Emergence of Plasmodium falciparum pfdhps A581G mutation in Southern Senegal under Seasonal Malaria Chemoprevention pressure

Background: Malaria prevention in Senegal includes the use of Seasonal Malaria Chemoprevention with sulfadoxine-pyrimethamine plus amodiaquine. Prolonged use of sulfadoxine-pyrimethamine, however, can select for mutations in thePlasmodium falciparum mutations in pfdhfr and pfdhps genes. Methods: We analyse dried-blood-spot samples collected during therapeutic-efficacy studies in two SMC districts (Kolda, Kédougou) between 2020 and 2023. Using targeted amplicon deep sequencing we determine the prevalence of pfdhfr and pfdhps mutations by year and site. Results: The pfdhfr triple mutant genotype (N51I + C59R + S108N) is near-fixed in the parasite population (> 90 %). The pfdhps A437G mutation is also common (47–100 %). The K540E mutation is absent in 2020 and appears only sporadically thereafter—14 % of Kédougou isolates in 2021 (1/7), 5.4 % in Kolda and 2.1 % in Kédougou in 2022, and < 2 % in both sites in 2023. The A581G mutation emerges in 2022 (8.1 % in Kolda) and rises to 14.9 % in Kolda and 6.5 % in Kédougou by 2023. Mutation frequencies are similar in children = 5 years and 6–10 years. Conclusions: After a decade of seasonal chemoprevention, P. falciparum in southern Senegal carries multiple genetic markers associated with resistance to sulfadoxine–pyrimethamine, including a recent increase in the pfdhps A581G mutation to over 10 %. Although the sulfadoxine–pyrimethamine plus amodiaquine regimen remains clinically effective, the growing frequency of pfdhps A581G mutation warrants close monitoring.