Molecular Epidemiology of Plasmodium falciparum Drug Resistance Markers in Six Geopolitical Zones of Nigeria

Artemisinin partial resistance in Plasmodium falciparum poses a growing threat to malaria treatment efficacy in sub-Saharan Africa, with molecular surveillance offering early warning signals before clinical resistance becomes widespread. This study investigated the distribution of P. falciparum drug resistance molecular markers across Nigeria's six geopolitical zones using archived dried blood spot samples collected from 600 malaria-positive patients at sentinel health facilities. DNA was extracted and PCR-based genotyping performed for kelch13 (K13) propeller domain mutations, pfmdr1 polymorphisms, and pfcrt codon 76 mutations. K13 polymorphisms associated with artemisinin partial resistance were detected in 3.8 percent of samples, predominantly in samples from the North Central and South South zones. Pfcrt 76T mutation frequency was 42.1 percent nationally, confirming residual chloroquine resistance alleles. Pfmdr1 N86Y and Y184F haplotypes varied significantly across zones. Mixed genotype infections were present in 61.4 percent of samples. Regional clustering of K13 variants suggests independent local emergence rather than importation. The findings provide the most geographically comprehensive baseline for drug resistance marker surveillance in Nigeria to date and underscore the urgency of integrating molecular surveillance into the national malaria programme's therapeutic efficacy monitoring framework. Keywords: Plasmodium falciparum, drug resistance, kelch13, molecular epidemiology, Nigeria.