Abstract
BACKGROUND: Mosquito resistance to insecticides presents a major obstacle to the global control of vector-borne diseases, such as malaria, dengue, and Zika virus. Understanding the biochemical and physiological mechanisms underlying resistance is critical for sustaining the effectiveness of vector-control strategies. OBJECTIVES: This systematic review aimed to synthesize current knowledge on the biochemical and physiological mechanisms of insecticide resistance in mosquitoes, assess the geographic and species-specific distribution of resistance, and identify research gaps to inform sustainable vector control approaches. METHODS: A systematic literature search was conducted using the PubMed, Web of Science, and Scopus databases from inception to December 31, 2024. Eligible studies included original articles and reviews that reported biochemical or physiological resistance mechanisms in Anopheles, Aedes, and Culex mosquitoes. Data extraction and quality assessment were performed using the modified Joanna Briggs Institute checklist. Narrative synthesis was conducted only because of the heterogeneity across studies, and no meta-analysis was performed. RESULTS: Of the 1432 identified records, 147 full-text articles were assessed for eligibility, and 11 studies met the inclusion criteria and were included in the final qualitative synthesis. The most common resistance mechanisms were metabolic detoxification (cytochrome P450 monooxygenases, glutathione S-transferases, and carboxylesterases) and target-site mutations (notably knockdown resistance mutations). Physiological adaptations such as cuticle thickening and behavioral avoidance also contributed to resistance. Pyrethroid resistance was the most frequently reported pattern, with increasing evidence of cross-resistance across multiple regions, particularly Africa, Southeast Asia, and Latin America. CONCLUSIONS: Mosquitoes exhibit multiple mechanisms of insecticide resistance that threaten the efficacy of current vector control interventions. Integrated vector management, development of novel insecticides, biological control methods, and resistance surveillance are essential for mitigating the evolution of resistance and maintaining public health gains.