Analysis of drug resistance marker genes of after implementation of artemisinin-based combination therapy in Pune district, India.

The global emergence and spread of malaria parasites resistant to antimalarial drugs is a major problem in malaria control and elimination. In this study, samples from Pune district were characterized to determine prevalence of molecular markers of resistance to chloroquine ( codons C72S, M74I, N75E, K76T and -1 N86Y, Y184F), pyrimethamine ( C50R, N51I, C59R, S108N), sulfadoxine (, S436A, A437G, K540E, A581G), and artemisinin (, C580Y, R539T). The K76T mutation was found in 78% samples as CVMNT, SVMNT and CVIET haplotype. The N86Y and Y184F mutations were found in 54% of samples. The double mutation C59R + S108N was present in 67% of samples, while the triple mutation (N51I + C59R + S108N) was not detected. The mutations A437G and K540E were found in 67% of samples. Single mutants of were rare, with K540E detected in only 6 patient samples. Similarly, A581G was found in 13 of the isolates. The molecular markers associated with artemisinin resistance (mutations in C580Y, R539T) were not detected in any of the isolates. These results suggest an emerging problem with multidrug-resistant . Though the genotype conventionally associated with artemisinin resistance was not observed, chloroquine-resistant genotype has reached complete fixation in the population. Moreover, the prevalence of mutations in both and , with the presence of the quadruple mutant, indicates that continued monitoring is required to assess whether sulfadoxine-pyrimethamine can be used efficiently as a partner drug for artemisinin for the treatment of .