Single Nucleotide Polymorphism Analysis of Pvmdr-1 in Plasmodium Vivax Isolated From Military Personnel of Republic of Korea in 2016 and 2017
Abstract Background: Malaria chemoprophylaxis using chloroquine and primaquine has been administered to resident soldiers in the 3rd Army of Republic of Korea (ROK) to prevent malaria infection since the year 1997. Due to mass chemoprophylaxis against malaria, concern exists about occurrence of chloroquine resistance. Herein, we investigated the single nucleotide polymorphisms (SNPs) of the Plasmodium vivax multi-drug resistance protein-1 (Pvmdr-1) gene to monitor the risk of chloroquine resistance.Methods: To evaluate the risk of malaria chemoprophylaxis, SNPs of the Pvmdr-1 gene were analysed in 73 soldiers of the 3rd Army of ROK diagnosed with infection by Plasmodium vivax. Results: Quintuple mutations (G698S, L845F, M908L, T958M, and F1076L) were detected in 73 soldiers. Mutation in the Y541C position was detected in soldiers at a frequency of 1.3% (1/73). In addition, silent mutations were detected at positions 44K, 493L, 529T, and 1233E. Based on these SNPs, Pvmdr-1 sequences of ROK were classified into 6 haplotypes. Phylogenetic analysis showed that the neighbourhood of the 6 haplotypes were Chaina_NB-16 and Papua New Guinea-PNG58 (Figure 1).Conclusions: Genetic- or phenotypic-based chloroquine resistance was not observed. However, various SNPs including a newly identified non-synonymous mutation (Y541C) have been introduced into Plasmodium vivax malaria endemic areas in ROK. Thus, to prevent the emergence of chloroquine resistance, continuous surveillance for SNPs of Pvmdr-1 related with chloroquine resistance is essential in the malaria chemoprophylaxis-executed regions of ROK.