Therapeutic efficacy and pfkelch13 molecular surveillance of artemether–lumefantrine for uncomplicated Plasmodium falciparum malaria in Mauritania: first national evaluation in two sentinel sites

Routine monitoring of antimalarial drug efficacy is essential to guide national malaria treatment policies and ensure the continued effectiveness of first- and second-line therapies. Artemisinin-based combination therapies (ACTs) have been recommended in Mauritania since 2006. Artemether–lumefantrine (AL) is currently used as second-line treatment for uncomplicated Plasmodium falciparum malaria. This study assessed the therapeutic efficacy of AL and investigated P. falciparum kelch13 ( pfk13 ) polymorphism associated with artemisinin partial resistance. A prospective single-arm, therapeutic efficacy study was conducted between August and October 2023 in two sentinel sites in southeastern Mauritania (Kobeni and Timbedra). Patients aged ≥ 6 months with uncomplicated P. falciparum mono-infection were enrolled and treated with a standard six-dose regimen of AL over three days. Patients were followed for 28 days, in accordance with WHO 2009 guidelines. Treatment outcomes were classified as early treatment failure, late clinical failure, late parasitological failure, or adequate clinical and parasitological response (ACPR). PCR genotyping was performed to distinguish recrudescence from reinfection. Day 0 samples were analysed for mutations in the pfk13 propeller-encoding domain. A total of 132 patients were enrolled, of whom 121 completed the 28-day follow-up. Two recurrent infections were detected in Kobeni and were confirmed as recrudescence by molecular genotyping. The PCR-corrected ACPR was 96.6% in Kobeni and 100% in Timbedra. All patients cleared parasitaemia by Day 3. Among 112 successfully sequenced isolates, no WHO-validated pfk13 mutations associated with artemisinin partial resistance were identified. Only one isolate carried a non-synonymous mutation S522N, which has not been associated with reduced artemisinin susceptibility. This first national evaluation of AL in Mauritania demonstrates that the drug combination remains highly effective for the treatment of uncomplicated P. falciparum malaria. The complete parasite clearance observed by Day 3 and the absence of validated pfk13 resistance-associated mutations provide convergent clinical and molecular evidence that artemisinin partial resistance has not yet emerged in the study areas. Continued therapeutic effectiveness supports malaria control efforts.