Mutation patterns in the antimalarial drug resistance markers- pvdhfr, pvdhps, pvmdr1 and pvk12 genes, among Plasmodium vivax isolates from a tertiary care setting in Puducherry

Abstract

Abstract Antimalarial drug efficacy is monitored through various methods in vivo and in vitro. The in vivo methods include therapeutic efficacy studies(TES) which track clinical and parasitological outcomes among patients receiving antimalarial treatment whereas the invitro methods aims at detecting mutations in the drug targets in the parasite which can render the parasite resistant to the drug. This study is aimed at detecting the mutation patterns in the parasite that confer resistance to the common antimalarial agents used in India. A total of 27 Plasmodium vivax isolates collected over a three year period were sequenced to detect mutations in the genes pvmdr1, pvdhfr, pvdhps and pvk12 which serve as the molecular targets to detect resistance to chloroquine, pyrimethamine, sulfadoxine and artemisinin respectively. The study found T958M F1076L double mutants of pvmdr1 in 52%(14/27) isolates, S58R S117N double mutants of pvdhfr in 67% (18/27) isolates, A383G A553G double mutant pvdhps in 59% (16/27) isolates and wild type of pvk12 gene in all the isolates. There was a rise in the double mutants of pvmdr1 and pvdhfr over time. Those cases with double mutant pvmdr1 gene in their isolates were found to have a prolonged hospital stay compared to those without, indicating reduced clinical response to chloroquine.