The economic evaluation of human papillomavirus vaccination strategies against cervical cancer in women in Lao PDR: a mathematical modelling approach Phetsavanh Chanthavilay1,2*, Daniel Reinharz2,3, Mayfong Mayxay1,4,5, Keokedthong Phongsavan6, Donald E Marsden5, Lynne Moore2 and Lisa J White7,8 1Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Lao PDR, 2Department of Social and Preventive Medicine, Faculty of Medicine, Laval University. Quebec, Canada, 3Institut de la Francophonie pour la Médecine tropicale, Vientiane, Lao PDR, 4Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR, 5Centre for Tropical Medicine and Global Health, Churchill Hospital, University of Oxford, Oxford, UK., 6Gynecologic Oncology Unit, Setthathirath Hospital, Vientiane, Lao PDR., 7Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand, 8Nuffield Department of Medicine, University of Oxford, Oxford, UK Contact - Phetsavanh Chanthavilay: [email protected] Background: Cervical cancer, a preventable disease, is the third leading cause of cancer morbidity and mortality in the Lao People’s Democratic Republic (Lao PDR). Since many cervical cancers are linked to human papilloma virus (HPV) infection, vaccination against this virus may lead to a reduction in these types of cancer. The study described here is the first to compare the cost-effectiveness of different HPV vaccination options in Lao PDR. Methods: A dynamic compartment model was created. The model included routine screening activities already in place, as well as theoretical interventions that included a 10-year-old girl-only vaccination programme combined with/without a 10-year-old boy vaccination programme and/or a catch-up component. The simulation was run over 100 years. In base case analyses, we assumed 70% vaccination coverage with lifelong protection and 100% efficacy against HPV types 16/18. The outcomes of interest were the incremental cost per Disability-Adjusted Life Year (DALY) averted. Results: In base case analyses, according to the WHO definition of cost-effectiveness thresholds, vaccinating 10- year-old girls was very cost-effective. Adding a catch-up vaccination element for females aged 11-25 years was also very cost-effective, costing 1,559 international dollars (I$) per DALY averted. Increasing the age limit of the catch-up vaccination component to 75 years old showed that this remained a cost-effective option (I$ 5,840 per DALY averted). Adding a vaccination programme for 10-year-old boys was not found to be cost-effective unless a short time simulation (30 years or less) was considered, along with a catch-up vaccination component for both males and females. Conclusions: Adding a catch-up female vaccination component is more attractive than adding a 10-year-old boy vaccination component.
Key words: Economic evaluation, HPV vaccination, cervical cancer and Lao PDR.
Low immunogenicity of pentavalent childhood vaccine in Lao People’s Democratic Republic
Konstantin Evdokimov1,2, Phonethipsavanh Nouanthong1, Lisa Hefele1,2, Kong Sayasinh3, Keooudomphone Vilivong1, Bounthome Samountry4, Darouny Phonekeo5, Michel Strobel3, Frank Haegeman6, Peter Heiman6, Claude P Muller1,2, Antony P Black1
1Lao-Lux Laboratory, Institut Pasteur du Laos, Vientiane, Lao PDR, 2Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Grand-Duchy of Luxembourg, 3Institut de la Francophonie pour la Médecine Tropicale, Vientiane, Lao PDR, 4Department of Pathology, Faculty of Medicine, University of Health Sciences, Vientiane, Lao PDR, 5Institut Pasteur du Laos, Vientiane, Lao PDR, 6Luxembourg Development Cooperation Agency, Vientiane, Lao PDR
Contact - Antony Black: [email protected] Introduction: In Lao People’s Democratic Republic (PDR), outbreaks of vaccine-preventable infectious diseases such as diphtheria and measles are common and hepatitis B remains endemic. Such high burden of disease can result from not only low vaccination coverage but also low immune response to vaccine. This study was done to determine the immune response to the pentavalent diphtheria–tetanus–whole cell pertussis–hepatitis B– Haemophilus influenzae type b (DTPw–HepB–Hib) vaccine in Lao children after documented vaccination with three doses.
Methods: 1131 mother-child pairs were recruited from three provinces in Lao PDR. Children were aged 9-50 months and all had records of at least three injections of the pentavalent vaccine. Serum was analysed by ELISA for HBsAg, anti-HBs, anti-HBc, anti-diphtheria, anti-tetanus, anti-Hib and anti-pertussis antibodies. Demographic and nutritional information were obtained in addition to stool samples for detection of parasites.
Results: Protective levels of antibodies against hepatitis B virus (HBV) were found in only 37.9% of children; 55.6%, 85.2% and 57.9% of children were seroprotected against diphtheria, tetanus and Hib, respectively. 23.5% of the children had antibody levels indicating vaccination or exposure to pertussis. Time since vaccination or age, home-birth, malnutrition and location could partially explain the poor vaccine responses.
Conclusions: In Lao children with a full documented course of childhood pentavalent vaccination, seroprotective rates are very low. Although it was not possible to fully explain the reasons for low responses they could include malnutrition, parasite infestation and vaccine management. Thus, besides coverage, vaccine immunogenicity is of major concern in Lao PDR.
3 Keywords. Vaccine, immunogenicity, hepatitis
Measles seroprevalence survey in Sri Lanka: Evidence of herd immunity for a national policy to protect infants
Deepa Gamage, Samitha Ginige, Paba Palihawadana
Epidemiology Unit, Ministry of Health, Sri Lanka
Contact - Deepa Gamage: [email protected]
Introduction: Sri Lanka has experienced an outbreak of measles since 2013 to 2015, despite the high vaccination coverage (MMR vaccination at ages 1 and 3 years). Majority of scattered cases were in bipolar age distribution as of infants and above 40 years. Though maternal antibodies are expected to provide protection for infants, high proportion of reported cases were among 6-11 month infants. In this background a measles serological survey was carried out to assess the measles herd immunity with the objective to assess community level serological protection to measles virus among different age categories
Methods: A descriptive cross-sectional study (in districts of Colombo, Monaragala, Anuradhapura and Vavuniya) was conducted among a total of 800 study subjects. Sample size was separately calculated for each selected age category and was 100 in each and 200 for 30-39 age category (expected prevalence 90% except 50% for 30-39 years, precession 7%, design effect 1.5) subjects of selected age groups (6-8 months, 9-11 months,2 years,5 years,15-16 years,20-29 years and 30-39 years) was carried out using multistage cluster sampling technique. Venous blood sample (2ml) was collected and tested for presence of serum anti-measles immunoglobulin (Ig) G antibody levels using ELISA method. Socio-demographic and anthropometric information were collected by using interviewer administered questionnaire and by physical examination. Test results of measles IgG antibody level >200mIU/ml were considered as protective levels.
