Rapid increase of A581G mutation in Southern Senegal under seasonal malaria chemoprevention pressure

Seasonal malaria chemoprevention (SMC) with sulfadoxine–pyrimethamine (SP) plus amodiaquine (AQ) has reduced malaria incidence among children in many African countries, including Senegal. However, prolonged SP usage can promote the selection of drug-resistant parasites. Here, we investigated P. falciparum molecular resistance markers in two regions of southern Senegal (Kolda and Kedougou) from 2020 to 2023. The pf dhfr triple-mutant alleles (N51I, C59R, S108N) were nearly fixed throughout, confirming widespread pyrimethamine resistance. Critically, the pf dhps A581G mutation, undetected in 2020–2021, emerged at 8.1% in Kolda in 2022 and rose to 15% by 2023, while appearing at 6.5% in Kedougou in 2023. The pf dhps A437G mutation likewise remained prevalent, and K540E was sporadically detected. The rising frequency of A581G, known to confer high-level SP resistance, presents a significant threat to SMC efficacy. Enhanced molecular surveillance and adaptive policies are crucial to prevent the erosion of SMC’s protective effect in these high-burden settings.