Emergence of Plasmodium falciparum pfdhps A581G mutation in Southern Senegal under Seasonal Malaria Chemoprevention pressure, 2020-2023

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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 the Plasmodium falciparum mutations in pfdhfr and pfdhps genes. 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. 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. 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. Malaria remains a major health challenge in Africa. As a preventive measure, children in Senegal receive medication during the rainy season, specifically sulfadoxine–pyrimethamine and amodiaquine, which inhibit the growth of malaria parasites. We investigated whether the parasite has become less sensitive to these medicines over time. Analysing malaria samples collected between 2020 and 2023 in southern Senegal, we identified several genetic changes that reduce the parasite’s susceptibility to these drugs. One notable mutation, A581G, appeared for the first time and increased in frequency over time. Although current treatments remain effective, this trend underscores the importance of regular monitoring and proactive planning to maintain the effectiveness of malaria prevention strategies. Diallo et al. analyse malaria parasite samples from southern Senegal between 2020 and 2023 to monitor genetic markers of drug resistance. A581G emerges and exceeds 10%, indicating potential signs of drug selection pressure under seasonal malaria chemoprevention.

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