High concentrations of membrane fed ivermectin are required for substantial lethal and sublethal impacts on Aedes aegypti

Background

With widespread insecticide resistance in mosquito vectors, there is a pressing need to evaluate alternatives with different modes of action. Blood containing the antihelminthic drug ivermectin has been shown to have lethal and sub-lethal effects on mosquitoes. Almost all work to date has been on Anopheles spp., but impacts on other anthropophagic vectors could provide new options for their control, or additional value to anti-malarial ivermectin programmes.

Methods

Using dose-response assays delivered by membrane feeding, we evaluated the effects of ivermectin on daily mortality (up to 14-days post blood-feed) and fecundity of an Indian strain of Aedes aegypti.

Results

The 7-day LC50 of ivermectin was calculated to be 178.6 ng/ml (95% CIs 142.3 – 218.4), much higher than recorded in all previous studies of Anopheles spp. In addition, significant effects on fecundity and egg hatch rates were only recorded at high ivermectin concentrations (≥ 250 ng/ul).

Conclusion

Our results suggest that levels present in human blood with current dosing regimes from mass drug administration or even a recent higher-dose antimalaria trial are unlikely to have a substantial impact on Ae. aegypti. Moreover, owing to the strong anthropophagy of Ae. aegypti, delivery of higher levels in livestock blood is also unlikely to be an effective option. However, other potential toxic impacts from ivermectin metabolites, accumulation in tissues, sublethal effects on behaviour, or antiviral action might increase the efficacy of ivermectin against Ae. aegypti and the arboviral diseases it transmits, and require further

investigation.