Genomic analysis reveals the emergence of molecular insecticide resistance in the malaria vector, Anopheles gambiae, from Western Ethiopia

Title : Genomic analysis reveals the emergence of molecular insecticide resistance in the malaria vector, Anopheles gambiae, from Western Ethiopia

Abstract:

Insecticide resistance poses a significant challenge to malaria control, driven by diverse molecular mechanisms whose distribution remains poorly characterized in Ethiopia. This study presents the first study using whole-genome sequence data of Anopheles gambiae from Ethiopia, confirming its presence in the western region of the country and expanding its known geographical distribution. Analysis of single-nucleotide polymorphisms and copy number variations focused on key target site insecticide resistance genes, including the voltage-gated sodium channel (Vgsc), acetylcholinesterase-1 (Ace-1), the resistance to dieldrin (Rdl) gene, as well as metabolic resistance loci such as cytochrome P450s (Cyp6m2,Cyp6aa/p, Cyp9k1) and carboxylesterases (Coeae2f, Coeae2–6g). Genomic analysis revealed high frequencies of Vgsc-L995F (kdr-west) mutations, alongside amplifications at cyp6aa/p, cyp9k1, and gste2. Notably, frequencies of Vgsc and gste2 variants exhibited differences on a local scale, while Vgsc and Cyp9k1 variant frequencies also fluctuated seasonally. Findings highlight the need for site-specific monitoring on a fine temporal scale. Genome-wide selection scans using phased haplotypes identified emerging signals of selection at loci with a potential link to insecticide resistance, including a signal spanning 2L:33,039,186–34,168,017, expanding the catalogue of candidate loci for functional validation. Together, the results suggest that An. gambiae populations may be largely refractory to pyrethroids and moderately resistant to organophosphate (OPs) insecticides in western Ethiopia. Findings necessitate a better understanding of the An. gambiae geographical distribution in Ethiopia, accompanied by resistance-informed malaria control interventions targeting the vector.

Keywords: Anopheles gambiae sensu stricto, target site insecticide resistance, metabolic insecticide resistance, selection scans, Ethiopia, whole-genome sequencing, malaria vector.

Biography:

Fekadu Gemechu Gudeta is currently working as a public health entomology researcher at the Ethiopian Public Health Institute (EPHI). He is a PhD fellow at Addis Ababa University, Aklilu Lemma Institute of Health Research. His PhD research focuses on Anopheles mosquito genomic signatures, population structure, and diversity in Ethiopia. Previously, he worked as a lecturer and researcher at Dilla University, Ethiopia. He is an entomologist and a tropical and infectious diseases professional, with a particular focus on malaria vectors.