Molecular Characterization and Spatiotemporal Evidence Synthesis of Antimalarial Drug Resistance Markers in Plasmodium Falciparum Isolates from Southeastern Nigeria

Abstract

Malaria remains a major public health challenge in Nigeria, and antimalarial drug resistance continues to threaten treatment efficacy and malaria control. This revised manuscript explicitly defines the work as a retrospective evidence synthesis of published molecular studies, supported by a proposed multi-centre surveillance framework for Southeastern Nigeria rather than as a primary laboratory investigation. Published evidence from Southeast and adjacent southern Nigerian sentinel sites was reviewed to describe molecular markers associated with chloroquine, sulfadoxine-pyrimethamine (SP), and artemisinin-based combination therapy resistance in Plasmodium falciparum. The synthesis focused on pfcrt, pfmdr1, pfdhfr, pfdhps, and pfk13/k13 markers, with particular attention to their spatial distribution, temporal relevance, and implications for national malaria treatment policy. Extracted findings showed persistent high prevalence of pfcrt 76T in Anambra/Nnewi isolates, near-fixation of pfdhfr triple-mutant markers in antenatal populations, high frequencies of pfdhps A437G and A613S/A581G in southern Nigeria, and the regional emergence of pfdhps I431V, including a high signal in Enugu. Validated artemisinin-resistance pfk13 mutations have not been widely reported from Southeastern Nigeria, but regional evidence from Africa demonstrates the need for early warning surveillance. The revised methods provide clear eligibility criteria, data extraction procedures, sample size guidance for future primary surveillance, laboratory quality assurance measures, sequencing options, statistical analysis approaches, GIS mapping procedures, and ethical considerations. The findings support intensified molecular surveillance integrated with Nigeria’s National Malaria Elimination Programme to guide ACT efficacy monitoring, IPTp-SP policy review, and targeted resistance containment.