bronzan, Rachel N. 1928, 506, 508 Burgess, Stacey L. 1136, 1291 Bonaparte, Matthew 1223, 553 Boyle, Charlie R. 1097 Bronzoni, Roberta V. de Morais. Burgess, Timothy 1048, 648 Bonawitz, Rachael E. 623 Boyle, Michelle J. 17, 329 1435 Burgio, Gaetan 1873 Boncy, Jacques 155 Boyom, Fabrice F. 402 Brooke, Basil 712 Buriticá, Lucía 1632 Bone, Mary A. 1430 Bozdech, Zbynek 1873 Brooker, Simon J. 1045, 227, 461, Burke, Rachel M. 440 Boni, Maciej F. 1217, 1508, 617, Braack, Leo 300 464, 51, 54 Burke, Robin L. 45 250 Bracken, Tara C. 43 Brooks, Benjamin 1337 Burkett-Cadena, Nathan D. 725 Bonini-Domingos, Claudia R. 324 Brackney, Doug E. 1446, 1852 Brooks, Krista 62, 794 Burkhard, Peter 376 Bonizzoni, Mariangela 1382, 1383 Bradley, Catherine 699 Brooks, Krista M. Burkman, Erica 1724, 668, 1714 Bonkoungou, Moumouni 969 Bradley, John 1869, 601 Brooks, Tim 1178 Burkot, Thomas R. 846 Bonne-Annee, Sandra 1244, 608 Bradley, Mark H. 1338 Brooks, W. Abdullah 1839 Burnett, Eleanor M. 1664 Bonnet, Emmanuel 776 Brady, Adam 1426 Brousse, Paul 308 Burns, Matthew 867 Bonney, Joseph H. K. 482 Brady, Molly 456 Broutin, Hélène 1323 Burr, Sarah 1319 Bontje, Daniel M. 1250 Brady, Oliver J. 437, 595 Brown, Andrea 384 Burri, Christian 1327 Bonu-Ire, Martin 130 Braga, Cynthia 150 Brown, Arthur E. 45 Burrows, Jeremy 852 Boodoo, Richard 262 Brai, Bartholomew 1568 Brown, Evan 76 Burton, Robert 1333, 1520, 1538, Boonyuen, Usa 355 Brandão Filho, Sinval P. 1252 Brown, Hannah 1182 1543, 1734, 235 Boothe, Emily 1888 Brandful, James 482 Brown, Heidi E. 704 Burton, Robert A. 274 Bopp, Selina 1469, 1488, 48 Brando, Clara 1360 Brown, Joelle 1208 Burton, Timothy 127, 369, 950, Borbor-Cordova, Mercy J. 1423, Brannock, Tracy A. 62 Brownell, Jessica 1608 1285 1793 Brashear, Awtum 1490 Brownstein, John S. 1457 Busatti, Haendel 1137 Borchert, Matthias 1182 Brasil, Patricia 1428 Bruce, Jane 842 Büscher, Philippe 878 Borges, Iara A. 1114 Bratcher, Jade 794 Brugnara, Carlo 1299 Bush, Ruth L. 1692, 688 Borges, Valéria M. 1092 Brault, Aaron C. 1448, 1853, Bruls, Myriam 371 Bushdid, Paul 260 Borrego, Andrea B. 964 1856, 793 Brunette, Gary W. 1439, 437 Bustos, Javier 1036, 1037, 572 Borrini Mayori, Katty 103, 1754, Bravo Nevarro, Roxana 29 Brunetti, Enrico 1696, 575 Bustos, Javier A. 571 1756 Brazeau, Nicholas F. 882 Brunk, Brian P. 922 Butler, Brandi 1635, 941 Borrow, Ray 1019, 1325 Brazier, Andrew J. 626 Brust, Tarsis 1377 Butler, Noah S. 558 astmh.org A-596 Abstract Author Index The number(s) following author name refers to the abstract number.

Butts, Jessica K. 1901, 885 Campbell, Lindsay P. 732 Carrasco, Adela J. 1160 Cauchemez, Simon 139, 36, 773 Buxton, Samuel 609 Campbell, Stewart 362 Carrasco, Alison 161 Caugant, Dominique 1324 Buza, Joram 1801 Campbell, Suzy 26 Carrasco-Escobar, Gabriel 303, 567 Caughlin, Trevor T. 612 Bwalya, Benson 681 Campbell, Timothy C. 689 Carrera, Jean Paul 1421, 744, Caulfield, Laura E. 1864 Bwanika, John Baptist 1507, 839 Campino, Susana 1829 1461 Cavalcanti, Marta G. 539 Byers, Antony 553 Campino, Suzana 325 Carrilho, Carla 1269, 618 Cavalcanti, Milena P. 1252 Bygbjerg, Ib C. 1489, 1694 Campo, Brice 733 Carrion, Gladys R. 785 Cavanagh, David R. 1176 Campo, Joseph 559, 938 Carroll, Darin 1454, 1455, 791 Ceesay, Serign J. 1582, 889 Campos, Kalina 424 Carroll, Lauren 685 Ceesay, Sukai 213 Campos, Lucia M. M.. 1221 Carter, Dariyen 1635, 1648, 878, Cejas, Rosa G. 477 C Campos, Maribel 1219 941, 991 Celes, Fabiana S. 1092 Campos, Sergio R. S. L. 1413 Carter, Darrick 1649 Celestino, Daniela 521 Cabada, Miguel M. 472 Campos, Tais 517 Carter, Gary 1183 Celhay, Olivier 963, 999 Caballero, Alexi 738 Campos Ponce, Maiza 610 Carter, Jennifer M. 1833 Cerami, Carla 625 Cabarca, Sindy 143 Canada-China Team, 1735 Carter, Jessica 1723 Cercone, Emily 1839 Cabello, Ines 1751, 1752 Canal, Enrique 406, 705 Carter, Joseph 1188, 241 Cerpas, Cristhiam 761 Cabezas, Cesar 565 Canales, Marco 1155, 479 Carvalho, Ana W. S. 1252 Cerqueira, Dominique 289 Cabrera, Ana 350, 429 Canavati, Sara E. 8, 872, 9 Carvalho, Augusto 1848 Cerqueira, Gustavo C. 583 Cabrera, Lilia 1450, 1795 Cancino, Marcela 1799 Carvalho, Edgar M. 1083, 1745, Cespedes, Manuel 786 Cabrera, Marta 477 Cangalaya, Carla 1035, 1037, 1848, 517, 519, 521, 1849 Cespedes, Nora 1632, 368 Cabrera, Mynthia 1490, 1491 1036 Carvalho, Francisco G. 1252 Cestari, Igor 1922 Cabrera, Ricardo M. 1160 Cano, Flora S. 340 Carvalho, Leonardo J. M. 1529, Cevallos, William 1306, 22 Cabrera-Mora, Monica 366, 367 Cano, Jorge 1045, 464 321, 942 Cha, Sung-Jae 1297 Caccone, Adalgisa 545 Cantera, Jason 476 Carvalho, Liege 1428 Chabadova, Maria 493 Cáceres Rey, Omar 1088 Cantey, Paul 56, 1926 Carvalho, Lucas P. 517, 521, 1848, Chabi, Joseph 351 Cademil, Abelard 1860 Canyon, Deon 766 519 Chacky, Frank 386, 1905 Cadet, Jean Ronald 897 Cao, Xiaohang 669 Carvalho, Luzia H. 340 Chadewa, Jasmine W. 680 Cai, Francisco 1395 Cao, Yi 365 Carvalho, Noemia B. 1101 Chaffa, Evelyne 67 Caicedo Burbano, Paola A. 1363, Cao-Lormeau, Van-Mai 765 Carvalho, Rita C. F. 1125 Chagas Disease Working Group in 1366 Capan, Meskure 854 Carvalho, Sonia P. 1819 Arequipa, Peru 1758 Cain, Natalie A. 94 Capitan, Zeuz 1345 Carvalho, Valéria L. 1465 Chaisathit, Chaiyaporn 323 Cairns, Matthew 803, 615 Capobianco, Marcela P. 324 Casandra, Debora 1493 Chaki, Prosper P. 598 Cairo, Cristiana 927 Capobiano, Marcella P. 340 Casapia, Martin 462, 857 Chakraborty, Poulomy 1792 Cairo, Hedley 308 Captain-Esoah, Millicent 130 Casimiro, Danilo R. 760 Chakravarty, Sumana 1014, 1204, Cajal, Pamela 1289 Caputo, Beniamino 1389, 635 Cassama, Eunice 1319 1596, 1635, 1638, 1639, 1647, Calcina, Juan 1036 Carabali, Mabel 1342, 1406, 1434, Cassera, Maria B. 256 377, 46, 938, 939, 941, 989 Calcutt, Ainslie 60 776 Cassiano, Gustavo C. 324, 340, Chalira, Alfred 307 Calderon Sanchez, Maritza 1095, Caraballo, Elba 1412 321 Chalker, John 1185 1751, 1752, 1795 Caraballo, Libardo 1053 Cassone, Bryan J. 1191 Chalon, Stephan 1207, 852, 857, Calderwood, Stephen B. 1202, Carabin, Hélène 573, 1039 Castañeda, Benjamin 1910 860 1861, 1862, 397, 392 Caramelo, Luiza C. 844 Castaneda-Casado, Pablo 260 Chalwe, Victor 1218, 278 Calla, Jaeson S. 1031, 1035 Caramico, Karina Almeida 988 Castellanos, Alejandro 1510, 1746, Chambers, Eric W. 1405 Callahan, Michael V. 1255 Caranci, Angela 104 1913 Champouillon, Nora 1804 Calvert, Amanda E. 793 Carapetis, Jonathan 419 Castellanos, Angélica 1571, 1632, Chamrouen, Sok 912 Calvo, Eric 636 Cardenas, Jenny C. 120 314, 1584 Chams, Linda M. 1170, 1171, Calzavara, Liviana 1735 Cárdenas, Washington B. 1423, Castellanos-Gonzales, Alejandro 1768 Calzavara-Silva, Carlos E. 1832, 687 1149, 1292, 395 Chan, Benedict Shing Bun 88 755 Cardenas-Garcia, Brianda 478 Castilho, Vera L. P. 1151 Chan, Chung-Hong 88 Cama, Vitaliano 1450, 1926, 1929, Cardona-Castro, Nora M. 1726 Castillo, Andreina 919 Chan, Jo-anne 11 1073 Cardosa, Jane 751 Castillo, Paola 1269, 618 Chan, Kuan Rong 165 Camacho Burgos, Erwin 1401, 143 Cardoso, Jedson F. 1465 Castillo, Roger 166 Chan, Ricky 202 Camara, Cheikhou 824 Cardoso, Maria R. A. 1413 Castillo, Ruth M. 1750 Chanarat, Nitima 10, 1132, 323 Camara, Mamadou 1317 Carias, Lenore L. 940 Castillo-Neyra, Ricardo 1116, Chandel, Kshitij 1374 Camara, Oumou 1317 Caridha, Diana 1525, 1531, 257 1756, 95, 99, 1754 Chandler, Clare 1523, 1699, 279, Camargo, Nelly 1826 Carland, Corinne 85 Castonguay-Vanier, Josee 423 357 Camargo, Rosina 1751, 1752 Carlier, Paul R. 256 Castro, Arnold 1680 Chandna, Arjun 1560, Camargo, Tarsila Mendes 988 Carlow, Clotilde K. S. 1080, 448 Castro, Enrique 1571 Chandramohan, Daniel 1494, Cameron, Ewan 296, 304 Carlson, Margaret 1010 Castro, Maria del Mar 1748 1498, 684, 803, 842 Campaore, Bertrand 776 Carlton, Jane M. 920 Castro-Llanos, Fanny 1357, 729 Chang, Aileen 570 Campbell, Corey L. 1196, 1852 Carmolli, Marya P. 1220, 1408, Casulli, Adriano 575 Chang, Howard H. 1897 Campbell, Danielle 1201 1411, 1700 Cataccora Rospigliossi, Andy 95 Chang, Hsiao-Han 584 Campbell, Doreen 471, 606 Carpi, Giovanna 545 Catteruccia, Flaminia 126, 1361, Chang, Michelle 1212, 1229, 876, Campbell, Karen M. 1436 Carpio, Arturo 1032 1387, 1390, 1395, 1890, 633 895, 897 astmh.org Abstract Author Index A-597

The number(s) following author name refers to the abstract number.

Chang, Michelle A. 1875, 947 Cheng, Qin 1874, 355, 845 Chomba, Lambwa 1788 Clapham, Hannah 1429, 1431, Chang, Ming 248 Cheng, Yao-Chieh 1719 Chongsuvivatwong, Virasakdi 1166 593, 170, 591 Chann, Soklyda 10, 1479, 15, Chern, Andy 62 Cho-Ngwa, Fidelis 1072 Clare, Rachel 1078 1502, 323, 862 Cheruiyot, Agnes 211 Chongwe, Gershom 1165 Clark, Daniel 1085, 29 Chansa, Geoffrey 1876 Cheruiyot, Agnes C. 850 Chonsawat, Putza 838 Clark, Heather 1670 Chanthavanich, Pornthep 779 Chery, Laura 1474, 626 Chookajorn, Thanat 1481, 1878 Clark, Jeffrey N. 1723 Chanthongthip, Anisone 423 Chesnais, Cédric B. 1716, 1815, Chopra, Ashok K. 1014 Clark, Leslie 1704 Chanudom, Ponsa 10 459 Chorazeczewski, Joanna 44 Clark, Taane G. 325, 918 Chao, Chien Chung 96 Chesnokov, Olga 261, 1526 Chotivanich, Kesinee 1172, 1481, Clark, Tamara D. 1210 Chaorattanakawee, Suwanna 323, Cheung, Chi-Ngai 88 1829, 1873 Clarke, Ed 363 802 Cheung, Grace 1895 Chotpitayasunondh, Tawee 178 Clarke, Siân E. 1184, 1800 Chaparro, Pablo 1577, 1584 Chevalier, Frédéric D. 1158, 1780, Choudhary, Shivani 609 Clarkson, Christopher S. 1286 Chaperouge, Alex 1137 1781, 1782, 669, 671 Choudhury, Feroza K. 1199 Clasen, Thomas F. 579 Chaponda, Mike 111, 1567, 1867, Chew, Glen 678 Chounna Ndongmo, Patrick N. Clavería, Isabel 510 1876, 903 Chiang, Yi-Hsuan 164 1717 Cleary, Thomas G. 1009 Chapotera-Kalanda, Gertrude 851 Chibsa, Sheleme 1372, 269 Chour, Char Meng 585 Cleaveland, Sarah 1105 Char, Chuor 1904 Chibwe, Kennedy M. 698 Chowdhury, Fahima 1861, 1862 Clementino, Marco A. F. 1012 Charbonneau, Mark 1006 Chibwe, Misho 30 Chretien, Jean-Paul 1736 Clements, Archie 26 Chareonviriyaphap, Theeraphap Chico, Martha 52, 649 Christian, David 1845 Clements, Michelle 1822, 536 289 Chico, R. Matthew 222 Christian, Elizabeth A. 549 Co, Katrina 1358 Charlebois, Edwin 1210 Chidlow, Glenys 770 Christiansen, Michael 981, 983 Coalson, Jenna E. 599, 654 Charles, Richelle C. 1202, 397, 392 Chiduo, Mercy 1558, 900 Christiansen, Mikkel 1386 Coberly, Jacqueline S. 689 Charlwood, Derek 1870 Chiduo, Sarah 1558, 833, 843, Christofferson, Rebecca C. 39, Coble, Katie A. 1692 Charman, Nikki 1347, 1619, 971 900, 910 1889 Coe, Megan 682 Chatterjee, Debasmita 398 Chieffi, Pedro Paulo 474 Christophel, Eva 1904 Coehlo, Giovanini 1419 Chatterjee, Soumya 1842 Chiegil, Robert 483 Christophides, George K. 1365, Coelho, Caio A. S. 147 Chaudhry, Suchita 927 Chifisi, Rhoda 682 870 Coelho, Camila H. 1137 Chauhan, L. S. 1459 Chigaru, Lario 33 Chu, Brian 1059, 1229, 458 Coelho, Giovanini E. 1415 Chauhan, Virander 938 Chigusa, Yuichi 531, 532 Chu, Haiyan 168 Coffeng, Luc E. 1250, 1715, 55, Chaumeau, Victor 289 Chikara, Surendra 1909 Chu, Virginia M. 102, 731 1721 Chaurasiya, Narayan D. 1535, 970, Chikawe, Maria 1062, 1065, 1687, Chu, Winnie 1693, 442, 687 Coffey, Lark L. 741 1528 1722, 1816, 1817, 505 Chuang, Ilin 814 Coffin, Jeanette M. 1183 Chavchich, Marina 1874, 262 Chikezie, Ifeanyi 483 Chuansumrit, Ampaiwan 162 Cohan, Deborah 1210 Chaverra-Rodriguez, Duverney Childs, Lauren M. 1395, 616 Chukwekezie, Okechukwu 1392 Cohee, Lauren M. 599, 654 1364 Chile, Nancy 1038 Chukwuocha, Adanna N. 1169, Cohen, Jessica L. 1519 Chaves, Bárbara A. 755 Chillag, Kata 1177, 80 354 Cohen, Joe 1276 Chawla, Bhavna 1153 Chimbiya, Nelson 599 Chukwuocha, Uchechukwu M. Cohen, Justin M. 1301, 1514, Chea, Sokha 1452 Chimuna, Tiyese 1127, 841 1169, 354 1542, 1554, 823, 863, 876, 866 Cheah, Phaik Yeong 1335 Ching, Wei Mei 96, 1678 Chung, Hyun J. 1202 Cohen, Justine M. 1536 Chebon, Lorna J. 208, 850, 211 Chinkhumba, Jobiba 307 Chuor, Char Meng 10, 15, 802 Cohn, Daniel 1231, 456 Checkley, Lisa 1293, 1826 Chinnasamy, Ramesh 758 Churcher, Thomas S. 1642, 1818, Cohnstaedt, Lee W. 1855 Cheeseman, Ian H. 1589, 1826, Chinnawirotpaisan, Piyawan 184 560, 880, 982 Cohuet, Anna 559, 560, 982 583 Chinnawirotpisan, Piyawan 739, Churgin, Matthew A. 1777 Cohuo-Rodriguez, Azael 117 Cheke, Robert 1721 783 Chusri, Sarunyou 1166, 1789 Colacicco-Mayhugh, Michelle G. Che-Mendoza, Azael 723 Chiodini, Peter 1178, 1804, 845 Chutasmit, Kitipumi 1829 1403 Chen, Angelica 1323 Chipeta, James 361 Cibulskis, Richard 1617, 230, 962 Colaco, Rajeev 268 Chen, Beth 991 Chipeta, Michael G. 285 Cicatelli, Susan B. 1276 Colanzi, Roni 1085, 29 Chen, Cheng 1680 Chiphwanya, John 1393 Cichewicz, Robert H. 1534 Colas, Romain A. 636 Chen, Edwin 1643, 557, 940 Chitale, Rohit A. 1736 Ciglenecki, Iza 1460 Coldiron, Matthew 1906 Chen, Hua-Wei 1678 Chitnis, Chetan 1553, 938 Cimino, Rubén 1089, 1289 Colebunders, Robert 1069 Chen, Ingrid 1208 Chitnis, Nakul 952 Cisney, Emily 1433 Colé Lô, Amy 1610 Chen, John J. 335, 932, 933 Chiu, Charles 187 Cissé, Assana 573 Coleman, Carie 331 Chen, Lin H. 646 Chiu, Wah 140 Cisse, Badara 1348, 1626, 1903, Coleman, Jane 388 Chen, Nanhua 1874 Chiu, Wei-Wei 415 270, 271, 1302, 272, 363, 975 Coleman, Marlize 502 Chen, Po-Chih 750 Cho, Alice 172 Cisse, Kadidia B. 1601 Coler, Rhea N. 1850 Chen, Shicheng 1362 Cho, Thein 1266 Cisse, Moussa B. 720 Colford, Jr., John M. 579 Chen, Tien-Huang 164 Chochua, Sopio 1770 Cisse, Moustapha 1626, 1652, Colgate, E. Ross 1700 Chen, Wei-June 164 Choi, Diane B. 1368 242, 310, 311, 353, 975 Colgate, Elizabeth R. 1411 Chen, Wenjun 1156 Choi, Jeong 1085, 29 Cissoko, Mody 1563 Colgate, Ross 1863 Chen, Xiaoguang 1381, 1382 Choi, Ryan 861 Cisteró, Pau 1553, 1553, 938 Collard, Alix 1219, 163 Chen, Zhenguo 1256 Choi, Young-Jun 1883 Cysticercosis Working Group in Collard, Jean-Marc 1019 Chenet, Stella M. 226, 565 Chokephaibulkit, Kulkanya 162, Peru 1031, 1036, 1035, 571, Collé Lô, Aminata 249 Cheng, Hua 1735 172 572 Coller, Beth-Ann G. 1222, 760 astmh.org A-598 Abstract Author Index The number(s) following author name refers to the abstract number.

Colley, Daniel G. 1243, 1785, 1833 Cornejo del Carpio, Juan G. 95 Crisanti, Andrea 1598 Dale, Martin 967, 971, 972 Colley, Gretchen 1851 Cornillot, Emmanuel 12 Criscione, Charles 664 D’Alessandro, Umberto 1018, 113, Collins, Frank H. 1386, 846 Corral, Marcelo A. 474 Cristina Guerra-Giraldez, Cristina 1215, 1582, 1676, 232, 303, Collins, Katharine 860 Correa, Edwin 1011, 1667 1035 371, 529, 804, 848, 871, 1399, Collins, Okoyo 464 Correa-Oliveira, Rodrigo 1832, 606 Croll, Roger P. 1783 888, 1213, 1615, 213, 653, 889 Coloma, Josefina 622, 764 Corredor-Medina, Claudia 1658 Crombe, Florence 113 D’Alessio, Flavia 363, 1201 Colpitts, Tonya M. 120, 1394, 746 Corstjens, Paul L. A.. M.. 1837 Crompton, Peter D. 1614, 1614, Dalgaard, Marlene 1500 Colwell, Rita 1007, 1790 Cortés, Sebastian 174 339, 902, 1609, 336, 934 Dalipanda, Tenneth 750 Comer, Eamon 1206, 1527 Cortez, Valerie 406 Crooks, Philippa 1788 Dalli, Jesmond P. 636 Comfort, Alison 681 Corti, Marcelo 1143 Crotty, Shane 552 Dalrymple, Ursula 304 Comoe, Esther 1822 Cortis, Giles 728 Crowley, Kathryn 1685, 1686, Dalton, John P. 1787 Compaore, Daniel Y. 818 Cosmas, Leonard 297, 788 1687, 1688, 503 Dama, Souleymane 820 Compaoré, Guillaume 1049 Cossio, Alexandra 1739, 1748 Crowley, Valerie M. 429 Damania, Ashish 1289 Conceicao, Luciana M. 340 Cossio-Duque, Alexandra 1750 Crowther, Gregory 281 Damas, Deogratias 1062, 1686, Conceição, Leia 1161 Costa, Adriana 1137 Crump, John A. 1105, 1326 1687, 1688, 1722, 505 Conceição, Luciana M. 324 Costa, Angela A. 1413 Cruz, Cristhopher D. 778, 1764 Damasceno, Leonardo 523 Concha Velasco, Fatima R. -. 1091 Costa, Germano 523 Cruz, Luis Afonso 1161 Damasceno, Luana S. 1428 Condo Jeanine, Jeanine 1340 Costa, Rubia 521 Cruz-Correa, Jesús 1422 Damayanti, Rita 1338 Condori, Beth J. 1038 Costa, Silvia F. 474 Cuellar, Adriana 1759 D’Ambrosio, Michael V. 1273 Condori, Carlos 99 Costa-Nascimento, Maria J. 844 Cuervo-Pardo, Lyda 1750 Damien, Barikissou B. 67 Condori, Cesar 1011 Cot, Michel 428, 854, 968 Cueto, Carmen 1550, 1579, 655 Damon, Inger K. 791, 1455 Condori Pino, Carlos 103, 1754 Cotrim, Denise 1428 Cueva, Cinthya K. 1423 Danforth, Mary E. 1447 Cong Khan, Nguyen 610 Cotte, Annett 885, 1369 Cui, Liwang 1383, 1490, 1491 Dang, Duc Anh 771 Conley, Jason M. 1377 Cotter, Chris 1552, 656, 865 Cullen, Karen A. 808 Dangour, Alan 823 Conn, Jan E. 102, 731, 125 Cottrell, Gilles 968 Cummings, Derek 139, 1429, Dani, Francesca 635 Connell, Nancy 1681 Coudeville, Laurent 1223, 1437 1431, 36, 1427, 170, 591, 593 Daniel-Ribeiro, Claudio T. 321, 942 Conner, Ruben 1546, 1626, 975 Coulibaly, Aboubacar S. 853 Cummings, James 814 Daniels, Rachel F. 1218, 584, 827, Connolly, Kristen M. 371 Coulibaly, Boubacar 337 Cummings, Richard D. 1785 931, 312, 875 Connor, Bradley A. 1005, 1272, Coulibaly, Drissa 1563, 1606, 835, Cunha, Aline F. Araujo. 539 Dann, Sara M. 395 646 921, 978 Cunha, Janaiara A. 942 Danso, Ebrima 625 Conrad, Melissa D. 1875, 227, Coulibaly, Jean T. 1273, 1821 Cunningham, Deirdre 926 Danso, Godfred F. 404 807, 811, 809 Coulibaly, Mamadou B. 1279, Cunningham, Elizabeth 682 Dantas, Gautam 1795 Conron, Emily 694 1398 Cunningham, Jane 1804 Dantzler, Kathleen W. 18 Conroy, Andrea L. 429, 629 Coulibaly, Michel E. 1690, 727 Curiel, David 366, 367 Dao, Francois 834 Constenla, Dagna 1415, 1417, Coulibaly, Moctar 834 Curriero, Frank C. 1567, 1867, Dao, Sounkalo 858 1418, 1419 Coulibaly, Nadine 1211 879, 903, 877, 886 Daou, Modiba 835 Conteh, Abdulai 1930 Coulibaly, Siaka Y. 1690, 727 Curtis, Kurt C. 1885 Daou, Modibou 1563 Conteh, Lesong 1348 Coulibaly, Yaya I. 1690, 727 Curtis-Robles, Rachel 664 Daouda, Ndiaye 1497 Conteh, Solomon 1648, 878 Courtenay, Orin 1252 Cutts, Julia C. 362 Daoust, Patricia 682 Contreras, Carmen A. 1009 Coutrier, Farah 656, 865 Cysticercosis Working Group in Dara, Antoine 835, 923 Contreras-Mancilla, Juan 567 Covini, Ilaria 575 Peru, 1037, 1034 Dara, Niawanlou 820, 834 Conway, David J. 194 Cowan, Graeme J. 1176 Czabotar, Peter E. 631 Darboe, Bakary 625 Conway, Michael J. 746 Cowardin, Carrie 1291 Czesny, Beata 992 Darbro, Jonathan 1237, 1806 Cook, Darren 645, 730 Cowgill, Karen D. 1069, 414 Darcy, Andrew W. 568 Cook, Elizabeth A. 662 Cowley, Daniel 1013 Dardzinski, Bernard J. 1077 Cook, Jackie 268, 601, 657 Cowman, Alan F. 631 Daré, Aboudou 527 Cooke, Elizabeth A. J.. 5 Cox, Jonathan 1560, 282 D Daring, Geraldo 1345 Cooke, Graham 1277 Cox, Jonathon 355 Darling, Anne M. 429 Da, Dari F. 560, 982 Cool, David R. 98 Cozijnsen, Anton 362 Daro, Kim 912 Dabbs, Rebecca 987 Cooley, Gretchen 1680, 56 Crabtree, Jean E. 1450 Darveaux, Blaise 1723 Dabira, Edgard 1215 Cooper, Caitlin 43 Crabtree-Ide, Christina 582 Das, Kishor K. 580 Dabiré, Roch K. 1192, 1234, 1281 Cooper, Philip J. 52, 649, 661 Craciunoiu, Sarah 1722, 505 Das, Pradeep 502 Dachlan, Sopiyudin 864 Cooper, Roland A. 807, 1531 Craft, David 1670, 1797 Das, Satadal 398 Dada-Adegbola, Hannah O. 1498, Coosemans, Marc 1213 Craig, Allen S. 388 Das, Smita 111, 122, 1538, 1543, 1603 Coote, Jessica 1118 Cramer, Jakob 646 836 Dadi, David 386 Coppens, Isabelle 1205 Cravo, Pedro 1487 Das, Sudipta 1205 Dadi, Netsanet H. D. 1409 Corbel, Vincent 1239, 289, 67 Crawford, Forrest W. 1671 Das, Suman 1255 Dadzie, Samuel 130, 351 Cordeiro, Marli T. 150 Crawford, Katrina 1021 Das, Sumon K. 28 Dagnon, Fortune 1188, 241 Cordova, Ezequiel 1143 Crawshaw, Alison F. 999 Das Gupta, Rudraprakash K. 502 Dai, Weili 1648, 375 Corey, Brendan 57 Crellen, Thomas 1824 da Silva, Juliana D. 69 Daimon, Lugano 657 Corey, Kristin 719 Crepaldi, Frederico 1137 DaSilva, Alexandre J. 808 Daitta, Mathurin 1399 Corey, Victoria C. 1206, 1533, Crespo, Benigno 800 Da Silva Castanha, Priscila M. 150 Dakorah1, Elijah A. 130 1827 Criado, Paulo R. 1151 Datagni, Gbati M. 506 astmh.org Abstract Author Index A-599

The number(s) following author name refers to the abstract number.

Date, Kashmira 1664 della Torre, Alessandra 1389, 635 Dhanaraj, Prabakaran 1560 Diesburg, Steven 1333, 1734 Datta, Dibyadyuti 361 Dellicour, Stephanie 848 Dhar Chowdhury, Parnali 780 Dietrich, Jes 60 Daubenberger, Claudia 1294, 1633 del Mar Castro, Maria 1750 Dhariwal, Akshay C. 502 Dieye, Baba 218 Daud, Ibrahim I. 331 De los Santos, Maxy 1913 Dhiman, Monisha 1753 Dieye, Tandakha 931 Daugla, Doumagoum Moto 1324 de los Santos, Tala 1070, 1075, Dhorda, Mehul 1829, 943 Dieye, Yakou 1544, 1626, 1903, Dauner, Allison 759 476 Dia, Anta Tal 192 975 Davey, Gail 1045, 495, 68, 70, 72 del Valle, Juana 401 Diabaté, Abdoulaye 1192, 1234, Diggle, Peter 1559, 651 David, Michael C. 663 Del Valle-Mendoza, Juana 1113, 1281, 1890, 633 Diggle, Peter J. 285 Davidson, Edgar 1, 1858, 549 1766 Diaby, Alou 826 Diggs, Carter 1278 Davidson, Jenna 846 Delves, Michael 993 Diagne, Nafissatou 381 Dijkhuizen, Marjoleine A. 610 Davidson, Silas 1275, 1278, 352, Demar, Magalie 308 Diakite, Mahamadou 1260 Dillip, Angel 598 1276 Demas, Allison 1469, 48 Diakite, Moussa L. 1576, 990 Dillon, Brian E. 327 Davidson, Whitni B. 791, 1454 de Mast, Quirijn 433 Diakité, Nouman 1901 Dimitrova, Kristina 740 Davies, Huw D. 1609 de Matos, Haroldo J. 1679 Diakite, Seidina A. S. 1260 Dimopoulos, George 1197, 1363, Davies, Jill 1076 Dembele, Adama 1601 Diakité, Souleymane 1901 634 Davies, Stephen J. 1831 Dembele, Massitan 727 Diallo, Abdallah A. 727 Ding, Xavier C. 1489, 249, 845 Davis, Jenna 25 Dembele, Rokiatou 618 Diallo, Abdoulaye 270, 271, 272 Dingemanse, Jasper 1488 Davis, Timothy M. E. 215 Deme, Awa B. 218, 312, 827 Diallo, Bouubakar 858 Dinglasan, Rhoel R. 1360, 946, Davong, Viegmon 423 Demilew, Ermias 1515 Diallo, Diakalia 602 993 Davun, Holl 1452 Deming, Michael 1063, 1227 Diallo, Diawo 192 Dinguirard, Nathalie 1779 Dawood, Fatimah S. 178 Deming, Regan 117 Diallo, Ibrahima 1652, 242, 310, Dinh, Ha S. 906 Day, Karen P. 216 Demissie, Gelila 1438 311, 353 Dionne, Pierre 824 Day, Nathan 313 De Mol, Patrick 290 Diallo, Kanny 1018, 1324 Diop, Samba 858 Day, Nicholas P. 254, 943, 1829, DEN-203 Study Group 1224 Diallo, Mawlouth 192 Diosque, Patricio 1089 214, 13 Deng, Bingbing 369, 950 Diallo, Mouctar 602 Dioubaté, Mohamed 1901 Daza, Glenda 248 Dengela, Dereje 1372, 720 Diallo, Nouhoum 834 Diouf, Ababacar 1260, 369, 931, de Alcântara, Marcelo H. 507 Denis, Mey Bouth 9 Diamond, Michael 41 950 de Almeida Oliveira, Giselle de 636 Deniskin, Roman 258 Diarra, Amidou 564, 853 Diouf, Ibrahima 1610 de Alwis, Ranjith 1658 Denlinger, David L. 1351 Diarra, Bakary S. 1601 Diouf, Lamine 353 Dean, Hansi 550 Dennison, Nathan J. 1197 Diarra, Ibrahim 1624, 602 Diouf, Mamadou L. 1652 Dear, Nicole F. 1866, 654 Denon, Yves Eric 244 Diarra, Issa 1563, 835 Diouf, Mamadou Lamine 242, 311 Deason, Nicholas A. 846 Dent, Arlene 21, 331 Diarra, Youssouf 1496 Diouf, Mame Birame 310, 311, Deborggraeve, Stijn 419 Denton, Jerod S. 715 Diatta, Bakary 824 826, 353 Debot, Margot 1645 Dentz, Holly 579 Diatta, Mathurin 113 Direny, Abdel 1229, 1814, 1059 Debrah, Alexander Y. 639, 443, Deol, Arminder K. 1823, 537 Diawara, Fatou 602 Di Santi, Silvia M. 1487, 844 1708, 1709 de Oliveira, Camila I. 1092 Diawara, Halimatou 1208, 602 Dismer, Amber 1664 de Carvalho, Camila A. 1099 de Ory, Fernando 744 Diawara, Sory I. 1583 Dissanayake, Gunawardena 1372, de Carvalho, Julie 1545 Deparis, Xavier 765 Diaz, Clemente 1219 269, 14 De Castro Catão, Rafael 147 Derbew, Miliard 1328, 1343, 690 Diaz, Yamilka 1410, 1461, 1421 Dissanayake, Harsha 1259 Dechavanne, Célia 1599, 1600 Deribe, Kebede 1045, 72 Díaz-Quijano, Fredi A. 1432 DiTanna, Gian Luca 1215, 888, Dechavanne, Sebastien 940 De Rissio, Ana María 1851 Dibernardo, Antonia 780 1399 Decuypere, Saskia 419 DeRoo, Sarah S. 923 Dickinson-Copeland, Carmen 1618 Ditsungnoen, Darunee 178 de Dood, Claudia J. 1837 Desai, Darash 698 Dicko, Alassane 1208, 1264, 1601, Dittrich, Sabine 542 Defang, Gabriel 1129, 1180 Desai, Meghna 297, 597, 883, 1624, 602 Diuk-Wasser, Maria 545 DeFilippis, Victor 41 911, 960, 683 Dicko, Ilo 1690, 727 Divala, Titus 1265, 1602, 1646, DeFrancesco, Alicia 1004 de Savigny, Don 959 Dickson, Benjamin F. R. 1813 927, 485 de Franco, Marcelo d. 964 de Silva, Aravinda M. 1416, 552, Dickson, Dorothy M. 1411, 1700, DiVita, Margaret A. 1839 Degaffe, Guenet 1729 548, 550 1408 Dixit, Amruta 956 de Gier, Brechje 610 de Silva, Aruna D. 552 Dickson, Emmanuel K. 194 Djenontin, Armel 67 de Glanville, William A. 5, 662 de Silva, Vipula C. 1102 Dickson, Laura B. 1196 Djimde, Abdoulaye 1211, 820, Degner, Ethan C. 1805 De Silvestri, Annalisa 575 Diclaro, Joseph W. 351, 737 834, 966 De Groot, Anne S. 1650 Desir, Luccene 1059, 1229, 1814 Didier, Bradley 863 Djimde, Moussa 820 Dehesh, Katayoon 1353 Deslouches, Yves Gaston 1664 Diedhiou, Younouss 826 Djontu, Claude 489 Deiss, Robert G. 1048 de Smet, Martin 1906 Diehl, Sean A. 1408, 1700, 1220, Djontu, Jean-Claude 1597 Deitz, Kevin C. 1388 Desprès, Philippe 765 1411 Djossou, Felix 308 de Jesus, Adriana 523 Desruisseaux, Mahalia 1086, 1175 Dieleman, Joseph L. 277, 674, 35 Djuardi, Yenny 468, 501 Dejon Agobe, Jean Claude 1651 Destura, Raul V. 153 Diémé, Yaya 824 Dlamini, Bongani A. 1536 Dek, Dalin 220 Devine, Greg 1310, 1806, 1237 Diemert, David 471, 606 Dmitriev, Igor 366, 367 Dela, Helena 1023, 1677 de Vlas, Sake J. 1022, 1250, 1679, Dieng, Thérèse 1610, 467 Dobaño, Carlota 371, 938 De La Barrera, Rafael 1219, 163 1715, 55 Dieng, Yémou 1610, 467 Dobbin, Caroline 860 De La Vega, Patricia 1638, 561 Dewey, Kathryn 1006 Dierickx, Susan 1213, 1615, 653, Dobbs, Katherine 21 Del Bianco, Gabriela 1729 Dey, Nilay 515 871 Dobinson, Hazel 1201 De León, Yéssika 745 Dey, Ranadhir 520 Dieringer, Kate 76 Doblecki-Lewis, Susanne 570 astmh.org A-600 Abstract Author Index The number(s) following author name refers to the abstract number.