Results: All enrolled (n=800) subjects completed the study and none response rate was 0%. Sero-protective proportion among 6-9 months and 9-11 months groups (prior to measles vaccination) were 2% and 1% respectively indicating they were unprotected for measles. Sero-protective proportion among ages 2, 5, 15-16, 20-29 and 30-39 years were 100%, 98% , 84% , 94% and 98% respectively indicating high population protection. After excluding infants, overall population protection was 95.2% (95% CI 93-96.7%). This illustrates the required measles herd immunity threshold (92-94%) which is maintained to prevent community transmission. Median antibody titre among all study subjects (n=800, including vaccination not recommended population) was 622 mIU/ml (IQR 105.5-1361.2 mIU/ml) and median antibody titre among vaccination due population (n=600) was 735 mIU/ml (IQR 462.9-1667.8 mIU/ml). No significant association of sero-prevalence and nutritional status was observed.
Conclusions: Infants of 6-11 months were not adequately protected against measles due to inadequate maternal antibodies and early measles vaccination (MCV) before 1 year would be required to protect infants and to prevent continuation of the measles outbreak.
(This recommendation led to the national policy decision of schedule change of MMR vaccine from 1 year to 9 months)
Keywords: IQR-interquartile range, CI-confidence interval,ELISA-Enzyme Linked Immunosorbant assay, MMR- Mumps, Measles, Rubella vaccine)
An open Label, randomised controlled non-inferiority trial, comparing two-dose priming with the 10- valent pneumococcal conjugate vaccine at 6 and 10 weeks to 6 and 14 weeks in Nepali children
Meeru Gurung1, Rama Kandasamy2, Stephen Thorson1, Shrijana Shrestha1, Imran Ansari1, Ganesh Shah1, Pratistha Maskey1, Manisha K.C1, Sarah Kelly2, Katherine L. O'Brien5, Ly-Mee Yu6, Ushma Galal6, David R. Murdoch3, Dominic F. Kelly2, 4, Andrew J. Pollard2, 4
1Paediatric Research Unit, Patan Academy of Health Sciences, Kathmandu, Nepal, 2Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom, 3Department of Pathology, University of Otago, Christchurch, New Zealand, 4NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom, 5International Vaccine Access Centre, Department of International Health, Johns Hopkins Bloomberg School of Health, 6Dept Primary Health Care Sciences, University of Oxford, Oxford, United Kingdom
Contact - Meeru Gurung: [email protected]
Background: PCV10 was introduced into the immunisation schedule of Nepal in Kathmandu Valley in August 2015, using a unique 3-dose schedule at 6 weeks, 10 weeks and 9 months of age (4-week interval between 2- priming doses). A previous Nepali study demonstrated better and longer-lasting immunity after the third dose of a 2p+1 schedule, with an 8-week interval between priming doses (6w/14w/9m) than after the 3p+0 schedule (6w/10w/14 w) used in most Gavi countries; both schedules are now WHO recommended. As the 6w/10w/9m schedule was not previously used in Gavi countries, a non-inferiority study comparing the Nepal schedule with the WHO-recommended schedule of 6+14 weeks and 9 months was undertaken.
Methods: A single centre open-label, parallel-group, randomised, controlled trial was undertaken to determine whether the 6w/10w schedule is non-inferior to the 6w/14w priming schedule, each followed by a booster dose at 9 months of age.
From August 2015 to April 2016, 304 healthy Nepali children were randomised to 2 groups of 152 participants each. Blood was collected one month after the PCV10 second priming dose, and pre-post boost at 9 and 10 months of age; serotype-specific antibody concentrations were determined by ELISA using 22F adsorption at a WHO pneumococcal serology reference laboratory.
Results: Of the total of 304 healthy children randomised, 287 participants completed the study and only 3 in each group missed their scheduled vaccination. At 9 months, based on the proportion of children with IgG ≥0.35μg/mL, the 6w/10w schedule was non-inferior to the 6w/14w schedule for serotypes 5, 9V, 14, and 19F, but not for serotypes 1, 4, 6B, 7F, 18C, and 23F. GMCs at 9 month differed only for serotypes 18C and 19F (slightly higher in 6w/14w group). At 10 months, there was no significant difference in IgG levels or GMCs for any serotype.
Conclusions: The 6-week, 10-week and 9-month and the 6-week, 14-week and 9-month schedules are comparably immunogenic following the 9-month booster. However, the 6-week, 14-week priming schedule is more immunogenic for some serotypes (18C, 19F) and should be preferred where delivery logistics allow.
Development of dengue vaccine in Indonesia
Whinie Lestari1, Beti Ernawati Dewi2, T. Mirawati Sudiro2, Tedjo Sasmono3, Benediktus Yohan3, Fifit Juniarti4, Sabar Pambudia4, Tri Wibawa5, Nastiti Wijayanti5, Neni Nurainy6, Dicky Mahardika T6
1NIHRD Ministry of Health Republic of Indonesia, 2University of Indonesia, 3Eijkman Institute for Molecular Biology, 4BPPT, 5University of Gadjah Mada, 6 PT Bio Farma
Contact - Neni Nurainy: [email protected]
Introduction: Dengue infection has been a constant global challenge in infectious diseases. Especially for a tropical country like Indonesia, there has been a demand for dengue vaccine since other measurement has not had a satisfactory result for dengue endemic prevention. In 2013, National Dengue Vaccine Consortium has been established in Indonesia. The members of the consortium are the National Institute of Health Research and Development (NIHRD)-Ministry of Health Republic of Indonesia, PT Bio Farma, Eijkman Institute for Molecular Biology, Center for Pharmaceutical Technology and Medica- BPPT, University of Indonesia and University of Gadjah Mada. The program of the consortium was focused initially on a vaccine for the prevention of dengue with a general aim to develop within Indonesia the capacity to produce recombinant-based subunit protein for vaccines and diagnostics. In this study, we have developed a recombinant protein-based dengue vaccine which comprises an expression cassette encoding pre-membrane and envelope protein (prM/E) which belongs to dengue virus (DENV) -1, DENV-2, DENV-3 and DENV- 4 of the genotype predominantly found in Indonesia.
Methods: Data of DENV surveillance in Indonesia generated by Eijkman Institute led to decision of each serotype DENV preference in vaccine design. Each Institution within the Consortium had their own task to produce the clone and the antigen. NIHRD for generating the clone of DENV-1 genotype I, UGM for DENV-1 genotype IV, UI for DENV-2 genotype Cosmopolitan, BPPT for DENV-3 genotype I, Eijkman for DENV-4 genotype II and Bio Farma for development of upstream and downstream protein production. An expression cassette containing a prM/E DNA of each DEN-V serotype isolate was cloned into pPICZaC plasmid to generate pPICZaC DENV in Pichia pastoris. Positive integrants were identified by PCR. The expression of prM/E was induced by methanol and the protein analyzed by SDS PAGE, Western Blotting and Transmission Electron Microscopy (TEM).
