Abstract
BackgroundWith 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.MethodsUsing dose-response assays, we evaluated the effects of ivermectin delivered by membrane feeding on daily mortality (up to 14 days post-blood feed) and fecundity of an Indian strain of Aedes aegypti.ResultsThe 7-day lethal concentration of ivermectin required to kill 50% of adult mosquitoes was calculated to be 178.6 ng/ml (95% confidence intervals 142.3–218.4) for Ae. aegypti, which is much higher than that recorded for Anopheles spp. in any previous study. In addition, significant effects on fecundity and egg hatch rates were only recorded at high ivermectin concentrations (≥ 250 ng/ul).ConclusionOur results suggest that levels of ivermectin present in human blood at current dosing regimes in mass drug administration campaigns, or even those in a recent higher-dose anti-malaria trial, are unlikely to have a substantial impact on Ae. aegypti. Moreover, owing to the strong anthropophagy of Ae. aegypti, delivery of higher levels of ivermectin in livestock blood is also unlikely to be an effective option for its control. However, other potential toxic impacts of 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.Graphical
Highlights
With widespread insecticide resistance in mosquito vectors, there is a pressing need to evaluate alternatives with different modes of action
Compounds with alternative modes of action including new and repurposed insecticides for long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are required and are becoming available but there remains an urgent need for tools that can target mosquitoes that bite diurnally or bite and rest outdoors [8, 9]
Since the 1990s, the drug has been extensively used in mass drug administration (MDA) campaigns to eliminate lymphatic filariasis and onchocerciasis in sub-Saharan Africa [13, 14]
Summary
With widespread insecticide resistance in mosquito vectors, there is a pressing need to evaluate alternatives with different modes of action. Escalating insecticide resistance [1, 2], recent high profile arboviral outbreaks [3,4,5,6] and the stalling of progress towards malaria elimination [7] highlight the need for improved tools to control mosquito vectors. Since the 1990s, the drug has been extensively used in mass drug administration (MDA) campaigns to eliminate lymphatic filariasis and onchocerciasis in sub-Saharan Africa [13, 14]. During these programmes, reductions in entomological indices and the proportion of Plasmodium-infective mosquitoes have been observed, compatible with mosquitocidal activity of ivermectin [11, 15, 16]. Ivermectin administration is currently proposed as a novel strategy to reduce malaria transmission [17,18,19]
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