Dobson, Andrew P. 1309 Doucoure, M’Bouye 1279, 990, Dunn, III, William A. 632 Eckhoff, Philip A. 1548, 1551, Dobson, Deborah E. 1316 1576 Dunod, Corinne 1223, 553 1760, 584, 954, 956, 957, 958, Doctor, Stephanie 1557 Doucouré, Souleymane 381 Duong, Tran Thanh 804 799, 613 Dodean, Rosie 1531 Dougherty, Michael W. 701 Duong, Veasna 1452, 590 Eckley, Sean 1527 Dodo, Mathurin 1655, 969 Douglass, Alyse 1608 Duparc, Stephan 1209, 852, 857, Eddie, Ricky 750 Dodoli, Wilfred 307 Douglass, Janet 1813, 641 889 Edgel, Kimberly A. 1644 Dodoo, Alfred K. 1322 Douine, Maylis 308 Dupnik, Kathryn M. 432 Edirisuriya, Chathura S. 1757 Dodson, Brittany 1808 Doumbia, Saibou 1260 Dupont, Catherine 661 Edoh, Dominic A. 404 Doe, Henrietta T. 330 Doumbia, Salif S. 727 Dupont-Turkowsky, J. Catherine Edstein, Michael D. 262 Doggett, Norman A. 1334, 1769 Doumbia, Seydou 1398, 1583, 406 Edwards, Kathryn M. 1770, 1840, Doggett, Richard T. 1841 1690 Duprez, Jessica S. 1240 1843 Dogovski, Con 1873 Doumbia, Sidy 1398 Duraisingh, Manoj T. 1299, 1473, Edwards, Nick 1277 Doherty, Justin F. 647 Doumbo, Ogobara K. 1211, 1563, 894 Egbo, Deborah 258 Doktor, Katherine 570 1606, 1609, 1633, 339, 902, Durand, David 1009 Egrot, Marc 67 Dolan, Stephanie 1347, 1619, 972 921, 978, 1279, 1576, 1624, Durand, Salomon 1510, 1710 Egu-Okoronkwo, Ngozi 1179 Dolenz, Charlotte 1214, 863 1636, 820, 834, 966, 990, 835 Durbin, Anna P. 1220, 1221, 1408, Egwang, Thomas G. 370, 374 Dolgert, Drew J. 1755 Doumbo, Safiatou 902 554 Egyir, Beverly 404 Dolo, Amagana 1279, 1636, 928 Doumbouya, Mory 1260 Durfee, Katelyn 827 Ehlers, Gerhard 728 Dolo, Housseini 727 Dowell, Floyd 1310 Duris, Martin 1733 Ehrenberger, Michelle 1484 Dombecki, Carey 1306 Dowler, Megan 1275, 352 Durnez, Lies 1213 Eisele, Thomas P. 1218, 278, 305, Domingo, Gonzalo J. 1070, 1075, Downs, Phil 1685 Durvasula, Ravi 1908, 722 1625 1218, 280, 281 Doyle, Trevor B. 1377 Dutary, Sahir 1473 Eisenberg, Joseph N. S. 22, 1306 Domingues, Carla 1415 Dozie, Ikechukwu N. 1169, 354 Duthie, Malcolm S. 1740, 1850 Ejendal, Karin F. 1377 Donaldson, Melvin T. 1477 Drabe, Camilla H. 1694 Dutra, Walderez O. 1849, 523 Ekali, Gabriel L. 1730 Donaldson, Ross 79 Drábek, Elliott F. 1640, 921, 923, Dutta, Sheetij 15, 1645, 938, 978 Ekawati, Lenny L. 869 Dondji, Blaise 478 924 Duvall, Jeremy 1527 Ekiyor, Christopher P. 354 Dondorp, Arjen 1829, 214 Drabo, Aly 870 Dwivedi, Ankit 12 Elaagip, Arwa 189 Dondorp, Arjen M. 1873, 254, Drakeley, Chris 1215, 1560, 1574, Dye, John M. 4 Elahi, Rubayet 316 617, 872, 9, 943, 1172 1598, 1614, 282, 298, 461, 564, Dykes, Cherry L. 717 Elanga, Emmanuel 67 Dong, Yi 161 588, 601, 918, 17, 279, 598, Dysoley, Lek 1479, 1502, 862 Elbadry, Maha A. 155 Dong, Yuemei 1197 559, 355 Dzib-Flórez, Sergio 117 Elder, Greg 1906 Dongus, Stefan 598 Dramaix-Wilmet, Michèle 74 Dzimianski, Michael T. 1714, 444 El-Din, El-Shiamaa M. Nour. 737 Donis, Ruben O. 193 Drame, Papa Makhtar 67, 1812 Dzinjalamala, Fraction 847 El Hag, Rehab 1453 Donkor, Martin N. 130 Dranchak, Patricia 377 Elizondo, Douglas 133 Donnachie, Elizabeth 1729 Draper, Simon 1462, 986, 987 Eller, Dirli E. 1832 Donnelly, Christl A. 1443 Drebot, Michael 740, 780 Elliot, Alison 434 Donnelly, Martin 113, 1389, 718, Driss, Adel 318 E Elliot, Karla P. 1136 1286, 717 Drum, Elizabeth T. 1328 Elliott, Suzanne M. 1207 E., Alyssa 334 Donnen, Philippe 74 Duan, Junhui 1635 Ellis, Michael W. 1021 Eapen, Alex 920 Donovan, Michael 1258 Duangdee, Chatnapa 816 Ellis, Ruth 1576, 990 Eappen, Abraham 1639, 46, 561, Donowitz, Jeffrey 1863 Dube, Queen 851 EL Mohammady, Hanan I. 1453 989 Doolan, Denise 830 Dubensky, Thomas W. 1647 Elphinstone, Robyn E. 1468, 629 Earle, Duncan 1544, 1626, 1903, Doranz, Benjamin J. 1, 176, 1858, Dubey, Sheri A. 760 ElRefaay, Samir 1129 975 38, 549 Dubhashi, Nagesh 1474 El Rifay, Samir 1762 Easom, Nicholas 434 Dorda, Mehul 11 DuBow, Joshua W. 399 Elsinga, Jelte 175, 756 Eastman, Richard T. 1173 Dorigatti, Ilaria 594, 773 Dubrovsky, Larisa 1835 ElSohly, Mahmoud 1528, 1535 Easton, Alice 461 Dorkenoo, Améyo M. 1928, 506, Duchars, Matthew 1256 Elvington, Andrew 1918 Easton, Alice V. 54 508 Duda, Rosemary B. 1341 Elyazar, Iqbal 864, 868 Eastwood, Gillian 1104 Dorlo, Thomas C. P. 1748 Dudova, Zuzana 492, 493 Embury, Paula 21 Ebel, Gregory D. 1445, 1852, 762, Dorlo, Thomas P. C. 1090 Duffy, Patrick E. 1264, 1279, 1476, Emch, Michael 1557, 543 1446, 1448 Dormoi, Jérôme 1532 1576, 1580, 1601, 1633, 1635, Emebuonye, Leslie 1514 Ebels, Kelly 1126 Dorn, Mauricio 1085, 29 1636, 1647, 1648, 375, 941, Emegbuonye, Leslie 1301, 823 Ebere, Nwabueze 1392 Dorny, Pierre 573 985, 990, 1624, 1649, 878, 991 Emerson, Claudia 677 Eberhard, Mark 452 Dorsey, Grant 1210, 1261, 1536, Dufour, Mi-suk Kang 866, 1536 Emerson, Paul M. 1321 Ebuehi, Albert O. 929 1614, 17, 1875, 227, 279, 283, Duggal, Nisha 1853, 1856 Emery, Aidan 1782 Ecca, Claudio 1034 313, 329, 332, 809, 811, 812, Dujardin, Jean-Claude 1318 Emrich, Scott J. 1193, 1386, 1172 Echalar, Ricardo 1545 947 Dull, Peter M. 423 Emukah, Emmanuel C. 452 Echavarria, Maria I. 738 Doshi, Reena H. 1117, 1464, 1466, Dumais, Mitchell 281 Enane, Leslie A. 1512 Echeverri-Garcia, Diego F. 846 1684, 1702, 6, 77, 795, 799 Duncan, Elizabeth H. 1278, 372, Enato, Izehiuwa G. 1494 Eckels, Kenneth H. 1219, 163 Dosoo, David K. 240 1641 Endersby, Nancy M. 713 Eckert, Erin 602, 898 Dotsey, Emmanuel Y. 1609 Dundaiah, Somashekar 1459 EEndy, Timothy P. 1423, 500, 525 Eckhoff, Grace 397 Doucoure, Elhadji 1626, 975 Dunford, James C. 737 Enebeli, Ugo U. 1771 Dunne, David W. 1243 Eng, Matthew W. 1359 astmh.org Abstract Author Index A-601

The number(s) following author name refers to the abstract number.

Eng, Nina 1781 Ezeigwe, Nnenna 1392, 837 Faye, Oumar 1610, 797 Fesobi, Olatoun 1568 Engelke, Helen 1118 Ezeiru, Sonachi 837 Faye, Ousmane 1373, 1690, 192, Fessler, Abigail G. 1052, 1731, 500 Engwerda, Christian 512, 518 Ezenduka, Ekene V. Phyllis. 66 270, 272 Fèvre, Eric M. 5, 662 Enquselassie, Fikre 1045 Eziefula, Alice C. 1215 Faye, Papa Coumba 1664 Fey, Julien 372 Enria, Delia 1856, 742 Fayette, Carl 1229, 1814, 1059 Fichera, Laura 1851 Enuameh, Yeetey 1305 Febir, Lawrence G. 842, 997 Fidelis Ferrão, Thiago 1099 Enya, Veronica 1568 Febo, Irma 1219 Fidock, David A. 1488, 1873, Enyong, Peter 1717 F Fedders, Charlotte 1275, 1634, 1878, 1879, 1484 Enzaru, Annet 1824 352 Fieck, Annabeth 1908 Fabbri, Cintia 742 Epopa, Patric S. Ngomé. 1192 Feemster, Kristen A. 1512 Field, Mark 1741 Fabris, Paolo 1696 Epp, Christian 337 Feeney, Margaret E. 1210, 17, 329, Field, Vanessa 646 Fahmy, Nermeen T. 737 Epstein, Judith 1275, 1613, 1634, 332 Fieldhouse, Jane 1188 Fahy, Joan 1817, 1927 352, 1633, 1640 Feeser, Karla 1926 Fields, Barry S. 417, 1041, 1203 Fairfax, Keke C. 1918 Epstein, Judith E. anki, Ambika Fehling, Sarah Katharina 180 Fields, Paul 1054, 149 Fairhurst, Rick M. 1173, 1260, 525 Feldmann, Heinz 3 Figueiredo, Gerusa M. 1413 127, 220, 940, 1829 Erasmus, Jesse 140, 748 Feldmeier, Hermann 1834 Figueiredo, Luisa M. 1921 Fairlamb, Alan 1741, 1914, 815 Erasto, Paul 1062 Felger, Ingrid 1262, 1263, 1555, Figueiredo, Walter M. 1413 Fairley, Jessica K. 507 Erber, Astrid 1094 1565 Filbert, Francis 1558, 900 Faix, Dennis 794 Ercumen, Ayse 25, 577 Felgner, Philip L. 1602, 1606, Filho, José Q. 63 Faiz, Md. Abul 1829 Erhart, Annette 1213, 303, 567, 1609, 1614, 1646, 336, 339, Filippova, Svetlana 1014 Falade, Catherine O. 1494, 1498, 804 943, 978, 559 Fillinger, Ulrike 1887 1603, 75, 825 Ernst, Timo 770 Felix, Alvina C. 1413 Findlow, Helen 1019 Falco, Richard 543 Eron, Joseph J. 1737 Feng, Gaoqian 11, 16 Findlow, Jamie 1325 Fall, Bécaye 1532, 824 Escalante, Ananias 1595, 919, Feng, Yuebiao 118 Fine, Ian 843, 910 Fall, Fatou B. 1626, 312, 584, 827, 1569 Feng, Zeng 1825 Finkelstein, Julia L. 1052, 1423, 855, 975 Escobar, Luis 1793 Feng, Zheng 1157 1693, 1731, 1773, 442, 500, Fall, Gamou 192 Escobedo-Vargas, Karin 1357, 729 Fenimore, Paul W. 1334, 1769 687 Fall, Mansour 824 Esemu, Livo 489 Fenton, Elizabeth 80 Finkmoore, Brooke 76 Falla, Alejandra 1830, 586 Esemu Forju, Livo 1597 Fenwick, Alan 1824, 1834 Finn, Timothy 1625, 278 Familiar-Lopez, Itziar 34 Esi, Queen U. 169 Ferdig, Michael 1293, 1829, 1826, Finn, Tyler 1222 Fan, Erkang 1292, 1314, 861 Esione, Amarachi U. 1120 1589 Firew, Heven Sime 480 Fançony, Cláudia 1796 Esmail, Hanif 1178 Fergus, Cristin A. 1617, 230, 962 Fischer, Elizabeth 991 Fanello, Caterina I. 13 Espada, Liz 100 Ferguson, Heather 1238 Fischer, Kerstin 1226 Fang, Hanwei 1818 Espinosa, Pablo 52 Ferguson, Neil M. 1443, 1562, Fischer, Peter U. 1074, 1226, 1883, Fang, Rui 335, 932, 933 Espírito-Santo, Maria Cristina C. 594, 619, 773, 777, 953 1885, 1886, 1894, 465, 501 Fang-Yen, Christopher 1777 1697 Fernandes, Ana Paula 1137 Fischer, Rebecca S. Bryson. 1015 Fanouillere, Karen 1223, 553 Esquivel, Carlos J. 1191 Fernandes, Andrea 698 Fishbaugher, Matthew 1613, 1826 Farag, Tamer H. 1203 Essel, Eunice 1046 Fernandes, Fabio 1912 Fisher, Ethan 1899 Farias, Samela 1877 Esterhuizen, Johan 676 Fernandes, José F. 849 Fitzpatrick, Christopher 82 Farley, Linda 1220 Estes, Sue M. 624 Fernandez, Cesar 64 Fitzsimmons, Colin M. M. 1243 Färnert, Anna 905 Estiu, Guillermina 1172 Fernandez, Eduardo 491 Flach, Clare 1302, 270 Farrant, Katie V. 1365 Estrada, Ana L. 738 Fernández, Facundo M. 819, 1489 Flaherty, Patrick 668 Farrar, Jeremy 617 Estrada, Marcus 281 Fernandez, Judy 537 Flannery, Luciana 246 Farrell, David 68, 495 Estrella, Luis A. 1016, 1024 Fernandez, Manolo 829 Fleece, Molly E. 1154 Farrington, Lila 329 Estupinan, Liliana 738 Fernandez, Maria Dolores 744 Fleming, Fiona 1822, 536, 537, Faruk, Omar 1861 Estupiñan Cárdenas, Maria I. 1055 Fernandez, Marisa L. 1143, 1851 1228 Faruque, Abu G. S. 27, 576 Eswarappa, Meghana 136, 592 Fernandez, Roberto 100 Fletcher, Daniel A. 1273 Faruque, Abul S. G. 28, 1010 Etheart, Melissa 1664 Fernandez, Stefan 1433, 148, 170, Florence, Salvatore 627 Fasinu, Pius S. 1528, 1535 Ettwiller, Laurence 448 171, 178, 184, 36, 591, 739, Florentini, Alejandro 1038, 1795 Fatiregun, Akinola 185 EuPathDB team 922 783 Florentini, Edgar A. 1751, 1752 Faulx, Dunia 1070, 1075, 1126 Evans, Carlton A. 1763 Fernandez de Cuadros, Carla 59 Flores, Carmen 705 Faust, Saul 1277 Evans, Christopher C. 1714 Fernandez-Sesma, Ana 1257, 1258 Flores, Jorge 1085, 29 Faustino, Margot 1795 Evans, Krystal 362 Fernandez-Velando, Esther 1620 Flores-Mendoza, Carmen 1357, Fauver, Joseph R. 1446, 188, 762 Evans, Jr., Thomas C. 448, 1080 Fernando, Charisma S. 1102 1367, 700 Favero, Rachel 315 Evelim Coelho, Giovanini 147 Fernando, Samitha 1259 Florey, Lia 441, 81 Fawzi, Wafaie W. 429 Eversley, Tatiana R. 787 Ferradas, Cusi 1795 Florey, Lia S. 898 Fay, Michael P. 1260, 369, 950, Everts, Bart 1915 Ferraz, Lorena C. Neres. 1832 Floridia-Yapur, Noelia 1089 1636, 1812 Ewer, Katie 1277, 1462, 180, 182, Ferreira, José A. G. 507 Florin, David 700 Faye, Babacar 1501, 1610, 242, 363 Ferreira, Marcelo U. 925, 940, Flower, Abigail 1050 249, 319, 363, 467, 845, 855 Existe, Alexandre 1212, 897 1605 Floyd, Jessica 1838, 615 Faye, Ernest 1302 Eze, Ukamaka T. 452 Ferro, Santiago 1799 Flueck, Christian 1879 Faye, Farba 1626, 1903, 975 Ezeabikwa, MaryFlora 452 Ferrufino, Lisbeth 1085, 29 Fobi, Grace 1715, 511 Faye, Ngor 381 Ezeamama, Amara E. 1727, 490 Ferrufino, Rosário Q. 1101 Fofana, Amfaal 113 astmh.org A-602 Abstract Author Index The number(s) following author name refers to the abstract number.

Fofana, Aminata 1211, 870 Fredericks, Anthony 1257 Galindo-Cabello, Nadia R. 1749 Garske, Tini 1443, 2, 619 Fofana, Bakary 834, 856 Freeman, Andrew 1079 Galinski, Mary R. 1471, 1482, 630 Garver, Lindsey 1275, 352 Fokoli, Lawrence S. III. 737 Freeman, Brandi 1086 Gallagher, Nancy M. 1439 Gasasira, Ann 1572 Folefoc, Asongna 235 Freeman, Brandi D. 1175 Gallichotte, Emily N. 548 Gasco, Alberto 1529 Foley, Desmond H. 737 Freeman, Matthew C. 464 Galloway, Renee 1422 Gasem, M. Hussein 433 Folly, Kouakou 855 Freer, Joseph 1784 Galviz Gómez, Luisa V. 1698 Gass, Katherine 1063, 1227, 458 Fomumbod, Enni 1638 Freire, Janaina 606 Gambhir, Manoj 389, 390 Gasten, Dagmar 716 Fong, Rachel H. 1, 38 Freire, Wilma B. 1693, 442, 687 Gamble, Joanne 645 Gaudard, Jean 1563 Fongnikin, Augustin 1370 Freire-Neto, Francisco P. 432 Gamboa, Dionicia 1518, 1595, 20, Gaudart, Jean 270, 381 Fongoro, Sahare 858, 859 Frempong, Kwadwo K. 130 233, 233, 567, 828, 829, 845 Gaudriault, Georges 1717 Fonseca, Ana Maria 1553 French, Issa 1268 Gamboa, Ricardo 1034, 475 Gaugler, Randy 1374 Fonseca, Jairo A. 366, 367 French, Michael 1232, 1823, 537 Gamero, Maria 1155 Gaultney, Robert A. 701 Fontana, Mary F. 17 Freundlich, Joel 1681 Gamez, Stephanie 1810, 1892 Gaur, Deepak 938 Fonville, Judith 554 Frevert, Ute 555 Gamo, Francisco-Javier 1533, 259, Gava, Sandra G. 1776 Foote, Simon 1873 Fried, Michal 1264, 1476, 1580, 800 Gave, Anthony 233 Foran, David 735 1601, 1624, 46 Gamougam, Kadija 1324 Gawas, Pooja 1474 Ford, Gavin W. 887 Friedman, Jennifer F. 1580 Gan, Esther S. 165 Gaye, Abdoulaye 1215 Ford, Louise 1076, 1078, 639, Friedrich, Lindsey R. 1587 Ganaba, Rasmané 573 Gaye, Omar 271 644, 645 Frimpong, Angela 482 Gandaho, Lola 1188 Gaye, Oumar 1302, 1348, 1501, Forde, Martin S. 1139 Frischmann, Sarah 1605, 925 Gandarilla, Omar 1085, 29 1610, 249, 270, 272, 319, 467, Forero-Peña, David A. 1632 Fröhlich, Holger Fröhlich 1708 Ganesan, Anuradha 1048, 648 855 Fornace, Kimberly M. 282 Frutos, Roger 1452 Ganesan, Subramanian 949 Gaye, Seynabou 1652, 311, 353, Fornadel, Christen 1372, 1392, Fruttero, Roberta 1529 Ganesan, Suresh M. 586 826 720 Fry, Alicia M. 1839 Ganeshan, Harini 1275, 1634, 352 Gazdik, Michelle 631 Forouzanfar, Mohammad H. 1791 Fu, King-Wa 88 Gankpala, Lincoln 1226 Gazzinelli, Andréa 1819 Forquer, Isaac 1531 Fuentes, Sandra 1660 Gansane, Adama 853 Gazzinelli, Maria F. 606 Forrat, Remi 1223, 774 Fujimori, Mahyumi 844 Gao, Jian-Chuan 1898 GBD Household Air Pollution Expert Forshey, Brett 166, 596 Fujiyoshi, Risa 378 Gao, Lixin 1014 Group, 1791 Fort, Robert 1604 Fukuda, Mark 814 Gaona, Heather 1531 Geary, Timothy G. 1724, 668 Fortuny, Enzo 1085, 29 Fukushima, Wakaba 374 Garbuz, Tamila 1150 Gebresilase, Tewodros T. 70 Foster, Jeremy M. 1882 Fulbier, Sandra 83 Garcia, André 459 Gebretsadik, Abeba 1045 Foster, Woody 993 Fuller, James A. 22 Garcia, Cristina 1417, 1418, 1419, Geded-Moreno, Eduardo 117 Foster-Nyarko, Ebenezer 1018, Fullman, Nancy 1337 1415 Gelanew, Tesfaye 1412 1676 Fung, Isaac Chun-Hai 389, 390, Garcia, Cybele C. 154 Gelaye, Woyneshet 1515 Fouet, Caroline 1810, 1892 413, 88 Garcia, Eduardo S. 1148 Gelderblom, Huub C. 1321 Fowkes, Freya J. I. 11, 1266, 603, Funk, Sebastian 82 Garcia, Guillermo 1003, 1660, Geldhof, Peter 461, 465 333 Funkhouser, Sheana 1394, 708 1661, 1662, 1869, 601 Geleishvili, Marika 706 Fowler, Robert 1268 Furini, Adriana A. Da Cruz 324, Garcia, H. H. 472 Gelin, Gedeon 876 Fox, Christopher B. 981, 1647 340 Garcia, Hector H. 1030, 1031, Gendernalik, Alex 1446 Fox, Ellen C. 1831 Fuseini, Godwin 1662 1034, 571, 572, 1037, 1035, Gendrin, Mathilde 870 Fox, LeAnne 1059, 1300 Fustec, Bénédicte 289 475, 1036 Genedy, Mohamed 1129 Fox, Matthew P. 623 Fyfe, Alex 987 García, John 314 Gentil, Coline 1476 Foy, Brian 1283, 1285, 880, 1354 Garcia, Jorge A. 909 Gentsch, Jon 1013 Fraga, Carlo G. 606 Garcia, Lineth 661 George, Christine M. 27, 576 Fraga, Valeria D. 324, 340 Garcia, Melissa N. 1247 George, Joby 841 Frame, I.J. 258 G Garcia, Rocio 477 George, Kristen 1372, 720 Franca, Camila 830 Garcia, Sarah 1707 George, Miriam 940, 1643 Gaarcia, Gabriel L. 1148 França, Caio Martinelle 558 García-Betancourt, Tatiana 1167 Gerardin, Jaline 1548, 1551, 613, Gabriel, Erin 1279, 1576, 1624, Franchard, Thierry 1511, 221, 302 García-Gubern, Carlos 1422 954, 957, 958 1635, 1636, 985 Francis, Donald P. 1221 Garcia-Luna, Selene 1446, 1852, Gerbasi, Robert V. 1316, 1710, Gabriel, Sarah 1426, 573 Francis, Filbert 1694 762 1644 Gabrieli, Paolo 1361, 1395 Franco, Leticia 1421, 744 Garcia-Mendonza, Paquita 1436 Gerber, Sue 1464, 1466, 1684, Gabryszewski, Stanislaw J. 1878 Franco, Virginia 800 García San Miguel, Lucía 5101746 1702, 77, 795 Gadalla, Nahla B. 223 Franco de Andrade Jr., Heitor 1099 Garcia-Sastre, Adolfo 1257 Gerrets, Rene 1213 Gadoth, Adva 1466 Francois, Jeannot 1664 Gardner, Malcolm J. 1596 Gershman, Mark 1439 Gaedigk, Andrea 202 Frangos, John 1529 Gardon, Jacques 1818 Gerth-Guyette, Emily 1126 Gaffar, Md. Abdul 1865 Franke, Molly F. 1860 Garey, Kevin W. 395 Gesase, Samuel 1801, 900, 917 Gaji, Raj 1293 Fransis, Filbert 904 Garg, Nisha J. 1084, 1753, 515 Getachew, Asefaw 1544, 1546, Gakidou, Emmanuela 1337 Fraser, Claire M. 924 Garimo, Issa A. 1216, 268, 112, 1628, 974 Galactionova, Katya 959 Fraser, Ellen A. 1408 600 Gething, Peter W. 296, 304, 697, Galarion, Ma. Jowina H. 153 Fraser, Jamie 1048, 1663, 648 Garn, Josh 464 913 Galdos Cardenas, Gerson 1085, Frato, Gabriel 1604 Garro, Katherine 20, 828 Getie, Sisay 206 29, 1911 Frawley, Hannah 504 Garruto, Ralph 770 Getnet, Gebeyaw 206 astmh.org Abstract Author Index A-603

The number(s) following author name refers to the abstract number.

Ghalib, Hashim 1740 Goita, Siaka 820 Gorchakov, Rodion V. 144, 1247 Greenwood, Brian for the Ghani, Azra 1574, 1642, 1838, Gokool, Suzanne 1071 Gordon, Aubree 133 MenAfriCar Consortium 1019, 880, 996 Goldberg, Daniel 664 Gordon, Catherine 1825 1676 Ghani, Azra C. 1562, 1564, 953 Golden, Allison 1070, 1075 Gordon, Jeffrey I. 1006 Greer, George 1905, 268, 386 Ghanney, Chantal E. 1725 Goldgof, Greg 1827 Gordon, Susan 641 Gregory, Christopher 416 Ghansah, Anita 216, 431, 899 Golding, Nick 1045 Gore Saravia, Nancy 1750 Greiner, Ashley L. 706 Ghasi, Samuel I. 1120 Goldstick, Jason 1306 Gorokhovich, Lyudmila 1301, Grenfell, Bryan 1323, 1325, 1456 Ghorbal, Mehdi 1172 Gollob, Kenneth J. 1849, 523 1514, 823 Gresh, Lionel 133, 136, 622, 761 Ghosh, Probir K. 577 Gomes, Cláudia 1113 Gosi, Panita 10, 1132, 323, 802 Gresham, Stephanie 260 Ghosh, Susanta K. 71 Gomes, Claudia 401 Gosling, Roly 1208, 1536, 1550, Gresty, Karryn J. 1874 Ghosh, Urmi 426 Gomes, Edwin 1474, 626 1579, 299, 655, 866, 236, 1552, Grice, Elizabeth A. 1847 Gibbons, Robert V. 171 Gomes, Laksiri 1259 563, 656, 865 Grieco, John P. 1368, 1403, 1811, Gibson, Greg 320 Gomes, Talita R. 1832 Gosnell, William 678 96, 104, 1308, 729 Gibson, Harry 697 Gomez, Carol 463 Gossaye, Yonatan 1214 Grier, Paltama 1220 Gidlewski, Tom 793 Gómez, Doris 745 Goswami, Jaya 485 Grier, Tama 1408 Gignoux, Etienne 1460 Gómez, Jorge 1110, 792 Gotia, Hanzel T. 1294 Griffin, Jamie T. 1562, 1564, 953 Gikic, Djordje 275 Gomez, Juan G. 509 Goto, Yasuyuki 197, 531, 532 Griffin, Marie R. 1770, 1840, 1843 Gil, Ana I. 1770, 1840, 1843 Gomez, Maria 1739 Gottardi, Maiara 474 Griffin, Paul 860 Gilani, Zunera 504 Gomez, Maria G. 800 Gottlieb, Michael 784 Griffin, Paul M. 1207 Gilbernair, Elia 158 Gomez, Maria L. 1533 Gotuzzo, Eduardo 472 Griffith, Matthew E. 1276 Gilbert, Ian H. 815, 1741 Gomez, Maria Adelaida 1748, Goupil, Brad A. 39 Grigg, Matthew J. 1560, 1902, Gilbert, Peter B. 371 1750 Gouvras, Anouk 1782 282, 355 Gilbert, Rebecca 1074 Gomez, Wilber 1414 Govella, Nicodem J. 598 Griggs, Allison D. 371 Gilbert, Sarah 1462, 182, 180 Gómez Bernate, Adriana M. 1698 Gowda, Bhavya 1513, 1538 Grignard, Lynn 564 Gilchrist, Carol A. 1136, 408 Gómez-Carmago, Doris E. 1053 Gowelo, Steve 1393 Grijalva, Carlos G. 1770, 1840, Gildas, Yahouedo 1287 Gomez-Perez, Gloria P. 938, 1633 Gower, Charlotte M. 1824 1843 Gillespie, John R. 1314 Gomez-Puerta, Luis A. 1030 Goyal, Navin 1209 Grijalva, Mario J. 1761, 509 Gilliland, Jr., Theron 759 Gomis, Jules 1497, 270 Goyoneche, Gabriela 475 Grimaldi, Raffaella 815 Gilman, Robert H. 103, 1034, Gomis, Jules F. 1302, 312, 271 Grabias, Bryan 1802 Grimsby, Jonna 371 1038, 1085, 1095, 1450, 1911, Gonahasa, Samuel 279, 812 Grabovac, Varja 1013 Grinnage-Pulley, Tara 524 29, 571, 1751, 1752, 1795 Goncalves, Bronner 588 Gracia, lisy 1768 Grippin, Crystal Grippin 1394 Gilmartin, Allissia A. 1135, 1665 Goncalves, Elenice M. N. 1151 Graham, Andrea L. 1309 Gripping, Crystal 120 Gimblet, Ciara 1847 Gonçalves, Bronner P. 564 Graham, Barney S. 1462, 1633, Grobusch, Martin P. 849 Ginny, Jason 1565 Gondorf, Fabian 1241, 1880 180, 182 Gross, Alexis M. 1097 Ginsburg, Amy S. 1126, 1127 Gondwe, Thandile 936 Grahe, Joshua 682 Grossi-Soyster, Elysse N. 5 Giordani, Maria T. 1696 Gonza, Remo 1751, 1911 Grahek, Shannon 471, 606 Grossman, Marissa 117, 723 Giorgi, Emanuele 1559 Gonzales, Isidro 571 Grandesso, Francesco 1906 Grosso, Ashley 31 Giraldo, Freddy 1632 Gonzales, Iveth J. 865 Granger, Donald L. 627 Grubaugh, Nathan D. 762, 1446 Girianella, Vania 1428 Gonzales, Rommel V. 659 Grant, Edward 1048, 648 Gruninger, Randon J. 1010 Girma, Samuel 14 Gonzales Hurtado, Patricia A. 46 Graves, Casey 35, 674 Grunwald, Jr., William C. 98 Githaka, Naftaly 1236 Gonzalez, Antonio 543 Graves, Justin C. 1301, 823, 1514 Gryschek, Ronaldo C. Borges. Githeko, Andrew 1391, 896 Gonzalez, Armando E. 1030, 1034, Graves, Patricia 641, 1813 1697, 1151, 474 Githure, John 1379 571, 1037, 1036 Gray, Darren 1825, 26 Gryseels, Charlotte 1213, 1615, Giusti, Cecilia 664 González, Gladys 1422 Gray, David W. 815, 1741 653, 871 Gkrania-Klotsas, Effrossyni 646 González, Grehete 181 Gray, Karen-Ann 1874 Gu, Se Hun 782 Glasner, Dustin 1253 Gonzalez, Iveth 657, 1489, 1804, Gray, Meg 1285, 1354 Gu, Wenjuan 1260 Glass, Greg 886 249, 656, 830, 845 Greatorex, Zoe 1452 Guagliardo, Sarah Anne 726 Glass Elrod, Mindy 1422 González, John M. 1759 Greco, Béatrice 83 Guastini, Cristina M. F. 1101 Gleave, Katherine 730 Gonzalez, Karla 754 Green, Angela 554 Guayaquiles Health Center 401 Glennie, Nelson D. 1846 González, Raquel 1553, 1570, 854 Green, Ann 32 Guedes, Marjorie M. 1012, 1668, Glennon, Elizabeth 1353 Gonzalez-Escobedo, Geoffrey 392, Green, Justin A. 1209 63 Glesby, Marshall 1848 397 Green, Michael D. 819, 1369 Guelbéogo, Wamdaogo M. 564, Gloekler, Emily 1619 González-Uribe, Catalina 1167, Greenaway, Christina 1703 1871 Gnadig, Nina 1484 174 Greenberg, Ali 1417 Guelig, Dylan 1333, 1734 Gneme, Awa 1871 Gonza Luque, Remo 1095 Greenberg, Robert M. 1777, 1778, Guernsey, III, David T. 78 Gnidehou, Sedami 976 Goo, Leslie 1854 1900 Guerra Giraldez, Cristina 1036 Gobeau, Nathalie 1207 Good, Michael F. 556, 60, 976 Greene, Sharon K. 1301 Guerra-Giraldez, Cristina 1031, Goel, Kapil 1459 Goodhew, Brook 1680 Greenhouse, Bryan 1261, 1353, 1037 Goenaga, Silvina 1856 Goodman, Catherine 1523 1536, 1594, 1598, 1614, 17, Guerrant, Richard 1004, 1290, Goentzel, Jarrod 85 Goodson, James 1459 656, 809, 865, 866 1674, 784 Goes, Alfredo M. 1832 Goonasekara, Charitha L. 769, 772 Greenwood, Brian 1018, 1324, Guerrant, Richard L. 1012, 1864, Goethert, Heidi 544 Gopalakrishnan, Sujatha 1071 1844 63 Goheen, Morgan M. 625 Gopinath, Varun 1040 Guerrero, Darwin 1761, 509 astmh.org A-604 Abstract Author Index The number(s) following author name refers to the abstract number.