Result: Nucleotide sequencing analysis showed that the inserted fragment encodes amino acids with 100% similarity compared to that designed for each DENV serotype. The PCR analysis showed that each P.pastoris integrated with prM/E expression cassette was successfully obtained with methanol utilizing slow (Muts) phenotype. Expression of prM/E was controlled by alcohol oxidase promoter (AOX1) and the protein band with apparent molecular weight which similar to prM/E size was detected based on a SDS PAGE and Western Blot analysis. Furthermore by TEM analysis, a recombinant viral like particle (VLP) composed of prM/E protein of each DEN-V serotype has been generated.
Conclusion: In this study, the Consortium generated a construct of four types of dengue recombinant vaccine encoding Indonesian prM/E in a Pichia pastoris expression system and successfully produced the VLPs of dengue. Preclinical development including the safety, immunogenicity and efficacy of the tetravalent vaccine in non-human primate model will be done in Indonesia in the next two years; the candidate ensures the continued influx of innovation into the vaccine pipeline, which is critical in maximizing the changes of success for dengue vaccine development.
Pattern of hepatitis B virus infection among blood donors and need for immunization in young adults of Lao P.D.R, an endemic country
P. Nouanthong1,2, A.P. Black1, Ch. Phetsavanh1, Kh.Vilaysone1, Ch. Keokhamphoui3, V. Sorinxay3, Ch. Souksakhone3, C.P.Muller4.
1Vaccine Preventable Disease Unit, Institut Pasteur du Laos, Lao PDR, 2National Immunization Technical Advisory Group, Lao PDR, 3National Blood Transfusion Center, Lao Red Cross Society, Lao PDR , 4Department of Infection and Immunity, Luxembourg Institute of Health, Luxembourg
Contact - Phonethipsavanh Nouanthong: [email protected]
Introduction: Approximately 2 billion people are infected with hepatitis B virus (HBV) worldwide and half of them die from HBV related cirrhosis and hepatocellular carcinoma (HHC). Lao PDR is highly endemic for HBV with approximately 9% of chronically infected adults. However, death from HHC and HBV infection in adults remains high.
Objectives: The aim of this study was to investigate the pattern HBV infection in Lao adults and to design a national strategy for adult HBV vaccination
Methods: A non-randomized community-based seroprevalence study was conducted. Blood donors from 3 representative regions (central, north, and south) were recruited from 2013-2015. More than 5000 samples were screened for HBV markers. The cost benefit exclusion of positive repeated donors will be forecasted. An approach in reduction the burden of infected blood units will be explored.
Results: Prevalence of current infections, as defined by presence of HBsAg was 9.7% among first time donors. The prevalence was higher in the north region (11.4%) than in central (4.3%) and south (7,0%). Overall, the prevalence was significantly higher in males (8.6%) than in females (4.4%; p<0.001) and varied according to age and occupation. Exposure to HBV (anti-HBc+) was high overall (41.2%), while protective immunity (anti-HBs) was less than 7% in all regions. Compared to historical data, the percentage of HBsAg positive among donors did not differ significantly between the years 2003 to 2015, although a previous study has suggested a reduction in HBsAg children who were born after vaccination introduction. This study suggests significant cost-benefit ratios for vaccination over the burden of infection and treatment.
Conclusions: In Lao PDR there remains a very high endemicity of HBV in adults, with very low immunity among blood donors who were born before the country’s HBV vaccination policy was implemented.
Recommendation: In addition to universal newborn and infant hepatitis B vaccination, results from this study suggest that HBV vaccination to high-risk populations would benefit to reduce the burden of HBV infection, the treatment and the death in Lao PDR.
Keywords: hepatitis B virus, immunity, vaccination
Poliovirus immunity in Lao People's Democratic Republic
Phonethipsavanh Nouanthong1, Antony P, Black1, Maude Pauly2, Phonepaseuth Khampanisong2, Judith M. Hübschen1, Naphavanh Nanthavong3, Kong Sayasinh3, Prapan Jutavijittum4, Bounthome Samountry5, Anonh Xeuatvongsa6, Sabine Diedrich7, Claude P. Muller1
1Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg, 2Lao-Lux-Laboratory, Institute Pasteur du Laos, Vientiane, Lao PDR, 3Institute de la Francophonie pour la Medecine Tropicale, Vientiane, Lao PDR, 4Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, 5Faculty of Basic Sciences, University of Health Sciences, Vientiane, Lao PDR, 6National Immunization Programme, Lao MOH, Vientiane, Lao PDR, 7Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany
Contact - Phonethipsavanh Nouanthong: [email protected]
Background: Poliovirus (PV) remains a challenge due to the circulation of vaccine-derived poliovirus (VDPV), especially in under-vaccinated populations. The detection of anti-PV IgG antibodies enables the identification of susceptible risk groups.
Objective: This serosurvey evalutes immunity levels against poliovirus in Lao children and adults before the VDPV outbreak in 2015
Methods: Children, including from hard-to-reach communities (n=1216), and adults (n=1228) were tested for IgG antibodies against poliovirus by ELISA. Protective antibody titers against the 3 vaccine strains were determined by microneutralization.
Results: Over 92% of the children had anti-poliovirus antibodies, but seroprevalence was only 81.7% in blood donors and 71.9% in health care workers. Most children and adults had neutralizing antibodies to poliovirus types 1-3, but some neutralisation data conflicted with the ELISA data in the elderly adults.
Conclusion: Participants born after introduction of poliovirus vaccination in Lao PDR were more likely to be sero-protective. However, waning of antibodies among adults may sustain silent circulation of poliovirus.
Recommendation: Vaccinated children had high levels of immunity suggesting the success of immunization activities in Lao PDR. To prevent the re-emergence of VDPV, vaccination campaigns with expanded age groups and targeting in particular health care professionals should be implemented.
Keywords: poliovirus, immunity, vaccination
A national immunization program recommendation: Seasonal influenza vaccine administration for hospital health care workers in Indonesia
Nurhayati, Anandika Pawitri, Mochamad Helmi Aziz, Deni Pepy Rentina Butarbutar, Wahyu Nawang Wulan, Dewi Lokida, Muhammad Karyana, Herman Kosasih
Contact - Nurhayati: [email protected]
Introduction: Influenza vaccination is mostly recommended for elderly, infants and immunocompromised individuals. In addition, health care workers (HCWs), who could easily spread influenza from one patient to another in hospital care setting, are also the target for annual seasonal influenza vaccination. Regardless, data regarding the need of seasonal influenza vaccination for health care workers (HCWs) in tropical countries, such as Indonesia are insufficient. These data are needed to inform and recommend the national immunization program. Here, we show the data from 8 tertiary hospitals across Indonesia on the proportion of seasonal influenza in hospitalized patients and the circulating types or subtypes
Methods: Throat and nasal swabs and/or sputum samples were collected from a subset of hospitalized febrile illness patients with respiratory signs and symptoms. Plasma samples were collected during acute illness and 14-28 days later. This study was conducted at 8 major hospitals throughout Indonesia from 2013-2016. At the reference laboratory, throat and nasal swabs and/or sputum were tested for influenza A and B viral RNA using RT-PCR. Plasma samples were tested using a panel of influenza viruses (H1N1 pandemic, H3N2, B Yamagata, and B Victoria) to detect the presence of hemagglutination antibodies, and using commercial ELISA kit to detect IgM and IgG influenza A and B antibodies.
