📖 ABSTRACT/OVERVIEW
Understanding the evolutionary dynamics that drive the acquisition and spread of drug resistance mutations in P. falciparum under the selection pressure of artemisinin-based combination therapies is fundamental to anticipating resistance emergence and designing resistance management strategies in high-burden nations like Nigeria. This doctoral research investigates the evolutionary dynamics of drug resistance in Nigerian P. falciparum populations using whole-genome sequencing of temporally spaced clinical isolates from four sentinel sites across Nigeria. Isolates were collected from 600 malaria-positive patients at two timepoints separated by five years (2019 and 2024) from sites in Kano, Lagos, Enugu, and Maiduguri, enabling temporal evolutionary analysis. Whole-genome sequences were analysed for selective sweeps using extended haplotype homozygosity statistics, population differentiation using FST analysis between temporal and geographic cohorts, and resistance allele frequency trajectories in pfkelch13, pfmdr1, pfcrt, pfdhfr, and pfdhps genes. Coalescent-based demographic modelling estimated the effective population size dynamics under drug selection. Evidence from 2020 to 2024 documents ongoing evolutionary change in West African P. falciparum drug resistance loci, including rising pfmdr1 copy number variants associated with lumefantrine tolerance. This research constitutes the first longitudinal whole-genome evolutionary study of P. falciparum resistance dynamics in Nigeria, providing foundational data for predictive resistance modelling and national drug policy review. Findings will be published in a top-quartile evolutionary biology or parasitology journal. Keywords: Plasmodium falciparum, drug resistance evolution, whole-genome sequencing, artemisinin, Nigeria.
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