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,