Molecular Markers of Antimalarial Drug Resistance in Plasmodium falciparum From Kumasi, Ghana, 2023.

OBJECTIVES: Artemisinin partial resistance has emerged in East Africa and is feared to spread across the continent, potentially compromising artemisinin-based combination treatment. Molecular markers can serve as early warning signals for the development of specific drug resistance. We aimed at updating information on relevant resistance markers among Plasmodium falciparum from Kumasi, Ghana, collected in 2023. METHODS: P. falciparum isolates were obtained from 200 patients with falciparum malaria. Mutations in pfk13 (propeller domain), pfcoronin (P76S), pfmdr1 (N86Y, Y184F, Y1246D) and pfaat1 (S258L) were genotyped. A subset of patients was microscopically examined for the presence of asexual malaria parasites on day-3 of treatment with artemether-lumefantrine. RESULTS: 2.2% of isolates exhibited non-synonymous pfk13 mutations including the candidate artemisinin partial resistance marker P527H in addition to S522C, C532S and I590V. Pfcoronin P76S, previously associated with artemether-lumefantrine failure in malaria imported from Africa, was present in 29.7% and associated with a lower parasite density. The predominance of the pfmdr1 pattern N86-184F-D1246 (NFD) suggested impaired sensitivity to lumefantrine. Pfaat1 S258L was common at 64.7%. The resistance markers were not associated with each other, and they were not linked with day-3 parasite positivity. CONCLUSIONS: While the efficacy of artemisinin-based combination treatment in Ghana is still high, isolated critical pfk13 polymorphisms were identified as well as a considerable prevalence of a potentially relevant pfcoronin marker, against a background of pfmdr1 signals for impaired lumefantrine sensitivity. Continuous molecular monitoring is necessary to detect threats to artemisinin-based combination treatment efficacy at an early stage.