Genomic Epidemiology of Plasmodium falciparum Kelch13 Mutations and Artemisinin Partial Resistance Emergence in West Africa with Reference to Nigeria

The emergence of artemisinin partial resistance in Africa, characterised by kelch13 (K13) propeller domain mutations, represents the most critical threat to global malaria control progress, and understanding its genomic epidemiology in West Africa is essential for containment policy. This doctoral study investigated the genomic epidemiology of K13 mutations and their artemisinin partial resistance phenotypes in Nigeria and contextualised findings within the West African regional landscape. Whole genome sequencing was performed on 480 P. falciparum isolates from eight states spanning all six geopolitical zones, selected through stratified sampling from febrile patient cohorts. K13 mutations were identified by targeted deep sequencing. Genomic selection signals were assessed using extended haplotype homozygosity statistics. Parasite clearance phenotyping was performed in a subset using the Worldwide Antimalarial Resistance Network protocol. Validated K13 mutations were detected in 6.2 percent of isolates, with C580Y, R539T, and I543T as the predominant variants. Selective sweep signatures flanking K13 loci were detected for C580Y and R539T, consistent with de novo emergence under drug pressure. Parasite clearance half-lives exceeded 5 hours in 9.1 percent of K13-mutant carriers. Phylogeographic analysis positioned Nigerian K13 lineages as independently evolving from Southeast Asian clades. These findings provide the most comprehensive genomic evidence to date for K13-driven partial resistance emergence in Nigeria and inform urgent adaptive treatment policy responses. Keywords: kelch13 mutations, artemisinin partial resistance, whole genome sequencing, West Africa, Nigeria.