Clinical and molecular surveillance of drug resistant vivax malaria in Myanmar (2009-2016)

Abstract

Background: 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.

Methods: To 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.

Results: Clinical 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.

Conclusions: Although 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.

Keywords: Drug resistance; Malaria; Molecular surveillance; Myanmar; Plasmodium vivax.

Fig. 1

Retrospective and prospective analysis of the clinical surveillance of drug resistance in vivax malaria in Myanmar (2009–2016). Retrospective analysis was conducted in 906 vivax infected cases in nine sentinel sites. Prospective study with molecular surveillance was conducted in Buthidaung (western Myanmar in 2015), Shwegyin (central Myanmar in 2014) and Kawthaung (southern Myanmar in 2015–2016). Clinical failure cases were found only at southern and western Myanmar

Fig. 2

Molecular marker analysis of drug resistance in vivax malaria in three sentinel sites in Myanmar (2014–2016). A total of 208 from three sentinel sites were included for molecular marker analysis. K10 (AAG) insert of pvcrt-O gene, and mutations of pvmdr1, pvdhps and pvdhfr were shown. Among three sites, the prevalence of all markers except F1076L of pvmdr1 were fewest in Buthidaung site