Molecular surveillance of antimalarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India: A decade after CQ withdrawal

Abstract BACKGROUND: India has targeted to eliminate malaria by 2030. Surveillance of drug-resistant malaria parasites in different endemic settings country is a pressing need to achieve the target in the face of emerging drug resistance. In Odisha, the highest contributor of malaria cases to the national pool has changed the drug policy in 2009 following increasing of failure rate of treatment with chloroquine (CQ). The aim of this study was to determine the prevalence of Plasmodium falciparum molecular markers that are associated with resistance to CQ, S-P, and ART in Odisha 10 years after the institution of the new policy. METHODS: The study was conducted from July 2018 to November 2020 among the patients attending Government Health facilities, selected randomly in four different physiographical regions of the state. The prevalence of critical point mutations in the genes of Pfcrt (codon 76), Pfmdr1(codon 86), Pfdhfr (codons, 16, 50, 51, 59, 108, and 164), Pfdhps (codons 436, 437, 540, 581, and 613) and PfK13 gene were examined in parasite isolates. RESULTS: The prevalence of Pfcrt (K76T) was 2.1% and Pfmdr1 (N86Y) 3.4%. None of the five mutations in the Pfkelch13 gene associated with resistance to artemisininwas detected. The overall prevalence of Pfdhfr mutations was 50.4% with a total number of 12 genotypes. The Pfdhfr C59R mutation was the most common (41.8%), followed by the C50R mutation (40.8%) and S108N mutation (39.2%). The overall prevalence of Pfdhps mutations was 40.1% with a total number of 26 genotypes. The maximum number of mutations was found at codon S436A (26.7%) followed by A613S (17.6%) and K540E(17.2%). No isolate with Pfdhfr triple mutation (N51I/ C59R/S108N) combined with Pfdhps double mutation (A437G/K540E) was found in the studied sample. CONCLUSION: These results predict the return of susceptibility of P. falciparum to CQ ten years after the change of malaria treatment policy, while confirming the emergence of parasite resistance to S-P in the state of Odisha. Additional surveillance in the same region and other malaria-endemic parts of the country may help to provide evidence for drug policy updates.