Toxicity of ivermectin on multiple insecticide-resistant populations of Anopheles gambiae sensu lato, Aedes aegypti, and Culex mosquitoes.

Ivermectin is an emerging vector control; however, its toxicity against insecticide-resistant mosquito populations with multiple resistance mechanisms remains unclear. This study investigated the toxic effects of ivermectin on three multiple insecticide-resistant mosquito populations from Ghana. Susceptibility to different insecticides, target-site mutations associated with insecticide resistance, and metabolic resistance mechanisms were determined among field mosquito populations of Anopheles gambiae sensu lato, Aedes aegypti, Culex species, and susceptible Anopheles gambiae sensu stricto Kisumu (laboratory strain). Dose-response bioassays were performed by feeding the mosquito populations with different concentrations of ivermectin dissolved in a 10% sugar solution. Mortality was recorded post-feeding every 12 h for 48 h. The field mosquito populations were resistant to most of the insecticides tested, particularly the pyrethroids. Different kdr mutations and metabolic resistance mechanisms were detected in the field populations. The susceptible An. gambiae s.s. Kisumu strain had a significantly higher hazard of death compared with the insecticide-resistant An. gambiae s.l. (exhibiting kdr, Ace-1 mutations and metabolic resistance mechanisms), across all the ivermectin concentrations (P ≤ 0.001). Furthermore, the lethal doses of ivermectin that killed 95% wild An. gambiae s.l. and Culex spp. (permethrin, deltamethrin, and dichloro-diphenyl-trichloroethane [DDT] resistant) were comparable, but lower than the dosage that killed 95% wild Ae. aegypti with F1534C, V410L, and V1016I mutations and metabolic resistance mechanisms. The study showed that the multiple insecticide-resistant An. gambiae s.l. population was more tolerant to ivermectin compared with the susceptible strain, but more susceptible to the drug compared with Ae. aegypti. These findings suggest heterogeneity in ivermectin responses across the mosquito species and resistant phenotypes, and therefore, further studies are needed to identify the mechanisms underlying these differences and to assess their relevance under broader epidemiological and ecological contexts.