Results: As no epidemiology data of influenza and/or no influenza diagnostic tests are available at the hospitals, none of the 1,486 subjects enrolled was diagnosed with influenza infection. At the reference laboratory, influenza viruses were found to be the etiology of hospitalization in 69 subjects with 48 (69.5%) cases caused by influenza A and 21 (30.5%) cases by influenza B. Using PCR and hemagglutination inhibition assay, we were able to identify 12 influenza A H1N1 pandemic, 12 influenza A H3N2, 6 influenza B Victoria, and 2 influenza B Yamagata, which were the seasonal influenza strains. From those 69 subjects, 4 (5.7%) fatal cases and 5 (7.2%) co-infections with other pathogens (Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenza, Salmonella typhi, and RSV) were observed. All of the fatal cases were adults aged > 49 years old with underlying diseases, such as stroke, coronary heart disease, rheumatic heart disease, congestive heart failure, and mediastinum tumor. 50.8% cured subjects were reported having underlying diseases with lung tuberculosis as the most frequent disease (15.4%).
Conclusion: Our data showed that seasonal influenza was present as the etiology of respiratory infections that needed hospitalization in Indonesia. None of these subjects was diagnosed as influenza infection since data on the epidemiology of influenza in hospitalized patients are not available, and the hospitals did not have the capacity to do influenza diagnostic tests. To avoid influenza transmission from patients to HCWs and from HCWs to other patients, it is recommended that HCWs should be vaccinated.
The epidemiology of dengue in Indonesian pediatrics: The need for a safe and effective vaccine
Anandika Pawitri, Nurhayati, Mochamad Helmi Aziz, Ungke AntonJaya, Dewi Lokida, Muhammad Karyana, Herman Kosasih
Contact - Anandika Pawitri: [email protected]
Introduction: Dengue remains the most important infectious disease in pediatrics. As a result of the antibody dependent enhancement phenomena, secondary infection by a different dengue virus serotype is an important risk factor for the development of DHF, in which 20% may develop dengue shock syndrome. Worldwide, children younger than 15 years make up 90% of DHF cases.
Several vaccine candidates are under development, with the CYD-TDV is the most advanced. Recently, a problem regarding safety was announced, indicating that vaccination in naïve immune subjects is like introducing primary infection and therefore puts these subjects at risk of severe manifestations when natural dengue infection occurred.
We would like to present the epidemiology of dengue in pediatrics in Indonesia, and determine the need of dengue vaccine.
Methods: In a fever study conducted at 7 large cities in Indonesia, hospitalized pediatric subjects (ages 1-18) were enrolled and were visited 24 hours, 14-28 days, and 3 months after enrollment. Blood specimens and clinical data were collected during these visits. Acute and convalescent blood samples were tested for dengue IgM and IgG antibodies. When IgM and/or IgG antibodies were sero-converted or increased, acute specimens were tested for dengue RT-PCR and NS1 antigen.
Results: Dengue IgG antibodies were detected in 67% of the subjects. Immune status of >90% was found in subjects from 11 years of age. Dengue infection was identified in 243 of 600 subjects enrolled. Severe dengue cases were significantly more frequent (p<0.01, 95% CI (18.7 to 48.7)) in secondary (60.7 %) than in primary infection (25.5 %). Dengue cases were found in all cities, and all serotypes circulated with DENV-1 and DENV-3 as the most prevalent, except for DENV-4, which was absent in Semarang and Surabaya. One subject experiencing secondary infection caused by DENV-3 died.
Conclusion: Dengue is the most common cause of fever in pediatrics in Indonesia. As a result of appropriate management, the mortality was <1%. However, the morbidity was still high despite a mass vector-control campaign. In addition, severe cases were associated with secondary infection. These findings highlight the importance of developing safe and effective vaccines.
Immunogenicity of AP205 bacteriophage-based virus-like particle displaying the major house dust mite allergen Der p 2
Termsri Peepim1, Chris Janitzek2, Susan Thrane2, Karntichar Mongkorntanyatip1, Adam F. Sander2 and Alain Jacquet1
1Chula Vaccine Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 2Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
Contact - Termsri Peepim: [email protected]
Background: Allergen-specific immunotherapy based on repetitive administrations of house dust mite (HDM) allergen extracts represents, up to now, the unique protocol to treat HDM allergic patients. As such administration of allergens can induce side effects in patients, new safe and highly immunogenic recombinant vaccines are needed to induce notably strong allergen-specific IgG-blocking antibodies capable to inhibit the binding of IgE to allergens. The goal of the present study was to evaluate the immunogenicity of a AP205-based virus-like particle (VLP) vaccine displaying the major HDM allergen Der p 2 in vivo.
Methods: VLP-Der p 2 was obtained by the mixing of purified SpyCatcher-VLPs with rDer p 2-SpyTag, both expressed in E.coli. The immunogenicity of VLP-Der p 2 in Balb/C mice was compared with that of unconjugated rDer p 2 mixed with VLP. As a control, mice were also immunized with rDer p 2 produced in Pichia pastoris. We also evaluated the importance of the adjuvant co-administration on the induction of anti-Der p 2 specific immune responses. Finally, the different sera were tested for their ability to inhibit IgE recognition of Der p 2 in ELISA.
Results: Intramuscular mice immunizations with VLP-Der p 2 induced a much stronger antibody response compared with the one measured following injections of unconjugated VLP + Der p 2. Similar results were observed when antigens were formulated with alum. Remarkably, the administration of VLP-Der p 2 triggered a potent Th1-biased antibody production characterized by a high specific IgG2a/IgG1 ratio. The formulation with alum did not change the levels of specific IgG2a production but increased the production of Der p 2-specific IgG1 antibodies. Finally, competition ELISA clearly showed that the Der p 2-specific antisera generated in mice by immunizations with VLP-Der p 2 inhibit the binding of human IgE to Der p 2.
