Frequencies of molecular markers of drug resistance in the context of two different Seasonal Malaria Chemoprevention (SMC) treatment regimens in the Koulikoro health district, Mali

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ABSTRACT With growing concern about parasite resistance to sulfadoxine-pyrimethamine (SP) in West Africa, the effectiveness of dihydroartemisinin-piperaquine (DHA + PQ) was assessed as an alternative drug regimen for Seasonal Malaria Chemoprevention (SMC). This study aims to determine the prevalence of molecular markers of resistance to SP + AQ and DHA + PQ in Koulikoro (Mali), where SMC has been implemented since 2014. Plasmodium falciparum -positive samples were analyzed by either next-generation sequencing, focusing on SNPs in genes known to be associated with resistance: Pfmdr1, PfK13, Pfcrt, Pfdhfr, Pfdhps, and Pfexo genes, and using qPCR for copy number variations (CNVs) of Pfmdr1 and Pfplasmepsin2 . A total of 564 PCR-positive P. falciparum samples were analyzed: 218 in 2019 and 346 in 2020. In both years, the Pfdhfr 51I-59R-108N haplotype was highly prevalent (>93%). In both arms, the Pfdhps single mutant ( 437G ) was the most prevalent (~60%). In 2020, the combined haplotype Pfdhfr/Pfdhps IRN/ IA G KA S and IRN/V A G K GS was detected at 9.6% and 1.2%, respectively. The Pfmdr1 haplotype (N86- F184 -S1034-N1042-D1246) represented more than 52.0%, and no difference was observed between the years, while a significant increase in the Pfcrt wild-type haplotype (C72-V73-M74-N75-K76) from 39% in 2019 to 52% in 2020 ( P = 0.01) was observed. Some PfK13 non-synonymous mutations were observed in both years, including Y 493H and C 580R . The identification of the IRN I / IA G KA S quintuple mutant, along with emerging Pfdhps -431V and non-synonymous PfK13- Y493H variants, underscores the importance of continued surveillance of resistance markers.

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