Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow

Malaria Journal

Research

Khin Myo Aye¹  Myat Phone Kyaw¹  Myo Win Htun¹  Nan Cho Nwe Mon¹  Chan Myae Hlaing¹  Hidayat Trimarsanto²  Pascal Ringwald³  Kamala Thriemer⁴  Irene Handayuni⁴  Sarah Auburn⁴  Ric N. Price⁵  Dorina Bustos⁶ 

[1] Department of Medical Research, 11191, Yangon, Myanmar;Eijkman Institute for Molecular Biology, Jl. Diponegoro 69, 10430, Central Jakarta, Indonesia;The Ministry of Research and Technology (RISTEK), Jakarta, Indonesia;Agency for Assessment and Application of Technology, Jl. MH Thamrin 8, 10340, Jakarta, Indonesia;Global Malaria Programme, World Health Organization, 20 Avenue Appia, 1211, Geneva, 27, Switzerland;Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, 0810, Darwin, NT, Australia;Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, 0810, Darwin, NT, Australia;Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford Old Road Campus, Oxford, UK;World Health Organization, Country Office for Thailand, Ministry of Public Health, Nonthaburi, Thailand;

关键词: Malaria;    Plasmodium;    Vivax;    Chloroquine;    Efficacy;    Resistance;    Genotyping;    Diversity;    Transmission;    pvmdr1;    Copy number;    Myanmar;   

DOI  :  10.1186/s12936-017-1912-y

 received in 2017-04-13, accepted in 2017-06-26,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPlasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts.MethodsPatients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and microsatellite diversity were assessed on samples from the patients enrolled in the clinical study and additional cross-sectional surveys undertaken in Myawaddy and Shwegyin in 2012.ResultsA total of 85 patients were enrolled in the CQ clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy (1.2%) had an early treatment failure and two patients (2.3%) in Kawthoung presented with late treatment failures on day 28. The day 28 efficacy was 92.0% (95% CI 71.6–97.9) in Myawaddy and 98.3% (95% CI 88.7–99.8) in Kawthoung. By day 2, 92.2% (23/25) in Myawaddy and 85.0% (51/60) in Kawthoung were aparasitaemic. Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification was observed in 3.2% (1/31) of isolates in Myawaddy, 0% (0/49) in Kawthoung and 2.5% (1/40) in Shwegyin. Diversity was high in all sites (HE 0.855–0.876), with low inter-population differentiation (FST 0.016–0.026, P < 0.05).ConclusionsTreatment failures after chloroquine were observed following chloroquine monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin. The results emphasize the importance of ongoing P. vivax drug resistance surveillance in Myanmar, particularly given the potential connectivity between parasite population at different sites.

【 授权许可】

CC BY   
© The Author(s) 2017