Genomic Surveillance of Plasmodium falciparum in Southeastern Nigeria: Implications for Artemisinin-Based Therapy Policy

Background and Objective: Malaria, driven by Plasmodium falciparum, imposes a heavy burden in Nigeria, with artemisinin-based combination therapies (ACTs) facing emerging resistance. This study conducted genomic surveillance of resistance markers in Abia State, southeastern Nigeria, to inform ACT policy adaptations amid rising pfkelch13 and pfmdr1 variants. Materials and Methods: From August 2024 to July 2025, a prospective cohort of 200 febrile patients (aged ≥6 months) with uncomplicated P. falciparum mono-infection underwent 28-day therapeutic efficacy monitoring for Artemether-lumefantrine (AL) following WHO protocols. Dried blood spots were genotyped for pfkelch13 propeller domain, pfmdr1 SNPs/copy number, and associated markers (pfcrt, pfdhfr) through nested PCR/Sanger sequencing. Outcomes included prevalence, temporal trends, clinical correlations (e.g., delayed clearance), and SIR modelling for resistance projections. Results: The pfkelch13 mutations occurred in 8.4% (R561H 3.7%, C580Y 2.6%), with pfmdr1 N86Y at 55.2% (up-trending to 62% by study end; OR 1.3/quarter, p = 0.02). PCR-corrected adequate clinical and parasitological response was 97.8%, but pfkelch13 mutants showed 3.2-fold higher delayed clearance odds (95% CI 1.1-9.4, p = 0.03) and 4.1-fold late failure risk (95% CI 1.2-14.0, p = 0.02). Modelling predicted a 15% ACT failure rise by 2030, avertable by triple ACTs. Conclusions: While the AL efficacy holds, emerging pfkelch13 and pfmdr1 threats in Abia signal an urgent need for genomic integration into Nigeria’s Malaria Strategic Plan, promoting triple ACTs to sustain elimination goals.