Characterising recent antimalarial resistance in West Africa: Insights from amplicon sequencing of 17,384 Plasmodium falciparum infection samples

Background Plasmodium falciparum ( P. falciparum ) infection remains a significant public health threat in West Africa, where chemoprevention and first-line therapies are key interventions against malaria. However, the development and spread of resistance to commonly used antimalarials poses a growing threat to the efficacy of these strategies. Methods This study characterises the recent landscape of antimalarial resistance in West Africa by analysing targeted amplicon sequences from 17,384 P. falciparum infections, sampled predominantly between 2018 and 2023 across eight countries (The Gambia, Senegal, Sierra Leone, Guinea, Mali, Ghana, Nigeria, Cameroon). Prevalence of resistance-associated alleles within genes mdr1 , dhfr, crt, dhps, kelch13 was estimated by aggregating samples at country and country-year level. Results Across countries, the prevalence of the pyrimethamine resistance–associated dhfr triple mutant allele (51I/59R/108N) exceeded 80%, while its combination with the sulfadoxine resistance–associated dhps 437G exceeded 60% of infections. Unlike the parasite genotypes in East Africa, the prevalence of the dhps 540E mutant was low (1.5%), whereas dhps 436A was common (43.8%). The chloroquine resistance marker crt 76T showed greatest geographic heterogeneity, ranging from low prevalence in Ghana (1.3%) to very common in The Gambia (64.9%). Non-synonymous mutants of kelch13 were uncommon, most with unknown relevance to artemisinin resistance and observed for the first time in Africa. However, mutants that are artemisinin resistance-associated elsewhere were detected in three infection samples from Ghana (574L, 561H, 469Y), and one in Cameroon (538V). Conclusion This large-scale genomic surveillance of P. falciparum infections highlights the need for ongoing monitoring of drug resistance and for data integration throughout the region.