Conclusion: Our results suggest that AP205-based VLP displaying Der p 2 represents a promising and effective immunotherapeutic treatment for HDM allergy
Proteomics of leptospiral extracellular vesicles for identification of potential vaccine antigens Eakalak Phanchamnan1,2,Theerapat Phoka1,2, Pratomporn Krangvichian1,2, Suwitra Sathean-Anan-Kun1,2, Patcharin Prakobwat1,2, Trairak Pisitkun3 and Kanitha Patarakul1,2
1 Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 2 Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Bangkok, Thailand, 3Chulalongkorn University Systems Biology (CUSB) Center, Chulalongkorn University, Bangkok, Thailand
Contact - Eakalak Phanchamnan: [email protected]
Introduction: New leptospirosis vaccines with higher protective efficacy and lower adverse reactions are essential for overcoming the disadvantages of commercially killed whole-cell vaccines. Surface-exposed outer membrane proteins (OMPs) are intensively investigated as the promising vaccine candidates for subunit vaccines. Several pathogenic bacteria including Leptospira produce small extracellular vesicles (ECVs) possibly derived from the bacterial outer membrane. A previous report demonstrated that leptospiral ECV-based vaccines conferred protective immunity against lethal infection in an animal model. Therefore, leptospiral ECVs may contain potential vaccine antigens. We aimed to identify and characterize proteins of ECVs from pathogenic Leptospira interrogans serovar Pomona to search for novel vaccine candidates.
Methods: L. interrogans serovar Pomona were grown in Ellinghausen-McCullough-Johnson-Harris (EMJH) medium until the log phase (approximately 2-5x108 cells/ml) was reached. The supernatant fraction of leptospiral culture was used to obtain natural ECVs (nECVs) by filtration and ultracentrifugation. Chemically induced ECVs (iECVs) were prepared by using 0.1 M citrate buffer pH 3 to break down leptospiral cell walls that subsequently reformed to vesicles. Both samples of ECVs were further purified by density sucrose-gradient ultracentrifugation and examined by transmission electron microscopy (TEM). The proteins contents of nECVs and iECVs were separated by 15% SDS-PAGE and characterized by liquid chromatography-tandem mass spectrometry (LC- MS/MS). The prediction of protein localization was assessed by PSORTb v3.0 software.
Results: The purified nECVs and iECVs were separated mainly into 50% w/v sucrose fractions. TEM demonstrated that nECVs and iECVs were spherical nanosize vesicles but the size of iECVs were smaller. The LC-MS/MS and PSORTb analysis results showed that 3.4% (10/987) and 2.72% (28/1026) leptospiral proteins were found to be OMPs, respectively. The most abundant known OMPs were LipL21, LipL32 and OmpA.
Conclusion: Pathogenic Leptospira spontaneously produced ECVs (nECVs) during routine culture in EMJH medium. The chemically induced ECVs (iECVs), prepared by treatment of intact cells with 0.1 M citrate buffer pH 3, increased number of protein content compared to that of nECVs. OMPs localized on ECVs should be further investigated as novel candidates for subunit vaccines against leptospirosis.
Efficacy of a non-antibiotic based drug, and a passive immunotherapeutic agent, for the treatment of diarrhea in rhesus monkey model
Nattaya Ruamsap, Rawiwan Imerbsin, Robert W Kaminski (WRAIR), MAJ Brett E Swierczewski (WRAIR), MAJ John M. Crawford and Dilara Islam
Contact - Dilara Islan [email protected]
Enteric infections cause high morbidity and mortality on a global scale, with multiple pathogens contributing to this disease burden. Entero-invasive Gram negative bacteria and necrotizing enterocolitis cause life threatening disease by stimulating intense toll-like receptor (TLR) 4 - myeloid differentiation factor 2 (MD-2)- lipopolysaccharide (LPS) cytokine-induced and neutrophil mediated gut wall damage. Cytokine-mediated- inflammation leads to excessive neutrophil infiltration and vasculitis of the colon that presents as bloody diarrhea. There are currently no commercially available vaccines to prevent these enteric infections. Treatment with antibiotics can lead to the emergence of resistant strains, and do not prevent the potential post-infectious complications of infection. In the absence of a licensed vaccine, alternative non-antibiotic prophylactic modalities would serve a definite role in mitigation of disease burden.
Small dendrimer based drugs are showing increasing promise as novel polyvalent medicines in several animal models of infection and inflammation. We already have shown that when rhesus macaques were infected with Shigella and treated those infected monkeys orally with polypropyletherimine dendrimer glucosamine (PETIM-DG) protected the rhesus macaques’ colon and rectum epithelial barrier from neutrophil-mediated tissue necrosis, and the gut mucosa from vasculitis-induced pro-inflammatory cytokine-induced damage.
Hyperimmune bovine colostrum (HBC) induced by vaccination of a cow during gestation and obtained from resulting lactation is rich in targeted immunoglobulins and can be used to treat a variety of diseases. HBC was investigated as a passive immunotherapeutic agent against a wide variety of enteric pathogens. Presently, there is only one HBC product from Immuron Ltd, Australia, commercial name is Travelan, specifically designed to reduce the risk of infection by ETEC, Shigella, Salmonella and other bacteria that cause Travelers’ Diarrhea. HBC neutralizes several enteric pathogens by blocking their attachment to the intestinal wall and preventing diarrhea.
Future studies are required to check combined effect of PETIM-DG and HBC to prevent/cure diarrheal diseases. A number of pre-clinical studies are required to check efficacy of PETIM-DG and HBC against a broad range of enteric pathogens.
Neglected vaccine-preventable diseases: Lessons from a 3-month cough caused by Bordetella pertussis in an HIV-infected girl
Ida Safitri, Mochamad Helmi Aziz, Wahyu Nawang Wulan, Dewi Lokida, Nurhayati, Muhammad Karyana, Herman Kosasih, Tri Wibawa
Contact - Machamad Helmi Aziz: [email protected]
Introduction: In immune-compromised individuals, the persistent cough is usually associated with Mycobacterium tuberculosis infection, and pertussis diagnosis is rarely made. Pertussis vaccine does not induce lifelong protection; therefore, adolescents and adults are susceptible to Bordetella pertussis infection.
Methods: Throat and nasal swabs and sputum samples were collected through the Acute Febrile Illness Requiring Hospitalization (AFIRE) cohort from 2013-2016 from a subset of febrile illness patients with respiratory symptoms. We evaluated the presence of Bordetella pertussis DNA in patients who developed acute upper-lower respiratory symptoms using Real Time-PCR targeting IS481 of Bordetella pertussis.
