First Detection of WHO-validated artemisinin resistance Plasmodium falciparum K13 C469Y mutation in patient from Senegal.

Abstract

Artemisinin-based Combination Therapies (ACTs) remain the first-line treatment for uncomplicated Plasmodium falciparum malaria in Senegal. The recent emergence of World Health Organization (WHO)-validated Pfkelch13 (K13) mutations associated with artemisinin partial resistance in Africa highlights the need for continuous molecular surveillance. We conducted a nationwidegenomic surveillance study of 3,800 P. falciparum isolates collected from nine malaria-endemic regions of Senegal during 2023-2024. Mutations in the K13 gene were detected using targeted amplicon deep sequencing, and mutations were independently confirmed by allele-specific quantitative PCR (qPCR). Among all isolates analyzed, a single sample collected in Kafountine, Ziguinchor Region, harbored the WHO-validated K13 C469Y mutation at a allele frequency of approximately 15%, indicating a minority mutant parasite population. Allele-specific qPCR confirmed the presence of the mutant allele, and epidemiologic investigation indicated the patient had no recent travel history outside the study area, suggesting local acquisition. No additional WHO-validated K13 resistance mutations were detected, and the patient recovered completely following treatment with artemether-lumefantrine. To our knowledge, this finding represents the first detection of the WHO-validated K13 C469Y mutation in Senegal. Although identified in a single mixed infection and not associated with clinical evidence of ACT failure, the detection of a validated artemisinin resistance mutation prompts deeper investigation and underscores the importance of integrating molecular surveillance into routine malaria control programs to enable early detection of emerging resistance to support evidence-based public health decision-making.