Molecular Evidence for Plasmodium falciparum Resistance to Sulfadoxine-Pyrimethamine but Absence of K13 Mutations in Mangaluru, Southwestern India

Abstract

In most of India, sulfadoxine-pyrimethamine (SP) plus artesunate serves as first-line treatment for uncomplicated falciparum malaria. In 112 clinical Plasmodium falciparum isolates from Mangaluru, southwestern India, we sequenced molecular markers associated with resistance to SP, lumefantrine, and artemisinin (pfdhfr, pfdhps, pfmdr1, and K13). The pfdhfr double mutation 59R-108N combined with the dhps 437G mutation occurred in 39.3% and the pfdhfr double mutation plus the pfdhps double mutation 437G-540E in additional 24.1%. As for pfmdr1, the allele combination N86-184F-D1246 dominated (98.2%). K13 variants were absent. No evidence for artemisinin resistance was seen. However, the antifolate resistance alleles compromise the current first-line antimalarial sulfadoxine-pyrimethamine plus artesunate, which may facilitate the emergence of artemisinin resistance. Artemether-lumefantrine, introduced in northeastern parts of the country, in the study area faces the predominant pfmdr1 NFD genotype, known to impair lumefantrine efficacy. Further monitoring of resistance alleles and treatment trials on alternative artemisinin-based combination therapies are required.