Guerrier, Gilles 1044 Haddad, Danny 1319 Hanley, Kathryn A. 121, 751, 758 Hawdon, John 471 Guesses, Girma 1546, 1628, 1629 Haddow, Andrew D. 748, 749 Hannah, Dada- Adegbola 75 Hawes, Harvey 1349 Guevara, Carolina 1131, 596, 786, Hadi, Melinda P. 1378 Hansen, Brenda K. 1723 Hawes, Stephen E. 1160 792 Haenchen, Steven D. 704 Hansen, Immo A. 121, 1350 Hawkes, Michael 629 Gueye, Alioune Badara 242, 311, Hage, Eduardo F. 1119 Hansen, Kristian S. 1184, 1228, Hawley, William 864 353, 826 Haggen, Anne 1685 1800 Hawley, William A. 656, 865 Guezala, M. Claudia 132, 661, 705 Hahn, Beatrice H. 894 Happi, Anise 1115 Hay, Simon I. 1045, 296, 437, 595, Guezala Villavicencio, M. Claudia Haidara, Aboubacrine 1211 Haque, C. Emdad 780 913 406 Haidara, Kadidiatou 1211 Haque, Rashidul 1136, 1154, Hayde, Michael 1336 Guggisberg, Ann M. 225 Haigwood, Nancy L. 1225 1411, 1665, 1700, 1863, 1865, Hayette, Marie-Pierre 290 Gughova, Andrea 1733 Hailu, Asrat 1045 27, 316, 408, 576 Haynes, John A. 624 Guglielmi, Nicoletta 1097 Haindongo, Erastus 1579, 563 Haque, Ubydul 238 He, Zhong 1898 Guglielmo, Stefano 1529 Haindongo, Erastus H. H. 299 Harb, Omar S. 922 Head, Jennifer R. 1897 Guhl, Felipe 1246 Hainsworth, Michael 1544, 1626, Harbin, Julie N. 1855 Healy, Sara A. 1279, 1576, 1633, Guilavogui, Timothée 1901 1627, 1629, 1903, 975 Harding, Simon 1803 1635, 1636, 941, 985, 990 Guillot, Andrea 1301, 823 Haji, Khamis A. 112, 1235, 657 Hare, Brian A. 666 Heasly, Benjamin 1003, 1661 Guimarães, Luiz Henrique 1251, Hakizimana, Emmanuel 1379, Harenberg, Anke 553 Heath, Claire J. 1123, 1124, 741, 1848, 1849, 539, 1745 1868, 263, 380 Hariharan, Karen M. 1301 151 Guindo, Boureima 1563 Halasa, Yara A. 1304, 1424, 360, Harimanana, Aina 885 Heath, Paul 411 Guindo, Merepen A. 1279, 1576, 781 Harman, Christopher 927 Hedje, Judith 1369, 885 1636, 990 Halatoko, Wemboo 506, 508 Harn, Donald 1825 Heffelfinger, James D. 768 Guiney, Donald G. 415 Halback, Alaina 814 Harrington, Laura C. 1312, 1355, Heffernan, Gavin D. 262 Guinot, Philippe 1544, 1626, Haldar, Kasturi 1172 1404, 1805 Heffernan, Michael J. 1747 1903, 975 Haldeman, Kristin 1436 Harrington, Whitney E. 1476 Hegarty, Robert E. 1183 Guinovart, Caterina 1218, 1546, Halder, Dipankar 398 Harris, Eva 1253, 133, 136, 1410, Hegewisch, Jennifer 1553 1570, 1626, 1628, 974, 975 Halidou, Tinto 1049 156, 554, 592, 622, 754, 761, Heggen, Anne 1320 Guioti, Felipe 1435 Hall, Brantley 1385 764 Heineman, Regina 759 Guler, Jennifer 1474 Hall, Emily 76 Harris, Ivor 568 Heise, Mark 41, 156 Gulia-Nuss, Monika 1377 Hall, Eric R. 1021, 1024, 1016, 57 Harris, Jason B. 1860, 1861, 1862, Heitkamp, Rae 1024, 57 Gunanti, Inong 28 Hall, Matthew 1807 397 Heitzinger, Kristen 1160 Gunasekera, Anusha 1636 Halliday, Jo E. B.. 1105 Harrison, Abby G. L. 317 Hejduk, Janusz 782 Gunawardena, Dissanayake 566 Hall-Mendelin, Sonja 728 Harrison, Dustin 1479, 1502 Helb, Danica 1536, 1598, 1614 Gundersen, Svein G. 1834 Hallyburton, Irene 815 Harrison, G.L. Abby 568 Heller, Brigitte 1325 Gundogdu, Ozan 325 Halpin, Rebecca 1255 Harrison, Shannon T. 1606 Hemming, Elizabeth 1391 Guo, Fengguang 1139 Halsey, Eric S. 131, 1436, 1901, Hart, Erica 608 Henao-Giraldo, Juliana 1632, 314 Gupta, Bhavna 1490 218, 439, 596, 786, 86 Hart, Kevin J. 1174 Henderson, Elizabeth 1422 Gurley, Emily 139, 788, 768 Halter, Francois-Baptiste 59 Hart, P. John 669 Henderson, Ralph H. 1925 Gusovsky, Fabian 1527 Hamad, Alli 1637 Harter, Briana 1786 Henein, Sandra 550 Gutarra, Carlos 401 Hamade, Prudence 1498, 229 Hartinger, Stella 1843, 661 Heng, Pisal 9 Gutierrez, Freddy 1518 Hamainza, Busiku 1218, 1547, Hartl, Daniel L. 584, 875 Heng, Seng 1132 Gutierrez, Ramiro 1663 1623, 278, 388, 881 Hartley, Angela 1544 Heng, Thay Kheang 10 Gutierrez, Sonia 565 Hamano, Akiko 482 Hartman, Daniel 1236 Hengartner, Nicolas W. 1334, 1769 Gutman, Julie 228, 307, 358, 883 Hamapumbu, Harry 1397, 301, Hartnell, Felicity 1462 Hennessee, Ian 1901 Guy, Andrew J. 16, 831, 937 342, 877, 879 Harun, Dostogir 582 Henriques, Gisela 1503, 1879 Guy, Bruno 1223, 553 Hamayobe, Danver 1876 Harvey, Steven A. 1190, 695, 1621 Henry, Marie-Claire 67 Guzman, Hilda 1442 Hamed, Kamal 889 Hasang, Wina 1612 Henry, Mathew 1016, 57, 1024 Guzman, Mitchel 1518 Hameed, Jessica M. 62 Haselden, John 260 Henry, Michael 1310 Gwadz, Robert 127 Hamel, Mary J. 371, 597, 683, 911 Haselden, John N. 259 Henry, Noelie 853 Gwanmesia, Philomena 1597 Hamer, Davidson H. 1162, 646 Hashim, Ramadhani 306 Henry, Ronald 437 Gyapong, Margaret 1049, 1701 Hamer, Gabriel L. 1888, 664 Hasker, Epco C. 1250 Herath, Bandera 1528 Gyeltshen, Nima Wangdi 1396 Hamer, Sarah 664 Hassan, Hassan K. 725 Herath, HMT B. 1535 Gyorkos, Theresa W. 462 Hami-Adiamoh, Majidah B. A. 92 Hassan, Wahida 268, 600 Herbein, Joel 408 Hamilton, Stuart 1793 Hassan-King, Moussa 1324 Herbst, Abraham J. 677 Haminza, Busiku 681 Hasselquist, Dennis 905 Heresi, Gloria P. 1729 Hamlin, Rebecca E. 1258 Hast, Marisa A. 1567, 903 Hergott, Dianna B. 1003, 1660, H Hamm Rush, Sarah 1544 Hathaway, Nicholas J. 915, 916, 1661, 1662, 1869, 1637 Hampton, Shay 924 543 Herica, Soraya 507 Haakenstad, Annie 277, 35, 674 Hamre, Karen E. S.. 326 Hauns, Kevin D. 1276, 1278 Herlihy, Julie M. 623 Haas, Jere D. 1693, 442 Han, Kay-Thwe 943, 1581 Hauser, W. Allen 1032 Herman, Lou 601 Habashy, Engy E. 1133 Hanan, El Mohammady 1024 Hausmann-Muela, Susanna 1213 Hermance, Meghan E. 546 Habib, Mohamed R. 1783 Hancher, Matthew D. 697 Havlir, Diane 1210, 313 Hermida, Felipe D. Hermida. 964 Habluetzel, Annette 1234 Handy, Scott 1097 Havt, Alexandre 1012, 1668, 1669, Hermsen, Robert 1613 Habte, Tedila 1774, 1775 Hanke, Christiane R. 1770 63 Hernandez, Adrián V. 1766 astmh.org Abstract Author Index A-605

The number(s) following author name refers to the abstract number.

Hernandez, Filiberto 1907, 840 Hoang Johnson, Diep K. 710 Horne, John 1128 Hurley, Emily 1190, 1621, 695 Hernandez, Jean N. 1420 Hochman, Sarah 205, 33 Hosie, Heather 1641 Hurwitz, Ivy 1908, 722 Hernandez, Leda 458 Hodanics, Charles J. 689 Hosie, Heather E. 1278, 372 Husain, Mansoor 1468 Hernandez, Lourdes 744 Hodder, Anthony N. 334, 631 Hospitales del Sistema Nacional de Huskins, Noelle 1760 Hernandez, Luis 1171 Hodel, Eva Maria 847, 851, 812 Salud, 744 Hussain, Ejaz 1772 Hernandez-Sanabria, Mayra 734 Hodges, Mary H. 1930 Hossain, Md. Iqbal 1865 Husseini, Azra 1209 Herold, Christine 1708 Hoehne, Alexandra 23 Hossain, Shakhawat 780 Hussem, Kittinun 783 Herpri Sasongko, Pandu 433 Hoekstra, Rinke C. 1250 Hossen, Emran 1200 Hutchinson, Eleanor 1800 Herrera, Claudia P. 1247 Hoel, David 1658 Hotez, Peter 1289, 463, 52, 606, Hutyra, Carolyn A. 1826 Herrera, Henry 1595, 233 Hoel, David F. 96 649, 1747, 461 Huu, Tung N. 482 Herrera, Manuela 1887 Hoelscher, Michael 1707 Houpt, Eric R. 1013, 1865, 1864 Huy, Rekol 8, 872, 9 Herrera, Sócrates 1571, 1577, Hoerauf, Achim 1071, 1076, 1078, Houri-Yaifn, Arnon 237 Huyler, Anne 1670 1584, 1632, 314, 320, 567, 1241, 1708, 1709, 1880, 443, House, Brent L. 1133 Hviid, Lars 1176 1569 639, 644 Houtoukpe, Andre T. C. 1002 Hwang, Jennifer 399 Herrera, Victor M. 1406 Hoest, Christel 784 Howard, Leigh M. 1840 Hwang, Jimee 14, 269, 566 Herrera, Yenny O. 659 Hofer, Anthony 1529 Howard, Randall F. 1649, 1740, Hyatt, Donna 1222 Herrera-Alzamora, Angella 1766 Hoff, Nicole A. 1117, 1464, 1466, 1850, 981 Hyman, James M. 1334 Herrera Galindo, Victor M. 1055, 1684, 1702, 6, 77, 795, 799 Howes, Rosalind E. 1511, 202, 1698 Hoffman, Stephen L. 1014, 1204, 221, 296, 302, 913 Herrero, Laura 744 1596, 1633, 1635, 1636, 1637, Hoy, Ronald R. 1312 Herrick, Jesica 1144 1638, 1639, 1640, 1647, 377, Hristov, Angélica D. 1487 I Herricks, Thurston 626 561, 924, 938, 939, 941, 989, Hsiang, Michelle 1536, 1594, 866, Iamsirithaworn, Sopon 1429, 593 Herrod, Jessica 878 46, 1613 656, 865 Ianni, Barbara M. 1912 Hershow, Ronald 1144 Hoffman, Victoria 513 Hsieh, Michael 1836, 538, 672, Ibikounlé, Moudachirou 527 Hess, Jessica 608 Hoffmann, Ary A. 713 1245, 1895 Ibitokou, Samad 327 Hettenbach, Susan M. 1855 Hofmann, Natalie E. 1262, 1263 Hsieh, Yi-Ju 1895 Ibrahim, Sulaiman S. 1284 Hewett, Gary 280 Hofmeister, Robert 1884 Hsu, Haoting 927 Idampitiya, Damayanthi 1259 Hewitt, Philip 83 Hofmeyer, Kimberly A. 1850 Hu, Wei 1157 Idowu, Emmanuel 1586 Heymann, David 677 Hogan, Jessica 1349 Hu, Yan 473 Idowu, Olufunmilayo A. 287 Hibberd, Martin L. 1270 Hogges, Jamesa 390 Huaman, Alfredo 792 Idris, Jide 994 Hibbs, Danielle 93 Hohmann, Elizabeth 1198 Huaman, Jose L. 785 Ifeonu, Olukemi O. 1152 Hickey, Bradley 1275, 1613, 1634, Hohnerlein, Stefan 1707 Huancabamba, Health Center 401 Igbasi, Uche 935 352 Hoibak, Sarah 1213 Huang, Chiung-Yu 339 Igbasi, Uche T. 1607 Hickman, Mark R. 257, 891 Hokke, Cornelius H. 465 Huang, Fang 893 Ilboudo, Hamidou 1317 Hicks, Derrick 1353 Hol, Wim G. 1314 Huang, Henry 1637, 1638 Ilika, Amobi L. I. 1683 Hien, Tran Tinh 943 Holesova, Maria 492 Huang, Jun 1275, 1634, 352 Ilika, Frances N. 1683 Higgins, Sarah H. 253 Holland, Martin 1319 Huang, Stanley Ching-Cheng 1915 Ilika, Valentine C. 1683 Higgins, Stephen 1702 Holland, Thomas 1041 Huang, Wenlin 1314, 861 Ilin, Chuang 1132 Higgs, Stephen 1441, 1855 Holloway, Kathleen A. 1185 Huang, Yan-Jang S. 1441, 1855 Ilkayeva, Olga 1006 High, Daniel 149 Holloway, Kimberly 740 Huart, Michael 765 Imai, Natsuko 594, 773 Higuera-Mendieta, Diana R. 1167, Holme, Daniel 1019 Hubbard, Alan E. 1614 Imamura, Hideo 1318 1400 Holmes, Jon 1079 Huber, Curtis S. 226 Im-erbsin, Rawiwan 45 Higuera-Mendieta, Diana Rocio Holroyd, Nancy 1835 Hübner, Marc P. 1241, 1880 Imoukhuede, Egeruan B. 1277, 174 Holston, James 764 Huda, Naureen 1884 1462, 363 Hii, Jeffrey 999 Homann, Manijeh V. 905 Hudmon, Andy 1293 Imoukuhede, Egeruan B. 180, 182 Hildenwall, Helena 1047, 1122 Honeycutt, Jared 1245 Huezo, Stephanie J. 807, 1531 Imrie, Allison 1407, 766, 770 Hill, Adrian 1277, 1462, 182, 986, Hong, Nguyen Van 804 Huff, Doug 1763 Imus Misiuda, Katherine 1513, . 987, 180, 363 Hongvanthong, Bouasy 1829, 346 Hughes, Angela 1238 1538, 1543, 836 Hill, Catherine A. 1307, 1377 Hontz, Robert D. 439, 759, 775, Hughes, Christine M. 1454, 791 Imwong, Mallika 1829, 214, 355 Hill, Danika L. 930 785, 786, 86, 1131, 166, 596 Hughes, Grant L. 1364, 1808 Inada, Davi T. 1465 Hillesland, Heidi 1141, 496 Hooft, Anneka M. 650 Hughes, Molly 1008 Inamnuay, Laksanee 45 Hinjoy, Soawapak 1429, 593 Hooper, PJ 1321 Hul, Vibol 1452 Incardona, Sandra 1804 Hinojosa, Juan-Carlos 857 Hopkins, Adrian 511 Hulseberg, Christine 391 Infante, Beronica 828, 829 Hinrichs, Dave 1531 Hopkins, Donald 452 Hulverson, Matthew A. 861 Ingabire, Chantal 263, 380 Hirota, Yoshio 374 Hopkins, Heidi 1522, 1699 Hume, Jen C. C. 1279, 1635, 985 Ingasia, Luicer 211, 208, 850 Hirsch, Alec J. 1425 Hoq, Mohammad Rubel 1862 Humphries, Judith 1786 Inglese, James 377 Hiscox, Alexandra 379 Hoque, Mohammad E. 28 Hun, Lewis 638 Iñiguez, Volga 440 Hlanzi, Muzi 1303 Hori, Takanori 482 Hung, Chris 559 Innis, Bruce L. 1219, 163 Ho, Lara 1182 Horii, Toshihiro 370, 374 Hung, Le Xuan 804 Inoue, Juliana 1487, 844 Ho, Nga T. 698 Horn, David 1741 Hunsperger, Elizabeth 1412, 1422, Inoue, Noboru 531, 532 Ho, Trung D. 906 Horn, Joanne M. 1183, 692 37 Inyama, Petrus U. 1392 Hoadley, Alfred W. 1660 Horn, Karin 1370, 716 Hupalo, Daniel 920 Inyang, Uwem 1392 Hoang, Hang B. 250 Hornberg, Claudia 1770 Huq, Anwar 1790 astmh.org A-606 Abstract Author Index The number(s) following author name refers to the abstract number.

Inyanga, Precious 452 Jackson, Nicholas 1223, 553 Jean, Kévin 619, 1443 Jones, Amy J. 1093 Iordanskiy, Sergei 1835 Jackson, Nikki 13 Jean, Samuel E. 1212, 895, 897 Jones, Chris 112 Iovinella, Immacolata 635 Jacob, Benjamin 1067 Jeewandara, Chandima 1259 Jones, Christine 122 Iqbal, Najeeha T. 1008 Jacob, Christopher G. 1606, 1829, Jegede, Ayodele S. 1498 Jones, Christopher M. 1286 Irani, Julia 1615, 653 978 Jelip, Jenarun 1902, 282 Jones, Claire 1201 Irani, Vashti 16, 831, 937 Jacobs, Anna 57 Jemu, Samuel 536 Jones, David 1647, 1649, 991, Iriarte, R. I. 135 Jacobs, Emily 1675 Jennings, Todd 1544 1279, 985 Iriemenam, Nnaemeka C. 935 Jacobs, Jan 232, 419 Jennison, Charlie 1296, 631 Jones, Dean P. 1482, 630 Irish, Seth 721 Jacobs, Jolanta S. 1765, 692 Jentes, Emily S. 1439, 437 Jones, Kathryn M. 1747 Irving, Helen 1284 Jacobs-Lorena, Marcelo 1297 Jeong, Wooseog 1109 Jones, Kiah 478 Isaac, Abraam 1349 Jacobson, Jerry 1550, 655 Jeronimo, Selma M. B. 432 Jones, Scott 1077 Isaac, Andre 1349 Jacobson, Julie 497 Jeun, Rebecca 1289 Jones, Sion 1209 Isaac, Clement 1711 Jacobus, David P. 262 Jhonston, Erik 1110, 792 Jongert, Erik 1276 Isaacson, Sinead C. 788 Jacobus, Laura R. 262 Jia, Peng 286 Jongo, Said A. 123, 1631, 1633 Isern, Sharon 176 Jacqueline, Lim 1342 Jiang, Nona 1136 Jongsakul, Krisada 814 Ishengoma, Deus 1558, 900, 917, Jaenisch, Thomas 1254 Jiang, Qing-Wu 1898 Jonhson, Jeannetta K. 488 1801, 562, 904 Jaffe, David B. 1195 Jiang, Rays H. Y. 587, 445 Joof, Fatou 1582, 219 Ishii, Ken J. 374 Jagannathan, Prasanna 1210, Jiang, Xiaofang 1385 Jordao, Dercio 1269 Ishino, Tomoko 1298, 199, 200, 1261, 17, 332, 329 Jiggins, Francis M. 1196 Jose, Joyce 1256 984 Jagne, Ya Jankey 363 Jima, Daddi 14, 566 Joseph, Chabi 105 Ishizuka, Andrew 1613, 939 Jahan, Assis 1772 Jimenez, Alfons 938 Joshi, Vinayak 1803 Islam, Akhterul 1829 Jahan, Nusrat 146 Jimenez, Ana I. 1345 Jost, Heather 1786 Islam, Kamrul 1200 Jain, Jagrati 970 Jiménez, Gerson 1422 Jost, Philipp J. 946 Islam, Manoshi 1839 Jain, Jay P. 949 Jimenez, Juan 571 Jourdan, Peter M. 1834 Islam, Munirul 1865 Jain, Surendra K. 1087 Jimenez, Sylvia 509 Journel, Ito 1212, 895, 897 Ismagulova, Gulnara 1765 Jairoce, Chenjerai 1553, 1553 Jimenez-Navarro, Elena 260 Juarez, Marisa 1289 Ismail, Hanafy M. 502 Jaiswal, Shalini 1077 Jimma, Daddi 1438 Julceus, Fabrice E. 1860 Ismail, Mamudo R. 1269, 618 Jaiteh, Fatou 1615, 273, 653 Jin, Albert 976 Juliano, Jonathan J. 103, 1085, Isoe, Jun 1358 Jally, Shadrach 1262, 1565 Jin, Li 1157 1650, 585, 802, 915, 916, 543 Isoe, Yurika 1358 Jambo, Kondwani 936 Jin, Xiannu 255 Julião, Fred 1161 Isokawa, Shoko 197 James, Alison 260 Jin Kyung, Park 1342 Juma, Bonventure W. 417 Issa, Kheri 386 James, Anthony A. 632 Jip, Nimzing F. 452 Juma, Dennis W. 207, 209, 210, Issa, Nébié 928 James, Eric R. 1014, 1633, 1637, Jittamala, Podjanee 1829 211 Issiaka, Djibrilla 1601 1638, 1639, 1636, 938 Jittmittraphap, Akanitt 757 Juma, Elijah O. 1378 Issiaka, Djirilla 1624 James, Richard 1901 Jmonneau, Vincent 1317 Juma, Elizabeth 1483 Ito, Akira 1028 Jameson, Samuel 1394 Jo, Matthew 1408 Juma, Jane 1203 Ito, Kazuya 374 Jancaryova, Danica 1233 Johansson, Emily W. 1047 Juneja, Punita 1196 Itoe, Maurice A. 128 Jang, Ihn Kyung 1520, 1538, Johansson, Michael 142, 437 Jung, Ha-Na 1147, 1449 Ittiprasert, Wannaporn 672 1543, 836, 274 Johansson, Michael A. 160 Jung, Min-Kyung 78 Ittiverakul, Mali 1479, 1502, 323 Janga, Dennis 1558, 833, 843, John, Chandy C. 1056, 1475, Junghanss, Thomas 1254 Ivanga, Marcos Mbulito 1003, 891, 900, 910 1477, 195, 326, 629, 1051 Jungkind, Donald 1054 1660, 1869 Jangpatarapongsa, Kulachart 349 John Bockarie, Moses 1929 Junior, Alfredo M. 844 Ivens, Alasdair 443 Janiak, Anna 1220 Johns, Benjamin 681, 1622, 309 Jura, Reginald O. 850 Ivers, Louise C. 1860 Jankechova, Monika 1733 Johnsen, Mark 1888 Jurado Salazar, Hugo 94 Iverson, Lara J. 1331 Janko, Mark 1557 Johnsen, Peter 1325 Juraska, Michal 371 Ivinson, Karen L. 1277 Jannat, Kaniz Khatun E 1164 Johnson, Brian J. 728 Just, Matthew R. 389 Iwalokun, Bamidele A. 929, 1568 Janse, Chris J. 1296, 1647, 559 Johnson, Derrick 1293 Jutla, Antarpreet 1007, 1790 Iwunze, Rosemary C. 570 Jansen, Cassie 1806 Johnson, Elizabeth 277, 35, 674 The Ixodes scapularis Genome Jaramillo, Alexandra 1306 Johnson, Erik P. 1695 Consortium 1307 Jarju, Sheikh 1018, 1676, 411 Johnson, Hugh T. 987 Iyori, Mitsuhiro 378 Jarman, Richard G. 1219, 163, Johnson, Mark D. 1048, 648 K Izadnegahdar, Rasa 1838 171, 183 Johnson, Monika 1840, 1843 Kaadan, Abdulnasser 425 Izurieta, Ricardo 484 Jarvis, Adrienne P. 1408 Johnson, Philip C. 463 Kaatera, Fred 263 Izzo, Robin 1325 Jäschke, Anja S. 337 Johnson, Roshawn 555 Kabamba, Joelle 1454, 1455, 791 Jasinskas, Aldis 1606 Johnston, Deborah 283 Kabanywanyi, Abdunoor M. 1049, Jasinskas, Algis 1602, 1646, 943, Johnston, Kelly 1078 854 978 Joice, Regina 1471 Kabatereine, Narcis B. 1228, 1824 J Jatapai, Anchalee 416 Jois, Malasa 1911 Kabayiza, Allan 1578 Jawara, Musa 113, 1399, 1582, Jojoa, Sandra J. 1750 Jack, Darby 1305 Kabir, Furqan 1008 888 Jokrate, Possawat 416 Jacko, D. 1733 Kabir, Mamum 1154 Jawhari, Badeia 1349 Jolly, Pauline 204 Jackson, Belinda M. 1077 Kabir, Mamun 1136, 408 Jawo Ceesay, Serign 529 Joly, Damien O. 1452, 187 Jackson, Bryan 993 Kabona, George 1686, 1687, 1688 Jayashankar, Lakshmi 1850 Jones, Alex 469 astmh.org Abstract Author Index A-607

The number(s) following author name refers to the abstract number.

Kabore, Achille 1685, 456, 527 Kamstra, Rhiannon L. 1703 Kassahun, Belay 1572 Keereecharoen, Lily 1266 Kabore, Jean Moise T. 853 Kamugisha, Erasmus 1801 Kassim, Kamaka R. 364 Keesen, Tatjana S. L. 1849 Kabre, Gustave B. 1871 Kamugisha, Mathias 1686, 1687, Kastner, Randee 1060 Kefyalew, Takele 229 Kabue, Mark 1330 1688, 904 Kasule, Mathias 1572 Keiser, Jennifer 1273 Kabula, Bilali 1286, 718 Kamuliwo, Mulakwa 1627, 1629, Kasungami, Dyness 1330 Keita, Abdoul S. 1260 Kabyemela, Edward R. 1580, 1264 388, 1218, 278 Katabarwa, Moses N. 451, 452 Keita, Mohamed 1624 Kachani, Malika 1118 Kamwezi, Richard 847 Katamba, Achilles 1767 Keita, Moussa 1901 Kachur, S. Patrick 14, 1901, 960, Kamya, Moses R. 1210, 1261, Katamba, Henry 1572 Keita, Sekouba 1576, 1601, 990 305, 597, 911, 566 1614, 1875, 227, 279, 809, 811, Katebe-Sakala, Cecilia 388 Keller-McLaughlin, Sarah 926 Kachurin, Anatoly 553 812, 283, 313, 329, 332, 947 Kateera, Fredrick 380, 348 Kelley, James F. 757, 790 Kadarkarai, Murugan 295 Kandeel, Amr 1762 Kathcart, April K. 1276, 1278 Kelly, Gerard C. 873 Kading, Rebekah 1236 Kandula, Deepika 1536, 1554 Kathende, Sosthenes 31 Kelly, Jane 487 Kaelber, Jason 140 Kang, Gagandeep 1013, 1864, Katile, Abdoulaye 1636 Kelly, Jane X. 1531 Kafuko, Jessica M. 268, 1392 396 Kato, Nobutaka 1206, 1527 Kelly, Paul M. 1165 Kahle, Kristen M. 176, 38, 549 Kang, Laiyi 1735 Kato, Tomoyo 203 Kelly-Hope, Louise 1067, 1817, Kahn, Maria 1218, 1520, 280 Kang, Seokyoung 1197 Katokele, Stark 863 1927, 727, 1816, 457, 642 Kain, Kevin C. 1468, 253, 350, Kang, Seung-Won 1147, 1449 Katooka, Oswell 1788, 581 Kelvin, Elizabeth A. 1032 429, 629 Kangam, Lafortune 908 Katowa, Ben 111, 1590, 342 Kemere, Jordan 1594 Kaisar, Maria 501 Kang Sung, Lee 1342 Katrak, Shereen 1261, 313 Kemigisha, Elizabeth 65 Kaisar, Maria M. M. 468 Kanjala, Maxwell 485 Katsube, Riko 200 Kemirembe, Karen 1490 Kaj, Malonga 414 Kannady, Khadija 598 Kattenberg, Johanna H. 1262, Kempaiah, Prakasha 1591, 1592, Kakaire, Robert 1727, 1727, 490 Kanoi, Bernard N. 370, 979, 374 1565 1593, 1769, 589, 1334 Kakani, Evdoxia G. 1390, 1395, Kanoute, Moussa B. 1601 Kattula, Deepthi 396 Kempf, Dale 1071, 1078, 645 126, 1387 Kansembe, Henry 681 Katureebe, Agaba 1261 Kenji, Obadia Mfuh 1597 Kaker, Faizullah 214 Kanteh, Ebrima 363 Katureebe, Charles 1572, 1875 Kennedy, Mark 861, 1174 Kakolwa, Mwaka A 854 Kapar, Naomi 268 Katusele, Michelle 735 Kennedy-Stoskopf, Suzanne 666 Kakompe, Kalenga 1627, 1629 Kapella, Bryan 1572, 1875, 947 Katz, Aaron T. 689 Kenneth, John 1773 Kakumanu, Madhavi 1311, 708 Kapito-Tembo, Atupele 599, 654, Katzelnick, Leah 554 Kenney, Joan L. 1856 Kakuru, Abel 1210 914 Kaufman, Phillip E. 1404 Kenny, Shannon 1873 Kakutia, Natia 706 Kaplan, Peter 1051 Kaunda, Blessings 841 Kepha, Stella 461, 54 Kalabric, Luciano 1161 Kappe, Stefan 1274, 1608, 248, Kaur, Harparkash 1653, 819 Kerac, Marko 1301, 823 Kalavska, Andrea 493 1613, 1589, 1826 Kaushansky, Alexis 1608 Kerdahi, Khalil 1675 Kalavsky, Erich 493 Kaptoge, Stephen K. 1216 Kavere, Emmy 1833 Kerleguer, Alexandra 1904 Kalayanarooj, Siripen 170, 171, Kapulu, Melissa C. 987 Kavishe, Reginald 1500 Kerlin, Tim 728 591 Karabou, Potchoziou 506 Kawazu, Shin-ichiro 531, 532 Kerr, Nicola 857 Kaldor, John 541 Karanja, Diana M. 1243, 1785, Kawende, Bienvenu 882 Kerridge, Simon 1201 Kale, Oluwafemi 1492 1833 Kawu, Issa 837 Kerry, Vanessa 682 Kale, Sonal 920 Karch, Christopher 376 Kayembe, Dyna 882 Kessler, Anne 205 Kalengamaliro, Humphreys 841 Karema, Corine 1340, 1379, 315, Kayembe, Jean-Marie N. 290 Kessler, Maureen 122 Kalilani, Linda 1556 1578, 1868 Kayentao, Kassoum 898, 902 Kessy, Stella 109 Kalimuthu, Kovendan 295 Karhemere, Stomy 1454, 1455, Kayungwa, Benjamin 1625 Kesteman, Thomas 116, 885 Kalinga, Akili 1558, 833, 843, 891, 791, 878 Kazura, James 1262, 1604, 21, Keven, John B. 735 910 Karia, Francis P. 1326 568, 735, 1565, 1719 Keyloun, Katelyn R. 861 Källander, Karin 1774, 1775 Karim, Zachary S. 1591, 1592, Kazwala, Rudovick R. 1105 Keystone, Jay S. 646 Kallas, Esper G. 1221, 761 1593, 1769, 589 KC, Astha 1791 Khairallah, Carole 1556, 883 Kalnoky, Michael 1546, 1626, 975 Kariuki, Sam 5 KC, Natasha 1014, 377 Khalil, Insaf 1489 Kama, Mike 541, 663 Kariuki, Simon 597, 911, 960, 683 Ke, Changwen 1107 Khaliq, Mansoora 1256 Kamagaté, Mamadou 158 Kariyawasam, Udeshika L. 1757 Kean, Casey 388 Khamis, Mwinyi 657 Kaman, Lama E. 889 Karmacharya, Biraj 1198 Keany, Melissa 471 Khan, Ashraful I. 1861, 1862 Kamata, Teddy 4 Karunajeewa, Harin 568 Keasey, Sarah 4 Khan, Farhat 1645 Kamate, Beh 602 Karunaweera, Nadira D. 1102, Keating, Joe 278 Khan, Ikhlas 1528, 1535 Kamate, Bourama 1636 1757 Keating, M. K. 37 Khan, Maria 281 Kamau, Edwin 207, 208, 210, 211, Kas, Arnold 980 Keatts, Lucy 1452 Khan, Md Rakibul H. 1790 347, 850 Kasamba, Eric 414 Kebede, Amha 1045, 14, 566 Khan, Shabana 1528, 1535 Kambagha, Athoman 266 Kasdin, Rachel 1488 Kebede, Henok 269 Khan, Shahid 559, 1296, 1647 Kamdem, Colince 1810, 1892 Kasinathan, Ravi S. 1900 Kebede, Zelalem 229 Khan, Shaila S. 1154 Kamgno, Joseph 1818 Kaslow, David C. 1276 Kebela-Illunga, Benoit 1117, 6, Khan, Wasif A. 316, 886, 1829 Kamhawi, Shaden 1690 Kaspar, Naomi 1905, 386 799 Khanal, Amsul 1895, 538 Kaminta, Slyvester 404 Kasper, David C. 1336 Keck, Forrest 747 Khanam, Farhana 1199, 1200, Kamphorst, Sylvie M. O. 1819 Kasper, Matthew 183, 705, 1764 Keeler, Corina 543 1202, 392 Kampmann, Beate 1018, 1676, Kasper, Matthew R. Kassa, Hailu Keeler, Corinna 1557 Khanthavong, Maniphone 1829 363, 411 1140 Keeling, Matt J. 1744 Kharabora, Oksana 916 Kampondeni, Samuel 177 Kassa, Moges 14, 566 Keenan, John 204 Khatamzas, Elham 1178 astmh.org A-608 Abstract Author Index The number(s) following author name refers to the abstract number.