Results and Case Description: A 7-year-old HIV-infected girl was admitted to the Dr Sardjito hospital with a history of 13-day fever and cough. On physical examination, her respiratory rate was 48x/ minute, heart rate (HR) was 128x/minute, rales were detected in both lungs, anemic conjunctiva, splenomegaly, and lymphadenopathy were observed. Laboratory workup at the hospital revealed that blood culture for both arms were negative, influenza A and B were negative, and tuberculosis workups, including AFB and GeneXpert sputum, were also negative. Sputum and feces culture revealed Streptococcus viridans, and patient was diagnosed with bronchiectasis with acute exacerbation. The stored sputum, throat and nasal swabs were assessed for a panel of respiratory pathogens by PCR. The sputum was positive for Bordetella pertussis and Streptococcus pneumoniae. At 14-28 days and 3 month follow-ups after hospitalization, the cough still persisted.
Conclusion: Early diagnosis of pertussis is crucial in the management of the disease and to prevent transmission to individuals who come in contact, including health care workers. This case report demonstrates the susceptibility of pertussis among immunocompromised patients and therefore, pertussis booster vaccine is required.
The finding of measles in hospitalized patients: A better strategy for vaccination programs is needed
Venty Muliana Sari Soeroso, Dewi Murniati, Dwiyanti Puspitasari, Ida Safitri, I Made Susila Utama, Risna Halim Murbin, M.M.D.E.A.H Hapsari, Usman Hadi, Herman Kosasih, Muhammad Karyana Contact - [email protected]
Introduction: Measles is a highly contagious airborne disease caused by the measles virus. The transmission rate among naïve individuals is 90%. With supportive therapy, illness usually lasts for 7-10 days. However, measles may be fatal, in 0.2% of cases, when complication such as diarrhea, encephalitis or pneumonia occurs. Antibodies to measles virus provide life-long protection; thus measles vaccine is effective to prevent the disease. Measles vaccine was given in combination with rubella vaccine to infants 9 months of age; a vaccine booster was given on 18 months, and 6 years of age. In 2016, although the coverage of vaccine in Indonesia satisfied the WHO target (90%), 115 outbreaks occurred, with 7000 measles cases (2.7 cases/100,000 population) and mortality of 0.07% were reported. Here we report measles cases that were identified in our acute febrile illness requiring hospitalization (AFIRE) study, highlighting the importance of ensuring vaccination program in the communities. Methods: This study was conducted at 8 large hospitals in Indonesia in 2013-2016, enrolling participants one year of age or older. Acute and convalescent (14-28 days after enrollment) blood specimens were collected. Measles virus was one of the causes of fever to search. Plasma and buffy coat specimens from participants with clinical diagnosis of measles and/or from participants with cough accompanied by coryza, conjunctivitis or rash, were tested. Acute and plasma specimens were tested for measles IgM and IgG antibodies using ELISA commercial kit (Sirion, Germany). Acute plasma and buffy coat from participants with sero-conversion or increasing measles IgM and/or IgG antibodies were further tested by RT-PCR. Result: Measles virus infection was identified in 14 of 75 participants tested, 9 were confirmed by RT-PCR and ELISA, and 5 were by ELISA only. Clinically 11 of them were diagnosed as measles on site hospitals, whereas 3 others were diagnosed as dengue (2) or typhoid fever (1). Measles cases came from Jakarta (3 cases), Surabaya (3), Makassar (3), Yogyakarta (2), Denpasar, Bali (2), and Semarang (1). No case was detected from Bandung. There were 4 adult cases. The median age of the participants was 5.8 years old, ranging from 1 year to 28.4 years old. No fatalities were found, although in 5 cases complications occurred (pneumoniae (3), diarrhea, otitis media). The mean number of days of illness when they were admitted to the hospitals was 6.8 days (range 4-13 days). All 14 participants had no or very low titers of IgG antibodies during enrollment, suggesting of no exposure of measles virus previously. In addition, IgG antibodies were also negative in 6 other participants, all from Yogyakarta, indicating that they had never been vaccinated. Conclusion: Measles virus was one of the most important pathogens identified in hospitalized patients. The combination of ELISA and RT-PCR may be used as an alternative to virus culture to confirm the infection. As in all cases, no or very low titers of IgG antibodies were detected, the government should ensure the vaccination program conducted at the community level reaches the targeted population.
Immunogenicity of multivalent subunit vaccines containing leptospiral factor H binding proteins in animal models Teerasit Techawiwattanaboon1,2*, Prayoon Lae-ngee2,7, Angsana Ayukhen2,7, Christophe Barnier-Quer3, Tanapat Palaga4, Alain Jacquet2,6, Noppadon Sangjun5, Pat Komanee5 and Kanitha Patarakul1,2
1 Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 2 Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Bangkok, Thailand, 3 Vaccine Formulation Laboratory, Department of Biochemistry, University of Lausanne, Switzerland, 4 Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand, 5 Armed Force Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand, 6 Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand , 7 Interdisciplinary Program of Medical Microbiology, Graduate School, Chulalongkorn University, Bangkok, Thailand
Contact - Teerasit Techawiwattanaboon: [email protected]
Introduction: Leptospirosis vaccines with higher potency and lesser adverse effects are currently required for humans. Numerous leptospiral outer membrane proteins have been tested as vaccine candidates. However, none were able to induce sterile immunity in animal models. Several factor H binding proteins (FHBPs) on pathogenic Leptospira have been shown to interact with host factor H (FH) leading to immune evasion by inhibition of membrane attack complex formation and complement-mediated killing. Inhibition of the interactions by specific antibodies against leptospiral FHBPs may be a potential strategy to clear leptospires in the host. We aimed to evaluate the immunogenicity of multivalent subunit vaccines consisting of four known leptospiral FHBPs in animal models, initially in BALB/c mice and subsequently in hamsters, the acute lethal infection model of leptospirosis.
Methods: Each six-week old female BALB/c mice (three mice per group) were immunized subcutaneously for three times at two-week intervals with monovalent and multivalent vaccine formulations containing four recombinant FHBPs including C-terminal LigA domain 7-13 (LigAc), LenA, LcpA and Lsa23 combined with LMQ (neutral liposome, monophosphoryl lipid A or MPL, and Quillaja saponaria fraction 21 or QS21) or Freund’s adjuvants. Next, each six-week-old female golden Syrian hamster (five hamsters per group) were immunized subcutaneously three times at two-week intervals with multivalent vaccine formulations containing four recombinant FHBPs adjuvanted with LMQ or alum. Specific antibodies (total IgG) against each antigen in sera of mice and hamsters at one week after each immunization were measured by enzyme-linked immunosorbent assay (ELISA).
Results: After three immunizations in BALB/c mice, monovalent and multivalent vaccine formulations consisted of leptospiral FHBPs combined with LMQ induced high antibody level to each vaccine antigen. There were no significant differences between antibody titers induced by LMQ and Freund’s adjuvants. Unexpectedly, in hamsters immunized with the multivalent vaccine formulated with LMQ, high antibody responses were only observed against LigAc and LenA after the third immunization. In addition, antibody levels against LigAc and LenA were significantly higher in hamsters immunized with the vaccine formulation containing LMQ than in those immunized with the alum-adjuvanted vaccine.
