Contact exposure to ivermectin induces acute mortality and inhibits parasite development in malaria vectors

Resistance to insecticides and associated behavioural shifts are being increasingly reported in malaria vectors. To counter these adaptations, there is a pressing need to explore novel control tools and interventions. In line with this, the present study evaluates the potential of ivermectin as a contact-toxin for both malaria vectors and parasite. Laboratory reared female An. culicifacies and An. stephensi mosquitoes were exposed to different concentrations of ivermectin through topical and bottle bioassays. Mortality data was used to calculate the LD₅₀ and LD₉₀ values. Infection studies with Plasmodium berghei were done in female An. stephensi to check the transmission blocking activity of ivermectin. Following contact exposure to ivermectin, the midguts of exposed mosquitoes were dissected and oocysts were counted to calculate oocyst intensity and prevalence. Ivermectin demonstrated high contact toxicity against both An. stephensi and An. culicifacies mosquitoes inducing 100% mortality in both vector species within 24-48 h of exposure at higher dosages of ivermectin. In topical bioassay, after 48 h the LD₅₀ value for An. stephensi and An. culicifacies was 0.017 ng/mg (95% CI 0.008-0.30) and 0.002 ng/mg (95% CI 0.000-0.005) respectively. The corresponding LD₉₀ values were 0.264 ng/mg (95% CI 0.138-.703) and 0.174 ng/mg (95% CI 0.063-1.173) for An. stephensi and An. culicifacies. Whereas in bottle bioassay after 48 h, the LD₅₀ value for An. stephensi and An. culicifacies was 4.245 µg/bottle (95% CI 3.018-5.715) and 1.768 µg/ bottle (95% CI 1.211-2.528) respectively. The LD₉₀ value of An. stephensi and An. culicifacies was 13.10 µg/bottle (95% CI 10.56-17.50) and 5.218 µg/ bottle (95% CI 4.02-7.63). Additionally, contact exposure to ivermectin significantly impaired oocyst development in mosquitoes. A reduction of 71% in oocyst numbers was observed at 0.01 µM concentration of ivermectin. Our study establishes ivermectin as an effective contact mosquitocidal and transmission blocking agent. These findings further contribute to the growing body of evidence supporting the use of ivermectin as a novel vector control tool capable of simultaneously reducing vector population and interrupting malaria transmission.