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

<ns5:p> Background <ns5:italic>Plasmodium falciparum</ns5:italic> ( <ns5:italic>P. falciparum</ns5:italic> ) 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 <ns5:italic>P. falciparum</ns5:italic> 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 <ns5:italic>mdr1</ns5:italic> , <ns5:italic>dhfr, crt, dhps, kelch13</ns5:italic> was estimated by aggregating samples at country and country-year level. Results Across countries, the prevalence of the pyrimethamine resistance–associated <ns5:italic>dhfr</ns5:italic> triple mutant allele (51I/59R/108N) exceeded 80%, while its combination with the sulfadoxine resistance–associated <ns5:italic>dhps</ns5:italic> 437G exceeded 60% of infections. Unlike the parasite genotypes in East Africa, the prevalence of the <ns5:italic>dhps</ns5:italic> 540E mutant was low (1.5%), whereas <ns5:italic>dhps</ns5:italic> 436A was common (43.8%). The chloroquine resistance marker <ns5:italic>crt</ns5:italic> 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 <ns5:italic>kelch13</ns5:italic> 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 <ns5:italic>P. falciparum</ns5:italic> infections highlights the need for ongoing monitoring of drug resistance and for data integration throughout the region. </ns5:p>