Conclusion: In BALB/c mice, antibody levels against all four FHBP antigens of monovalent and multivalent vaccines combined with LMQ were comparable to those with Freund’s adjuvant. However, only LigAc and LenA in the multivalent vaccine were immunogenic in hamsters. Therefore, immunogenicity of LcpA and Lsa23 needs to be enhanced before testing the protective efficacy of the vaccine formulation in the future. Surface proteomics of Leptospira interrogans serovar Pomona to search for novel vaccine candidates
Praparat Thaibankluay1,3, Prayoon Lae-ngee2,3, Suwitra Sathean-Anan-Kun2,3, Patcharin Prakobwat2,3, Trairak Pisitkun4 and Kanitha Patarakul2,3
1 Medical Science, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 2 Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 3 Chula Vaccine Research Center (Chula VRC), Center of Excellence in Vaccine Research and Development, Chulalongkorn University, Bangkok, Thailand, 4 Chulalongkorn University Systems Biology (CUSB) Center, Chulalongkorn University, Bangkok, Thailand
Contact - Prayoon Lae-ngee: [email protected]
Introduction: Leptospirosis is a re-emerging zoonosis of global distribution including Thailand. Currently available killed whole-cell vaccines confer serovar-specific and short-term protection with several adverse effects. Therefore, subunit vaccines containing leptospiral outer membrane proteins (OMPs) have been tested in animal models. However, none can induce complete protection. Surface-exposed OMPs are crucial for interactions with the host immune system including antibodies and should be potential targets for vaccine development. Therefore, the objective of this study was to study surface proteomics of pathogenic Leptospira to search for novel vaccine candidates.
Methods: Optimal concentrations of proteinase K for surface shaving of intact 1x1010 leptospires were determined. Surface-exposed proteins were shaved by various concentrations of proteinase K at 0, 0.5, 1, 2, and 5 g/ml and detected by Western blot using antibodies against known surface-exposed OmpL47 and periplasmic FlaA1. Cleaved surface-exposed proteins obtained from the samples with no cell lysis were subsequently characterized by one-dimensional gel-based liquid chromatography tandem-mass spectrometry (LC-MS/MS). PSORTb v3.0 bioinformatics tool was used for subcellular localization prediction of leptospiral proteins.
Results: We found that proteinase K at a concentration of 1 µg/ml was optimal for shaving surface proteins of leptospires. The 1,451 total proteins obtained from LC-MS/MS were predicted subcellular localization using PSORTb to be 24 (1.7%) extracellular, 34 (2.3%) outer membrane, 32 (2.2%) periplasmic, 106 (7.3%) cytoplasmic membrane, 927 (63.9%) cytoplasmic, and 328 (22.6%) unknown localization. Novel 7 hypothetical proteins were shown to be putative surface-exposed OMPs in this study.
Conclusion: Surface proteomics by proteinase K shaving yielded putative novel surface exposed OMPs of pathogenic leptospires. These proteins will be further confirmed their localization. Surface-exposed proteins may be used as novel vaccine candidates against leptospirosis.
Issues surrounding the uptake of Expanded Program on Immunization (EPI) and Maternal and Neonatal Tetanus (MNT) in rural South Vietnam Ha Nguyen Thanh2, Huong Van Thuy Qui2, Dr. Louise Thwaites2, Dr Mai Thi Phuoc Loan1, Dr Pham Van Lao1, Prof Michael Parker3, Dr. Mary Chambers2
1Preventative Medicine Center, Dak Lak, 2Oxford University Clinical Research Unit, Ho Chi Minh City, 3ETHOX Center, Oxford
Contact - Ha Nguyen Thanh : [email protected]
Introduction: The Expanded Program on Immunization (EPI) was introduced in Vietnam in 1983, followed by the maternal and neonatal tetanus initiative in 1995: both aiming to eliminate vaccine preventable diseases in infants and children. Reported coverage of these vaccines is high but a continual low-level rate of neonatal tetanus and sporadic outbreaks of other diseases such as diphtheria and measles indicate that there are significant gaps in the vaccination program. Recent studies by local Preventative Medicine Centre (PMC) and Oxford University Clinical Research Unit-HCM indicate that ethnic minority rural communities have the lowest vaccination coverage and that there are specific cultural and ethical issues surrounding acceptance and uptake of vaccinations which may be important, in addition to the practical difficulties in implementing an immunization program in remote communities. We are currently undertaking research to understand the practical constraints and attitudes and cultural issues surrounding vaccination uptake in two rural communities in Binh Phuoc and Dak Lak Provinces.
Aims and objectives 1. To explore attitudes and perceptions of selected communities related to vaccination. 2. To develop and implement appropriate community engagement activities based on the results of the above work in order to increase awareness of the issues surrounding vaccination among targeted communities. 3. To assess effectiveness of the engagement activities through change in vaccination rate of under 1yo.
Methods: Our target groups are: • women 15-35 (never pregnant) years old; • women currently pregnant or; • women with a child 2 years-old or under. • From both low and high vaccination uptake communes.
1. Quantitative survey: a face-to-face survey of 210-270 women in each province; 2. In-depth interviews and focus group discussions with women from each target group including mothers of known cases of childhood tetanus in the last five years. 3. Key Informant Interviews, including commune health staff and leaders of the commune. 4. Based on findings from the surveys and interviews public engagement (PE) activities will be designed to communicate about the upcoming vaccination programme that will be taken to 40 low-uptake communes. Extra, additional engagement activities will be conducted in the 20 selected low uptake ‘intervention’ communes. In the other 20 low uptake ‘control’ communes, PMC staff will roll out the vaccination programme in a similar manner to previous years. 5. A second phase of IDI will be conducted after PE & vaccination programmes – including women and health staff who had been active in the vaccination programme.
Results and Conclusions: This research is ongoing and data is currently being analyzed. We will present preliminary findings at the meeting.