Khatib, Bakar O. 1235 Kirby, Matthew J. 1371 Kobylinski, Kevin C. 1283, 880 Kostov, Ivan 1209 Khatib, Bakari O. 112 Kirenga, Bruce 1767 Koch, Claus 1489 Kotloff, Karen L. 1203, 28 Khatun-e-Jannat, Kaniz 1839 Kirera, Ronald 391 Koch, David 473 Kouakou, Ilunga M. M. 1074 Kheang, Soy Ty 1001, 1539, 1540, Kirinoki, Masashi 531, 532 Koch, Tyree 551 Koudou, Benjamin G. 115 251 Kirkpatrick, Beth D. 1220, 1408, Kochel, Tadeusz J. 596 Kouly Tine, Roger Clément 1610 Kheang Heng, Thay 15 1411, 1700, 1863 Kocher, Claudine 709 Kouodjip Nono, Larissa 908 Kheng, Sim 1904 Kirkwood, Carl D. 1013 Kodio, Aly 1000 Kourany-Lefoll, Elli 83 Khieu, Virak 1904 Kirkwood, Geoffrey 1544 Koelle, Katia 159 Kouriba, Bourema 1563, 835, 978 Khim, Nimol 12, 9 Kironde, Fred 343 Koenker, Hannah 1566, 1616, 384 Kousa, Youssef 1051 Khor, Chiea Chuen 1270 Kirumbi, Edward 1685, 1686, Koenraadt, Constantianus J. 380, Kovácˇ, Pavol 397, 1861 Khouri, Ricardo 1092 1687, 1688 1379 Kovacic, Vanja 676 Khyang, Jacob 886 Kirunda, James 1658 KoKoepfli, Cristian 1262, 1555, Kovacs, Stephanie 228, 848 Kibona, Tito J. 1105 Kisia, Caroline 1337 568 Kowal, Ashley 388 Kibria, Mohammad Golam 1411, Kisinza, William 1870, 306, 360, Koffi, Alphonsine A. 1370 Koyoc-Cardeña, Edgar 117, 723 316 718 Koffi, Mathurin 1317 Kraemer, Moritz U. G. 1440 Kibuuka, Afizi 812 Kissinger, Jessica C. 1152, 1471, Kofoed, Poul-Erik L. 1500 Krähling, Verena 180 Kien, Duong T. Hue. 594 922 Koh, Gavin C. K. W. 1209 Krai, Priscilla M. 256 Kieta, Moussa 1398 Kissi-Twum, Abena A. 402 Kohi, Yadon M. 1558, 900 Kramer, Karen 386 Kiggundu, Moses 1505 Kitau, Jovin 1371 Koh Paw, Moo 1266 Kramer, Kenton 678 Kigondu, Sanyu N. 385 Kite, Whitney A. 1485 Koimbu, Gussy 735 Kramer, Laura 1808, 731 Kigozi, Ruth 1875, 947 Kitron, Uriel 124, 156, 507, 726 Koita, Fanta 1208 Kramer, Laura D. Krasucki, Peter Kigozi, Simon P. 279 Kitsahawong, Bubpha 652 Koita, Ousmane A. 1496, 858, 859 E. 262 Kiguli, Sarah 1505 Kittikraisak, Wanitchaya 178 Koivogui, Lamine 889 Kratz, Thomas 1182 Kihara, Jimmy H. 464, 54, 25 Kittitrakul, Chatporn 652 Kojom Foko, Loick P. 908 Krause, Michael A. 1260 Kihombo, Aggrey 360 Kittur, Nupur 1243, 1833 Koju, Rajendra 1198 Krause, Peter 545 Kiketa, Landry 882 Kitumbukile, Mohammed 1893 Koko, Vanda 335, 932, 933 Krcmery, Vladimir 1733, 1737, Kikonyogo, Ruth N. 620 Kitutu, Freddy E. 1047 Koku, Roberta 431 492, 493 Kilangalanga, Janvier 1685 Kiwanuka, Gertrude 1575, 292 Kolakalur, Sripriya D. 1130 Krecek, Rosina Claudia 1139 Kilembe, Bernard 1687, 503, 505 Kiwanuka, Noah 1727, 490 Kolarich, Daniel 16 Kreishman-Deitrick, Mara 255 Kilian, Albert 384 Kiware, Samson S. 598 Kolesnichenko, Olena 667 Kreklywich, Craig 41 Killeen, Gerald F. 1893 Kizza, Florence N. 1727, 490 Kolling, Glynis 1290, 1674 Kremsner, Peter G. 1633, 322, Killeen, Gerry F. 598 Kjetland, Eyrun F. 1834 Kolyada, Lena 1372 938, 854, 1651 Kim, Andrea A. 417 Klarkowski, Derryck 833 Kolyada, Yelena 1392 Krentel, Alison 1226, 1338 Kim, Charles C. 17 Klarmann-Schulz, Ute 1709, 639, Kombut, Benishar 1262 Kreppel, Katharina 1809 Kim, Do Soon 1109 644 Komisar, Jack 1278 Kress, Adrian T. 1276 Kim, Eui Young 89 Klein, Kerenaftali 1207 Komisar, Jack L. 1276 Krettli, Antoniana 252 Kim, Kami 205, 33 Klein, Marina 1703 Konadu, Peter 639 Krezanoski, Paul J. 1872 Kim, Min-Sik 1297 Klein, Meredith 1190, 695, 1621 Konate, Amadou 1279 Krogstad, Donald Krogstad, Donald Kim, Saorin 1904, 9 Kleine, Christian 854 Konate, Drissa 1260 J. 1398, 1496, 1497, 1583, 858, Kim, So Young 1077, 1713 Kleinschmidt, Immo 1870, 236, Konaté, Lassana 1192, 1373, 272 859, 218 Kim, Tae Yun 1159 563, 601 Konate, Siaka 727 Krolewiecki, Alejandro 1289 Kim, Yongsang 1109 Kleinshmidt, Immo 1869 Kone, Abdoulaye K. 1563 Kroon, Erna G. 1114 Kim, Young-Ha 1147, 1449 Kleps, Jason 1660 Kone, Diakalia 1624 Kropp, Laura E. 1712 Kimita, Gathii 412 Kligerman, Maxwell 675 Kone, Douda 602 Krudsood, Srivicha 838 Kimura, Daisuke 330 Klimstra, William B. 137, 138, Kone, Mamady 1279, 1576, 990 Kruger, Philip 264 Kimura, Kazumi 330 1444, 42, 746 Kong, Nareth 10, 1502 Kruger, Taneshka 264 Kindé-Gazard, Dorothée 527 Klion, Amy D. 1881, 727 Konradt, Christoph 1845 Krull, Wolfgang 698 King, Charles H. 1124, 1242, 156, Klonis, Nick 1873 Koo, Sue-Jie 514 Krusood, Srivicha 816 1123, 124, 151 Kloprogge, Frank L. 945 Kopecko, Dennis J. 1014, 1204 Krytus, Kimberly 1839 King, Christine A. 1423 Klugman, Keith P. 1770 Koppinger, Kaitlin L. 478 Ku, Tiffany 1791 King, Christopher L. 1242, 1565, Klungthong, Chonticha 1221, 170, Koram, Kwadwo 1480, 482, 907 Kuan, Guillermina 136 1599, 1600, 1604, 1719, 925, 171, 178, 184, 36, 591, 739, Koram, Kwadwo A. 216, 899 Kublin, James 248, 1274 930, 940, 1605 783 Korir, Harrison K. 1833 Kubofick, Joseph 1812, 1881 King, Jarrod B. 1534 Knight, Rob 543 Kornelis, Dieuwke 1837 Kubota, Mayumi 401 King, Jonas G. 1360, 946, 993 Knipes, Alaine K. 1059, 1229 Koroi, Aminiasi 541 Kuehn, Andrea 830 King, Kevin 149 Knobel, Darryn L. 1108 Koroivueta, Josefa 541 Kuesel, Annette C. 1715 Kiniboro, Benson 1262, 334 Knobler, Stacey 784 Koroma, Joseph B. 1930 Kuhn, Richard J. 1256 Kinney, Patrick 1305 Knoll, Maria 1017 Kosal, Khem 1904 Kuile, Feiko O. ter. 960 Kinunghi, Safari 1782 Knols, Bart 109 Kosasih, Ayleen A. 294, 864 Kuklinski, Wojtek 1285 Kinya, Beth M. 412 Knowles, Jessenia 1661 Koscalova, Alena 1906 Kukuruga, Mark 44 Kioko, Elizabeth N. 90 Knowles, Sarah 1232 Kosek, Margaret 1864, 393, 394, Kumar, Anil 1459, 7 Kip, Anke 1748 Kobayashi, Tamaki 111, 1567, 576 Kumar, Ashkita 688 Kip, Antonia E. 1090 1590, 301, 342, 877, 879, 903 Kosoko, Ayokulehin M. 1603 Kumar, Ashwani 1474 astmh.org Abstract Author Index A-609

The number(s) following author name refers to the abstract number.

Kumar, Nirbhay 1295, 361, 365 Laguna, V. Alberto 1436 Lasonder, Edwin 559 Lee, Ming-Chieh 956 Kumar, Pavan 1842 Laguna-Torres, Victor A. 792, 1110 Lasry, Estrella 1906 Lee, Patricia 255 Kumar, Rajiv 512, 518 Lahon, Anismrita 734 Lasso, Paola 1759 Lee, Sangmi 708 Kumar, Ritu 1626, 975 Lai, Chih-Yun 1407 Last, Anna 1319 Lee, Stuart 317 Kumar, Sanjai 1153, 1295, 1802, Lai, Wen-Ter 750 Lataillade, J. P. 1692 Lee, Xia 710 44, 699 Laing, Nicolas 434 Latham, Catherine F. 16 Lee, Yan 638 Kumar, Swapna 582 Lainhart, William 102, 125 Lau, Colleen L. 663 Lee, Yeuk-Mui 1243 Kumar, Vijay 502 Laktabai, Jeremiah 1041, 1187, Lau, Louis 554 Leegwater, Anthony 681 Kumar Das, Manoja 1126 239 Laucella, Susana A. 1851 Leelawong, Mindy 1644 Kumari, Priti 1294 Lal, Sham 1184, 1800, 684 Laudisoit, Anne 1069 Leepipatpiboon, Natchanun 254 Kumkhaek, Chutima 672 Lalani, Tahaniyat 1048, 648 Lauer, Peter 1647 Leeuwis, Cees 379 Kumpornsin, Krittikorn 1481 Lalji, Shabbir 1216, 268, 386, 600 Lauer, Stephen A. 593, 1429 Lefèvre, Gilbert 949 Kunene, Simon 1536, 866 Lalloo, David G. 851, 1559 Laufer, Miriam K. 1265, 1602, Lefevre, Thierry 633, 982, 560 Kunstadter, Peter 1329 Lam, Aminata 249 1646, 485, 599, 654, 923, 18, Legac, Jennifer 227 Kuntawunginn, Worachet 10, Lam, Ha Minh 617 927 Legarda, Almudena 938 1479, 15, 1502, 814 Lam, L.K. Metthew 1444, 746 Laurens, Matthew B. 1563, 1606, Leger, Raymond J. St.. 1281 Kunthy, Sok 912 Lam, Long K. M. 138 1633, 485, 921, 978, 835 Legras-Lachuer, Catherine 1857 Kuri, Pablo 167 Lama, Marcel 1659, 971 Laursen, Erik 1176 Leguia, Mariana 1764, 183, 705, Kurosaki, Yohei 179 Lambert, Christophe G. 589 Lauthier, Juan José 1089 709, 778 Kurtis, Jonathan D. 1264, 1271, Lambert, Grant 149 Lauzardo, Michael 1841 Lehane, Michael 676 1580 Lambert, Lynn 1635, 1648, 1649, Lavarello, Roberto J. 1910 Lehman, Leopold G. 908 Kushinga, Garikai 926 375, 878, 941, 991 Lavery, Jim 1234 Lehnig, Chris 1436 Kusriastuti, Rita 864 Lambert Chalachala, Jean 882 Law, Natasha 1021 Lehrer, Axel T. 3 Kwak, Stephen 399 Lamberton, Poppy H. L. 1824, 461 Law, Sha 814 Leisnham, Paul T. 1402 Kwakye, Cynthia 1023, 1677 Lambrechts, Louis 590 Lawford, Harrriet L. S. 9 Leite, Álvaro M. 1012, 63 Kwansomboon, Nithipa 289 Lammie, Patrick 1229, 1680, 458, Lawrence, William S. 1014 Leite, Jose Paulo G. 1013 Kwarisiima, Dalsone 313 1059 Lawrie, Alison 1277, 1462, 363 Leiva, Karina P. 1644 Kwiatkowski, Dominic 1389, 1828, LaMonte, Gregory 1827 Lay, Srey Rath 590 Leke, Rose G. F. 1597, 245, 489, 1829, 317 Lanar, David 376, 946 Layibo, Yao 506, 508 932, 335, 933, 1798 Kwofie, Kofi D. 431 Lanata, Claudio F. 1770, 1840, Layland, Laura E. 1241 Lell, Bertrand 1633, 618, 938 Kwong, Laura 25, 577 1843 Lazaga, Nelson 678 Le Menach, Arnaud 1214, 1301, Kyagulanyi, Tonny 1507, 839 Landman, Keren Z. 14 Lazarus, Wilfred 1816, 1817 1514, 1542, 1554, 823, 863, Kyaw, Myat P. 1581, 1829, 943, Landmesser, Mary E. 19 L’Azou, Maïna 158, 595, 774, 167 866, 876, 1536 999 Landry, Jasmine A. 1785 Lazzarini, Luca 1696 Lemenze, Alexander 1681 Kyeba, Johnson 1893 Lane, Whitney C. 137 Le, Dui T. 145 Lemnge, Martha M. 1694, 562, Kyelem, Dominique 727 Lang, Trudie 1094 Le, Hung X. 906 904, 1801, 917 Kyeremeh, Kwadwo F. 1080 Langhorne, Jean 926 Leach, Amanda 371 Lemoine, Jean Frantz 1212, 1229, Kyle, Dennis E. 1493, 1611 Langshaw, Emma 60 Leal, Grace 140 1814, 897, 1059, 876, 895 Langsjoen, Rose M. 1442 Leang, Bunthai 8 Leneghan, Darren 986, 987 Lanier, Jeffrey B. 1021 Leang, Rithea 8, 872, 9 Lenhart, Audrey 117, 723 Lanier, Lewis 1410 Leaungwutiwong, Pornsawan 757, Lenihan, Patricia 463 L Lanke, Kjerstin 588 790 Lennon, Niall J. 371 Lanteri, Charlotte A. 323, 802, LeBihan, Amelie 1488 Leo, Yee-Sin 1270 Labaeka, Yemi 345 1829, 585 Le Clec’h, Winka 1158, 1780, Leon, Juan 440 Laban, Natasha M. 301, 879, 1876 Lapierre, Didier 371 1781, 671, 1782 León, Renato 1423 LaBarre, Paul 1333, 1513, 1520, Lapika, Bruno 882 Leder, Karin 646 Leonardo, Lydia R. 531, 532 1538, 1543, 1734, 235, 274, Lara, Victor 1347, 967, 971 Ledesma, Nicholas 1404 Leong, Meredith L. 1647 836 Larasati, Tri A. 864 Ledgerwood, Julie E. 1462, 1633, León Janampa, Nancy 1106 LaBeaud, A. Desiree 1054, 1123, Lardner, Deborah A. 78 180, 1854, 182 León-Quispe, Jorge 1749 1124, 1242, 156, 5, 1509, 741, Larmat, Michelle 368 Lednicky, John 155 Lepine, Edith 1219, 163 151, 650, 124 Larmat-Delgado, Michelle 1632 Le Doare, Kirsty 411 Leroy, Didier 220 labib, Manal 1762 LaRocque, Regina C. 397 Lee, Cynthia K. 1276, 1277 Leroy, Odile 1201, 363 Lacerda, Marcus V. G. 1482, 630, Larremore, Daniel B. 931 Lee, Deborah 56 Lertjuthaporn, Sakaorat 162 830 Larsen, David 1567 Lee, Diana J. 794 le Rutte, Epke A. 1250 Lachau-Durand, Sophie 1720 Larsen, David A. 1788, 23, 24, Lee, Gwenyth O. 27, 576, 1864 Lescano, Andres G. 1510, 1644, Lacroix, Audrey 1452 581, 867 Lee, Hakho 1202 1710, 1913, 472, 475, 100, LaDeau, Shannon 1402 Larson, Bruce 1547, 1623, 881 Lee, Hee-Soo 1147, 1449 1316, 132, 1357 Lado, Paula 93 Larsson, Catherine J. 1220, 1408 Lee, Jung Seok 1406, 1434, 776, Leslie, Denise 1032 Lafrance, Alexander 399 LaRue, Nicole 280, 281 779 Lessa, Marcus 1251 Lagarde, Mylene 684 Lasala, Fatima 744 Lee, Kang Sung 1406, 1434, 771, Lesser, Adriane 1187, 239 Lagatie, Ole 1079 Laserson, Kayla F. 1203, 1459 776, 779 Lessler, Justin 139, 1429, 1456, Lago, Catherine B. 36 Lash, R. Ryan 437 Lee, Lisa M. 80 1666, 1859, 593 Lago, Ednaldo 1848 Laskowski, Michelle 1638 Lee, Lydia 235 Lessler, Justin T. 170, 591 astmh.org A-610 Abstract Author Index The number(s) following author name refers to the abstract number.

Leto, Dezarae 1332 Lim, Yvonne A. 1029 Lloyd, Melanie 1074, 1894 Lovane, Lucilia 1269 Leung, Daniel T. 1010, 1861, 1862, Lima, Aldo A. M. 1012, 1668, Lloyd, Yuki 678 Lovchik, Janece 1220, 1408 397 1669, 63 Lloyd, Yukie M. 335, 932, 933 Love, R R. 1195 Leurent, Baptiste 1522 Lima, Clayton P. S.. 1465 Lo, Eugenia 1391 Lover, Andrew A. 1217, 1508, 250, Leutscher, Peter 1834 Lima, Giselle F. M. C. 1487, 844 Lo, Nathan C. 1821 873, 874 Levi, Jose E. 1413, 844 Lima, Ila F. N. 1012, 1668, 1669, Lobo, Neil Lobo, Neil F. 1397, LoVerde, Philip T. 1781, 1782, 669, Levine, Myron M. 1152, 1203, 28 63 1811, 846, 864, 1809, 598 671 Levine, Rebecca 37 Lima, Juliana F. C. 1252 Locksley, Richard M. 605 Lovett, Brian Richard 1281 Levis, S. 1856 Lima, Luciana 988 Lodh, Nilanjan 528 Lowe, Rachel 147 Levis, Silvana 742 Lima, Ma Angeles 1906 Loesche, Michael A. 1847 Lowenberger, Carl 1363, 1366 Levitz, Lauren 1557, 1650 Lima, Noélia L. 1012, 63 Loescher, Thomas 1707 Lowry, John H. 663 Levy, Jens W. 36, 739 Limkittikul, Kriengsak 779 Logan, Josanne 672 Loyola, Steev 700, 705, 709 Levy, Michael Z. 103, 1116, 1754, Limsalakpeth, Amporn 15 Lohfeld, Lynne 1537 Lozano, Anyela 1406 1755, 1756, 711, 95, 99, 1758 Lin, Clara S. 334 Lok, James B. 1778, 608 Lozano, Marisa 1357 Lewallen, Susan 1803 Lin, Enmoore 334 Lomax, Jane 446 Lozano-Fuentes, Saul 1196, 1236 Lewis, David 1277 Lin, Jessica 10, 15, 1502, 585, 802 Lombardini, Eric D. 45 L Saunders, David 1132, 323 Lewis, James 1763 Lin, Jingwen 926 Lombore, Bart 1719 Lu, Kai 38 Lewis, Sheryl A. 689 Lin, Leyi 1219, 163 Lon, Chanthap 10, 1132, 1479, Lu, Louise 50 Lewis, Timothy 1527 Lin, Ping-Chang 750 15, 1502, 1829, 323, 585, 802, Lu, Miao 1863 Lezama, Percy 1011 Lin, Ren-yong 1026, 1027, 574 862 Lu, Ziyue 253 Li, Benwen 447 Lin, Zaw 1581 Londono, Berlin L. 1394 Luang Suarkia, Dagwin 770 Li, Chenxi 1051, 651 Linares, Maria 800 Londono-Renteria, Berlin L. 120 Lubell, Yoel 955 Li, Daniel 1455 Linárez, Oscar M. 1042, 430 Long, Carole A. 1260, 369, 931, Lubinda, Jailos 1537, 877, 903 Li, Jun 1534, 558 Lindblade, Kimberly 178, 178, 597, 979, 987, 992, 950, 986 Lubis, Chairuddin P. 1504 Li, Lee 986 911 Long, Kanya C. 131, 590 Lubis, Inke N. D. 1504 Li, Lin-Han 1898 Lindegardh, Niklas 254 Long, Kurt Z. 28 Lubis, Munar 1504 Li, Minglin 1014, 1204, 1639, Linder, Daniel 413 Long, Thulan 1531 Luby, Stephen P. 1164, 1839, 580, 1647, 46, 989 Lindner, Scott E. 1174, 861 Longley, Rhea 830 582, 577 Li, Ping 1193 Lindoso, José Ângelo L. 1101 Longwe, Herbert 936 Lucak, Susan 1005, 1272 Li, Qigui 1525, 255, 257, 1531 Lindsay, Robbin 740, 780 Looney, David 415 Lucas, Bradford 720 Li, Sarah 672 Lindsay, Steve W. 1887, 283 Loor, Martha 52 Lucchi, Naomi W. 246, 628 Li, Shanping 902 Lines, Jo 723 Loor, Sophia 52, 649 Luchavez, Jennifer 1804 Li, Suzanne 49 Linguba, Joseph 456 Lopaticki, Sash 1296, 631 Lucidarme, Jay 1324 Li, Tao 1639, 46, 561, 989 Linton, Yvonne-Marie 1357 Lopera-Mesa, Tatiana M. 1260 Lucien, Mentor A. 1706 Li, Xiaolian 1490 Liomba, Alice 33 Lopes, Victor G. 539 Luck, Ashley N. 1882 Li, Yan 193 Liss, Nathan 38 Lopez, Ambrosio 669 Luckhart, Shirley 1353 Li, Yu 1454, 1455, 791 Littrell, Megan 1524, 817 Lopez, Brenda 133 Lufesi, Norman 1127 Li, Yue-Sheng 1825 Liu, Changchun 1778 Lopez, Carolina 1478 Lugaajju, Allan 343 Li, Yuexin 1531 Liu, Chengfang 50 Lopez, Martha 472 Lugemwa, Myers 1572, 1875 Liang, Hong-Erh 605 Liu, Eugene 336 Lopez, Miguel 1024 Luhanga, Misheck 307, 686 Liang, Neal 1107 Liu, Haining 1172 Lopez, Velma 1306 Luka, Madalitso 358 Liang, Song 1898 Liu, Hui 387, 893 López, Victor 729 Lukama, Chinyama 1788, 23, 24, Liang, Xiaoying 1490 Liu, Jie 1008, 1013 Lopez Carvajal, Liliana 1094 581 Liang, Yousheng 530 Liu, Lindy 1454 Lopez-Perez, Mary 1569, 1632 Lukas, Heather 1678 Liao, Joseph C. 1836 Liu, M. 204 Lopez-Rubio, Jose-Juan 1172 Lukens, Amanda K. 1206, 1533, Liberski, Paweł P. 782 Liu, Mingli 1618 Lopez-Sifuentes, Victor 1357 1527 Libman, Michael 646 Liu, Weimin 894 Lopez-Urbina, Maria T. 1030 Lumbala, Crispin 1103, 1743, Lichtenberger, Paola 570 Liu, Wenjun 789 Lopez-Verges, Sandra 1421, 1461, 1760 Lieber, Allison 697 Liu, Xia 338 1410 Lumsden, Joanne 1275, 1613, Lieberman, Michael M. 3 Liu, Xiaofang 1450 Lorena, Marcelo J. 1281 1634, 352, 977 Liebman, Katherine M. 1495 Liu, Yaobao 1594 Lorenzi, Olga D. 1422 Luna, Christian A. 1804 Lienhardt, Nathan 1003, 1661 Livezey, Jeffrey R. 1276 Lorenzoni, Cesaltina 1269 Luna, Expedito J. A. Lietz, Henrike 673 Livingston, Jerry L. 688 Lorsuwannarat, Natcha 200 Luna, Expedito J. Albuquerque Lievens, Marc 1276, 371 Li Wai Suen, Connie S. N.. 830 Losada, Liliana 1596 1697, 1413 Likafi, Toutou 1454, 1455, 791 Lizarazo, Erley 175, 756 Los Ranchos, Health Center 401 Lund, Emily 633 Likwela, Joris L. 1557, 1659 Lizewski, Rhonda A. 1180 Lotfipour, Mona 1797 Lund, Ole 1500 Likwela, Josias 1926 Lizewski, Stephen 1180 Loucoubar, Cheikh 192 Lungu, Chris 1625, 1627, 1629 Lilay, Abrham 1438 Ljolje, Dragan 246, 808 Louis, Yves J. 155 Luo, Alex 1552 Liles, W. Conrad 429, 629 Llanos-Cuentas, Alejandro 1518, Louisa, Melva 804 Luong, Bao N. 771 Lim, Jacqueline K. 1406, 1434, 1595, 1910, 303, 567, 857 Lourenço, Christopher 863, 612, Luong, Thu-lan 255 771, 776, 779 Llewellyn, Martin S. 1246 1554 Lupiya, James 1567, 903 Lim, Pharath 1829, 220 Llewllyn, Stacey 26 Loutfy, Mona 1735 Luplertlop, Natthanej 757 Lim, Sl-Ki 1434, 771, 779 Llinas, Manuel 1469 Louw, Braam 264 Lupone, Christina D. 1423 astmh.org Abstract Author Index A-611

The number(s) following author name refers to the abstract number.

Luppo, Victoria C. 742 Machicado, Jorge D. 1155 Maiden, Martin M. 1324 Maloney, Kathleen 1301, 1514, Luque, Richard T. 201 Macias, Vanessa M. 632 Maier, Alexander G. 1470 823 Lushima, Robert S. 1454, 1455 MacInnis, Bronwyn 1829 Maiga, Hamidou 1192 Maloney, Patrick 1144 Lusingu, John 420 MacIntyre, Charles 884 Maiga, Hamma 820 Malonga, Françoise K. 74 Lussiana, Cristina 1347, 972 Mackanga, Jean-Rodolphe 854 Main, Bradley J. 1194 Malonza, Isaac M. 385 Lust, Lydia 1708 Mackenzie, Charles 1816, 642 Maini, Mala 434 Malpede, Brian M. 557 Lustigman, Sara 460, 643, 667, MacKenzie, Matthew 1470 Maiolatesi, Santina 1634, 352 Malta, Fernanda M. 1151 670 Maclean, Erick 1408 Maiteki, Catherine Sebuguzi. 279 Maltha, Jessica 419 Luthra, Priya 1257 Maclean, Mary J. 444 Maixenchs, Maria 618 Maltseva, Elina 1765 Lutumba, Pascal 1103, 1743, 1760 MacLeod, Annette 1317 Majam, Victoria 44 Malugu, Regina 1122 Lutwama, Fredrick 329, 332 MacLeod, Bruce 1003, 1661 Majambere, Silas 598, 657, 1235 Malviya, Paritosh 702 Luxemburger, Christine 158 Macpherson, Calum 1054 Majid, Elazia 347 Malvy, Denis 192 Lwanga, Harriet 1227 MacRaild, Christopher A. 937 Majors, Catherine E. 1043 Mameli, Enzo 126, 1361, 1387 Lweikiza, Jane 386 Maculuve, Sonia 1570 Majumder, Anwesha 1017 Mamuchishvili, Nana 706 Lwin, Khin Maung 1335 Madaline, Theresa 33 Majumder, Maimuna S. 1457 Manamela, Jack M. 1303 Ly, Po 1904 Madamet, Marylin 1532, 824 Majwala, Albert 1050 Manamperi, Nuwani H. 1102 Ly, Sovann 1132 Madanitsa, Mwayi 915 Makabuza, Jacquie 1760 Manangi, Abel 1788, 581 Ly, Sowath 590 Maddur Ganesan, Suresh 1830 Makenga, Geofrey 306 Manary, Mark 1006 Lye, David C 1270 Madebe, Rashid 1801 Makepeace, Benjamin L. 443 Manasatienkij, Wudtichai 171, Lyimo, Dafrossa 503 Madey, Gregory R. 1386 Makerere, Clara 360 184, 739 Lyimo, Issa 109 Madhup, Surendra K. 1198 Makhaza-Jere, Tikhala 851 Mand, Sabine 1709 Lyke, Kirsten E. 1606, 1633, 978 Madinga, Munashe 1214 Maki, Elin 1855 Mandala, Wilson 936 Lynam, Timothy 1338 Madushanka, Praveen 1259 Maki, Jennifer 1474, 626 Mandalakas, Anna M. 494 Lynch, Matthew 384 Mady, Charles 1912 Makiya, Michelle 1881 Mandana, Norbert 1659 Lynch, Michael 1617, 230, 962 Maestre, Amanda 976 Makomva, Kudzai 1214 Mandara, Celine 1801, 917 Lyon, Caroline E. 1411 Maffioli, Elisa 1187 Makowski, Kai 740 Mandike, Renata 1905, 386, 917 Lysenko, Nikita 1310 Mafuz, Mustafa 784 Makoyo, Job 972 Mandike, Renatha 1801 Magalhães, Belisa 1482, 630 Makprasert, Sirirat 416 Mandlik, Anjali 397 Magalhães, Maíra R. 1697 Makunga, Christina 598 Mandomando, Inacio 415 Magee, Charles D. 1276 Makuru, Victoria 846 Mandro, Michel 1069 M Magesa, Stephen M. 112, 1235, Makuta, Georgina 358 Manga, Isaac A. 1501 386, 718 Makuwa, Maria 186, 187 Mangeni, Judith 383, 293, 719 Ma, Hai-zhang 1026, 1027, 574 Maggioni, Viviana 1549 Malaga, Edith 1751, 1752 Mangesho, Peter 306, 360 Ma, Jennie 1008, 1863, 1136 Magistrado, Pamela 1469, 1533, Malaga Chavez, Fernando S. 95 Mangwiro, Tawona 676 Ma, Junli 1078 48 Malaga Machaca, Edith S. 1095 Manianga, Celestin 1573 Maas, Carl 1637 Magnuson, Kendall 1538 Malama, Prudence 1627, 1629 Manigart, Olivier 1018, 1019, Mabayoje, Victor O. 481 Magnussen, Pascal 1184, 1800, Malambe, Calisile 1536 1324, 1676 Mabey, David C. W. 82, 1319 684, 805 Malaria DPU, Diseases of the Manitta, Joe 831 Mabey, Lesley 1019 Magogo, Said 306 Developing World 1620 Manjarrez, Merab 1401 Mabila, Manu 38 Magombedze, Gesham 996 Malau, Elisheba 1262 Manjurano, Alphaxard 918 Mableson, Hayley 1816, 1817 Maguiña, Edson 1357 Malavige, Gathsaurie N. 1259 Mann, Victoria H. 1835 Macareo, Louis R. 1221, 170, 171, Mahajan, Babita 1295 Malecela, Ezekiel K. 904 Manne-Goehler, Jen 1248 591, 739, 783, 36 Mahama, Emmanuel 997 Malecela, Mwelecele 1687, 1817, Manning, Jessica 1479, 1502, 862 MacCallum, Robert M. 1386 Mahamane, Ali 1019 1065, 562 Manoff, Susan B. 1222 MacCormick, Ian 1803, 651 Mahamar, Almahamoudou 1208, Malek, M.a. 1010 Manoj, Anita 1633, 1636, 1637, MacDonald, Amanda 912 1601, 602 Malekani, Jean 1454, 1455, 791 1638, 1639 MacDonald, Nicholas 1279, 1648, Mahanta, Jagadish 1474 Maleta, Ken 1006 Manore, Carrie A. 1334 985 Mahanty, Siddhartha 1031, 1035, Malheiros, Antonio F. 1148 Manrique, Paulo 1595, 233 MacDonald, Noni E 65 1036, 1037, 569 Malhotra, Indu 1123, 1124, 1242, Manrique-Saide, Pablo 117, 723 MacDonald, Susan 646 Mahapatro, Samarendra 1126 1599, 1600 Manske, Magnus 317 Mace, Kimberly E. 1212, 876, 895, Maharaj, Rajendra 658 Malima, Robert 306, 360, 718 Mansour, Hoda 1180 897, 1229 Mahdi, Ramsan 1905 Malishee, Alpha 1816, 1817, 598 Mansour, Moustafa 1180 Macedo, Bruna 964 Mahende, Coline 420 Maliti, Deodatus F. 107 Mante, Sunny 1709 Macedo de Oliveira, Alexandre Mahende, Muhidin K. 1049 Maljkovic Berry, Irina 183 Mantel, Nathalie 1857 1877, 226 Maher, Steven P. 1611 Mallet, Henri-pierre 765 Mantila, Daisy 1262, 1565, 1600 Macelela, Mwelecele 1816 Mahfuz, Mustafa 1865 Mallewa, Jane 485, 847 Mantshumba, Jean Caurent 344 Macete, Eusebio 1049, 1553, Mahikwano, Lucas 833 Mallick, Prashant K. 920 Manuli, Erika R. 1101, 1912 1570, 618, 854 Mahmoud, Adel 1325 Malloy, Michael 11 Manwani, Bhavish 943 Mach, Kathleen 1836 Mahmoud, Manar 1762 Malm, Keziah 1480, 1561 Manyazewal, Mesfin T. 1409 Machado, Paulo 1848, 1849, 521, Mahmud, Rohela 1029 Malm, Keziah LMalmlov, Ashley Manzoni, Federica 575 1251, 1745 The MaHPIC Consortium 1471 190 Mao, Sivanna 220 Machado, Ricardo L. D. 321, 324, Maia, Marta F. 1809, 266, 995, Malone, David 1233 Mapp, Carla T. 388 340 123 Malone, Joseph 269, 566, 14 Mappin, Bonnie 304 astmh.org A-612 Abstract Author Index The number(s) following author name refers to the abstract number.

Mapua, Salum 265, 276 Mascarenhas, Anjali 1474, 626 Mazimba, Sharon 23 McKibben, Maxim 1242 Mapua, Salum A. S. Masendu, Hieronymo 309 Mbabazi, Pamela 1230 McLean, Alistair 333, 603 Marayati, Bahjat Fadi 1311 Masesa, Clemens 1559 Mbachu, Chinyere 483 McLennan, John 1339 Marcelin, Glendie 1451 Mashauri, Fabian 1807, 724 Mba Eyono, Jeremias Nzamio McMahon, Benjamin H. 1334, Marcenac, Perrine 1890, 633 Masiga, Daniel 379, 665 1003, 1660, 1869 1769 Marchesini, Paola 1877 Maslen, Gareth 1386 Mbainadji, Lodoum 1324 McMahon, Jamie 728 Marcos, Luis A. 1155 Mason, Carl 784 Mbala, Placide K. 186, 187 McMahon, Shannon A. 1182 Marcsisin, Sean 1531, 255, 257, Masoud, Salum O. 268 Mbalabu, Oshwa B. 344 McManus, Donald P. 1157, 1825 1535 Massa Ramalho, Walter 147 Mbambo, Gillian 893 McMullen, Chelsea L. 1117, 6, 666 Marfurt, Jutta 355, 865 Masse-Deragon, Nicolas 1857 Mbengue, Alassane 1172 McMurray, Stephen E. 1894 Margolis, Harold S. 1422, 37, 437 Massinga-Loembe, Marguerite Mberikunashe, Joseph 1214 McNeil, Edward 1166, 1789 Mariama, Cherif 928 1651 Mbeye, Nyanyiwe M. 30, 936 McNulty, Margaret A. 39 Mariconti, Mara 575 Massobodgi, Achille 968 Mbiakop Kemajou, Gaëlle 908 McNulty, Samantha 1886 Marie, Chelsea 1134 Massougbodgi, Achille 854 Mbise, Christina 1687, 1688 McNulty, Samantha N. 1883, 1885 Mariko, Saito 134 Massougbodji, Achille 428 Mbonye, Anthony K. 1800 McPhun, Virginia 556 Marinho-Junior, José F. 1252 Mataro, Chacha 1371 Mboshya, Paul 1788, 24, 581 McQueen, Kelly 1328, 1343, 690 Marini, Elisabetta 1529 Matata, Lena 1774, 1775 Mboup, Balla M. 1903 Mduluza, Takafira 361 Marino, Ana Paula M. P. 513 Matebule, Grace 33 Mboup, Souleymane 931 Meachum, Susan 1332 Marken, Lindy 1719 Mathanga, Don P. 1866, 307, 654, McAdams, David 1333, 1734 Meagher, Karen 80 Markle, Laurie 1788, 23, 581 736, 841, 914, 358, 599 McBride, Colleen 495, 68 Means, Arianna R. 496, 497 Markowitz, Elizabeth 794 Mathatha, Eva D. 1303 McBride, William J. 1813 Medawar, Evelyn 976 Markowski, Janusz 782 Matheson, Alastair I. 1585 McBurney, Sean P. 1225 Medeiros, Daniele B. A.. 1465 Markowski, Marcin 782 Mathias, Derrick K. 993 McCaffery, Jessica N. 366 Medeiros, Pedro H. Q. S. 1012, Marks, Michael E. 647, 82 Mathiopoulos, Jason 1238 McCaffrey, Ramona 62, 794 1668, 1669 Marks, Nikki J. 607 Mathis, Demetrius 1422 McCall, Philip J. 1807, 724 Medina, Alexis 50 Markus, Miles B. 196 Mathison, Blaine A. 808 McCann, Robert 285 Medina-Barreiro, Anuar 117, 723 Markwalter, Christine 274 Matias, Wilfredo R. 1860 McCardle, Wes 1283 Meehan, Conor 419 Marquart, Louise 1207 Matimelo, Selenia 1788, 581 McCarthy, Anne 646 Mehlotra, Rajeev K. 202 Marques, Jr., Ernesto T. A. 150 Matovu, Enock 1742 McCarthy, Florence M. 1930 Mehta, Rohin 525 Marquette, Meghan 561 Matovu, Fred 1228 McCarthy, James S. 1207, 26, 845, Mehta, Saurabh 1052, 1423, Marquez, Ricardo 1739, 1750 Matowo, Johnson 1286, 718 1488, 860 1693, 1731, 1773, 442, 500 Marsh, Kennan 1078, 645 Matowo, Nancy S. 265, 276 McCarthy, Kevin A. 954 Mehta, Vishisht 1128 Martelli, Celina T. 150 Matsumoto, Yoshitsugu 197 Mccaw, Jane 109 Meireles, Luciana R. Meireles. 1145 Martensson, Andreas 657 Matta, Jose Antonio 565 McChesney, James D. 1535, 970 Meisel, Dirce M. 474 Marthey, Daniel 358 Matte, Michael 231 McClellan, Holly 375 Meite, Aboulaye 1074 Marti, Matthias 18 Matthews, Scott 722 McClung, Colleen M. 1882 Mejia, Rojelio 1289, 463, 52, 649 Martin, Coralie 1071 Matthias, Michael A. 59, 424 McCollum, Andrea M. 1114, 1454, Mekasha, Addis 14 Martin, Diana 1680, 56 Mattia, Kimberly-Anne 549, 38 791, 1455 Mekuria, Asrat H. 1740 Martin, Estelle 766 Matwale, Gabriel K. 1066 McCormick, David W. 416 Melaku, Zenebe 14 Martin, Gregory J. 62 Mauck, Daniel 288, 787 McCornack, Jocelyn 478 Melby, Peter C. 1510, 1746, 1913, Martin, Jason 1222 Mauk, Michael 1778 McCoy, Andrea J. 62 522 Martin, Laura B. 1201 Maule, Aaron G. 607 McCoy, Ciaran J. 607 Melchor, Stephanie J. 1134 Martin, Nicholas 1217, 250, 873, Maung, Thae Maung 999 McCracken, Michael K. 39 Melendez, Mónica 567 874, 906 Mawindo, Patricia 1265, 1602, McDew-White, Marina 1589, 583 Melendez-Muniz, Viviana 1485 Martin, Richard J. 1072, 607, 609 1646 McDonald, Chloe R. 429 Melendrez, Melanie 183, 709 Martin, William D. 1650 May, Anthony 1645 McDonald, Circe 1073 Mello, Luciane S. 321 Martin del Campo, Jorge 1417, May, Susanne 1127 McDonald, Tim 696 Melnikov, Alexander 583 1418 Mayagaya, Valeliana 1809 McDonough, Erin 86 Melo, Adriana B. 1832 Martine, Jackline 1807, 724 Mayanja, Harriet 17 McElroy, Peter 268, 1901 Melo, Gessica B. 1151 Martinez, Luis J. 1219, 163 Mayanja-Kizza, Harriet 1614 McElvany, Benjamin D. 1408, 1220 Melo, Gisely C. 1482, 6309 Martínez, María K. 181 Mayieka, Lilian M. 796 McFadden, Geoff I. 362 Melody, David 841 Martinez, Miguel J. 1269 Mayland, Health Center 401 McGalliard, Zachary 413 Melubo, Matayo L. 1105 Martínez, Nora 1632, 314 Mayneris-Perxachs, Jordi 63 McGraw, Elizabeth 161, 173 Mena, Stephanie 463 Martinez, Pedro A. 524 Mayor, Alfredo 1553, 1570, 854, McGray, Sarah 280 Menard, Didier 1904, 224, 8, 12, Martinez, Ruth 752 938 McGready, Rose 1266, 333 1587, 1804, 845, Martinez, Sindy 143 Mayora, Chrispus 1047 McGregor, Alastair 1178 Menda, Gil 1312 Martinez-Vega, Ruth 1424, 1432 Mayo-Smith, Leslie M. 1860 McGuire, Kathleen A. 992 Mendell, Nicole L. 61 Martins, António 1067, 1796 Mayta, Holger 1095, 1450, 1751, Mcha, Juma H. 112, 1235 Mendelsohn, Joshua 1735 Martins, Yuri C. 1175 1752 McHardy, Stanton F. 669 Mendelson, Marc 646 Maruta, Celina W. 1151 Mayxay, Mayfong 1829, 943 McIntyre, Charles 1041 Mendes, Felisberto 51 Marzi, Andrea 3 Mazarati, Jean Baptiste 1379, McIntyre, Tara 332 Mendoza, Benjamin 745 Masabho, Peter 1310 1868, 315 McKain, Shanice 149 Mendoza, Elke L. 659 Masae, Patrick 1687, 1688 Mazhari-Tabrizi, Ramin 362 McKay, Mike 600 astmh.org Abstract Author Index A-613

The number(s) following author name refers to the abstract number.

