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.

Stable high frequencies of sulfadoxine–pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine–pyrimethamine in Ujjain, Madhya Pradesh, India

“…Similar to findings in western Madhya Pradesh and Southwestern India but unlike findings in Northeastern India and West Bengal there were no mutations in the kelch- 13 propeller domain suggesting that parasites remained artemisinin susceptible at the study site [2,29,32,33]. ASP efficacy was 99.6% in the Madhya Pradesh study and 84% in the West Bengal study [2,29].…”

Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India

“…Similar to ndings in western Madhya Pradesh and Southwestern India but unlike ndings in Norteastern India and West Bengal there were no mutations in the kelch-13 propeller domain suggesting that parasites remained artemisinin susceptible at the study site [2,29,32,33]. ASP e cacy was 99.6% in the Madya Pradesh study and 84% in the West Bengal study [2,29].…”

Stable high frequencies of sulfadoxine-pyrimethamine resistance associated mutations and absence of K13 mutations in Plasmodium falciparum 3 and 4 years after the introduction of artesunate plus sulfadoxine-pyrimethamine in Ujjain, Madhya Pradesh, India

“…The 82% frequency of pfdhfr 59R108N plus pfdhps 436F and the 11% frequency pfdhfr 59R108N plus pfdhps 436F437G thus suggests that the parasites are at least SP tolerant verging on resistant at our site. In line with these data, triple mutation pfdhfr 59R108N + pfdhps 437G have been associated with SP treatment failure in India[31].Similar to findings in western Madhya Pradesh and Southwestern India but unlike findings inNorteastern India and West Bengal there were no mutations in the Kelch-13 propeller domain suggesting that parasites remained artemisinin susceptible at our site [2,29,32,33]. ASP efficacy was 99.6% in the Madya Pradesh study and 84% in the West Bengal study[2,29].…”