Abstract
BackgroundOne of the major challenges for control and elimination of malaria is ongoing spread and emergence of drug resistance. While epidemiology and surveillance of the drug resistance in falciparum malaria is being explored globally, there are few studies on drug resistance vivax malaria.MethodsTo assess the spread of drug-resistant vivax malaria in Myanmar, a multisite, prospective, longitudinal study with retrospective analysis of previous therapeutic efficacy studies, was conducted. A total of 906 from nine study sites were included in retrospective analysis and 208 from three study sites in prospective study. Uncomplicated vivax mono-infected patients were recruited and monitored with longitudinal follow-up until day 28 after treatment with chloroquine. Amplification and sequence analysis of molecular markers, such as mutations in pvcrt-O, pvmdr1, pvdhps and pvdhfr, were done in day-0 samples in prospective study.ResultsClinical failure cases were found only in Kawthaung, southern Myanmar and western Myanmar sites within 2009–2016. Chloroquine resistance markers, pvcrt-O ‘AAG’ insertion and pvmdr1 mutation (Y976F) showed higher mutant rate in southern and central Myanmar than western site: 66.7, 72.7 vs 48.3% and 26.7, 17.0 vs 1.7%, respectively. A similar pattern of significantly higher mutant rate of antifolate resistance markers, pvdhps (S382A, K512M, A553G) and pvdhfr (F57L/I, S58R, T61M, S117T/N) were noted.ConclusionsAlthough clinical failure rate was low, widespread distribution of chloroquine and antifolate resistance molecular makers alert to the emergence and spread of drug resistance vivax malaria in Myanmar. Proper strategy and action plan to eliminate and contain the resistant strain strengthened together with clinical and molecular surveillance on drug resistance vivax is recommended.
Highlights
One of the major challenges for control and elimination of malaria is ongoing spread and emergence of drug resistance
Study site and participants The study included the retrospective analysis of previously conducted therapeutic efficacy studies (TES) of chloroquine in uncomplicated vivax malaria in Myanmar and prospective multi-site, longitudinal study by clinical and molecular markers analysis
From 2009 to 2012, TES on vivax malaria was conducted in nine sentinel sites (Fig. 1) which covered most of the malaria-endemic areas in Myanmar
Summary
One of the major challenges for control and elimination of malaria is ongoing spread and emergence of drug resistance. While epidemiology and surveillance of the drug resistance in falciparum malaria is being explored globally, there are few studies on drug resistance vivax malaria. Plasmodium vivax is the most globally widespread malaria parasite, causing significant high public health issues in many countries. World Health Organization (WHO) estimated 13.8 million vivax cases globally in 2015. One of the major challenges to achieve the elimination goal is drug-resistant falciparum and vivax infection. Drug-resistant vivax is difficult to detect, confirm and monitor because of the nature of vivax malaria, such as the presence of hypnotize stage, low level parasitaemia, asymptomatic carriers, and lack of long-term in vitro testing [2, 3].
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