Mendoza de Molano, Belén E. Mico, Arcadio Edu 1662 Mitchell, Brooks 678 Molofsky, Ari B. 605 1759 Midzi, Nicholas 361 Mitchell, George 1054 Molteni, Fabrizio 1216, 268 Meneghei, Mario 252 Mier-y-Teran-Romero, Luis 142 Mitchell, Kate 1824 Molyneux, David 1067 Menéndez, Clara 1269, 1553, Mihalska, Emilia 1733 Mitchell, Robert 555 Mombo-Ngoma, Ghyslain 854 1570, 618, 854 Mihigo, Jules 602, 720 Mitchell, Sara N. 1390, 1395 Monagin, Corina 1107, 186, 187 Meng Chuor, Char 323 Mikita, Kei 528 Mitchell, Sarah T. 1105 Moncayo, Ana L. 1761 Menon, Jayaram 1560, 1902 Mikolajczak, Sebastian 1274, 248, Mitchell, Sheila M. 1723 Moncunill, Gemma 938 Mens, Petra F. 341 1613 Mitchell, Tarissa 56 Mondal, Dinesh 1740, 1850, 1865 Mensah, Benedicta A. 899 Mikolasova, Gertruda 1733, 493 Mitja, Oriol 1680, 82 Mondini, Adriano 1435 Mensah, David 907 Milali, Masabho P. 382 Mitre, Edward 1077, 1712, 1713 Mondragon, Enid 734 Mensah, Sedzro 907 Milani, Sadaf 1617 Mitreva, Makedonka 1883, 1885 Monestime, Franck 1059, 1229, Mensah, Victorine 363 Milch Hariharan, Karen 823 Miura, Kazutoyo 1260, 369, 931, 1814 Mensah-Brown, Henrietta E. 194 Miles, Alistar 1389, 1828 950, 979, 986, 987, 992 Moniz, Sonia 1741 Menten, Joris 1740 Miles, Michael A. 1246 Miyakoda, Mana 330 Monje Rumi, Mercedes 1089 Mentink-Kane, Margaret 1895, Milet, Jacqueline 1317 Mizobuchi, Haruka 197 Monroe, Benjamin 1454 672 Millar, Eugene V. 1021 Mjungu, Deus C. 894 Monroy Nicola, Jorge 94 Menya, Diana 1041, 1187, 239 Millar, Justin 238 Mkali, Humphrey R. 1216, 600, Monroy-Pérez, Eric 405 Mercado, Juan 1401 Millard, Ann 664 1558, 268 Montano, Silvia M. 1160 Mercado, Marcela 167 Miller, Adam 38, 549 Mkandawire, Felix 485 Montavon, Celine 1812 Merceron, Sébastien 765 Miller, Andre’ 672 Mkhonta, Nomcebo 1536, 866 Montazeau, Céline 289 Merchant, Amina 1343 Miller, Andrew 1256 Mkocha, Harran 1687, 1688 Montecino, Diego 1380 Merchant, Amina I. 690 Miller, Becky 127 Mkude, Sigsbert 1801, 917 Monteiro, Glória R. G. 432 Meremikwu, Joshua T. 198 Miller, Becky A. 1829 Mkwanda, Square 1227, 1927, Monteiro, Wuelton M. 1482, 630 Meremikwu, Martin 837 Miller, John 1544, 1547, 1623, 642 Montgomery, Joel M. 1108, 1203, Merino, Emilio F. 256 1627, 1629, 696, 1218, 1625, Mlacha, Yeromin 598 132, 1585, 297, 417, 788 Merino, Paloma 510 278, 881 Mlambo, Godfree 1295 Montgomery, Michelle A. 1032 Merritt, Ethan A. 861 Miller, Joseph R. 407 Mlay, Bertha 386 Monthei, Derek 703 Meshnick, Steven R. 103, 1394, Miller, Laura 1182 Mlotha, Rachel 682 Monti, Feliciano 601 1556, 396, 543, 708, 915, 916, Miller, Mark 784 Mmbando, Arnold 1893 Montibeller, Gilberto 85 1085, 1557, 1650, 882 Miller, Mark W. 1783 Mmbando, Bruno P. 904, 562 Montilla-Guedez, Henry 1670 Mesias, Andrea 1084 Miller, Robin H. 916 Mmbuji, Peter 917 Montoya, Magelda 592 Messenger, Louisa 1085 Miller, William C. 1737 Mnyone, Ladislaus 109 Montoya, Rosario 1763 Messenger, Louisa A. 1246, 1911 Milligan, Paul 1501, 1906, 270, Mnzava, Kunda W. 1105 Montresor, Antonio 1823 Messer, William 1225, 1426, 1416 271, 272, 855, 1348, 1302 Mnzava, Ruth 360 Moo, Oh 1266 Mestra, Alberto 1171 Millington, David S. 627 Mock, Charles N. 1160 Moon, James E. 1276, 1278 Mestra, Laureano 499 Millogo, Athanase 573 Modi, Evelyne 1769 Moon, Oun-Kyong 1109 Metcalf, C J. E. 1456 Millogo, Ourohire 84 Moehrle, Joerg J. 852, 857, 860 Moon, Troy D. 32 Meth, Rathana 1804 Mills, Harriet 798 Moendeg, Kharleezelle 531, 532 Moonga, Hawela 1218 Metz, James 1071 Mills, James 661 Mofid, Layla S. 462 Moore, Brioni R. 215 Meyer, Jason M. 1377 Mills-Robertson, Felix C. 1682 Mogeni, Ondari 1585 Moore, Catrin M. 423 Meyer, Kirsten J. 1315 Milner, Dan 1472, 33, 584 Mohamath, Raodoh 1740 Moore, Christopher C. 1050 Meyers, Jacob I. 1354 Mina, Neila J. 738 Mohamed, Abdi 1544 Moore, John 1290 Meyin A Ebong, Solange 1138 Minaya Gómez, Gloria S. 1088, Mohamed, Ally 1801, 386, 917 Moore, Julie M. 43, 628 Meza, Adriana 1024 1749 Mohamed, Khadeeja 1209 Moore, Kerryn A. 1266, 603 Meza, Graciela 394 Minesi, Fanny 666 Mohamed-Hadley, Alisha 422, 741 Moore, Sarah 1809 Mfuh, Kenji O. 1798 Minta, Anna A. 902 Mohammed, Wahjib 1561 Moore, Sean M. 1859, 1666 Mgata, Saidi 833 Minta-Asare, Keren 482 Mohan, Ruchika 1836 Moore, Sean R. 63 Mghamba, Janneth 1801, 917 Mintz, Eric D. 1203 Mohanan, Manoj 1187 Moorhead, Andrew R. 1714 Mharakurwa, Sungano 1590 Miotto, Olivo 1829, 317, 872 Mohandas, Narla 1172 Moorhead, Andy 668 Mhashilkar, Amruta 445 Miranda, Alesson M. 432 Mohareb, Emad 1129, 1180, Moormann, Ann M. 1271 Mhehe, Enock 1905 Miranda, Julio 1595 1762, 1133 Moorthy, Vasee 1462 Miao, Jun 1490, 1491 Miranda, Vitor H. Simões. 1832 Mohon, Abu Naser 316 Moraes Barros, Roberto R. 1630 Michael, Daniel 1619 Miranda Montoya, Maria C. 1698 Mohon, Abu Nasir 206 Mora-García, Gustavo 1053 Michael, Edwin 562 Mireku, Michael O. 428 Mohon, Md Abu Naser 235 Morales, Cristhian 1584 Michael, Obaro S. 1498 Miri, Emmanuel S. 452 Möhrle, Jörg 1207 Morales, Maria L. 472 Michael, Scott F. 176 Mirrashed, Hannah 1118 Mok, Sachel 1873 Morales, Maria Alejandra 742 Michalikova, Lenka 1733, 493 Misganaw, Awoke 1045 Mokake, Flavius M. 403 Morales, Sandra 828, 829 Michalski, Shelly 1882 Mishra, Sailesh K. 1321 Mokashi, Vishwesh 1016 Morales-Plaza, Cristhian 1632, 314 Michault, Alain 38 Mishra, Satish 47 Moke, Fenny 1203 Mordmüller, Benjamin 1633, 1651, Michel, Anita L. 1108 Mishra, Shobhna 920 Molina, Douglas 559 849, 938 Michelo, Charles 1165 Missamou, François 1716, 1815, Molina-Cruz, Alvaro 1356 Moreira, Carlos H. V.. 1101, 1912 Michelucci, Elena 635 459 Molina-Gómez, Karen 1577, 1632 Morelle, Danielle 1276, 1277 Mickum, Megan L. 1785 Mistry, Zarna S. 689 Mollard, Vanessa 362 Moreno, Alberto 1471, 366, 367 astmh.org A-614 Abstract Author Index The number(s) following author name refers to the abstract number.

Moreno, Brechla 1461 Mousley, Angela 607 Mulenga, Modest 111, 1567, Musralina, Lyazzat 1765 Moreno, Marta 102, 125, 733 Mousley, Elizabeth 72 1867, 903 Mussa, Moise A. 1069 Mores, Christopher N. 1394, 39, Moustapha, Lingani 673 Muleya, Sarrah 1788 Musset, Lise 308 1889 Moxon, Christopher 651 Müller, Pie 114, 1233 Musso, Didier 765 Moretz, Samuel E. 1260 Moya-Alvarez, Violeta 968 Mulogo, Edgar 231 Musyoka, Augustine M. 1326 Morgan, Catherine 629 Moyano Vidal, Luz Maria 572, Mulry, Jim 83 Musyoka, Raymond N. 417 Morgan, Grace A. 1417, 1418 1034, 475 Mulumba, Audry 77 Mutabazi, Alphonse 1868 Morgan, Juliette 706 Moyes, Catherine 1112 Muluneh, Dereje 269 Mutafungwa, Anold 386 Morgan, Marjorie S. 98 Moyo, Dubulao 307 Mulvaney, Shawn P. 86 Mutai, Beth 703 Mori, Yasuyoshi 1739 Mpagala Kihomo, Robert 360 Mumba, Dieudonné N. 1573 Mutai, Noah 151 Morinaga, Osamu 482 Mpeka, Betty 1658 Mumba, Peter 907 Mutayoba, Rita 680 Morita, Masayuki 370, 830, 979 Mphahlele, Jeffrey 1013 Mumba Ngoyi, Dieudonné 1926 Mutesa, Leon 263, 380 Morlais, Isabelle 559 Mphalala, Gugu 1536 Mumbengegwi, Davis 1550, 1579, Mutuku, Francis 1123, 1124, Morningstar, Marshall 1527 Mphuru, Alex 503 236, 655, 299, 563 1509, 151, 650, 124, 156 Morris, Glenn 155 Mpimbaza, Arthur 947 Mumtaz, Noreen 146 Mutunda, Anne 23, 24, 581 Morris, J. G. 1841 Mpofu, Conart 1214 Munayco, Cesar V. 1436 Muwalo, Francis 485 Morris, Natashia 658 Mremi, Irene 1065, 1816, 1817 Munde, Elly O. 1592, 1593 Muwanguzi-Karugaba, Julian 821 Morris, Nathsan 1242 Msellem, Mwinyi 268, 657, 305 Mundongo, Henri 414 Muwonge, Constantine 1658 Morris, Sheldon 338 Msellemu, Daniel 598 Mundy, Gary 912 Muyembe, Jean-Jacques 1117, Morris, Ulrika 657 Mswanya, Christopher 1558, 833, Muné, Mayra 181 187, 6, 77, 1466, 1684, 186, Morrisey, Joanne M. 1205 843, 891, 910 Mungai, Peter 1123, 1242 791, 1464, 1702, 799, 795 Morrison, Amy C. 1131, 131, Mtema, Zac 598 Munganga, Manko Kennedy 456 Muzinga wa Muzinga, Jacques 1436, 1811, 439, 775, 786, 86, Mtove, George 306, 360 Munguambe, Khatia 618 1926 166, 596, 726 Mu, Amy 835, 893 Munguti, Kaendi 1340, 1578 Mvula, Godfrey 927 Morrison, Kathryn 1457 Mubarik, Yusif 1708, 639 Mungwira, Randy 1265, 1602, Mvumbi, Dieudonné M. 290 Morrison, Robert 1476 Muchenje, Tendayi 1622 1646, 927 Mvumbi, Georges L. 290 Morrison, Thomas 41 Muchiri, Eric 1242 Mungwira, Randy G. 485 Mwaikambo, Esther D. 627 Morse, Alexander N. 89 Mucunguzi, Akasiima 1774, 1775 Muniz, Aline 1848 Mwaipape, Osia 268 Mortari, Naíma 1697 Muehlbauer, Michael 1006 Munoz, Elyse E. 1174 Mwakalinga, Victoria 598 Mortensen, Rasmus 60 Muehlenbachs, Atis 793 Muñoz, Jorge 1422 Mwakingwe, Agnes 1635, 941, Morton, Howard 1078 Muela Ribera, Joan 1213 Munoz, Marie 776 985 Moser, Janice 1223, 553 Mueller, Ivo 1262, 1263, 1555, Munoz-Jordan, Jorge 37 Mwalimu, Charles D. 386 Moser, Kara A. 1640, 924 1565, 16, 1604, 215, 317, 334, Munsosa, Robert 1422 Mwandagalirwa, Kashamuka 916 Moses, Penias 1680 568, 830, 864 Munster, Vincent 190 Mwandagalirwa, Melchior K. 1557 Mosha, Frank 306, 360 Muench, Marcus O. 38 Munstermann, Leonard E. 1396 Mwandama, Dyson 358 Mosha, Franklin 1371, 1870, 718 Mugasa, Joseph 306, 360 Munthali, Clyton A. P. 851 Mwandawiro, Charles S. 461, Mosha, Jacklin 1870 Mugerwa, Robert 1507 Munyakanage, Dunia 1379, 1868 464, 54 Mosha, Neema 1122 Muhammad, Abdul K. 889 Munyaneza, Tharcisse 315 Mwanga, Ally 1722 Mosher, Aryc 497 Muhammad, Ilias 1087 Münz, Christian 1271 Mwanga-Amumpaire, Juliet 1575, Moshi, Irene R. N.A. N.A. 998 Muhili, Athumani 598 Mupongo, Tumba 24, 581 292 Mosi, Lydia 1322 Muhindo, Mary 1210 Muratova, Olga 985 Mwanje, Mariam T. 464 Mosquito, Susan 1009 Muiru, Anthony 231 Murdoch, David M. 423 Mwansat, Georgina S. 1392 Moss, Delynn 895 Muiruri, Charles 1326 Murindahabi Ruyange, Monique Mwanza, Mercy 1627, 1629 Moss, Eli L. 371, 875 Muiruri, Peninah 210 1340 Mwanziva, Charles 833, 843, 900, Moss, William J. 1567, 1590, Mujtaba, Mohammed 1305 Muro, Florida J. 1122 910, 1558, 891 1867, 301, 342, 877, 879, 903, Mukadi, Patrick 1117, 1464, 1466, Murphy, James R. 1729 Mwapasa, Victor 1556, 847, 915 122, 111 1684, 1702, 6, 77, 795, 799, Murphy, Jittawadee R. 96 Mwatele, Cassian 54 Mosser, David 517, 521 191 Murphy, Max 1594 Mwenda, Jason 1013 Mossoko, Mathais 799 Mukaka, Mavuto 847, 851 Murphy, Philip M. 513 Mwenesi, Halima 1516, 1517 Mossore, Mba 351 Mukanga, David 1838 Murphy, Sarah 1247 Mwesigwa, Julia 113, 1615, 213, Mostafa, Amani 1453 Mukarugwiro, Beata 315 Murphy, Sean C. 1274, 248, 980 529, 653, 871, 1399, 888 Mostafa, Eman 444 Mukhtar, Maowia 1740 Murray, Gregory 724 Mweso, Ndamiwe 30 Mota, Mânlio T. O. 755 Mukoko, Dunstan 1123, 124, Murray, Kristy O. 1247 Mwikisa, Chris 511 Mota, Maria M. 1296 1509, 151, 156, 650 Murrieta, Reyes D. 1445, 1446 Mwinde, Jackson 1123 Motawea, M S. 421 Mukosha, Leonard 581 Murunga, Peninah 1126 Mwingira, Upendo 1062, 1063, Motobe Vaz, Liberato 1869 Mukundan, Harshini 1334, 1769 Musaki, Sandra 156 1065, 1816, 1817, 503, 505, Mott, Joshua 1041 Mukwakwa, Chime 620 Musene, Kamy K. 795 1058, 1685, 1686, 1687, 1688 Mouatcho, Joel C. 300 Mulama, David H. 1271 Musey, Luwy 1222 My, Mok 15 Mouhamadou, Chouaïbou S. 115 Mulder, Lubertus 1257 Musgrave, Paul 463 Mychaleckyj, Josyf C. 1700 Moura, Alessandra F. 1012, 63 Muleba, Mbanga 111, 122, 1867 Musho, Matthew 280 Myers, Christopher A. 86 Moura, Izabella 1251 Mulebeke, Ronald 284 Musinguzi, Kenneth 329, 332 Myers, Todd 1054 Mourão, Marina M. 1776 Mulembakani, Prime 187, 186, Musonda, Engervell 1788, 23, 24, Myers-Hansen, James 899 Mousam, Aneela 1549 1117 581 Myette, James 551 astmh.org Abstract Author Index A-615

The number(s) following author name refers to the abstract number.

Mysore, Keshava 1193 Narain, Jai P. 1459 Ndiop, Medoune 1501, 1652, 242, Ngapmen Yamadji, Arlette L. 908 Mzilahowa, Themba 1393, 1866, Naraine, Ravindra 149 310, 311, 353 Ngasala, Billy 420, 534 736 Narasimhan, Prakash Babu 1884 Ndiop, Medpune 312 Ngati, Elise P. 335, 932, 933 Mziray, Abubakary 306 Narayanan, Aarthi 141, 747 Ndiopg, Médoune 584 Ngatunga, Deogratias 1801 Narbe, Maxime 1324 Ndir, Oumar 1610 Ngay, Ipos L. 186, 187 Nardin, Elizabeth 555 Ndirangu, Gathari 385 Ngindu, Augustine M. N. 385 Narh, Charles A. 216 Ndjakani, Yassa D. 1926 Ngo, Katherine 494 N Naro, Gillian 1408 Ndjemba, Jean 1685 Ngo, Thang D. 1217, 250, 873, Narra, Roberta 1696, 575 Ndombe, Martin 456 874, 906 N, Vidhya 7 Narum, David 333, 375, 985, 991, Ndombi, Eric M. 1243, 1785, 1833 Ngo, Thinh D. 873 Nabicassa, Meno 1319 1279, 1649 Ndong, Isaiah 386 Ngogang, Jeane Y. 488 Nabirye, Christine 357 Narvaez, Federico 133, 136 Ndonye, Janet 391 Ngom, Algaye 1903 Nacher, Mathieu 308 Nasamu, Sebastian 1830 Ndour, Moussa 353 Ngoma, Thandiwe 1547, 1623, Nachon, Marie 1827 Nasar, Farooq 140, 144, 748, 749 Ndour, Papa Alioune 1470 881 Nada, Rania A. 1453 Nascimento, Eduardo J. M. 150 N’dri, Abou 1822 Ngondi, Jeremiah M. 1216, 1235, Nadan, Sandrama 1013 Nascimento, Larissa S. 432 Nduka, Florence O. 890 1685, 1686, 1687, 1688, 268, Nadler, Kyle 102 Nascimento, Maria 1019 Ndula, Miranda 1284 386, 1905, 600, 112 Nadugala, Mahesha N. S. 769, 772 Nash, Theodore 1035, 1036, 1037, Ndung’u, Joseph M. 1103, 1249, Ngonga, Daniel 703 Nag, Sidsel 1500, 319 1031, 1033, 569 1742, 1743 Ngonyani, Hasan 1893 Naghavi, Mohsen 1045 Nasreen, Sharifa 1163, 582 Ndungu, Paul 496 Ngowo, Halfan 265 Nagodavithana, Kumara C. 1925 Nasrin, Dilruba 28 Ndyomugyenyi, Richard 1184, 684 N’Guessan, Raphael 1282, 1370, Nagraj, Sushma 924 Nasser, Julio 1089, 1289 Ndzinu, Jerry 482 1239 Naguib, Amel 1762 Naszeerah, Wan Nurul 1396 Neafsey, Daniel E. 1195, 1286, Nguete, Beatrice 1454, 791 Nagy, Lauren H. 1021 Nataro, James P. 1203, 28 371, 583, 584, 875, 931 Nguetse, Christian N. 322 Nahum, Alain 889 Natesan, Mohan 4 Neal, Aaron T. 1173 Ngufor, Corine 1370 Nair, Meera G. 470 Natureeba, Paul 1210 Nebie, Stanislas 969 Ngugi, Njenga 124 Nair, Shalini 1589, 1826, 583 Naulikha, Jaqueline 1141, 496 Nebie, Stanislas P. 1655 Ngui, Romano 1029 Najdi, Adil 1098 Naumenko, Anastasia 1385 Nedjati-Gilani, Gemma 594, 777 Nguku, Patrick 1186, 185 Nakajima, Rie 1602, 1606, 1646, Nava, Samantha 1149 Neeley, Sydney 948 Ngulube, Vernon 1788 943, 978 Nava, Santiago 93 Negredo, Anabel 744 Nguon, Chea 1172 Nakalembe, Miriam 1210 Navarro, Miriam 1057, 1707, 510 Negreiros, Suiane 1877 Nguyen, Anh Q. 250, 873, 874, Nakanwagi, Grace 1507 Navas, Adriana 1748, 1750 Nejjari, Chakib 1098 906 Nakanwagi Ssekabira, Grace 839 Navaza, Bárbara 510 Nelson, Eric J. 1010 Nguyen, Chilinh 1285 Nakasujja, Neoline 34 Nawa, Mukumbuta 1623 Nelson, J. L. 1476 Nguyen, Hung M. 906 Nakazawa Hewitt, Steve 281 Nayak, Uma 1700 Nelson, Jennifer 255 Nguyen, Loan 1670 Nakhasi, Hira 520 Nayakwadi Singer, Monica 1123 Nelson, Kara 25 Nguyen, Phu H. 250 Nakhimovsky, Sharon 681 Nayiga, Susan 357 Nelson, Martha I. 183 Nguyen, Phuc T. 250 Nakiboneka, Priscilla 1767 Naylor, Caitlin 1291 Nemeth, Sheila 1803 Nguyen, Thang X. 1217, 873, 874 Nakoulima, Aminata 824 Ncogo Oyana, Raul Nguema 1662 Nene, Vishvaneth M. 1294, 1236 Nguyen, Thanh-Thanh 473 Nalubega, Mayimuna 329, 332 Ndakala Gyamba, Nestor 1926 Nentwich, Oliver 797 Nguyen, Thi H. 771 Nalubowa, Florence 1505 Ndam, Nicaise T. 915 Nerlander, Maximilian P. 1059 Nguyen, Thieu Q. Nguyen Q. 906 Nalule, Yolisa J. 1232 Ndao, Momar 1787 Nerurkar, Vivek R. 766, 790, 1798 Nguyen, Thinh D. 660 Naluwu, Kate 329, 332 Ndaw, Amy 363 Nery, Susana V. 26 Nguyen, Tran Dang 617 Nam, Sinh V. 660 Ndege, Samson K. 435 Nettel-Aguirre, Alberto 1339 Nguyen, Uyen T 1470 Namae, Jane 383 Ndekhedehe, Enobong U. 1656, Neumann, Anna-Lena 1241, 1880 Nguyen, Van T. 250 Namango, Isaac 598 1657 Neuvonen, Mikko 588 Nguyen, Xa X. 250, 873, 874, 906 Namara, Geoffrey 839 Ndenga, Bryson 124, 1509, 650, Newbold, Chris I. 1173 Ngwa, Alfred A. 889, 1582 Namasopo, Sophie 629 151, 156 Newgard, Christopher B. 1006 Ngwa, Fidelis C. 670 Namayanja, Rosemary 65 Ndhlovu, Ketty 1623 Newport, Melanie 70, 1045 Ngwira, Andrew 599 Namazzi, Ruth 1056, 1475 Ndiath, Ousmane 381 Newsome, Anthony L. 1097 Ngwira, Bagrey 1927 Namgay, Rinzin 1396 Ndiaye, Daouda 1496, 1501, Newton, Paul 1829 Nhacolo, Arsenio 1553, 854 Namo, Hadi 750 1610, 218, 312, 584, 826, 827, Newton, Paul N. 1489, 423, 542, Nhem, Sina 1804 Namukuta, Annet 1824 859, 931 943 Ni, Zhuoyu 759 Nanai, Alphonsina 1687, 1688 NDiaye, Jean Louis 1348, 319, 467, Neyra, Joan M. 58 Niagaly, Moussa 902 Nanayakkara, Dhammika 1528 1610, 272 N’Falé, Sagnon 564 Niang, Abdoulaye 1192 Nanayakkara, NP D. 970, 1535 Ndiaye, Jean Louis A. 1501, 249, Ng, Caroline L. 1488 Niangaly, Amadou 1563, 1606, Nankabirwa, Joaniter I. 227, 229 1302, 855 Ng, Dianna 37 1636, 835, 921 Nankya, Florence 812 Ndiaye, Magatte 1500, 1501, Ngabo, Fidele 315 Niangaly, Hamidou 1211, 820, 966 Nantachit, Nattika 152 1610, 249, 319, 855 Ngadaya, Esther 1801, 917 Niare, Karamoko 1636 Nanteza, Ann 1505 Ndiaye, Maguette 467 Ngadoua, Cyriaque 1324 Nic Fhogartaigh, Caoimhe 1178 Naorat, Sathapana 416 NDiaye, Mouhamadou 1610, 218 Ngalulua, Anne-Marie 666 Nicholas, Sarala 999 Naquira, Cesar 1116, 1754, 1756, Ndiaye, Mouhamed 1348 Ngambi, Joseph 24, 581 Nichols, Kim 1725 99 Ndiaye, Yaye D. 218, 312 Ngan, Chantha 590 Nicholson, Brady 1041 astmh.org A-616 Abstract Author Index The number(s) following author name refers to the abstract number.

Nicolete, Vanessa 1605, 940, 925 Norris, Douglas 111, 122, 342, Nyanjom, Steven G. R. 412 Odom, Audrey R. 225 Nicosia, Alfredo 1462 1397, 1867 Nyarko, Alexander K. 402 Odongo, Wycliffe O. 597, 911 Niemand, Jandeli 264 Norris, Laura C. 306, 1392 Nyarko, Edward Owusu 1023, O’Donnell, James 831 Niemi, Mikko 588 Nortey-Mensah, Richard 813 1677 Odoom, John K. 482 Nierman, William 1596 Norton, Raymond S. 937 Nyasulu, Peter 487 Odoya, Ebube M. 1711 Niessen, Louis W. 960 Norval, Suzanne 1914, 815 Nyathi, Emanuel 784 Odundo, Elizabeth 391 Nieto-Sanchez, Claudia 1761, 509 Nosten, Francois 11, 1208, 13, Nyirenda, Osward M. 485 Oduola, Adedayo 1654, 994 Nikiema, Frédéric 224, 818 1335, 1589, 1829, 333, 583, Nylen, Susanne 512 Oduro, Abraham 1049, 216, 1701 Nikolaeva, Daria 987 943, 1826, 1266, 603 Nyoni, Waziri 657 Odutola, Aderonke 1018, 1676 Nikolay, Birgit 464, 51 Nou, Samon 1132, 15 Nyundo, Bruno 109 Oelnik, T 1733 Nikolov, Milen 1548, 1551, 957 Novais, Fernanda 517, 519, 521 Nyunt, Myaing M. 1581, 886, 893 O’Flaherty, Katherine 11 Niles, Jacquin C. 586, 1830 Novak, Robert 1067 Nze Nchama, Lucas Ondo 1003, Ofori, Michael F. 194, 351 Nilles, Eric J. 663 Noviyanti, Rintis 656, 865 1869 Ogg, Graham 1259 Nimol, Khim 224 Novotny, Joseph 866 Nzowa, Mary B. 386 Ogle, Janie 1332 Nimo-Paintsil, Shirley 1023, 1677 Nozaki, Mamoru 1298, 199 Nzuobontane, Divine 1514 Ogola, Eric 1108 The NIMPE Advisory Group Nshala, Andreas 1065, 1686, Ogolla, Sidney O. 331 Members 906 1688, 505 Ogoma, Sheila B. 995 Ning, Yue 1900 Nsibu, Célestin N. 290, 1573 Ogony, Jack 347 Ninsiima, Harriet 807 Nsobya, Samuel L. 807, 809, 811, O Oguike, Mary C. 1494, 325, 825 Ninsiima, Hope 243 1505 Oguma, Geoffrey 620 Oakley, Miranda S. 1295, 44 Nip, Vincent 1128 Nsoesie, Elaine O. 1440 Ogunbosi, Babatunde 345 Obai, Gerald 1767 Nisalak, Ananda 148, 170, 171, Nsona, Humphrey 841 Ogutu, Bernard 207, 1483, 1049 Obala, Andrew 293, 383, 719, 884 36, 591 Nsona, Humphreys 686 O’Hanlon, Simon 1721 Obaldia, Nicanor I. 1473 Niska, Richard W. 1392 Nsue Maye, Valeriano Oluy 1662 O’Hare, Bernadette 33 Obama, Anita Eyang 1662 Niu, Guodong 1534, 558 Ntadom, Godwin 810 Ohenhen, Reginah E. 1711 Obama Nsue, Jose Luis 1660 Nix, William A. 1422 Ntambue, Abel M. 414, 74 Ohlrogge, Eric 1786 Obenauer, Peter J. 737 Nizame, Fosiul A. 580, 1164 Ntamtungiro, Alex 598 Ohrt, Colin 1217, 1508, 1558, Obeng-Adjei, Nyamekye 934 Njagi, Purity 1347, 972 Ntaro, Moses 231 250, 843, 873, 874, 900, 906, Oberlies, Nicolas H. 1723 Njau, Ritha 1801, 917 Ntege, Edward 374, 370 910 Oberste, Steve 1422 Njenga, Sammy M. 461, 464, 54, Ntshalintshali, Nyasatu 1536, 866 Ohta, Nobou 431 Obi, Emmanuel 384 25, 456 Ntuku, Henry 1557 Ohuabunwo, Chima 1186 Obiezu, Josephine I. 452 Njie, Sarjo 232 Ntumngia, Francis B. 1643, 557, Ojaku, Alex 243 Oboegbulem, Steve I. 66 Njimoh, Dieudonne L. 1172 49 Ojeda, Sergio 133 Obonyo, Charles O. 1483 Njoki, Nancy 972 Nuckols, John T. 1441 Ojo, Abiodun 1516, 1517 Oboth, Paul 620 Njuguna, Henry N. 297 Null, Clair 25, 579 Ojo, Kayode K. 1292, 861 Ocampo, Clara B. 1363, 1366, 738 Nkanaunena, Kondwani 599, 654, Nunes, Márcio Roberto T. 1465 Okafor, Chidinma B. 1467, 157 Ocampo, Karen 424 914 Nuñez, Andrea 133, 136 Okal, Michael N. 1887 Ocaña-Mayorga, Sofia1 1761 Nkawa, Frida 1454, 1455, 791 Nunez, Andres G. 1650 Okamoto, Michiko 1450 Occi, James 1681 Nkhata, Ilenga 24 Nunez, Marlon 1473 Okeagu, Okechukwu M. 935 Ochai, Leon 167 Nkhoma, Standwell 1589 Nunziangeli, Luisa 1598 Okeakpu, Jacinta 1018, 1676 Ochako, Rhoune 972 Nkosi, Thandile 30 Nuorti, Pekka J. 1203 Okebe, Joseph 1215, 213, 232, Ochanda, Horace 1243 Nkouawa, Agathe 1028 Nurat, Akin-Kolapo B. 967 871, 889 Ochiai, Leon 595 Nkoumou, Yannick 1689 Nuruzzaman, Mohammad 580 Okech, Bernard 155 Ochiai, R. Leon 774 Nkwata, Allan K. 1727, 490 Nuss, Andrew B. 1377 Okeke, Iruka N. 399 Ochieng, Joan 1769 Nmorsi, Onyeabuchi P. G. 1711 Nussbaum, Jesse C. 605 Okeke, Ogochukwu C. 526 Ochieng, John B. 1203 Noakes, Eric 1308 Nussenzweig, Victor 47 Okell, Lucy 806 Ochoa, Cesar 1118 Noa Noatina, Blaise 1689 Nutman, Thomas B. 1075, 1244, Okello, Steven 812 Ochoa, Margarita M. 745 Nobre, Maurício L. 432 1690, 1812, 1842, 1881, 1883, Okhmatovskaia, Anya 685 Ochoa, Theresa J. 1009 Noedl, Harald 1829 54, 640, 643, 670, 727, 1884 Okia, Michael 1658, 300 Ochoa-Orozco, Sergio A. 1632, Noel, Dolland 1054 Nuwa, Anthony 1572, 243 Okiring, Jaffer 812 314 Noel, Trevor 1054 Nwadinigwe, Judith 1492 Okitolonda, Emile 1117, 1466, Ochola, Emmanuel 434 Nogaro, Sarah 1822 Nwakanma, Davis 1215, 1496, 1684, 1702, 6, 1454, 1455, 186, Ockenhouse, Christian F. 1276, Nogueira, Mauricio L. 1435, 755 1582, 232, 529, 92 77, 1464, 795, 799 1277, 19 Nolan, Christina 1531 Nwakwuo, Geoffrey C. 1169, 354 Okoh, Hilary 1568 Ockenhouse, Christian F. 1278 Nolan, Thomas J. 1778, 608 Nwankanma, Davis 213 Okonkwo, Paul O. 1120 O’Connell, Elise M. 54, 643 Nolasco, Oscar 1595, 233 Nwanta, John A. 66 Okorie, Patricia N. 457 Odame, Michael 1682 Nolla, Nicolas 908 Nwe, Thet Wai 1813 Okoth, Edward 1236 Odeny, Jacob 1769 Noor, Abdisalan M. 1578 Nwoke, Bertram E. B. 452 Okoth, George 597, 911 Odero, Norbert A. 597, 911 Noor, Zannatun 1291 Nwokolo, Ernest 837 Okoth, Sheila A. 565 Odey, Friday A. 198 Noormal, Bashir 421 Nyabeyeu Nyabeyeu, Herve 908 OKpala, Njideka T. 452 Odhiambo, Frank 618, 788 Norcross, Neil R. 815 Nyagonde, Nyagonde 1694 Okui, Peter 1572, 1875, 243 Odhiambo, Fredrick 234 Norice, Carmelle T. 1883, 640 Nyaku, Mawuli 1341 Okuma, Peter O. 683 Odiere, Maurice R. 54 Noriega, Fernando 1223, 167, 774 Nyang, Haddy 213 Okumu, Fredros O. 276, 995, 265 astmh.org Abstract Author Index A-617

The number(s) following author name refers to the abstract number.

