Insecticide Resistance Mechanisms and Their Evolutionary Dynamics in Aedes aegypti Across Urban Centres of South West Nigeria: An Original Genomic Analysis

This dissertation provides an original genomic analysis of insecticide resistance mechanisms and their evolutionary dynamics in Aedes aegypti across the major urban centres of South West Nigeria, encompassing Lagos, Ibadan, Abeokuta, Ado-Ekiti, Akure, and Osogbo. Aedes aegypti is the primary vector of dengue, chikungunya, yellow fever, and Zika in Nigeria, and understanding the molecular basis, geographic distribution, and evolutionary trajectory of insecticide resistance is critical for sustainable vector control. The dissertation employs whole-genome pool sequencing of 400 field-collected adult females from 20 sites across the six cities, combined with targeted genotyping of established kdr mutations and metabolic resistance gene copy number analysis, and bioassay-derived resistance phenotypes. Resistance allele frequency mapping, selection coefficient estimation, and population genomic analysis of selective sweeps around resistance loci are conducted. An original Resistance Evolutionary Dynamics Model (REDM) is developed to project resistance allele spread under different insecticide rotation schedules. Results confirm near-fixation of kdr L1014F in all populations, with emergence of a novel kdr variant (F1534C) at high frequency in Lagos. Genome-wide selection scans identify five previously undescribed selective sweep regions, including one near a cytochrome P450 gene cluster. Modelling shows that continuing pyrethroid-only application will drive resistance frequency to theoretical fixation within five years. The dissertation proposes an evidence-based resistance management strategy for South West Nigeria incorporating insecticide rotation and pyrethroid-free indoor residual spraying seasons. Keywords: insecticide resistance, Aedes aegypti, genomics, kdr mutation, South West Nigeria.