AUTHOR=Zeng Weilin , Zhao Hui , Zhao Wei , Yang Qi , Li Xinxin , Li Xiaosong , Duan Mengxi , Wang Xun , Li Cuiying , Xiang Zheng , Chen Xi , Cui Liwang , Yang Zhaoqing 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 11 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.738075

DOI=10.3389/fcimb.2021.738075

ISSN=2235-2988

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