Oladosu, Oladipo O. 217 Onapa, Ambrose 1066, 1320 Ortiz, Eduardo 1748 Owusu-Agyei, Seth 1049, 1305, Olakiigbe, Abiodun 1568, 1654 Oñate, José 1632 Ortu, Guiseppina 1232 240, 842, 997, 1701 Olalubi, Oluwasogo A. 488 Ondigo, Bartholomew 326 Orvis, Joshua 1294 Owusu-Dabo, Ellis 400 Olaniyonu, Iyanu 1492 ONeal, Seth E. 1034 Osa Nfumu, Jose Osa 1003, 1660, Owusu-Kwarteng, James 130 Olaya, Sandra 1034 O’Neill, Maeghan 1724, 668 1869 Oxborough, Richard 1282 Olayemi, Sunday 1492 O’Neill, Matthew T. 1296, 631 Osarfo, Joseph 805 Oyebola, Muyiwa K. 1586 Olayinka, Adebola 185 O’Neill, Paul 1718 Osbert, Nicolas 1788, 23, 24, 581 Oyet, Caesar 1575, 292 Oldja, Lauren 27, 576 O’Neill, Sarah 871, 1615, 653 Osborne, Jane 1178 Oyibo, Wellington A. 1607, 169, Oleinikov, Andrew V. 1526, 261, O’Neill, Scott 161, 594 Osei, Isaac 1049 935 334 Onema, Willy 971 Osei-Atweneboana, Mike Y. 1080 Ozersky, Philip 1883 Oleinikov, Irina V. 1526 Ong’echa, John M. 1769, 589, Osei-Mensah, Jubin 1708, 639 Oliva, Exgar 572 1271, 1591, 1592, 1593 Osei, Isaac on behalf of the Oliveira, Fabiano 1690 Ongoiba, Aissata 1609, 336, 902 MenAfriCar Consortium 1020 Oliveira, Guilherme 1776, 1781, Onlamoon, Nattawat 162, 172 Oshitani, Hitoshi 1450 P 1782 Onuoha, Ogechi C. 967 Osorio, Elvia Y. 522 P, Rajshree 1459 Oliveira, Jothelma 1161 Onwona, Christiana O. 216 Osorio, Jorge E 168, 550, 743 Pablo, Jozelyn 1602, 1606, 1646, Oliveira, Léa C. 1101, 1912 Onwujekwe, Obinna 483 Osorio, Manuel 1014 559, 943 Oliveira, Rita G. 461, 54 Onyamboko, Marie A. 13 Osse, Razaki 106 Pablo, Jozelyn V. 978 Oliveira, Rodrigo C. 1819 Onyambu, Frank G. 1592 Osuna-Cabello, Maria 815 Paccha, Blanca 1107 Oliver, Shune 712 Onyango, Irene 211 Osuntoki, Akiniyi A. 929 Pace, Cheryl 851 Olkowski, Sandra 439, 775 Onyango, Irene A. 347 Ota-Sullivan, Kaede 1512 Pacheco, Maria Andreina 919, Olliaro, Piero 1094, 1530, 617, Onyeka, Cynthia I. 1682 Otchere, Joseph 431 1569 1820 Onyemaechi, Jane O. 801 Oti, Samuel 788 Pacheco, Victor 661 Olmeda, Paul 1531 Oo, Kyaw S. 838 Otiang’, Elkanah S. O. 1108 Paczkowski, Magdalena 358 Olomi, Raimos 1122 Ooi, Eng Eong 165 Otieno, Dan James 1330 Padda, Preeti 7 Olo Motu, Diosdado 1869 Oparaugo, Nkechi 1568 Otieno, Juliana A. 1271 Paden, Clinton 193 Oloniniyi, Olamide K. 179 Opata, Michael M. 327 Otieno, Kephas 597, 911 Padilla, Julio 1577, 1584 Oloo, Stellamaris 1769 Operario, Darwin J. 1013 Otieno, Linus O. 1108 PADNET Team 1002 Olotu, Ally 1633, 1637 Opoka, Robert O. 1056, 1475, Otieno, Nicholas O. 1769 Padonou, Gil 106 O’Loughlin, Samantha 1384 1477, 195, 629, 1051, 34 Otieno, Peter 911 Paes, Cheryl 38, 549 Olsen, Cara H. 1403 Opondo, Charles 1301, 823 Ototo, Edna 896 Page, Nicola 1013 Olsen, David B. 1493 Opondo, Kevin O. 113 Otubanjo, Olubunmi 1586 Page-Sharp, Madhu 215 Olsen, Sonja J. 178 Oppong, Samuel 907 Ouattara, Abdoulaye 158 Pahlavan, Golbahar 854 Olsho, Lauren 681 Oraka, Chinedu O. 418, 801 Ouattara, Amed 1606, 1640, Paine, Mark J. I. 502, 717 Olson, Ken E. 40 Orcutt, Andrew 1648, 991 1646, 835, 921, 924, 978 Paintain, Lucy 684 Olson, Sarah H. 1452 Ordanovich, Dariya 286 Ouattara, Daouda 853 Paireau, Juliette 1323 Olubayo, Luicer I. A. 207 Ordi, Jaume 1269, 618 Ouattara, Mamadou 1273 Pajuelo, Monica 1030 Oluduro, Anthonia O. 892 Ordonez, Kathleen 578 Ouattara, Maurice S. 853 Pal, Sampa 1218, 280, 281 Olukosi, Adeola 1586, 1568 O’Reilly, Ciara E. 1203 Ouédraogo, Alphonse 564 Pal, Subhamoy 759 Olveda, Remigio 1825 Oreta Graza-Pan, Maria Cecilia 458 Ouédraogo, André Lin 1551, 613, Palacios, Gustavo 1764 Omaer, Samya 1762 Oria, Prisca A. 379 954, 1548 Palacios, Ricardo 1221, 1632 O’Maera, Wendy P. 293 Oriá, Reinaldo B. 63 Ouedraogo, Issa N. 853 Palacpac, Nirianne M. Q.. 370, 374 Omaliss, Keo 1452 Oriero, Eniyou C. 232 Ouedraogo, Jean B. Palencia, Diana 1406 Omanje, Vincent 1769 Orimadegun, Adebola E. 1498 Ouédraogo, Jean Bosco 560, 1211, Paliga, John M. 995 Omaswa, Freda 1636 Oriokot, Francis 65 870, 573, 818 Palihawadana, Paba 767 Omballa, Victor O. 417 Orizondo, Monica 491 Ouédraogo, Smaïla 854, 968 Paller, Vachel Gay V. 1111, 578 O’Meara, Wendy P. 1187, 383, Orji, Bright C. 1656, 1657 Ouedraogo, Thierry 1655, 969 Palma, Noemi 401 435, 239, 719, 1041 Orjuela-Sanchez, Pamela 1529, Ouma, Collins 1592, 331 Palma, Sandra 1038 Ome-Kaius, Maria 1262, 1565, 733 Ouma, Peter 960 Palmieri, James 1332 1599, 1600 Orme, Maria 1604 Oundo, Joseph O. 297, 1203 Palpouguini, Lompo 419 Omenda, Maxwel M. 486 Orobio, Yenifer 1363, 1366 Ouoba, Aline 776 Palumbo, Anne 1085, 29 Omobowale, Olubukola C. 1732 Orok, Bassey A. 929, 1568 Ourdraogo, Jean-Bosco 224 Pan, William K. 132, 784, 1041 Omoera, Victoria 994 Orok, John 1656, 1657 Outhay, Malena A. 1328, 690, Pandey, Manisha 60 Omole, Oluwatosin 1179 Oropesa, Suset 181 1343 Pandharkar, Trupti 1172 Omololu-Aso, Joseph 892 Orozco, Alejandro 1759 Outtara, Drissa 602 Panesso-Gomez, Santiago 1759 Omololu-Aso, Oluwaseun O. 892 Orozco, Maria 1638 Owen, Jason 1214 Pang, Junxiong Vincent 1270 Omondi, Amos 1833 Orrego, Miguel A. 1031 Owen, Russell 504 Pangilinan, Coleen M. 153 Omondi, Angela 211, 207 Orrego Solano, Miguel Angel 1035 Owino, Simon O. 628 Panharith, Nou 912 Omondi, Michael W. 1326 Orr-Gonzales, Sachy 878 Owolabi, Alexander T. 892 Panhuis, Willem G. V. 150 Omoniwa, Omowunmi F. 1301, Orr-Gonzalez, Sachy 1635, 941 Owusu, Henry F. 114, 1233 Paniagua-Contreras, Gloria Luz 823 Ortega, Ynes R. 1146 Owusu, Irene Offei 458 405 Omore, Richard 1203 Ortiz, Betsi L. 1345 Owusu, Michael 400 Pan-ngum, Wirichada 652 Onah, Den-Chris N. 66 Ortiz, Domingo 1422 astmh.org A-618 Abstract Author Index The number(s) following author name refers to the abstract number.

Pannuti, Claudio S. 1413 Pathirana, Nishantha 1102 Pereira, Beatriz D. 1119 Phiri, Wonder Philip 1662, 1869 Pantoja, Petraleigh 1416, 1463 PATH Malaria Vaccine Initiative, Pereira, Ligia 1474, 626 Phok, Sochea 912 Panyanivong, Phonepasith 542 1611 Pereira, Rosiane 1137 Phommasone, Koukeo 423 Paohintang, Kirana 838 Patil, Asha 989 Pereira, Walquer V. Esteves. Phonpakobsin, Thipwipha 171 Paolino, Kristopher M. 1276, 1633, Patiño, Lilian 1011, 1667 Gonçalves. 1435 Phophak, Nanthaporn 816 1278, 163 Patrick, Shawn V. 407 Perera, Ann 1072 Phouyaphone, Kelly 346 Papa, Anna 1448 Pattanapanyasat, Kovit 162, 172 Perera, David 751 Phyo, Aung Pyae 603, 943, 1589 Papangelou, Alex 1209 Patterson, Stephen 1914 Perez, Luis M. 1542, 876 Piarroux, Renaud 1563 Parameswaran, Poornima 136, 592 Patton, John B. 608 Pérez, Norma 1729 Piatt, Michael 638 Parapini, Silvia 1530 Paukovova, Zuzana 1733 Perez-Padilla, Janice 37, 1422 Picado, Albert 1098 Paredes, Maribel 393, 394 Paul, Kishor 139, 768 Periago, Maria V. 477 Pichyangkul, Sathit 15 Pare/Toe, Lea 1234 Paul, Noah H. 361 Periago, Victoria 606 Pickering, Amy J. 577, 579, 25 Parikh, Sunil 1396, 1486, 1575, Paul, Proma 677 Perin, Jamie 27, 576 Pickering, Paul 789 292 Paul, Repon C. 768 Perkins, Alex P. 1811 Pickett, Gavin 589 Paris, Daniel H. 542 Paul, Richard 590 Perkins, Douglas J. 1334, 1591, Pickrell, Anthony M. 688 Paris, Robert 255 Paula, Fabiana M. 1151, 474 1592, 1593, 1769, 589 Piedrahita, Leidy D. 1414, 1463 Paris, Robert M. 1276, 1278 Paulino, Robert 491 Perng, Guey Chuen O. 753 Piepenburg, Olaf 797 Park, Daniel J. 371 Paulo, Rossely 1067 Perry, Megan 1660 Piera, Kim 355 Park, Gregory S. 1475, 1477, 195 Paulous, Sylvie 765 Perry, Nicolas 1149 Pierce, Kristen K. 1220, 1408, Park, Jay 1339 Paulucci-Holthauzen, Adriana 1458 Perryman, Alexander 1681 1411 Park, Jin Kyung 771 Paust, Silke 734 Persoons, Frederick 971 Pierce, Raymond J. 1776 Park, Jooyoung 225 Pauza, David 927 Persson, Kristina E. M. 343 Piermarini, Peter M. 1191, 1351, Park, Kisoo 1202 Pavia, Paula 1759 Petchampai, Natthida 1358 715 Park, Kiwon 1297 Pavic-Espinoza, Ivana 1766 Peters, Bjoern 1255, 552, 761 Pierre, Claudia 1706 Park, Lawrence 666 Pavlicek, Rebecca 57 Peters, David H. 1185 Pierrotti, Ligia 474 Park, Sangshin 1580 Pavlinac, Patricia 1141 Peters, Kevin G. 253 Pierson, Ted C. 1854 Parker, Josephine E. A. 1807, 724 Pawlowski, Michal 1043 Petersen, Christine A. 524, 1115 Pierson, Tony 57 Parker, Michael 1335 Paxton, Lynn 268, 1216 Peterson, A. Townsend 661 Pike, Andrew 1197 Parmiter, Minnie 955 Paye, Jusufu 1930 Peterson, Amy 1736 Pillai, Dylan R. 206, 235 Probek, Christian Payne, Ruth 1277, 1462, 180, 182 Peterson, David 1364 Pillay, Allan 1680 Parobek, Christian M. 585, 915, Pazirandeh, Mehran 372 Peterson, David S. 628 Pimenta, Paulo F. P. 755 543 Paz-Soldan, Valerie 661, 86 Peterson, Jennifer K. 1309 Pina-Costa, Anielle 901 Parola, Philippe 467, 646 Pearce, Cedric J. 1723 Peterson, Johnny W. 1014 Pinapati, Richard 1589, 1826 Parr, Jonathan B. 802 Pearce, Edward J. 1915, 1918 Peterson, Kassandra L. 734 Pinchoff, Jessie 1867, 879 Parr, Valentina 56, 56 Pearce, Erika L. 1915 Peterson, Stefan S. 1047 Pindolia, Deepa 1214, 866 Parra, Marcela 338 Peatey, Christopher 1874 Petri, Sarah E. 1136 Piñeyro, M. Dolores 1084 Parris, Tiffany K. 388 Peck, Roger B. 1070, 1075 Petri, Jr., William A. 1134, 1135, Pinfold, John 1788, 23, 581 Parsons, Emily 1271 Pedersen, Karl 408 1291, 1665, 408, 1154, 1136, Pinheiro, Tauyne M. 755 Parsons, Michele B. 1203 Pedro, Renata S. 1428 1700, 1865, 1863 Piñón, Alexander 181 Partidos, Charalambos 168, 550 Peeling, Rosanna 1740 Petros, Beyene 1140, 480 Pinsky, Benjamin A. 1509, 422, Partovi, Susan 1344, 79 Peery, Ashley 1385 Pett, Helmi E. 588, 1208 741 Parvez, Sarker Masud 577 Peeters, Koen G. 1615, 653 Peyton, David H. 1495 Piola, Patrice 885 Parvin, Tahmina 27, 576 Peeters Grietens, Koen 1213, 804, Pezua, Adriana 1155 Pion, Sébastien 1716, 1721, 1812, Pasay, Cielo 860 871 Pfaff, Jennifer M. 1858, 549 459, 1717, 1815, 1818 Pascale, Juan M. 1345, 1461 Peirano, Gisele 235 Pfarr, Kenneth 1708, 1709, 443, Pitche, Vincent 31 Pascual, Mercedes 216 Peirce, Matthew J. 1361 644 Pitt, Catherine 1348, 271 Paskewitz, Susan M. 710 Pelajo-Machado, Marcelo 942 Pfeiffer, Constanze 1327 Pitti, Arcelys 1410 Passafaro, Michael 78 Pellé, Karell G. 371 Pfrender, Michael 1172 Pitzer, Virginia E. 1671 Passos, Sara 517, 521 Pelletreau, Sonia 1063 Pham, Hung Q. 873, 874 Pizango, Melita 1797 Pastrana-Mena, Rebecca 993 Peña, José 754 Pham, Phuong Thao 1295 Plante, Jessica A. 1430 Patarroyo, Manuel A. 1478 Pendergast, Laura 1864 Pham, Thao P. 369, 950 Platt, Alyssa 1187, 383, 719, 884 Patel, Chirag G. 487 Penetra, Stephanit 1428 Phann, Sut Thang 15 Platts-Mills, James 1013, 1865 Patel, Jaymin C. 1556, 915, 1394 Pengruksa, Chaweewan 816 Phaosawasdi, Kamthorn 652 Pletz, Mathias W. 1770 Patel, Kaajal 1560 Pengruksa, Sorose 816 Phatharakokordbun, Phabele 289 Ploss, Alexander 1325 Patel, Ketan 1765 Pengruksa, Suntaree 838 Phelps Nishiguchi, Erika 1472 Plouffe, David 1488, 1827 Patel, Nishita 1118 Peniche, Alex G. 395 Phetsouvanh, Rattanaphone 542 Ploutz-Snyder, Robert 331 Patel, Pranav 797 Penney, Naomi 1308 Phillip, Matthew 1262 Plowe, Christopher V. 1563, 1581, Patel, Roopal 1664 Penny, Melissa 952 Phillips, Aaron T. 40 1602, 1606, 1633, 1640, 1646, Patel, Shailja 1836 Perales, Jonas 1137 Phillips, Margaret A. 857 1829, 893, 921, 923, 924, 943, Patel, Shraddha V. 689 Peralta, José M. 539 Phillips-Howard, Penelope A. 960 978, 835 Paternina, Margareth 1053 Perce-da-Silva, Daiana S. 321 Phiri, Ajib 1127, 682 Plucinski, Mateusz 1901 Paternina Gomez, Margaret 143 Perea, Wiliam 619, 1443 Phiri, Kamija 1559, 285, 936, 30 Plummer, Emily 1255 Pates Jamet, Helen 1378 Pereira, Amanda 1571 Phiri, Themba 841 Png, Eileen 1270 astmh.org Abstract Author Index A-619

The number(s) following author name refers to the abstract number.

Poche, Richard 1236 Pratt-Riccio, Lilian R. 321, 942 Qiu, Ping 857 Ram, Malathi 886 Podust, Larissa M. 1899 Precioso, Alexander 1221 Quackenbush, Sandra 190 Ram, Pavani K. 1163, 1839, 580, Poggensee, Gabriele 1186 Premaratne, Prasad H. 769, 772 Quakyi, Isabella A. 245 582 Pohl, Nicola L. 524 Premji, Zul 420 Quashie, Nancy 1480 Ramakrishnan, Girija 408 Poirot, Eugenie 1208, 855 Prendergast, Andrew 1784 Quashie, Neils 1480 Ramal, Cesar 394 Polhemus, Mark 500 Prenna, Enrico 1234 Quaye, Lydia 1480 Ramal-Asayag, Cesar 439 Politis, Maria 390 Prentice, Andrew M. 625 Queen, Krista 193 Ramalho-Ortigao, Marcelo 722 Pollak, Arnold 1336 Pressley, Keisha 390 Queiroz, Adriano 1251 Raman, Jaishree 264 Pollak, Joseph Joel 237 Preziosi, Michael 415 Quetz, Josiane S. 1669 Ramanathapuram, Lalitha 920 Pollard, Andrew J. 1201 Price, Ric 14 Quevedo, Tatiana 406, 705 Ramanatiaray, Tiana 1511, 221, Pollett, Simon 183 Priest, Jeff 895 Quiarim, Talita M. 1435 302 Polman, Katja 610, 727 Prieto, Carla 1764 Quick, Robert E. 1160 Ramani, Saliou 244 Polonio, Roy 1308 Pringle, Julia 111 Quicke, Kendra 638 Ramarokoto, Charles E. 1834 Polpanich, Duangporn 349 Pringle, Kimberly 1268 Quilaguy, Diana M. 395 Ramharter, Michael 854 Polsomboon, Suppaluck 96 Printz, Naomi 1616, 359, 961 Quinn, Ashlinn 1305 Ramiranirina, Brune 1511, 221, Ponce-Terashima, Rafael 1896 Pritchard, David 471 Quinones, Javier 1016 302 Pond-Tor, Sunthorn 1580 Pritsch, Michael 1707 Quiñones, Martha L. 1577 Ramirez, Jorge I. 738 Ponlawat, Alongkot 1283 Pritt, Bobbi S. 710 Quintana, Fernando A. 659 Ramirez, Jose Luis 636 Ponnusamy, Loganathan 1311, Priyamvada, Lalita 172 Quintana, Juan F. 443 Ramirez, Juan-David 1246 1394, 543, 708, 726 Proctor, Joshua L. 584, 958 Quintero, Cesia 8 Ramirez, Roberson 1518 Pons, Diego 948 Proietti, Carla 830 Quintero, Gustavo E. 1478 Ramirez, Ronald 1042, 430 Pons, Maria J. 1113, 1766 Prom, Satharath 15, 1502, 323 Quintero, Juliana 1167, 1400, 174 Ramirez Jaldin, Maritza 29 Poole, Catherine B. 448 Pros, Soy 1132 Quintó, Llorenç 1553 Ramiro de Assis, Rafael 1781, 1782 Poole-Smith, B. Katie 1412 Prosnitz, Debra 441, 686 Quiroz, Alejrandro 1710 Ramos, Eric 1763 PooNgoen, Apaipun 838 Protopopoff, Natacha 1653, 1870 Quispe, Antonio M. 1549, 659 Ramos, José 752 Poovorawan, Kittiyod 652 Prudhomme O’Meara, Wendy 884 Quispe, Mariella 233 Ramos-Castañeda, José 1424, Popov, Vsevolod 140, 1458, 1442 Prue, Chai S. 886 Qureshi, Shahida M. 1008, 1772 1432 Popovici, Jean 1587 Prusa, Andrea-Romana 1336 Ramos-Puebla, Miguel Angel 405 Popper, Stephen J. 423 Psathas, Petros 1720 Rampling, Thomas 180, 182, Popuche, Dina E. 166 Psychas, Paul 907 1277, 1462 Porciani, Angélique 108 Puerta, Concepción J. 1759 R Ramsan, Mahdi M. 112, 1216, Porter, Chad K. 62, 794 Puerta Guardo, Henry 1253 1235, 268, 386, 600 Ra, Sok 912 Porter, Mike 1645 Puffer, Bridget A. 549 Ramsay, Andrew 1268 Raballah, Evans 1593 Portugal, Silva 1609 Pugh, Christine 1433 Ramsland, Paul A. 16, 831, 937 Raballah, Evans O. 1592 Posada, Monica 1774, 1775 Pukrittayakamee, Sasithon 214, Ramstedt, Urban 1255, 1256 Rabinowitz, Peter 1107 Posner, Jourdan 678 254 Ranade, Ranae M. 1314 Rabiu, Olawunmi R. 1603 Postels, Douglas 651, 1051 Pukuta, Elisabeth 1454, 1455, Ranasinghe, Udaya S. B. 1925 Rachmat, Agus 887 Potente, Arantxa 744 1466, 791, 795 Randall, Arlo 559 Radford, Kay 1454, 791 Pothin, Emilie 614 Pullan, Rachel L. 1045, 464 Randall, Louise 1612 Radley, David 1222 Potter, Brittney 1531, 255, 257 Pullum, Tom 441 Randolph, Gwendalyn J. 1918 Ragone, Paula 1089 Poulton, Ian 1277 Punchihewa, Manjula W. 1925 Randriamaherijaona, Sanjiarizaha Rahman, Abid M. Quaiyum. 1839 Poveda, Andrea 1571 Punnen, Anu 426 116, 1239, 1369 Rahman, M. A. 1861, 1862 Povelones, Michael 1365, 1891 Puplampu, Naiki 1023, 1677 Randrianarivelojosia, Milijaona 275, Rahman, M. Waliur 139 Povoa, Marinete M. 1877, 340 Puri, Ankit 699 885 Rahman, Mahbubur 1164 Powell, Jessica 60 Pusey, Anne E. 894 Randrianasolo, Bodo S. 1834 Rahman, Mahmudur 139, 768 Powell, Rosanna 11, 603 Pushansky, Tatiana 1835 Ranford-Cartwright, Lisa C. 1173 Rahman, Md. Ridwanur 1829 Powell, Suzanne 244, 720 Pushpakumara, Pradeep D. 769, Rangel, Alfonso Calderon 1170 Rahman, Mohammed Z. 768 Powles, Maryann 1493 772 Ranjan Wijesinghe, Pushpa 1013 Rahman, Musarrat J. 577 Poyer, Stephen 1619, 971, 972 Putnam, Shannon D. 62, 794, 887 Ranji, Cyra 1433 Rahman, Mustafizur 1839 Pradines, Bruno 1532, 824 Putraprasert, Kwanyuen 838 Ranson, Hilary 1238 Raja, Amber 556 Prado, Lindsay 1518 Puttagunta, Raghuveer 1738, 494 Rao, Namratha 1190, 1621, 695 Rajahram, Giri 1560, 1902 Prado, Roberta O. 1819 Pyae Phyo, Aung 1829 Rao, Pavitra N. 920 Rajan, Roshni 426 Prahamanik, Santanu 1456 Pyana, Pati 878 Rao, Ramakrishna U. 1925 Rajaonarison, Pascal 275 Praharaj, Ira 1013 Pybus, Brandon S. 1535, 255 Raoult, Didier 467 Rajaram, Krithika 993 Prahl, Mary 332 Rasgon, Jason L. 1364, 1808 Rajwani, Jahanara 976 Prakash Babu, Senbagavalli 1881 Rashid, Mohamed 155 Rakasz, Eva 168 Prasad, Abhishek 1852 Rashid, Sujatha 1451 Raknam, Thanee 816 Prasad, Abhishek N. 1445 Q Rashu, Md. Rasheduzzaman 397 Rakotomalala, Emma 885 Prasanphanich, Nina S. 1785 Rashu, Rasheduzzaman 1202, Qabar, Aziz 1278, 1645, 1276 Rakotomanana, Fanjasoa 1834 Prathapan, Shamini 1259 1862 Qadri, Firdausi 1199, 1200, 1202, Rakotomanga, Tovonahary A. Pratlong, Francine 1316 Rasmussen, Zeba A. 1772 1411, 1673, 1700, 1861, 1862, 1511, 221, 302 Pratt, Abigail 912 Raso, Fiona 1299 392, 397 Ralston, Katherine S. 1135 Pratt, Christian 1268 Raso, Giovanna 1821 astmh.org A-620 Abstract Author Index The number(s) following author name refers to the abstract number.

Raso, José 1637 Remme, Jan H. F.. 1715 Riera, Sandra M. 1638 Rodriguez, Jessica 1345 Rasoloharimanana, Tsikiniaina L. Remoué, Franck 67 Riesen, Maurane 1807 Rodriguez, Pamela 20 885 Ren, Guang-Hui 1898 Rigby, Lisa M. 1237 Rodriguez, Virginia 1170, 1705 Ratchmat, Agus 1502 Rendell, Victoria R. 1911 Riggs, Michael W. 1292 Rodriguez Barraquer, Isabel 1055, Rathod, Pradipsinh K. 1474, 626 Renneker, Kristen 1059, 1229 Rijo-Ferreira, Filipa 1921 1427, 36 Ratnayake, Ruwan 1182 Respress, Jonathan L. 1747 Rijpma, Sanna 982 Rodríguez-Mantilla, Iván E. 1759 Ratsimandisa, Rova 1347 Restrepo Jaramillo, Berta N. 1414, Riley, Eleanor 1598, 918 Rodriquez, Bibiana 556 Ratsimbasoa, Arsène 1511, Arsene 1463 Rimarachin, Dolores 1710 Roe, Michael 543 221, 302, 202 Revollo, Rita 440 Rimoin, Anne W. 1117, 1464, Roeffen, Will 981, 983 Rausch, Kelly 1279, 1648, 1649, Rey, Gloria 1013 1466, 1684, 1702, 6, 795, 799, Roepe, Paul D. 822 375, 985, 991 Rey, Luís C. 1669 666, 77 Roetynck, Sophie 363 Ravaoalimalala, Vololomboahangy Reyburn, Hugh 1122 Rinaldi, Gabriel 1835 Roffe, Ester 513 E. 1834 Rey Caro, Luz A. 1698 Riner, Diana K. 1785, 1833, 1243 Rogawski, Elizabeth T. 396 Ravaoarisoa, Elisabeth 885 Reyes, Anatalio 1275, 1634, 352 Ringwald, Pascal 1829, 1904, 8, 9 Rogers, Andrew 1797 Ravel, Sophie 1317 Reyes, Faviola 1663 Rios, Jane 1764 Rogers, Ashley M. 444 Ravn, Pernille 1694 Reyes, Raquel 231 Rios, Paul 1024 Rogerson, Stephen 1599, 1600, Ravoniarimbinina, Pascaline 1834 Reyes, Sharina 1275, 1613, 1634, Rios, Ruby 1739 1612 Rawline, Barbara 315 352 Riscoe, Mike 1531 Rogier, Christophe 116, 1239, 381, Razavi, Michael 1605 Reynes, Christelle 12 Ritchie, Scott A. 1237, 728 67, 885 Rázuri, Hugo R. 705 Reynolds, Alison M. 953 Rivas, Kasey L. 1292, 861 Rogier, Eric 1212, 1229, 895 Read, Kevin D. 815 Reynolds, James 1118 Rivera, Aidsa 135, 1422, 37 Rogova, Maryna 1005, 1272 Read, Lisa T. 1525, 257, 1531, 255 Reynolds, Mary G. 1114, 1454, Rivera, Pilarita T. 532 Roh, Michelle 1575, 292 Ready, Andrew 1918 791, 1455 Rivera Garcia, Brenda 37 Rojas, Elsa 1406 Rebaudet, Stanislas 1563 Reynolds, Nathanael D. 1024, Riveron, Jacob M. 1284, 1373 Rojas, Roberto 409 Rebollo Polo, Maria 1063, 1929, 1663, 394, 393 Rizk, Shahir S. 1172 Rojas Garrido, Elsa M. 1698 1927, 1045 Rheingans, Richard D. 1792 Roald, Borghild 1834 Rojas Palomino, Nyshon M. 1088, Recalde, G. Cristina 1793 Rhodes, Julia 416 Roark, Brendan 1888 1749 Recuenco, Fernando 1752 Ribacke, Ulf 1469, 48, 640 Robbins, Dana 371 Rojas-Peña, Monica L. 320 Recuenco, Sergio 1110, 792 Ribeiro, Jose 636, 670 Robbins, Richard G. 96 Rollinson, David 1782 Reda, Abeba G. R. 832 Ribeiro, Ruy M. 1334 Robbins, Yvette L. 878 Rolon-Martinez, Solymar 1783 Reda, Hailemariam 1544 Ribeiro, Sidney J. L. 1092 Robello, Carlos 1084 Roman, Deogratius 1809 Reddy, Elizabeth A. 1326 Ribolla, Paulo E. 102 Roberge, Christophe 1717 Roman, Elaine 315 Redmond, Seth N. 1384 Ricaldi, Jessica N. 424, 59 Roberts, Adam 1914 Romani, Lucia 541 Reed, Steve G. Ricciardi, Alessandra 1787 Roberts, Christine 1222 Romano, Camila M. 1487 Reed, Steven G. 1647, 1740, 1850, Riccio, Evelyn K. P. 942 Roberts, David P. 1183 Romelo, Beatrice 76 981, 1649 Richard, Stephanie 1864 Roberts, Kathryn 655 Romero, Alessandra 1095 Rees-Channer, Roxanne R. 845, Richard, Vincent 192, 381 Roberts, Rachel 1277, 363 Romero-Ramirez, Alessandra 1751, 1804 Richard Ateme, Rosa Patricia 1003, Robertson, Alan P. 1072, 607, 609 1752 Regeimbal, James M. 1024, 57 1660, 1869 Robinson, Ellen 64 Romo, Hannah 1448 Regules, Jason A. 1276, 1278 Richards, Allen L. 700, 705, 709 Robinson, James E. 176, 763 Ronca, Raffaele 342 Rehman, Andrea M. 279, 601 Richards, Frank O. 452, 451 Robinson, Leanne J. 1262, 1263, Roncal, Norma 1525, 1531 Reich, Nicholas G. 1431, 593, Richards, Jack S. 16, 8, 831, 872, 1565, 1599, 830, 1600, 1604 Rönnberg, Caroline 343 1429 9, 937 Robinson, Luke 551 Rono, Winnie C. 435 Reichard, Gregory A. 1535, 255 Richards, Jenny 1538 Robinson, Nathan F. 1772 Ronse, Maya 1615, 653 Reid, Adam J. 926 Richards-Kortum, Rebecca 1043, Robinson, Sharon 260 Roobsoong, Wanlapa 49 Reid, Molly C. 861 1521 Robinson, Tanisha M. 946 Rood, Ente J. J. 691, 679 Reilling, Linda 16 Richardson, Jason 1283 Roca, Anna 1018, 1676 Rooijen, Nico V. 1297 Reiman, Jennifer M. 556 Richardus, Jan Hendrik 1022, 1679 Roca-Feltrer, Arantxa 1559, 999 Roos, David S. 922 Reimer, Lisa 730 Richie, Thomas L. 1633, 1636, Rocha, Claudio 1024, 1670, 1797, Root, J. J. 793 Reina Ortiz, Miguel 484 1637, 1275, 352 394, 1160 Rop, Mercy C. 239 Reiner, Jr., Robert C. 1811, 596, Richman, Adam M. 1639, 989 Roche, Claudine 765 Roque Jr, Vito G. 36 913 Ricketts, Delanie 620 Rochford, Rosemary 331 Rosa, Bruce A. 1885 Reinhard-Rupp, Jutta 535, 83 Ricks, Philip 907 Rock, Kat S. 1744 Rosanas-Urgell, Anna 303, 567, Reis, Mitermayer 1161, 1896 Rico, Amber B. 40 Rockett, Kirk 1389 804 Reis-Cunha, João L. 1316 Rico-Hesse, Rebecca 734 Rodó, Xavier 147 Rosario, Maria 857 Reisen, William K. 1447 Ricotta, Emily E. 1566 Rodpradit, Prinyada 739 Rosas, Angel 303 Reithinger, Richard 1045, 268, Ridde, Valéry 776 Rodrigues, Amabelia 1500 Rosas-Aguirre, Ángel 567 386, 566 Riddle, Mark S. 62, 794, 1663, 648 Rodrigues, Jaqueline P. 1142 Rose, Andreas 109 Rek, John 1261, 329, 283 Rider, Jr., S. Dean 98 Rodrigues, Maurício Martins 988 Rose, Michala V. 1694 Rekol, Huy 862 Rieders, Maria T. 1758 Rodrigues-Luiz, Gabriela F. 1316 Rose, Sharon 76 Relman, David A. 423 Riehle, Michael 638 Rodriguez, Gilhen 1729 Rosenberger, Kerstin 1254 Remais, Justin V. 1897 Riehle, Michelle M. 1871 Rodriguez, Hugo 303 Rosenjack, Julie 1511, 202 Remarque, Edmond J. 337 Riemer, Lisa J. 735 Rodriguez, Idia V. 1416 astmh.org Abstract Author Index A-621

The number(s) following author name refers to the abstract number.

