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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1770-7) contains supplementary material, which is available to authorized users.

Molecular Detection of Antimalarial Drug Resistance in Plasmodium vivax from Returned Travellers to NSW, Australia during 2008–2018

“…The increased rate of these mutations suggests that chloroquine resistance in P. vivax will become more common in the South Asia region where chloroquine has remained the first-line drug [39]. Our findings from clinical isolates from Southeast Asia were also similar to other studies in this location [5][6][7]16,40]. A clinical report of chloroquine-resistant P. vivax in a Thai pregnant woman indicated that recurrent parasites during Day 21 and 143 carried the double F976:L1076 mutation [40].…”

“…This double mutation was found in Thailand in 2008 (49.2%) and again in 2014 (18.4%) [7]. The same double mutations were found in 15.4% of samples in Myanmar between 2009 and 2016 [5]. This could indicate that chloroquine-resistant P. vivax is not only present in Thailand but also in neighbouring Myanmar.…”

“…Unlike other well-described mutations in the Pvmdr1 gene, the role of the K10 insertion in Pvcrt-o in chloroquine resistance in P. vivax is unclear because this mutation is present in some studies and absent in others [3,5,7,16,34,41]. In Thailand, the K10 insertion was found in 2008 [16], but was not detected again until recently [7,42].…”

“…Molecular markers of chloroquine resistance in P. vivax, Pvmdr1 and Pvcrt-o genes were used as they are orthologous to Pfmdr1 and Pfcrt genes, which are associated with chloroquine resistance in P. falciparum [6]. Among the studied samples herein, the presence of the F976 and L1076 mutations in the Pvmdr1 gene and the K10 insertion in the Pvcrt-o gene were shown previously to be related to chloroquine resistance in P. vivax by in vivo and in vitro studies [5,7,16,28,29].…”

“…Plasmodium falciparum remains the predominant malaria species, but P. vivax has become the major cause of human malaria in endemic regions outside of Africa, such as Asia, Central and South America and Oceania. Globally, it is estimated that there are between 80 million and up to 400 million vivax malaria cases each year [3][4][5]. Although malaria control and elimination programs are promoted in these countries, these programs are being hindered by the emergence of drug-resistant strains of P. vivax.…”