Prevalence of molecular markers of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from West Africa during 2012-2022

Abstract

Sulfadoxine-pyrimethamine (SP) is a key drug recommended by the World Health Organization for the chemoprevention of malaria. However, the strategy is affected by the parasite resistance to SP. This study evaluated Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, associated with SP resistance, from 508 P. falciparum isolates imported from West African countries to Henan Province, China, during 2012-2022. High mutant prevalence of the genes Pfdhfr (94.7%) and Pfdhps (96.8%) was observed. The mutants Pfdhfr N51I, C59R, S108N, and Pfdhps A437G were at high frequency in all countries analyzed. The overall prevalence of the mutant Pfdhps K540E was low (3.4%), but with a high frequency in Liberia (24.3%). The frequency of mutants Pfdhps I431V, A581G, and A613S was 11.7%, 9.8%, and 16.2%, respectively, all of which had the highest mutant prevalence in Nigeria. The mutant Pfdhps A581G and A613S were identified in the absence of K540E. The partially resistant haplotype (I₅₁R₅₉N₁₀₈ - G₄₃₇) was the most common (72.6%), and the fully resistant haplotype (I₅₁R₅₉N₁₀₈ - G₄₃₇E₅₄₀) had a low prevalence of 3.4% and mainly occurred in Liberia. No super resistant haplotype was identified. The mutant Pfdhps I431V and the octuple mutant haplotype I₅₁R₅₉N₁₀₈ - V₄₃₁A₄₃₆G₄₃₇G₅₈₁S₆₁₃ deserve more attention. In areas of high SP resistance, the intervention still reduces low birthweight and maternal anaemia. SP should continue to be used in areas of high SP resistance until more effective alternatives for malaria chemoprevention are found. It is important to continuously monitor the molecular markers associated with SP resistance to better implement intermittent preventive treatment policies in pregnancy (IPTp) and infants (IPTi).

Fig. 1

Prevalence of alleles and haplotypes in Pfdhfr (A) and Pfdhps (B) genes detected in Plasmodium falciparum isolates from West African countries during 2012–2022.