Genomic Epidemiology of Plasmodium falciparum Artemisinin Partial Resistance in West Africa: Implications for Nigerian Antimalarial Policy

The emergence and regional spread of Plasmodium falciparum partial resistance to artemisinin, initially confirmed in East Africa and Southeast Asia, poses an existential threat to artemisinin-based combination therapy, the clinical cornerstone of global malaria treatment. This doctoral research investigates the genomic epidemiology of P. falciparum artemisinin partial resistance across Nigerian states and contextualises findings within the broader West African genomic landscape. A prospective multi-site genomic surveillance study was conducted across eight sentinel sites spanning all six geopolitical zones of Nigeria. Clinical isolates were collected from 800 uncomplicated malaria patients over three transmission seasons. Whole-genome sequencing was performed using the Illumina platform, and Pfkelch13 propeller domain mutations, copy number variants in the plasmepsin II-III locus, and background resistance genome architecture were characterised. Population genomic analyses including identity-by-descent, selective sweep scans, and phylogenetic network analysis assessed the relatedness of Nigerian isolates to East African and Southeast Asian partial resistance lineages. Functional characterisation of novel Pfkelch13 mutations was performed using ring-stage survival assay. Evidence from 2020 to 2024 identifies multiple Pfkelch13 non-synonymous variants in West African isolates, with unclear functional significance requiring systematic assessment. This research produces the most comprehensive Nigerian P. falciparum genomic dataset to date and develops a genomic risk index for predicting artemisinin partial resistance spread. Findings will inform the Federal Ministry of Health's antimalarial treatment policy revision. Keywords: Plasmodium falciparum, artemisinin partial resistance, whole-genome sequencing, genomic epidemiology, West Africa.