Association between antibody responses to blood-stage parasitic antigens and protection from Plasmodium falciparum and Plasmodium vivax malaria in Timika, Papua, Indonesia
Retno Ayu Setya Utami1,4, Leily Trianty1, Dwi Apriyanti1, Agatha Mia Puspitasari1, Lisa Ioannidis4, Ann Ly4, Novita Sariyanti1, Enny Kenangalem2, Jeanne Rini Poespoprodjo2, Farah Coutrier1, Rintis Noviyanti1, Ric Price3, Alan Cowman4, Diana S. Hansen4
1Eijkman Institute for Molecular Biology, Jakarta, Indonesia; 2Yayasan Pengembangan Kesehatan dan Masyarakat Papua; 3Menzies School of Health Research, Darwin, Australia; 4The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Contact - Retno Ayu Setya Utami: [email protected]
Malaria is a major health problem causing over 210 million clinical cases every year around the world. In Indonesia, Timika is one of the highest malaria-endemic areas with a high annual parasite incidence (876 per 1,000 people per year). Moreover, massive antimalarial drug resistance cases were also reported from Timika, illustrating the need for developing other therapeutic tools such as vaccines to prevent disease. Clinical immunity to malaria only develops after many years of constant exposure to the parasites. This form of protection does not result in sterilising immunity but prevents clinical episodes by significantly reducing parasite burden. Naturally acquired immunity to malaria predominantly targets blood-stage parasites and is known to require antibody responses. Despite the key role that antibodies play in protection, the antigenic targets of immunity are not completely defined.
The aim of this study was to investigate associations between antibody responses and protection against clinical malaria from a field study conducted in Timika to identify targets of naturally acquired immunity to malaria. Naturally acquired immunity to seven Plasmodium falciparum and one Plasmodium vivax merozoite-stage vaccine candidate antigens were analysed by ELISA, parasite growth inhibition functional assays and ELISPOT. The main findings revealed that high antibody responses to P. falciparum reticulocyte-binding protein-like homologue 5 (PfRh5) and P. falciparum Rh5 interacting protein (PfRipr) predict protection from symptomatic malaria. Furthermore, malaria-exposed healthy controls and asymptomatic individuals have PfRh5-specific memory B cells. On the other hand, high antibody levels to P. falciparum erythrocyte antigen 140 (PfEBA140) Region III-V, P. falciparum reticulocyte binding protein-like homologue 4 (PfRh4), as well as P. vivax duffy binding protein (PvDBP) were associated with high parasitemia. It suggests that those antigens could be used as a serological marker for recent exposure. Together, these findings highlight that PfRh5 and PfRipr are important targets of naturally acquired immunity to malaria and promising vaccine candidates.
Seroprevalence and risk factors of hepatitis B and C virus infections in female workers of Lao garment factories
Kinnaly Xaydalasouk1,2, Michel Strobel1, Yves Buisson1 , Claude. P. Muller2,3, Antony P.Black2
1Institut de la Francophonie pour la Médecine Tropicale, Vientiane, Lao PDR, 2Lao-Lux Laboratory, Institute Pasteur du Laos, Ministry of Health, Vientiane, Lao PDR, 3Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Grand-Duchy of Luxembourg
Contact - Kinnaly Xaydalasouk : [email protected] Introduction: Hepatitis B and C virus (HBV and HCV) infections are indicative of sexual risk behaviors or intravenous drug abuse. It is expected that the prevalence of such infections is higher in vulnerable populations. Female workers employed in garment factories in Lao People’s Democratic Republic (PDR) could constitute a population at risk. These young women often come from remote areas, have a low level of education, can be subject to human and sex trafficking, and find themselves in difficult working conditions, away from the protective environment of their family and community. Such risks in this population have never been studied in Lao PDR. The objective of this study was to investigate the prevalence of HBV and HCV infections and associated risk factors in women working in Lao garment factories.
Methods: A cross-sectional study was performed on 400 female workers in garment factories in Vientiane capital. Women were tested for HBV surface antigen (HBsAg) and for specific antibodies anti-HBc, anti-HBs and anti-HCV with commercial ELISA. These data were supplemented by a standardized questionnaire on knowledge, attitude and practices regarding the risk for both infections.
Results: Sixteen women (4%) were HBsAg carriers, 7 (1.7%) had anti-HCV antibodies, 187 (46.7%) had anti- HBc antibodies and 116 (29%) had anti-HBs antibodies. Three factors were significantly associated with anti-HBc positivity: (i) residence in dormitories, (ii) more than one sexual partner, (iii) a history of abortion.
Conclusion: The prevalence of chronic HBV infection among female workers in the factories was at an intermediate/high level and exposure (anti-HBc antibody prevalence) was high. However, the prevalence of HCV infection was low. HBV and HCV infections were linked to factors over which it is possible to act by public health actions such as targeted information, promotion of condom use, reduction in sexual partners and especially vaccination against hepatitis B and monthly gynecological checkups.
Key words: Hepatitis B virus, Hepatitis C virus, Risk factors, Laos PDR, Garment factory
Seroprevalence of hepatitis A virus (HAV) and risk factors in XiengKhouang Province, Lao People’s Democratic Republic
Xaipasong XAIYAPHET1, Vilaysone KHOUNVISITH2, Phetsavanh CHANTHAVILAY1, Phonethipsavanh NOUANTHONG2, Bounta VONGPRACHANH2, Daniel REINHARZ1, Claude P. MULLER3, Antony P. BLACK2. 1Institute de la Francophonie pour la Medecine Tropicale, Vientiane, Lao PDR, 2Lao-Lux-Laboratory, Institut Pasteur du Laos, Vientiane, Lao PDR, 3Infectious Diseases Research Unit, Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg
Contact - Vilaysone KHOUNVISITH : [email protected]
Introduction: Hepatitis A virus (HAV) is a global public health problem that particularly affects underdeveloped countries. HAV emerges sporadically and is widespread globally, with approximately 102 million infections annually (symptomatic and asymptomatic). The outbreak is strongly related to sanitation and hygiene. Although several outbreaks of the disease have been recorded, little is known about the disease in Lao PDR. The prevalence of HAV in Lao PDR has not been reported. This study aimed to assess anti-HAV IgG seroprevalence and risk factors of Hepatitis A virus infection in people in Xieng Khouang Province, where a recent outbreak occurred in 2015.
Methods: A cross-sectional study was performed between March and June 2017 to detect anti-HAV IgG antibodies in a total of 400 participants aged 5 to 76 years old in 2 districts of Xieng Khouang Province. The seroprevalence of anti-HAV IgG was investigated by ELISA at the Institut Pasteur du Laos. HAV risk factors were assessed using a standardized questionnaire.
Results: Overall, anti-HAV IgG sero-positivity was detected in 249 (62.25%) of the samples. The lowest seroprevalence (24%) was in the youngest group of 5-10 years old and the highest seroprevalence (98%) in the age group more than 40 years old. There was a significant increase in seroprevalence with age. Regression models showed the main associated factors with anti-HAV positivity were: a non Tai-Lao ethnic group, eating snails, unsafe water sources and shared items and age.
Conclusions: This study found significant early exposure to HAV in children and an increase in seroprevalence with age, reflecting continuing exposure to risk factors. Risk factors varied according to age and ethnicity. Consumption of cooked foods and good hygiene practices should be encouraged from a young age, for example by awareness campaigns. Improved sanitation and access to clean water should be prioritized.
Keywords: Hepatitis A infection, risk factor, XiengKhouang province, Lao PDR