Genetic profiling of sulfadoxine-pyrimethamine resistance markers in Indian Plasmodium falciparum field isolates.

AIMS: Sulfadoxine-pyrimethamine (SP) is widely used as a partner drug in artemisinin combination therapy for Plasmodium falciparum malaria in India, except in the North-Eastern states. Drug resistance arises through mutations in Pfdhfr and Pfdhps, compromising treatment efficacy. The study investigated geographic distribution, temporal trends and molecular evolution of SP resistance markers in P. falciparum field isolates across India over three decades.

MATERIALS &

METHODS

A total of 307 isolates were collected across 14 states between 1993 and 2023, with successful sequencing of 243 Pfdhfr and 241 Pfdhps isolates. Mutations and haplotypes were characterized by Sanger sequencing, followed by phylogenetic, haplotype network, genetic diversity and selection analyses.

RESULTS

The most frequent Pfdhfr mutations were S108N (77.8%) and C59R (61.7%), while Pfdhps showed predominance of A437G (31.9%) and K540E/N (4.98%). Combined haplotype analysis revealed that 83% of isolates carried resistant alleles, with double and triple mutants predominating. Codon based analysis showed weak positive selection at Pfdhfr 51 and Pfdhps 436, 540 codons.

CONCLUSION

SP resistance is widespread across India with strong regional differences. The gradual rise of higher-order mutants, especially from the North-East regions raises concern for India's 2030 malaria elimination target. Thus, continuous molecular surveillance remains essential for guiding treatment policy.