Insecticide Resistance in Anopheles stephensi: A Systematic Review and Meta-Analysis of Native and Invasive Populations

Background: The rapid spread of the invasive malaria vector Anopheles stephensi in Africa, coupled with increasing reports of insecticide resistance, presents an emerging challenge for malaria vector control. We conducted a systematic review and meta-analysis to compare insecticide resistance profiles and underlying resistance mechanisms between native Asian and invasive African populations and assessed their implications for insecticide resistance management. Methods: PubMed, Google Scholar, Web of Science, WHO IRIS, and gray literature sources were searched using terms related to An. stephensi, insecticide susceptibility, and resistance mechanisms. Data were extracted into Excel, critically appraised using an adapted Joanna Briggs Institute checklist, and analyzed using Comprehensive Meta-analysis software. The protocol was registered in Prospero International Registrar for Systematic Review and Meta-analysis in April 2025 (ID: CRD420251007131). Results: Thirty-one studies published between 2000 and 2025 were included. Pooled mortality was lower in invasive than native populations for the pyrethroids assessed in both ranges, including deltamethrin (72.6% vs. 83.5%), permethrin (68.3% vs. 89.0%), and lambda-cyhalothrin (47.0% vs. 87.0%), as well as for DDT (36.0% vs. 47.7%). Mortality was also lower in invasive populations for bendiocarb and propoxur, although propoxur was assessed in only one native-range study. Between-study heterogeneity varied substantially. Target-site mutations were reported at low frequencies; L1014F ranged from 1.4% to 32.9% in native populations and was detected in one study in invasive-range (5.7%), while L1014S (21.4–35%) was reported only in native-range. Metabolic resistance mechanisms involved cytochrome P450s (CYP4 and CYP6 families), glutathione S-transferases (GSTe2 and GSTe4), and esterases, including esterase E4 and carboxylesterase-6. No acetylcholinesterase-1 (ace-1) mutations were reported. Conclusion: Anopheles stephensi exhibits resistance to multiple insecticide classes across its native and invasive ranges, with lower pooled mortality observed in the invasive range. Available evidence indicates an important contribution of metabolic detoxification, while target-site resistance markers, including vgsc L1014F/L1014S, were detected at lower frequencies and remain poorly characterized in invasive populations. High between-study heterogeneity warrants cautious interpretation and highlights the need for standardized phenotypic and molecular surveillance to guide locally tailored insecticide resistance management as An. stephensi continues to spread in Africa.