Regional Patterns and Temporal Trends of Pfdhfr and Pfdhps Markers of Antifolate Resistance in Plasmodium falciparum in East and West Africa, 2010–2025: A Systematic Review.

Abstract

Sulfadoxine–pyrimethamine (SP) remains central to malaria chemoprevention through intermittent preventive treatment in pregnancy, intermittent preventive treatment in infancy, and seasonal malaria chemoprevention, despite widespread resistance in Plasmodium falciparum. This systematic review compared regional patterns and temporal trends of Pfdhfr and Pfdhps mutations and haplotypes associated with SP resistance in East and West Africa. Following PRISMA 2020, PubMed, Web of Science, Google Scholar, and Europe PMC were searched for studies published between January 2010 and December 2025 reporting molecular SP resistance markers in field isolates from either region. Ninety-five studies met the inclusion criteria, representing nine East African and sixteen West African countries. East Africa showed very high prevalence of Pfdhfr N51I, C59R, and S108N, together with high prevalence of Pfdhps A437G and K540E, frequent quintuple haplotypes, and detectable A581G. In West Africa, the Pfdhfr triple-mutant background was also common, but K540E remained low and the canonical quintuple haplotype was rare. West Africa instead showed greater representation of alternative dhps-associated variants, including codon 431, 436, and 613 backgrounds. Temporal analyses showed persistently high prevalence of the major markers across East African intervals, whereas in West Africa Pfdhfr mutations and A437G remained moderate to high over time but K540E stayed low. These findings show marked regional heterogeneity in the genetic architecture of SP resistance and support region-specific molecular surveillance to inform malaria chemoprevention policy.