Rosenthal, Philip J. 1614, 1875, Russpatrick, Scott 1788, 23, 24, Saingam, Piyaporn 10 Sanchez, Maria J. 932, 933 227, 807, 809, 811 581 Saionz, Kurt W. 262 Sanchez, Maria Carmen A. 844 Rose Selwin, Winsley 426 Rutagwera, Marie-Reine 1547, Saito, Mayuko 1450 Sanchez, Maria Paz 744 Ross, Allen 1825 1627, 1629 Sakanari, Judy A. 667 Sanchez, Marisabel 1545 Ross, Amanda 1555, 1809 Rutherford, George 183 Sakata-Kato, Tomoyo 1206, 1527, Sanchez, Nery 133 Ross, Michelle E. 1755 Rutta, Acleus S. M. 562, 904 1533 Sanchez-Aparicio, Maria T. 1257 Ross, Perran A. 713 Rutvisuttinunt, Wiriya 184, 739, Sakhuja, Maneesha 80 Sanchez-Vargas, Irma 762 Ross-Degnan, Dennis 1185 783 Sako, Yasuhito 1028 Sande, John 307, 358, 841 Rossi, Shannan 140, 1442 Rwakimari, John 1658 Sakrejda, Krzysztof 1429, 1431, Sande, Shadreck 1622, 309 Roth, Alison E. 1611, 201 Ryan, Edward T. 1198, 1199, 1200, 593 Sanders, Mandy 926 Roth, Amanda 1024 1202, 1861, 1862, 392, 397 Sakuntabhai, Anavaj 590 Sanders, Paul 16 Roth, Lukas 698 Ryan, Elizabeth M. 371 Sakyi, Kwame 1181 Sandiford, Simone L. 1197 Rotondo, Lisa 1685, 1686, 1687, Ryan, Peter A. 594 Sala, Katarzyna 1642 Sandler, Robert S. 396 1688, 503 Ryan, Sadie J. 1423, 500, 687, Salanti, Ali 335, 932, 933 Sandoval, Carlos 52, 649 Rouamba, Noel 818 1793 Salazar, Renzo 1756, 99 Sandoval, Isabel 401 Roungou, Jean-Baptiste 1715, 511 Ryan, Yana 1172 Salazar Sanchez, Renzo S. 103, Sandoval Juárez, Aidé C. 1088 Rout, Jonathan 1300 Ryman, Kate D. 137, 138, 1444, 1754 Sang, Edna 239 Rowe, Alexander K. 1185 42, 746 Saldanha, Maíra G. 1083 Sang, Rosemary 665 Rowe, Christopher 991 Ryu, Chiun 247 Saldarriaga, Omar A. 1510, 1746, Sang, Rosemary C. 1104 Rowe, Samantha 1185 1913 Sangama, Jorge 1518 Rowland, Mark 1370, 1371, 1653, Saleh, Abdullah 1349 Sangare, Cheick P. O. 1211 1870 Saleh, Jalal-Eddeen A. 410 Sangare, Ibrahim 870 Rowland, Mark W. 1282 S Salgueiro, Jennifer B. 1428 Sangare, Kotou 1496, 859 Rowley, Kirk 551 Salifu, Hassana 1618, 204 Sangare, Lansana 1496, 858, 859 Sa, Juliana M. 1485, 1630 Rowton, Edgar D. 1403 Salinas, Jorge L. 1482, 630 Sangare, Modibo 727 Sá, Juliana M. Roy, Jason A. 1755 Salinas, Nichole D. 557 Sangare, Moussa B. 1690, 727 Saadi, Wajeeh 1611 Roy, Rajasree 1670 Salje, Henrik 139, 36, 768 Sangweme, Davison 1295 Saavedra, Marlon 102, 125 Royal, Scott R. 1416, 1430 Sall, Amadou 1438, 1443, 797 Sangwichian, Ornuma 416 Sabat, Grzegorz 1779 Roychoudhury, Rajarshi 524 Sall, Amadou A. Sanjoba, Chizu 197 Sabbagh, Audrey 459 Rozelle, Scott 50 Sall, Amadou Alpha 192 Sanogo, Daouda 1583 Sabino, Ester C. 1101, 1912 Rubach, Matthew P. 1326, 627 Sall, Guelaye 826 Sanogo, Koualy 1208 Sabitu, Kabir 185 Rubahika, Denis 1572, 947 Salman, Ahmed M. 1647 Sanogo, Sintry 1279, 1576, 990 Saborio, Saira 136 Ruben, Adam J. 1637, 1638, 1639 Salman, Sam 215 Sanon, Antoine 1281 Sabundayo, Beulah 1408 Ruck, Richard C. 163 Salmon, Gabriela 132 Sanon, Souleymane 853 Sabzevari, Helen 1884 Rucker, Joseph B. 38 Salmon-Mulanovich, Gabriela 406, Sanou, Roger 1234 Sá Carvalho, Marilia 147 Rueckert, Claudia 1445, 1446, 661, 705 Sanou, Soufiane 870 Sachair, Aucha 757 1852 Saloka, Goeffrey 24 Santara, Gaoussou 1601 Sachs, Jeffrey J. 760 Rueckle, Thomas 852, 857 Salpeter, Seth 237 Santelli, Ana Carolina 1877 Sack, Bradley 576 Rueda, Lourdes 965 Salum, Abdallah R. 112 Santiago, Helton C. 513 Sack, Brandon 1274, 1608, 1613 Ruel, Theodore 1210 Salyer, Stephanie J. 706 Santiago, Laurelis 201 Sack, David A. 886 Rug, Melanie 1470 Samake, Sibiri 1690 Santiago, William 1422 Sack, R B. 27 Ruhwald, Morten 1694 Samake, Yacouba 1636 Santos, Ana K. S. 1669 Sackey, William 907 Ruisenor-Escudero, Horacio 31, 34 Samarasekera, Sandhya D. 1925 Santos, Debora P. 1148 Sacks, David 512 Ruiz, Joaquim 401, 1113, 1009 Samb, Badara 1373 Santos, Rodrigo I. 546 Saddler, Adam 266 Ruiz, Viviana 143 Sambol, Nancy 1486 Santos, Stephany S. 1148 Sadi, Johari Y. 904 Ruiz, Yumary 89 Samdi, Lazarus M. 1392 Sanuku, Nelly 1719 Sadiq, Aishatu Abubakar. 1186 Ruizendaal, Esmée 341 Samean, Sourn 912 Sanya-Isijola, Frank 1215 Sadiq, Kamran 1008 Ruktanonchai, Corrine W. 612 Samel, Buth 1132 Sanz, Ariadna 966 Sadou, Aboubacar 602 Ruktanonchai, Nick 863, 876, 612 Sami, Israk N. 1861 Sanz, Laura M. 800 Sadruddin, Salim 1127 Rukundo, Alphonse 1578, 1868 Samie, Amidou 1004, 784 Saran, Indrani 1519 Saeed, Tamer 1180 Rukundo, Rukundo Alphonse 1340 Samje, Moses 1072 Saravia, Nancy 1739, 1748 Sáenz, Fabián E. 1571 Rulisa, Alexis 263, 380 Sampaio, Barbara F. C. 1145 Saravia, Nancy G. Saenza Vasquez, Eliana 29 Rumsey, Jeanne 1886 Sampath, Aruna 1255, 1256 Sarfo, Bismark 487 Sagara, Issaka 1279, 1576, 1624, Runcharoen, Ratchadaporn 1829 Samuel, Vincent J. 851 Sariol, Carlos A. 1416, 1463 602, 820, 834, 990 Rungorjcharoenkit, Kamonthip 178 Samuels, Aaron M. 597, 911 Sarkar, Rajiv 396 Sagerman, Dawn D. 580 Rungrojcharoenkit, Kamonthip 178 Samy, Abdallah M. 189 Sarr, Aïssatou 1610 Sagnon, N’Falé 1871 Rupérez, María 1553, 1570, 854 San, Savoeun 15 Sarr, Demba 43 Sahlu, Ida 573 Rush, Amy H. 447 San, Sorn 1452 Sarro, Joseph 1193 Sahoo, Malaya K. 422 Rusibamayila, Neema 503 Sanabria, Dario 37 Sarti, Elsa 167, 752 Sahr, Foday 1182 Russ, Carsten 371 Sanchez, Arianni R. 844 Sary, Men 127 Sahu, Priyadarshi S. 1029 Russell, Amy F. 1222 Sanchez, Herado 1911 Sastry, Jagannadha 463 Said, Mayar M. M. 1762, 1129 Russell, Tanya 846 Sanchez, Juan F. 1357 Satharath, Prom 862 Saidi, Alex 33 Sanchez, Leny 1085, 1911, 29 Sato, Alice 1600 astmh.org A-622 Abstract Author Index The number(s) following author name refers to the abstract number.

Satofan, Samson 1719 Schofield, Louis 362 Serrato, Idalba M. 1363, 1366 Sheoran, Abhineet S. 1152 Sattabongkot, Jetsumon 1611, Schoone, Gerard 1100, 1739 Serre, David 1587, 202, 221, 302, Shepard, Donald 306 362, 830 Schountz, Tony 190 302, 449 Shepard, Donald S. 1304, 1424, Saudan, Phillipe 1645 Schreiber, Stuart L. 1206, 1527 Serufo, Angela 1137 360, 767, 781 Sauerborn, Rainer 673 Schriefer, Albert 1251, 1745 Sesay, Santigie 1930 Sherlock, Mark 1559 Sauerwein, Robert 1613, 559, 588, Schritz, Anna 1820 Seshadri, Pratibha 69 Sherman, Michael 1442 981, 983 Schulte, Seth 202 Seth Asamoah, Yaw Frimpong Sherrard-Smith, Ellie 1642 Saulters, Kacie J. 1050 Schwab, Dale A. 1695 Mensah, 1046 Sheshi Baba, Ebenezer 839 Saunders, David 10, 1479, 15, Schwabe, Christopher 1003, 1660, Sethuraman, Karthik 1758 Shi, Ya Ping 14, 566, 597, 911 1502, 814, 862, 1829, 585, 802 1661, 1662, 1869, 1637, 601 Sette, Alessandro 552, 761 Shibata, Sayaka 1314 Saunders, Megan E. M. 1402 Schwartz, Alanna 1594, 656, 865 Sevene, Esperanca 1049, 848, Shibeshi, Messeret E. 619 Sausser, Michele L. 1222 Schwartz, Eli 646 1570, 854, 1553 Shidi, Calixte 77 Saúte, Francisco 1570 Schwartz, Joseph 1305 Severson, David W. 1193, 1359 Shieh, Hong-Ming 262 Sautter, Casey L. 1477 Schwem, Brian E. 153 Sevilimedu, Varadan 390 Shieh, Wun-Ju 37 Savadelis, Molly D. 1714 Scott, Callie 1546, 1547, 1623, Sevillano, Josmel 1795 Shields, Timothy M. 1567, 879, Savariar, Vincent 295 1626, 1628, 881, 974, 975 Sexton, Jessica 413 903, 1537, 877, 886 Saville, Melanie 1223, 774 Scott, Jessica 1077 Seydel, Karl 1472, 1521, 18, 205, Shiff, Clive 342, 528, 533 Savinov, Sergey 1377 Scott, Phillip 1845, 1846, 1847, 33, 651, 654, 927, 927, 1051, Shifflett, Jessica M. 1451 Savón, Clara 181 517, 519, 521 914 Shikatani, Eric 1468 Savransky, Tatyana 1641 Scott, Stephen 628 Seydou, Yaro 776 Shimbo, Daichi 1305 Sawa, Patrick 821 Scott, Thomas W. 1436, 1811, Seyoum, Aklilu 1392 Shindo, Nahoko 1268 Sawadogo, Amadé 224 590, 596, 775 Sgherza, Joe 1346 Shi-Nian, Cao 692 Sawadogo, Simon P. 1192 Scouten, William T. 62 Shaban, R. 1722 Shinzawa, Naoaki 200 Sawers, Larry 1300, 1336, 1728 Scroggs, Stacey L. P.. 758 Shabani, Estela 1475, 195 Shipley, Mackenzie M. 1174 Sayeed, Abu 1199 Scully, Erik J. 894 Shaban-Nejad, Arash 685 Shirai, Hiroki 374 Sayeed, Md A. 1200 Searle, Kelly M. 1567, 1590, 877, Shafi, Oumer 1045 Shiroya-Wadambwa, Makeba 1330 Sayeed, Md. Abu 397 879, 903, 111, 301 Shafique, Muhammad 999 Shongo, Robert 1117, 6 Sayeed, Sadath 682 Sears, Shalondria 261 Shafritz, Lonna 498 Shongo Lushima, Robert 791 Sayes, Morgane 1527 Sebuguzi, Catherine M. 812 Shah, Monica P. 307 Short, Sarah M. 634 Saylors, Karen 660 Seck, Mame C. 312, 1610 Shah, Sanjana 754 Shoyama, Yukihiro 482 Scandale, Ivan 1071 Secor, William E. 1785, 1833, 1243 Shah, Vishal 1911 Shresta, Sujan 1255 Scaraffia, Patricia 638, 1358 Sedegah, Martha 1275, 1634, 352 Shah, Wasiat Hasan 1772 Shrestha, Biraj 893 Scaria, Puthupparampil V. 991 Seder, Robert A. 1633, 939, 1613 Shahinas, Dea 206 Shrestha, Sony 1490 Scarpino, Samuel V. 160 Segal, Graeme 463 Shahum, Andrea 1737, 492, 493 Shrivastava, Prachur 976 Scarr, Ellen 76 Segura, Luis 1003, 1662, 601 Shaji, Daniel 1648 Shriver, Zachary 551 Schaefer, Deborah A. 1292 Seheri, Mapaseka 1013 Shandling, Adam 559 Shu, Elvis 1494 Schaffner, Stephen F. 584 Seidman, Jessica 1864, 784 Shankar, Arjun 1050 Siame, Mwiche 111, 1590, 1876 Schal, Coby 1311 Seif, Mohamed 360 Shanks, G. Dennis 291, 262 Sia-ngam, Piyaporn 1132, 323 Schallig, Henk 1100, 1739, 341 Seim, Anders 1928, 506 Shannon, Kerry L. 1666, 886 Siba, Matthew 1565 Schapira, Allan 952 Seiringer, Peter 1707 Shapiro, Oleg 525 Siba, Peter 1262, 1555, 1599, 16, Schaut, Robert G. 524 Sekandi, Juliet N. 1727, 490 Shapiro, Theresa A. 1315 1600, 1604, 317, 735, 1565, Scheel, Molly D. 1193 Sekuloski, Silvana 1207 Shapiyeva, Zhanna 1025 1719, 215, 334, 830 Schellens, Jan H. M. 1090 Selby, Ato 384 Sharakhov, Igor V. 1385 Sicard, Sébastien 765 Schellhorn, Nancy 1806 Sellu, Josephine 1268 Sharakhova, Maria V. 1385 Sichanthongtip, Odai 346 Scherer, Christina A. 1206, 1527 Selvarajah, Suganya 38 Sharapova, Umid 1459 Siciliano, Giulia 1488 Schiaffino, Francesca 1795 Semnani, Roshanak T. 1690 Sharma, Ambika 1474 Sicuri, Elisa 1098, 973 Schieffelin, John S. 176, 763 Sempa, Esther 1505 Sharma, Shekar 1321 Sidh, Dinesh K. 1130 Schiehser, Guy A. 262 Semper, Amanda 1178 Sharma, Vinita 484 Sidibe, Bakary 834 Schilling, Joel D. 1915 Sen, Reeshi 1041 Sharp, Joanne P. 1105 Sidibe, Bouran 834 Schindler, Christian 1297, 952 Sendra, Eli 1220 Sharp, Tyler 1422, 437, 37 Sidikiba, Sidibe 1901 Schlagenhauf, Patricia 646 Sene, Doudou 1626, 975 Shaw, Alexandra 676 Sidney, John 552, 761 Schlett, Carey D. 1021 Senerath, Upul 1757 Shaw, Jeffrey J. 1148, 1252 Sidu, Josephine 1268 Schlichting, Carl D. 731 Senga, Mikiko 1268 Shaw, Marc 646 Sié, Ali 673, 84, 1049 Schmid, D. S. 1454, 791 Sepping, Clare 29 Shaw, Robert 1890 Siedner, Mark 231 Schmid, Michael 754 Sepúlveda, Nuno 298, 918 Shaw, W. Robert 633 Siema, Peter 124 Schmidt, Alexander C. 1219, 163 Seraphin, Marie N. 1841 Shaw Saliba, Katy 1299, 1473 Sifuna, Peter 1121 Schmidt, David 1241, 1880 Serda, Belendia 1546, 1628, 696, Shayo, Alex 1801 Siguineau, Wilbens 897 Schmidt, Masja 175, 756 974 Shearer, Freya 1112 Sikulu, Maggy 1310, 860, 995 Schnabel, David 1558, 900 Serhan, Charles N. 636 Sheele, Johnathan 202 Sikyomu, Esther 329, 332 Schneider, Brad 186 Serhan, Fatima 1013 Shekalaghe, Seif A. 123, 1633, Silal, Sheetal P. 944 Schneider, Bradley S. 1107, 187 Serjan, Alicia 1851 1280 Siles, Crystyan 1131, 439, 786 Schneider, Brittany N. 1136 Serna, Alexis 1066, 1320 Shelite, Thomas R. 61 Silkey, Mariabeth 1263 Schneider, Kammerle 1544, 1544 Serrano-Coll, Hector A. 1726 Shelton, Lisa 1274, 248 astmh.org Abstract Author Index A-623

The number(s) following author name refers to the abstract number.

Silpapojakul, Kachornsakdi 1166, Singh, Sanjay 983 Smith, Thomas 1263, 614, 952, Souza, Rosana 1251 1789 Singh, Susheel K. 981 959 Souza, Thayna M. H. 1877 Silumbe, Kafula 1218, 1547, 1623, Sink, Joyce 408 Smyth, Gordon 830 Sovannaroth, Siv 127 278, 881 Sinoun, Muth 1904, 862 Sneed, Sarah D. 1891 Sovi, Arthur D. M. 119 Silva, Ana Carolina 1137 Sint, Nyan 999 Snook, Kassandra 390 Sovottha, Chan 912 Silva, Igor J. 942 Sintasath, David 346 Snow, Bob W. 284 Sow, Abdourahmane 192 Silva, Joana C. 1152, 1294, 1640, Siqueira, Andre M. 1482, 630 Soares, Alberto M. 63 Sow, Doudou 1610, 319, 466, 921, 923, 924 Sirikajornpan, Kanittha 148 Soares, Ânia 1796 467, 855 Silva, Juliana 1251 Sirima, Sodiomon B. 564, 588, 853 Soares, Irene da Silva 988 Sow, Gnagna D. 1903 Silva, Larissa N. L. 1148 Sirivichayakul, Chukiat 779 Sobela, Francois 511 Sow, Samba 618 Silva, Maria 1764, 785, 792 Siriwardana, Yamuna D. 1757 Sobngwi, Joelle 1730 Sowunmi, Akintunde 810 Silva, Maria E. V. 1148 Sirohi, Devika 1256 Sobuz, Shihab U. 1865 Spangenberg, Thomas 83 Silva, Mercy 1423 Sismandis, Charalambos 679, 691 Sodahlon, Yao 1928 Sparks, Hayley 1510, 1746, 395 Silva, Milagros 135 Sissako, Aliou 858, 859 Sodenkamp, Jan 926 Specht, Sabine 1071, 1076, 1078, Silva, Rosangela M. G. 1119 Sissinto-Savi de Tovè, Yolande 527 Sodha, Samir V. 7 1241, 1885, 639, 644 Silva, Sandro P. 1465 Sissoko, Kourane 1279, 1576, Sodji, Dometo 31 Speybroeck, Niko 303, 567, 804 Silva, Jr., Claudeir D. 150 1636, 990 Soeharno, Nugroho 1338 Spivak, Emily S. 1010 Silva-Caso, Willmer 1113 Sissoko, Lala B. 902 Sognikin, Koffi S. 506, 508 Spring, Michele 10, 1278, 15, 802, Silva-Flannery, Luciana M. 808 Sissoko, Mahamadou S. 1633, Sogoba, Nafomon 1398, 1583 814, 19, 585, 323 Silvas, Jesus A. 1458 1636, 966 Sogoloff, Brian 371 Sreenivasan, Nandini 1664 Sim, B. Kim Lee 1014, 1204, 1596, Sissoko, Mody 835 Sohel, Badrul Munir 1839 Sreenivasulu B, Reddy 343 1638, 1639, 1640, 1647, 46, Sissoko, Moussa 1690 Soisson, Lorraine 1278 Sreng, Sokunthea 1829, 220, 940 561, 924, 989, 1633, 1636, 938 Sissoko, Sekou 820 Sokhna, Cheikh 270, 381, 1302 Sriboonvorakul, Natthida 254 Sim, Betty K. L. 1637 Sitali, Lungowe 1506 Solis, Erick 167 Srichairatanakul, Utaiwan 15 Simanjuntak, Deddy R. 864 Situakibanza, Hippolyte N. 290 Soliz, Peter 1803 Sridhar, Saranya 1277 Simasathien, Sriluck 1221, 184, Sivasubramani, Satheesh K. 1014 Solomon, Anthony W. 82 Srikantaiah, Padmini 1459 783 Sjoberg, Hanna 645 Solomon, Hiwot 14, 566, 614 Srikiatkhachorn, Anon 36, 591, Simbiri, Kenneth 331 Skiba, Yuriy 1765 Solomon, Tess 1408 739, 790 Sime, Heven 1045, 1063, 566 Skinner, Jeff 1614, 336, 339 Solorzano, Nelson 1367 Srinivasan, Prakash 1297 Simfukwe, Emanuel 1809 Sladeckova, Veronika 1733 Some, Anyirékun Fabrice 224 Srinivasan, Surabhi 38 Simmons, Alicia 1275, 1634, 352 Slater, Hannah C. 1574, 880, 1721 Some, Fabrice A. 818 Sriprawat, Kanlaya 1589 Simmons, Cameron P. 145, 173, Slatko, Barton 1289, 1882 Somethy, Sok 10, 1479, 15, 1502, Srivastava, Aakash 7 594 Slebodnick, Carla 256 323, 862 Sriwichai, Sabaithip 814, 862 Simmons, Graham 38 Sleebs, Brad E. 631 Sommers, Theresa E. 1439 Ssaka, Kenneth 1658 Simmons, Monika 1054 Sloan, Lynne M. 710 Sonden, Klara 905 Ssekabira, Umaru B. 620 Simon, Alistidia 1686, 1687, 1688 Slotman, Michel A. 1388 Song, Jinzhao 1778 Ssekitoleko, Richard 1050 Simon, Jonathon L. 623 Sluydts, Vincent 1213 Song, Xiu-Xia 1898 Ssekitooleko, James 1498 Simon, Raphael 1152 Small, Scott T. 449 Sonnie, Mustapha 1930 Ssekubugu, Robert 1742 Simons, Lacy M. 992 Smidler, Andrea 126, 1387 Soong, Lynn 61 Ssemmondo, Emmanuel 313 Simons, Mark P. 1024, 1663, 393, Smith, Amber M. 1915 Soonthornworasiri, Ngamphol 652 Sserwanga, Asadu 947 394, 406, 705 Smith, Amy B. 1198 Sopha, Chantha 220 Ssewanyana, Isaac 1614, 17 Simpson, Andrew 1178 Smith, Barbara 388 Sornillo, Johanna B. 1804 Stabler, Thomas 1003 Simpson, Julie A. 11, 1266, 603, Smith, Brian J. 631 Sosa, Nestor R. 1345 Staedke, Sarah 333 Smith, Catherine 43 Sosa, Yvett 258 Staedke, Sarah G. 1875, 227, 279, Simpson, Morgan E. 256 Smith, Chelsey 1521 Sossou, Efoé 1928, 508 283, 812, 1261, 357 Simpson, Steven 1675 Smith, D. Scott 50 Sota, Katherine A. 571 Staedke, Sarah S. 947 Simubali, Limonty 1397 Smith, Darci 1852 Sothea, Khon 1904 Stafford, Richard E. 1014, 1639, Sinden, Robert 1277 Smith, Darci R. 1446 Sotir, Mark J. 1439, 437 1647 Singa, Benson 1141, 496 Smith, David Soto, Giselle 1663 Stahelin, Robert V. 1172 Singer, Alexandra 1275, 1634, Smith, David L. 1614, 612, 913, Souares, Aurélia 673 Stahl, Stacey R. 669 352, 1633 770 Soulama, Issiaka 853 Stamler, Jonathan S. 1468 Singer, Monica 1124 Smith, Derek 554 Soumaoro, Lamine 727 Stamper, Paul D. 1183, 1765 Singh, Bhawana 516 Smith, Emily 1644 Soumare, Harouna 1208 Stanaway, Jeff 781 Singh, Lavanya 277, 35, 674 Smith, Helen 676 Sousa, Jason 255, 257, 1535 Stanikzai, Nasir 421 Singh, Mrigendra P. 1162 Smith, Jenny 1550, 1579, 655 South, Adam 126, 1361, 1390, Stanley, Daphne A. 180 Singh, Naresh 1611 Smith, Jessica L. 1425 633 Stanton, Michelle C. 1816, 457, Singh, Neeloo 1909 Smith, Joseph D. 626 Southern Africa ICEMR Group 642, 1067, 1817 Singh, Neeru 1162 Smith, Katherine 317 1537, 1397 Starrock, Hugh 1536 Singh, Neetu 512, 518 Smith, Patricia 41 Souy, Phum 1904 Stassjins, Jorgen 1906 Singh, Om Prakash 920, 717 Smith, Philip 255 Souza, Ana C. M. F. 1413 Stauffer, Kendra 706 Singh, Rajesh Kumar 983 Smith, Ryan C. 1360 Souza, Ariani I. 150 Stauffer, William 56 Singh, Ranvir 920 Smith, Stephen C. 388 Souza, Marcela 1101, 1912 Stauft, Charles B. 40 Singh, Rudra P. 502 Souza, Nathalia C. S. 1413 Steel, Cathy 1075 astmh.org A-624 Abstract Author Index The number(s) following author name refers to the abstract number.

Steele, Matthew 1760 Striepen, Boris 1288 Sutanto, Inge 864 Talley, Jake 1436 Steele, Russell 1703 Stromlund, Chad A. 701 Suthachana, Suthanun 1429, 593 Talukder, Kaisar A. 27, 576 Steer, Andrew C. 541 Strunz, Eric 469 Sutherland, Colin 1503, 1504, Talundzic, Eldin 218, 628 Stefanie, Difa 501 Stuart, James 1018, 1019, 1324, 559, 821, 834, 1494, 1879, 325, Talyuli, Octavio C. 634 Stegniy, Vladimir 1385 1676 825 Tamarozzi, Francesca 575 Steinbaum, Lauren E. 25 Stuart, Kenneth 1922 Sutherland, Laura J. 1242 Tambo, Ernest 488 Steinhardt, Laura 602, 885 Stubblefield, Jeannie M. 1097 Suttiprapa, Sutas 1835 Tambo, Munyaradzi 236, 563 Steinmann, Peter 1060 Sturrock, Hugh 1550, 236, 299, Sutton, Stephen 587 Tamboura, Djeneba 858 Steketee, Richard 655, 1579 Suvada, Jozef 493 Tambwe, Mgeni M. 123 Steketee, Richard W. 1218, 278, Sturrock, Hugh J. W. 563 Suvannadabba, Saravudh 779 Tamfum, Jean-Jacques M. 1454, 1626, 1515, 1546, 1628, 974, Stuyver, Lieven 1079 Suzuki, Takashi 431 1455 975, 1903 Styczynski, Mark P. 1482, 630 Suzuki, Yasutsugu 1364 Tami, Adriana 175, 756 Stell, Frederick 1367, 700, 100, Su, Jing 1157 Svisva, Abaden 1214 Tamminga, Cindy 1275, 352 1357, 729 Suamani, James K. 1719 Swai, Remigi P. 1326 Tamo, John 489 Stenger, David 86 Suangtho, Paphanij 1429, 593 Swann, Jonathan R. 63 Tan, Hwee Cheng 165 Stephens, Robin 327 Suarez, Jose A. 1345 Swanson, Basil 1769 Tan, John C. 1829 Stephenson, David B. 147 Suazo-Laguna, Harold 764 Swanstrom, Jesica A. 1416, 1430, Tan, Kathrine R. 388 Stergachis, Andy 228, 848 Subramanian, Sathish 1006 550 Tan, Peck Szee 16 Sterk, Esther 1906 Subramanian, Savitha 1330 Swierczewski, Brett E. 391 Tan, Qiao Ye 362 Sternberg, Eleanore 1375 Subramony, Hariharan 816 Swihart, Bruce 1601, 369, 950 Tandoc, Amado 134 Stevens, Eric J. 1070, 1075 Succo, Tiphanie 158 Sword-Buster, Ashley L. 1039 Tang, Hanqi 42 Stevenson, Graeme 1093 Suchard, Melinda 1303 Sy, Ava Kristy 134 Tangboriboonrat, Pramuan 349 Stevenson, Jennifer 1867, 342 Suchatsoonthorn, Chaiyaporn Sy, Mame 975, 1626 Tangchaikeeree, Tienrat 349 Stevenson, Jennifer C. 1397 1829 Sy, Ousmane 1348, 270, 271, 272 Tangnararatchakit, Kanchana 162 Stevenson, Liz 1176 Suchdev, Parminder 440 Syafrudin, Din 378 Tangpukdee, Noppadon 816, 838 Stewart, Caroline 1136 Sudathip, Prayuth 1552 Sy-Ar, Mohamad 384 Tangwena, Andrew 309 Stewart, Christine P. 1164 Suderman, Michael T. 667 Syed, Zain 1308 Tanih, Nicoline 1004 Stewart, Lindsay B. 194 Sudo, Moe 984 Sykes, Jane 1115 Taniuchi, Mami 1865 Stewart, Romal 860 Sue-jie, Koo 1082 Sykes, Melissa L. 1096 Tannenbaum, Brynne 1222 Stewart, V. Ann 1271, 916, 1403 Sugiharto, Victor A. 1403 Sylla, Assane 826 Tanner, Marcel 1555, 1633, 1637, Stewart-Ibarra, Anna M. 1052, Sugino, Yuka 1298 Sylla, Khadime 1610, 249, 467, 959 1731, 500, 687, 1423, 1793 Sukapirom, Kasama 162 855 Tanner, Nathan A. 1080, 448 Stiles, Jonathan K. 1618, 318, 204 Sukthana, Yaowalark 254 Sylla, Khadyme 319 Tanowitz, Herbert 1086 Stillwaggon, Eileen 1300, 1336, Sulaiman, Irshad M. 1675 Szekeres, Karoly 49 Tao, Dingyin 1360, 946, 993 1728 Sullivan, David J. 1499, 274, 822, Szumlas, Daniel 1283 Tappero, Jordan 1486, 1614 Stinchcomb, Dan T. 550, 168 886, 1520, 315, 342 Taquiri, Carmen 571 Stins, Monique 1297 Sullivan, Gwyneth 1308 Taramelli, Donatella 1530 St. Laurent, Brandyce 127 Sullivan, Nancy J. 1462, 180, 182 Tarantola, Arnaud 590 Stockwell, Timothy 1255 Sullivan, Richard T. 17 T Tareke, Israle 1438 Stoddard, Steven T. 1811, 596 Sultana, Tania 397 Tarimo, Brian B. 1352 Taal, Makie A. 889 Stoeckert, Christian J. 922 Sultani, Hadley 464 Tarini, Ann 1689 Tabala, Martine 882 Stoffel-Wagner, Birgit 1709 Sultanov, Ahmetzhan 1025 Tarleton, Rick L. 1851 Tachfouti, Nabil 1098 Stokes, Sarah 1332 Suman, Devi 1374 Tarnagda, Zékiba 573 Tachibana, Mayumi 1298, 200, Stolarik, Deanne 1078 Sumba, Peter Odada 21, 331 Tarning, Joel 13, 254, 945 984 Stolk, Wilma 1721, 511, 1715 Sun, Chengqun 138 Tarragona, Sonia 1057 Tadele, Getnet 495, 68 Stone, Brad 980 Sundar, Shyam 512, 518 Tarui, Nicole 1344 Tadesse, Yehualashet 14 Stone, Chris 1060 Sundrakes, Siratchana 323 Tassi Yunga, Samuel 1597 Taffese, Hiwot S. 269 Stone, Will 559 Sunintaboon, Panya 152 Tassone, Ryan 1650 Tagbor, Harry K. 1691, 805, 803 Stoney, Rhett J. 1439 Sunkara, Gangadhar 949 Tatem, Andrew Tatem, Andrew J. Tageldin, Reham 737 Stoops, Craig 100, 1357, 1367, Sunshine, Justine E. 1225, 1426 1554, 612, 863, 876, 286 Taha, Nathalie T. 1074 1237, 729 Suntarattiwong, Piyarat 178, 790 Tatum, Amber 1794 Taing, Davy 15 Storey, Bob E. 444 Sunyakumthorn, Piyanate 45 Tavera, Gloria 930 Tairou, Fassiath 272 Storey, Helen 476 Suomie, Roland T. 441 Tavul, Livingstone 317 Tairou, Fassiatou 270, 271 Storme, Casey 1641, 1278 Suon, Seila 1829, 220, 940 Tay, Samuel C. K. 1682 Takahashi, Joseph S. 1921 Stoute, Jose A. 19, 194 Supali, Taniawati 465, 468, 501, Tayamun, Sujitra 45 Takala-Harrison, Shannon 1829, Straetemans, Masja 679, 691 51 Taylor, Alexander B. 669 921, 943, 893, 1581 Straimer, Judith 1484 Surveillance and Etiology of Taylor, Amy 49 Takashima, Eizo 11, 370, 830, 979 Streat, Elizabeth 1507, 243, 839, Undifferentiated Febrile Illness Taylor, Andrew 1003, 1661 Takken, Willem 1379, 1388, 379 85 Study in Cambodia Working Taylor, Cameron 81 Talaat, Maha M. 1133, 1762 Streblow, Daniel 41 Group 887 Taylor, David W. 1240, 443, 460 Talisuna, Ambrose O. 284 Strecker, Thomas 180 Surya, Asik 656, 864, 865 Taylor, Diane W. 1597, 245, 335, Tall, Adama 1626, 1903, 381, 975 Streit, Thomas 1229 Sutamardja, Awalludin 1508 489, 932, 933, 1798 Talles, Frederico 606 Stresman, Gillian H. 298 Sutamihardja, Awalludin 1217, 250 astmh.org Abstract Author Index A-625

The number(s) following author name refers to the abstract number.

