Population Genetic Structure of Plasmodium falciparum in Relation to Artemisinin-Based Combination Therapy Pressure in Kebbi State

Population genetic analysis of Plasmodium falciparum provides insights into the evolutionary impact of drug pressure on parasite populations, and such data are essential for early detection of selection signatures associated with artemisinin partial resistance emergence. This study investigated the population genetic structure of P. falciparum isolates in Kebbi State, Northwest Nigeria, with reference to artemisinin-based combination therapy treatment pressure. Dried blood spot samples from 240 malaria-positive patients were genotyped at 12 microsatellite loci and screened for K13 mutations. Population genetic indices including allelic richness, heterozygosity, and linkage disequilibrium were calculated. Bayesian population structure analysis was performed using STRUCTURE software. High allelic diversity (mean He = 0.81) and low linkage disequilibrium values were consistent with high recombination rates in a high-transmission setting. K13 mutations were detected in 4.6 percent of isolates, with C580Y and R539T variants identified. A significant association between K13 mutant haplotypes and reduced heterozygosity in flanking microsatellite loci suggested selective sweep signatures. Comparison with pre-artemisinin-based combination therapy era data from archived samples revealed a statistically significant increase in K13 mutation frequency over ten years. The study provides early molecular evidence consistent with emerging artemisinin selection pressure in Kebbi State and advocates for immediate therapeutic efficacy monitoring. Keywords: Plasmodium falciparum, population genetics, artemisinin resistance, K13 mutations, Kebbi State.