Molecular Surveillance and Ex Vivo Drug Susceptibilities of Plasmodium vivax Isolates From the China–Myanmar Border

Abstract

Drug resistance in <i>Plasmodium vivax</i> may pose a challenge to malaria elimination. Previous studies have found that <i>P. vivax</i> has a decreased sensitivity to antimalarial drugs in some areas of the Greater Mekong Sub-region. This study aims to investigate the <i>ex vivo</i> drug susceptibilities of <i>P</i>. <i>vivax</i> isolates from the China-Myanmar border and genetic variations of resistance-related genes. A total of 46 P. <i>vivax</i> clinical isolates were assessed for <i>ex vivo</i> susceptibility to seven antimalarial drugs using the schizont maturation assay. The medians of IC₅₀ (half-maximum inhibitory concentrations) for chloroquine, artesunate, and dihydroartemisinin from 46 parasite isolates were 96.48, 1.95, and 1.63 nM, respectively, while the medians of IC₅₀ values for piperaquine, pyronaridine, mefloquine, and quinine from 39 parasite isolates were 19.60, 15.53, 16.38, and 26.04 nM, respectively. Sequence polymorphisms in <i>pvmdr1</i> (<i>P</i>. <i>vivax</i> multidrug resistance-1), <i>pvmrp1</i> (<i>P</i>. <i>vivax</i> multidrug resistance protein 1), <i>pvdhfr</i> (<i>P</i>. <i>vivax</i> dihydrofolate reductase), and <i>pvdhps</i> (<i>P</i>. <i>vivax</i> dihydropteroate synthase) were determined by PCR and sequencing. <i>Pvmdr1</i> had 13 non-synonymous substitutions, of which, T908S and T958M were fixed, G698S (97.8%) and F1076L (93.5%) were highly prevalent, and other substitutions had relatively low prevalences. <i>Pvmrp1</i> had three non-synonymous substitutions, with Y1393D being fixed, G1419A approaching fixation (97.8%), and V1478I being rare (2.2%). Several <i>pvdhfr</i> and <i>pvdhps</i> mutations were relatively frequent in the studied parasite population. The <i>pvmdr1</i> G698S substitution was associated with a reduced sensitivity to chloroquine, artesunate, and dihydroartemisinin. This study suggests the possible emergence of <i>P</i>. <i>vivax</i> isolates resistant to certain antimalarial drugs at the China-Myanmar border, which demands continuous surveillance for drug resistance.