Taylor, Mark 1076, 1078, 1718, Teururai, Sylviane 765 Tilley, Leann 1873 Tounkara, Moctar 1624 644, 730, 639, 645 Tewabe, Tsehay 1515 Tillotson, Meagan 1723 Touray, Abdoulie 213 Taylor, Maxine 1209 Thaisomboonsuk, Butsaya 1221, Tin, Myo Win 999 Toure, Mahamoudou 1583 Taylor, Steve M. 1260, 1556, 915, 148, 171, 36, 591, 739, 783, Tinco, Carmen 401 Toure, Sekou 834 916, 1041 170 Tine, Roger 1501, 319, 855, 467 Touré, Yeya T. 727 Taylor, Terrie E. 1051, 1265, 1866, Thalagala, Neil 767 Tinelli, Carmine 575 Tovar, Marco 1763 205, 485, 599, 654, 736, 914, Thallinger, Gerhard 1360 Tinh, Ta Thi 804 Tovosia, Silent 750 584, 1472, 1521, 1602, 1646, Thangamani, Saravanan 546 Tinto, Halidou 419, 848 Towers, Catherine E. 1807, 724 18, 1803, 33, 651 Thanh, Pham Vinh 804 Tinto, Idriss 84 Towers, David 1807, 724 Taylor, Walter R. J. 1904 Thawer, Narjis G. 112, 1216, 386 Tiono, Alfred 564, 588, 853 Towle, Teresa M. 1451 Tchalla, Jules 31 Thaxton, Gracie 522 Tippins, Ashley 1341 Townes, Lindsay R. 914 Tcherniuk, Sergey O. 1526 Thea, Donald M. 623 Tirados, Inaki 676 Townley, Theresa 1128 Tchum, Samuel K. 240 Thein, Tun-Linn 1270 Tirta, Yusrifar K. 656, 865 Townsend, Reid R. 1885, 1886 Techasaensiri, Chonnamet 162 Theisen, Michael 1651, 981, 983 Tiruneh, Melkamu 1544 Townson, Simon 1071, 1079 Tediosi, Fabrizio 1060, 959 Theppangna, Watthana 1452 Tisch, Daniel 1262 Tozan, Yesim 673, 767, 89 Teissier, Anita 765 Thera, Mahamadou A. 1563, Tissera, Hasitha 767 Tracy, Dylan M. 711 Teixeira, Sonia 1161 1606, 921, 978, 835 Tissire, Hamid 551 Tran, Chuong 831 Teixeira, Sonilda 1161 Theresa Alera, Maria 36 Titaley, Christiana R. 1338 Tran, Dat 1729 Teka, Hiwot 14, 566 Thi, Aung 1581 Tiwari, Amy 1788, 23, 24, 581 Tran, Duong T. 1217, 250, 873, Tekete, Mamadou 1211 Thiam, Tidiane 1626, 975 Tkaczyk, Tomasz 1043 874, 906 Tekiel, Valeria 1089 Thitilertdecha, Premrutai 162 Tobby, Roslyn 1600 Tran, Tuan M. 902 Tekle, Afework 480, 511, 1715, Tho, Sochantha 1213 Todd, Jim 1122 Tran, Vanessa 350, 429 450 Thomaides-Brears, Helena 1201 Togo, Amadou 834 Traore, Abdramane 902 Teko, Menssah 1928 Thomas, Brent 1927 Togoh, Geoffrey 698 Traore, Boubacar 1609, 336, 339, Tekola-Ayele, Fasil 70 Thomas, Dana 37 Toh, Alain 1822 902 TTekwani, Babu L. 1528, 1535, Thomas, Elizabeth D. 1772 Tohme, Rania A. 1664 Traore, Djibril 1279 202, 970, 1087 Thomas, J. S. 1692 Toksanbayev, Daniyar 1025 Traore, Karim 1260, 1563, 835 Telarolli Jr., Rodolpho 1119, 1125 Thomas, Lian F. 5, 662 Tol, Bunkea 8, 9 Traore, Moussa 1601 Teleb, Nadia 1453 Thomas, Matthew 1375 Tola, Monday 1654 Traore, Oumar B. 820 Telford, III, Sam 544 Thomas, Peter 244 Tolia, Niraj H. 1643, 225, 557, 940 Traore, Sekou Traore, Sekou F. Temba, Filbert F. 562 Thomas, Stephen J. 1219, 163 Tolno, Benoit G. 889 1398, 1583, 727, 1496 Tembine, Intimbeye 1279 Thome, Beatriz 1221 Tolo, Youssouf 1563, 835, 921 Traore, Tiangoua 1624, 602 Tembo, Autman 386 Thompson, Katie 1319 Tolouei Semnani, Roshanak 1884 Trape, Jean-François 381 Temescu, Oana A. 1360 Thompson, Letitia K. 1891 Tomashek, Kay M. 1422 Traub, Rebecca 26 Temu, Lucky 1558, 833, 843, 891, Thompson, Trevor A. 1496, 858, Tomasini, Nicolás 1089 Travassos, Mark A. 1563, 1606, 900, 910 859 Tomczyk, Sara 72 1646, 921, 923, 978, 835, 1602, ten Bosch, Quirine A. 1811 Thomsen, Edward 735 Tomoka, Tamiwe 1265 924, 943 Tene, Gilbert 1730 Thomson, Rebecca 912 Tong, Carlos 125, 733 Travi, Bruno L. 1510, 1746, 1913, Teneza-Mora, Nimfa 1021, 1275, Thomson-Luque, Richard 49, 1473 Tong, Suxiang 193 522 352, 57, 977 Thongpaseuth, Soulignasak 542 Tonga, Calvin 908 Traylor, Daniel 64 Teneza-Mora, Nimfa C. 1024 Thorp, Aaron 547 Tongren, Eric 1340, 1379 Treeprasertsuk, Sombat 652 Teneza-Mora, Ninfa 1016 Thoyakulathu, Elizabeth 1738 Tonnetti, Laura 547 Trehan, Indi 1006 Tennant, Sharon M. 1152 Thriemer, Kamala 14 Tops, Narann 1904 Trejo, Bricia 1542 Tenu, Filemoni 360 Thuilliez, Josselin 966 Tor, Pety 1904 Trejos, Johanna 1632 Tenywa, Frank S. C. 266 Thuma, Philip E. 1876, 342, 877, Tora, Abebayehu 495, 68 Tretina, Kyle 1294 Tepage, Floribert 1069 879, 301 Torano, Holly 1648 Trett, Anna 723 Terashima, Angelica 1155, 479 Thuy Nga, Tran 610 Torgerson, Paul R. 1025 Trewin, Brendan 1806 ter Kuile, Feiko O. 1556, 228, 30, Thwai, Kyaw L. 1556, 915, 1557 Torigian, April 608 Triana Chávez, Omar 1309 883, 915, 615, 848 Thwaites, Guy E. 617 Torii, Motomi 1298, 199, 200, 984 Tribble, David 1048, 1663, 648 Terlouw, Dianne J. 285, 847, 851, Thwing, Julie 1501, 218, 311, 827, Torpey, Kwasi 483 Tricoche, Nancy 667 1559 312, 826 Torr, Stephen 676, 1744 Trindade, Giliane D. 1114 Terry, Frances 1650 Tianhoun, Edouard 498 Torres, Gladys 1793 Tripathi, Abhay 1295 Tesfay, Berhane 1546, 1628, 974 Tibenderana, James 229 Torres, Jose V. 37 Tripet, Frederic 1192, 1234 Tesfaye, Alemayehu Getachew Tibery, Cecilia 1220, 1408 Torres, Julian 424 Tritten, Lucienne 1724, 668 1372 Tiedje, Kathryn E. 216 Torres, Katherine 20, 828, 829 Trivedi, Surbhi B. 592 Tesh, Robert B. 144, 1442, 1461, Tiendrebeogo, Alexander 505 Torres, Maria 1146 Troell, Peter 358 748, 749, 1421 Tiendrebeogo, Regis W. 981 Torres, Silvia 424 Trong, Duoc V. 660 Tessema, Sofonias K. 334 Tiga, D. Carolina 1424 Torres, Vanessa R. 321 Trostle, James 1306 Tessier, Natacha 317, 568 Tihn Hien, Tran 1829 Torres-Castro, Marco 117 Trotter, Caroline 1018, 1019, 1324, Teti, Caroline 464 Tihon, Eliane E. 1318 Torto, Baldwyn 993 1676 Tettah, Kevin Tikoduadua, Lisi 541 Tosh, Donna 1278 Troupin, Andrea Troupin 120 Tetteh, Kevin K. A. 1598, 1614, Tilley, Drake H. 1160, 393 Tougoue, Jean Jacques 1685, 456, Trovatti, Eliane 1092 559 Tilley, Hamilton 1670, 1797 527 Troye-Blomberg, Marita 928 astmh.org A-626 Abstract Author Index The number(s) following author name refers to the abstract number.

Trucchi, Beatrice 993 Valcourt, Roodaline 76 Vargas, Ana 1036 Trufan, Sally 1107 U Valderrama, Liliana 1750 Vargas, Daniel 601 Trumbull, Emily J. 1118 Ubachukwu, Patience O. 526 Valdés, Odalys 181 Vargas, Danulka 135 Trung, Vu T. 594 Ubalee, Ratawan 10, 1283 Valdivia, Hugo O. 100, 1316 Vargas, Paola 1289 Truscott, James E. 53, 540 Ubben, David 889 Valea, Innocent 1049 Vargas-Calla, Ana M. 1030 Truwah, Zinenani 30 Ubol, Sukathida 152 Valecha, Neena 1474 Vargas-Lasalle, Luzeida 135 Try, Vorleak 220 Uc, Jose V. 117 Valencia, Braulio M. 1910 Vasconcelos, Pedro F. C.. 1465 Tsai, Isheng J. 1835 Uche, Chukwudi 837 Valencia, Edward 1911 Vasilakis, Nikos 751 Tsai, Jih-Jin 750 Uddin, Md. Jashim 1865 Valencia, Julio 1571 Vasquez, Carlos 1275, 1634, 352 Tsai, Wen-Yang 1407 Uddin, Mohammad Ikhtear 1862 Valente, Vanderson 606 Vasquez, Gissella 1367, 1644, 729, Tsbuoi, Takafumi 333 Uddin, Taher 1861 Valenzuela, Gabriela 1571 100, 1237, 1357 Tse, Zion Tsz Ho 88 Udenze, Kenneth 49, 201 Valenzuela, Jesus 1690 Vasquez, Rommel 131 Tsegay, Girmay 70 Udhayakumar, Venkatachalam Valim, Clarissa 371, 914 Vásquez-Jiménez, Juan M. 1632, Tsegaye, Mesfin M. 1438 1212, 1229, 14, 1877, 218, 226, Valle, Denis 238 314 Tsegaye, Wendimagegn 566 246, 565, 628, 808, 895 Vallejo, Andres Vasquez- Rios, George 1155, 479 Tshefu, Antoinette K. 13, 1557, Ugwi, Patience 1179 Vallejo, Andrés 320, 1569, 1571, Vaughan, Ashley 1613, 248, 1589, 1926, 916 Ugwu, Chidiebere E. 488 1632, 314 1826 Tshibangu, Evariste K. 344 Uisso, Cecilia 1062, 1817, 1816 Vallejo, Gustavo A. 1746 Vaughan, Jefferson A. 701 Tshibola Mbuyi, Marie Louise 1610 Uk, Sambunny 1213 Vallur, Aarthy 1740 Vaughn, Andrew F. 1672, 887, Tsouh, Patrick V. F. 402 Ukaga, Chinyere 452 Valmaseda, Aida 938 1502 Tsuboi, Takafumi 11, 1298, 199, Ulrich, Jill N. 97 Van, Nguyen Van 804 Vaughn, Meagan 1394, 708 200, 370, 830, 979, 984 Ulrich, Robert G. 1433, 4 Vanachayangkul, Pattaraporn 814 Vaz, Marina 626 Tsuji, Moriya 939 Umeh, Chukwuemeka 1248 van Dam, Govert J. 1837 Vazquez-Prokopec, Gonzalo 117, Tsujimoto, Hitoshi 121, 1350 Umesumbu, Solange B. 344 Van den Abbeele, Jan 1318 723, 726 Tsukayama, Pablo 1795 Umesumbu, Solange E. 1573 Van den Bogaart, Erika 1100 VectorBase consortium (1,2,3), Tu, Zhijian 1385 Umulisa, Irenee 315 Van Den Borne, Bart 380 1386 Tucker, David 38 Undurraga, Eduardo A. 1304, Van den Broeck, Frederik 1318 Vedovello, Danila 755 Tucker, Joseph D. 621 1424, 781 Vanden Eng, Jodi L. 388 Vega, Ricardo A. 1345 Tucker Lima, Joanna M. 238 Unger, Lucy C. 1328, 690, 1343 Vandepitte, Judith 373 Vekemans, Johan 1276, 1277, Tufton, Henry 434 Unicomb, Leanne 577, 580, 1164 Vandepitte, Warunee P. 171 1278 Tuicakau, Meciusela 541 Unlu, Isik 1374 van der Does, Willemijn 433 Velasco, John M. 36 Tujan, Ma. Angelica A. 1111 Unnasch, Thomas R. 1883, 445, Vanderpool, David M. 688 Velasco, Maria C. 1705 Tukahebwa, Edridah M. 1066, 725, 1067 van der Ven, Andre 433 Velasco-Salas, Zoraida I. 175 1227, 1228, 1320, 1824, 537 Uota, Shin 482 Van der Vliet, Diane 1223 Velavan, Thirumalaisamy P. 322 Tukwasibwe, Stephen 809, 811 Upfill-Brown, Alexander M. 1760 van de Vegte-Bolmer, Marga 983 Velez, Ivan D. 743 Tullo, Gregory S. 1260 Uplekar, Swapna 920 Vandi, Mohamed 1268 Velmurugan, Soundarapandian Tumwebaze, Patrick 807, 809, 811 Uppal, Karan 1482, 630 Van-Dumen, Pedro 1067 1638 Tumwine, Irene 926 Upton, Leanna 1642 van Dyken, Steven J. 605 Venkatesan, Meera 306 Tunal, Health Center 401 Urassa, Willy 429 van Eijk, Anna Maria 851 Venkatesh, S 7 Tungu, Patrick 718, 1376 Urizar, Fernando 572 van Eijk, Annemieke 848 Venkatraman, Navin 1277, 1462, Tunjungputri, Rahajeng N. 433 Urquía, Albino 100 Van geertruyden, Jean-Pierre 1215, 180, 182 Turell, Michael J. 1403 Ursing, Johan 1500 232 Vennervald, Birgitte J. 1834 Turner, Elizabeth 1187, 239 Ussene, Esperança 1269 van Griensven, Johan on behalf of Ventocilla, Julio A. 1644 Turner, Gareth 13, 45 Utama, Digjaya 334 the Ebola_Tx Consortium 1267 Ventrone, Cassandra 1220, 1408 Turner, Hugo C. 460, 464, 53 Uthaimongkol, Nichapat 1132 Van Kempen, Luuk 263 Verani, Jennifer R. 1108, 1585 Turner, Jerrold 1290 Uto, Takuhiro 482 Van Kerkhove, Maria D. 1443, 619 Veras, Herlice N. 1669 Turner, Joseph 1076, 1078, 645 Utzinger, Jürg 1273, 1821 Vanlandingham, Dana L. 1441, Verastegui, Hector A. 1770, 1843 Turpin, Cornelius 204 Uwimana, Aline 315 1855 Verastegui, Manuela 1038, 1751, Turturice, Benjamin A. 992 Uzochukwu, Benjamin 483 van Leeuwen, Elisabeth 341 1752, 1911, 29 Turyaguma, Patrick 1320, 1685 van Lieshout, Lisette 1834, 1837, VerBerkmoes, Nathan C. 1882 Tustin, Aaron 1756 468, 496, 51 Vercellotti, Gregory M. 195 Tusting, Lucy S. 283 Van Loon, Ine 529 Vereigh, Francis B. 130 Tuxun, Tuerhongjiang 1026, 1027, V Vann, W. F. 397 Veriegh, Francis B. D. 91 574 Vanna, Chan 1904 Verlinde, Christophe L. 1314 Tweedell, Rebecca E. 946 Va, Soch 15 van Oosterhout, Joep 485 Verma, Amit 612 Twing, Julie 1652, 353 Vaasjo, Lee O. 1783 Van Panhuis, Willem G. 677 Verma, Nitin K. 699 Twinomujuni, Silvano 65 Vaca, Maritza 649 van Schalkwyk, Donelly 1503, Vernick, Kenneth D. 1871 Twomey, Patrick S. 1276, 1278 Vaca, Sergio 405 1879 Verotta, Luisella 993 Tyagi, Rahul 1883 Vaidya, Akhil B 1205 Van Treuren, Will 543 Verra, Federica 1598 Tyner, Harmony L. 710 Vaidya, Krista 1198 Van Voorhis, Wesley C. 1141, Versteeg, Inge 1739 Tyrer, Hayley 1076, 645 Vaillant, Michel T. 1820 1292, 281, 852, 861 Versteeg, Leroy 604 Tzipori, Saul 1152 Val, Fernando F. 1482, 630 Van Vugt, Michele 263, 380 Verweij, Jaco J. 468 Vala, Anifa 1553, 1570, 854 Van Weyenbergh, Johan 1092 Vestergaard, Lasse S. 1694, 9 astmh.org Abstract Author Index A-627

The number(s) following author name refers to the abstract number.

Viana, Mafalda 1238 Voysey, Merryn 1201 Wamani, Henry 1047 Watson, Quentin D. 807 Vianez, João L. S.. G.. 1465 Vreden, Stephen 226, 308 Wamboga, Charles 1742 Watts, Val J. 1377 Vianna, Giselle R. 1877 Vu, David Vu, David M. 1123, Wamburu, Kabura B. 417, 1041 Waxman, Rachel 1655, 969 Vicuña, Yosselin 52 1124, 156, 151 Wamola, Newton 297 Wearing, Helen 1889 Vidal, Carlos E. 439 Vu, Dung K. 250 Wampfler, Rahel 1262, 1263 Weatherhead, Jill E. 649 Vidal, Jorge E. 1770 Vu, Nhu T. 145 Wamunyokoli, Fred A. W. 412 Weaver, Anne 582 Vidal, Marta 938 Vu, Trung T. 145 Wan, Wuzhou 513 Weaver, Anne M. 1839 Viebig, Nicola 363 Vujcic, Jelena 582 Wan, Xianxiu 1082 Weaver, Casey T. 1846 Vieira, Erica 1849 Vulu, Zimbombe 1573 Wandera, Bonnie 227 Weaver, Joseph 513 Viet, Phu Quoc 771 Vulule, John 124, 1271, 1509, Wang, Chengqi 587 Weaver, Scott C. 1104, 144, 1442, Vigan-Womas, Inès 885 151, 156, 21, 326, 650 Wang, Chunling 136, 554, 592 748, 749, 140 Vigil, Edgar 1827 Vuong, Chau 255, 257 Wang, Claire 860 Webster, Bonnie 1782 Vigneron, Aurelien 101, 637 Vuyisch, Momchilo 1334, 1769 Wang, Jingwen 101, 118 Webster, Jayne 1498, 842 Vijayan, Neeta 7 Vy, Dav 10 Wang, Julin 722 Webster, Joanne 1782 Vila, Jordi 1269 Wang, Lawrence T. 399 Webster, Joanne P. 1228, 1824, 54 Vilay, Phoutnalong 346 Wang, Molin 429 Weetman, David 113, 1286 Vilcarromero, Stalin 1131, 439, Wang, Qian 1747 Wegmuller, Rita 625 775, 786 W Wang, Wei 530 Weidmann, Manfred 797 Vilchez, Percy 1034, 572 Wang, Wei-Kung 1407 Weier, Chrisinta 1709 Wachira, Cyrus M. 417 Villa, Daisy 36 Wang, Wenjuan 441 Weil, Gary J. 1074, 1226, 1716, Wade, Boubacar 824 Villa, Zaira G. 733 Wang, Xiaoming 1381, 1382, 1815, 1883, 1885, 1886, 1925, Waggoner, Jesse J. 1509, 422, 741 Villacis, Anita G. 1761 1383 447, 465, 501 Wagner, Jeffrey C. 586 Villacorte, Elena A. 531, 532 Wang, Xiaoyun 1156 Weinberg, J. Brice 627 Wahid, Isra 864 Villamor, Eduardo 22 Wang, Yan-Hong 1528 Weinberg, Michelle 56 Wahl, Brian 1017 Villar, Luis A. 1406 Wang, Yi 1374 Weinkopff, Tiffany S. 1845 Wahlgren, Mats 343 Villar Centeno, Luis A. 1055, 1698 Wang, Yu-Hsuan 750 Weinlander, Eric 1786 Wai, Khin T. 1581 Villarreal, Susan M. 1355 Wang, Zenglei 1490 Weisenfeld, Neil I. 1195 Wai, Tint Tint 1014, 1204 Villasante, Eileen 1275, 1613, Wango, Roland 1660, 1660 Weiskopf, Daniela 552, 761 Waiboci, Lilian W. 417 1634, 1644, 352, 977 Wangrangsimakul, Tri 1178 Weisleder, Ralph 1202 Waisberg, Michael 339 Villasis, Elizabeth 828, 829 Wangraoua, Soumeya 870 Weiss, Brian L. 637 Waitumbi, John N. 412 Villaverde, Chandler 1056, 1475 Wanigatunga, Chandanie 1259 Weiss, Christopher M. 42 Waka, Charles 1330 Villinger, Jandouwe 665 Wanji, Samuel 1715, 1717, 443, Weiss, Daniel J. 304, 697 Wakefield, Jon 1585 Vincenti, Maria F. 175, 756 448, 645 Weissenberger, Giulia 1678 Wakimoto, Mayumi 1428 Vinci, Robert J. 623 Wannemuehler, Kathleen 1664 Weitzel, Thomas 120 Walana, Willimas 1682 Vineis, Joseph 731 Wanzira, Humphrey 947 Weldon, Alexandra 1822 Walke, Jayashri 1474, 626 Vinetz, Joseph M. 102, 733, 1518, Wanzira, Humprey 1572 Wellems, Thomas E. 1485, 1630, Walker, Andrea 1344 1595, 20, 424, 59, 125, 233, Ward, Abigail V. 823, 1301 223 Walker, David H. 61 233, 233 Ward, Honorine D. 396 Wellhausen, Jeffrey 1075 Walker, Edward D. 1362, 1866, Vinit, Rebecca 735 Ward, Stephen 1078, 645, 1076, Wells, Timothy 852 735, 736 Viotti, Rodolfo 1851 1718 Weltzin, Richard 1276, 1277 Walker, Larry A. 1535, 202, 970, Vischer, Nerina 1327 Wardrop, Nicola A. 662 Wemakoy Okitolonda, Emile 791 1087, 1528 Vishi, Annold 1514 Ware, JeanAnne 1033, 569 Wen, Hao 1026, 1027, 574 Walker, Leah A. 822 Visitsunthorn, Kittipos 1787 Warehime, Jenna 1332 Wen, Jianjun 1081, 1082 Walker, Martin 1818, 1823, 460, Viswanathan, Karthik 551 Warfield, Kelly L. 1255 Wen, Shawn 1198 537 Vital-Brazil, Juliana M. 422 Warnock, Neil D. 607 Wendabeku, Million 1438 Walker, Patrick G. T. 1562, 1564, Vivekanandan, Renuga 1128 Warrell, Mary 436 Wende, Andy 797 615, 953 Vlaminck, Johnny 461, 465 Warren, Chris 356 Wenger, Edward A. 1548, 1551, Wall, Richard 1741 Vo, Long T. 145 Warren, Cirle 1290 1588, 584, 954, 956, 957, 958, Wallace, Derek 1224 Voets, Marieke 1720 Warrenfeltz, Susanne W. 922 613 Wallace, John 708 Vogt, Megan 734 Wartel-Tram, Anh 1223 WWeppelmann, Thomas A. 1168 Walldorf, Jenny A. 1602, 1646, Volk, Susan W. 1846 Wasfy, Momtaz O. 421 Were, Florence A. 683 599, 654 Volkman, Sarah K. 1496, 371, 584, Wasim, Saba 1772 Were, Vincent O. 683, 960 Walsh, Mary Claire 1700 827, 859, 875, 931, 1218, 1469, Wasonga, Chrispine 1769 Werre, Stephen R. 1139 Walson, Judd 1141, 496, 497, 218, 312, 48 Wassawa, Peter 1515 Wertheim, Heiman 660 1585, 51 Vomaske, Jennifer 41 Wasserberg, Gideon 1311 Wertheim, Joel O. 415 Walter, Evelyn 1336 von Geldern, Thomas 1071, 1078, Watanabe, Aripuanã S. A. 755 Wesley, Bonam 1773 Walter, Katharine S. 545 645 Watanabe, Koji 1136 Wesolowski, Amy W. 951 Walther, Michael 1636 VonGoedert, Tracie 1274 Watanaveeradej, Veerachia 1221 Wesson, Dawn 726, 1394 Waltmann, Andreea 568 Vongsouvath, Manivanh 423 Waterhouse, David 1076 West, Philippa 1699 Walusimbi, Denis 1572 von Saldern, Charlotte 1707 Waters, Norman C. 1276, 1278, West, Richard 1405 Wamae, Claire N. 662 von Seidlein, Lorenz 14, 282 1874, 1645 West, Sheila 1321 Wamae, Njeri C. 5 Vora, Kalpit A. 760 Watson, Alan M. 1444, 746 Westreich, Daniel J. 396 Wamala, Samuel 329, 332 Vowels, Travis 463 Watson, Conall H. 663 Whalen, Christopher C. 1727, 490 astmh.org A-628 Abstract Author Index The number(s) following author name refers to the abstract number.

Whistler, Toni 416 Wilson-Barthes, Marta 1415, 1417, Worrell, Mary Claire 1059 Yactayo, Sergio 1443, 619 White, A. Clinton 1292, 472, 1149 1419, 1418 Worwui, Archibald 1399, 888 Yadi, Gumal 215 White, Bradley J. 1810, 1892 Win, Aung Ye Naung 999 Wotodjo, Amélé N. 381 Yadouléton, Anges 106 White, Heather 476 Win, San San 1813 Woyessa, Adugna 566 Yagi, Masanori 374 White, John 1474 Wingfield, Tom 1042, 1763, 430 Wrammert, Jens 172 Yagui, Martin 1436 White, Lisa J. 944 Winichagoon, Pattanee 610 Wrangham, Richard W. 894 Yah, Clarence S. 488 White, Michael 298, 611, 953 Winskill, Peter 1564 Wree, Melanie 1827 Yakob, Laith 1313 White, Nicholas Winter, Amy K. 1456 Wright, Alexandra 1870 Yakovleva, Anna 471, 606 White, Nicholas J. 11, 1266, 214, Winter, Rebecca A. 441 Wright, Danny 1277, 1462, 180, Yakpa, Kossi G. 1928, 506, 508 254, 617, 943, 1829, 355, 13 Winter, Rolf 1531 182 Yamadjako, Sandra 67 Whitehead, Stephen S. 1220, Winters, Anna 1547, 23, 867 Wright, David W. 274 Yamakoshi, Sachiko 197 1221, 1408, 554 Winters, Benjamin 1788, 23, 24, Wright, Lauren 1653 Yamaoka, Shoji 482 Whitesell, Amy 1557 581 Wright, Marcia 408 Yamauchi, Masato 642 Whitfeld, Margot J. 541 Winterstein, Eric 478 Wu, Andrew 1843 Yambo, Phantica 1599, 1600 Whittaker, Maxine 568 Winzeler, Elizabeth A. 1206, 1533, Wu, De 1107 Yaméogo, Bienvenue K. 560 Whitton, Jane M. 536, 1232 733, 1488, 1827 Wu, Jin-Yi 1898 Yan, Guiyun 1381, 1382, 1383, Whitty, Christopher 647 Wirth, Dyann F. 1206, 1218, 1469, Wu, Lindsey 1838 1391, 896, 956 Whyte, Olga 1005, 1272 1533, 203, 371, 48, 584, 827, Wu, Shuenn-Jue 759 Yan, Hong-bin 1835 Widen, Steve G. 751 875, 931, 1527 Wu, Xiaoting 1051 Yanagihara, Richard 782 Widjaja, Susana 1054 Wirtz, Robert Wirtz, Robert A. Wu, Yimin 1279, 1576, 375, 985, Yang, Amy 338 Widman, Douglas G. 1416, 548, 388, 1310 990 Yang, Annie 631 550 Wirtz, Veronika J. 1248 Wu, Yineng 637 Yang, Henglin 893 Widmer, Giovanni 1152 Wismann-Horther, Isa I. 1328, Wu, Yun 1014, 1204, 1596, 1639, Yang, Kui 193 Wiegand, Ryan E. 1059, 1785, 1343, 690 1647, 46, 989 Yang, Liu 1351 883, 885, 895 Wittlin, Sergio 1488 Wuletaw, Yonas 1438 Yang, Zhaoqing 1490 Wieringa, Frank T. 610 Wiwa, Owens 1301, 823 Wurapa, Eyako 1558, 833, 843, Yanow, Stephanie 976 Wiest, Olaf 1172 Wogu, Michael N. 890 891, 900, 910 Yao, Zhong-Ke 256 Wiethoff, Christopher M. 992 Wojcik, Richard A. 689 Wurie, Isatta 488 Yasmin, Tahirah 1861 Wijaya, Hendri 1504 Wojcikiewicz, Ewa P. 261 Wyatt, Paul 1741 Yasnot, Maria F. 1478, 1705, 1768 Wijewickrama, Ananda 1259 Wojnarski, Mariusz 1276 Wyka, Katarzyna 1032 Yassin, Aymen S. 1133 Wiladphaingern, Jacher 1266 Wolfner, Mariana F. 1355 Wylie, Blair 1162, 1305 Yassin-Rajkumar, Bebi 1276, 1277 Wilairatana, Polrat 652, 816, 838 Wolken, David 1663 Wyllie, Susan 1741, 1914 Yasuda, Jiro 179 Wilder, Richard 677 Wollum, Alexandra 1337 Yatich, Nelly 204 Wilder-Smith, Annelies 767 Wolstenholm, Allen 1209 Ya-Umphan, Phubet 289 Wiley, Michael 1764 Wolstenholme, Adrian J. 1072, Yawson, Abena 1049 Wilkes, Chris 1560 444 X Yayo, Abdulsalami M. 1392 Wilkins, Kimberly 1454, 1455, 791 Won, Kimberly 1229, 458 Yazdanbakhsh, Maria 468 Xa, Nguyen Xuan 804 Wille-Reece, Ulrike 1276, 1277 Wonarunkotchakorn, Saowaluk Ye, Henry Yixin 161 Xavier, Ding 830 William, Timothy 1560, 1902, 282, 323 Ye, Tun 1680 Xayavong, Maniphet 808 355 Wondji, Charles S. 1284, 1373 Ye, Yazoume 81 Xia, Jeff 668 Williams, David 1899 Wong, Pak K. 1836 Yé, Yazoume 898 Xia, Jianguo 1724 Williams, Gail M. 1825 Wong, Teri-Ann S. 3 Yeager, Linsey A. 1014 Xia, Zhigui 893 Williams, Gregory M. 1374 Wong, Wesley 584, 875 Yearwood, Katherine 1054 Xiao, Honglin 846 Williams, John V. 1840, 1843 Wongarunkochakorn, Saowaluk Yeboah-Antwi, Kojo 1162 Xiao, Lihua 1140 Williams, Steven 668, 1724 814 Yeboah-Manu, Dorothy 402 Xiao, Xiangming 661 Williamson, John 1203, 597, 911 Wong-Madden, Sharon 985 Yeda, Redemptah 267 Xie, Lisa 1525, 1531, 255, 257 Williamson, Kim C. 339, 992 Wongravee, Kanet 254 Yee, Rebecca 993 Xie, Sherrie 1756, 707 Willians, Maya 166 Woo, Hea Sun 1159 Yeebiyo, Yemane 1372 Xie, Stanley C. 1873 Willilo, Ritha A. 1905, 386 Wood, Angela M. 1264 Yeka, Adoke 1875, 284, 374, 947 Xu, Guang 61 Willis, Paul A. 852, 815 Wood, Christopher 1041 Yen, Chi N. Thi. 660 Xu, Guolei 118 Wills, Bridget 1254 Wood, Thomas G. 751 Yeo, Tsin W. 1902, 282, 355, 627, Xu, Jiabao 1381, 1382, 1383 Wilson, Colin M. 1077 Woodrow, Charles J. 214 1560 Xu, Jianwei 893, 893 Wilson, Mark 1436 Woods, Christopher W. 423, 666 Yepes, Alexander U. 743 Xu, Peng 1861, 397 Wilson, Mark L. 1866, 654, 736, Woodson, Michael 1442 Yeramilli, Venkata A. 1846 Xu, Ray 1014 914 Woolheater, Katelyn 1514 Yerbanga, Rakiswendé S. 870, 560 Xu, Shulin 201 Wilson, Mary E. 1251 Worges, Matt 1002 Yerbanga, Serge 633, 982 Xue, Rui-De 1404 Wilson, Mary E. for the GeoSentinel Workie, Worku 1546, 1628, 1629 Yeshiwondim, Asnakew 1546, Surveillance Network 646 World Health Organization Ebola 974, 1628 Wilson, Michael D. 1322 Response Team 798, 2 Yetgang Airy, Barriere 489 Wilson, Micheal 318 World Health Organization Global Yeung, Shunmay 1523, 1699, 912, Wilson, N. O. 204 Malaria Programme 1617, 230, Y 955 Wilson, Nana 1926, 318 962 Y, Maurice 84 Yewhalaw, Delenasaw 110 Wilson, Patrick C. 172 WormBase Consortium 446 Yi, Chenda 887 astmh.org Abstract Author Index A-629

The number(s) following author name refers to the abstract number.

Yi, Poravuth 1829 Yutavorasit, Soparat 254 Zeleke, Melkamu 1546, 1628, Zhou, Shuisen 893 Yin, Mingbo 1157 1629 Zhou, Xiaonong 1157 Yman, Victor 905 Zelman, Brittany 656, 865 Zhou, Yi-Biao 1898 Yohane, Maxwell 847 Zeng, Qiang 1525, 257 Zhou, Ying 598 Yokobe, Lindsay 1070, 1075 Z Zerpa, Rito 1011, 1667, 409 Zhou, Zhiyong 566 Yong, Tai-Soon 1159 Zhang, Genwei 1534, 558 Zhu, Daming 1279, 375, 985 Zachaeus, Uwadiegwu 1169 Yongvanitchit, Kosol 15 Zhang, Guoqing 1140 Zhu, Guan 1139 Zaenker, Edna 1290 Yoo, Mi-Sun 1147, 1449 Zhang, Haoyue 627 Zhu, Yuwei 1840, 1843 Zageye, Elias A. 1628 Yoon, Hachung 1109 Zhang, Helen L. 1105, 1326 Zhumabayeva, Aziza 1025 Zago, M. Paola 1084 Yoon, In-Kyu 148, 170, 171, 178, Zhang, Heng 1026, 1027, 574 Zielinski-Gutiérrez, Emily 618 Zaidi, Irfan 1635, 1636, 941 184, 36, 591, 739, 783, 790 Zhang, Jing 1525, 255, 257 Zigirumugabe, Sixte 1369, 885 Zaidi, Shujaat 618 Yoon, Pryscilla 1881 Zhang, Linxiu 50 Zikursh, Melinda 1511 Zaidi, Syed Sohail Zahoor 1772 Yoon, Steven S. 305, 947 Zhang, Min 47 Zimba, Rabson 1788, 24 Zaitchik, Benjamin 1666 Yoshida, Shigeto 378 Zhang, Ping 1525, 255, 257 Zimba, Tomas 415 Zakhashvili, Khatuna 706 Yoshinaka, Yoshiyuki 482 Zhang, Veronica 1874 Zimmerman, Cynthia 1765 Zakhour, Ramia 1729 Yoshino, Timothy P. 1779 Zhang, Weihe 1729 Zimmerman, Peter A. 1511, 202, Zaki, Sherif R. 37, 793 Yotebieng, Marcel 882 Zhang, Yaobi 1689, 1930 221, 302, 449, 735, 913 Zakutansky, Sara 1642 Young, Alyson 1792 Zhang, Yinhua 1080, 448 Ziniel, Peter D. 1899 Zaky, Weam 1724, 668 Young, Katherine 1493 Zhang, Zhongsheng 1292, 1314, Zinszer, Kate 1457, 685 Zale, Amy 1024, 57 Young, Katherine I. 751 861 Zoerhoff, Katie 1230, 504 Zalisk, Kirsten 686 Yount, Boyd 548, 1416, 1430 Zhao, Lei 651 Zoleko-Manego, Rella 854 Zalucki, Myron 1806 Yourkavitch, Jennifer 686 Zhao, Wenyi 262 Zompi, Simona 1410 Zalwango, Sarah K. 1727, 490 Yu, Elaine A. 1773 Zhao, Xin 101 Zongo, Issaka 224, 818 Zaman, Muhammad H. 698 Yu, Jihnhee 1839, 580 Zhao, Zhengyang 530 Zorian, Aline 79 Zambrano, Andrea I. 1321 Yu, Qing 371 Zheng, Hong 1295, 699 Zornetzer, Heather 622 Zam-Ngono, Celestin 908 Yu, Xinbing 1156 Zheng, Hong-Xiang 1157 Zorrilla, Victor 100 Zanini, Graziela M. 1529 Yu, Xuejie 1458 Zheng, Jie 922 Zoungrana, Jeremie 315 Zaraza Moncayo, Milena 1055 Yuhas, Krista 496 Zheng, Sheng-Bang 1898 Zoure, Honorat 511, 1715, 505 Zarlinda, Iska 656, 865 Yui, Katsuyuki 330 Zhong, Daibin 1381, 1382, 1383, Zumer, Maria 471 Zecca, Italo 664 Yukich, Joshua 1566, 881, 278 1391 Zurawski, Daniel 57 Zegers de Beyl, Celine 384 Yumiseva, Cesar A. 1761 Zhou, Guofa 1381, 896 Zvietcovich, Fernando 1910 Zegeye, Elias 1546 Yun, Heather 1048, 648 Zhou, Huiqiong 1107 Zwingerman, Nora 1799 Zeighmami, Reza 794 Yuosembom, Emile 489, 1597 Zhou, Luwen 369, 950

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