Abstract
The control of mosquito populations with insecticide treated bed nets and indoor residual sprays remains the cornerstone of malaria reduction and elimination programs. In light of widespread insecticide resistance in mosquitoes, however, alternative strategies for reducing transmission by the mosquito vector are urgently needed, including the identification of safe compounds that affect vectorial capacity via mechanisms that differ from fast-acting insecticides. Here, we show that compounds targeting steroid hormone signaling disrupt multiple biological processes that are key to the ability of mosquitoes to transmit malaria. When an agonist of the steroid hormone 20-hydroxyecdysone (20E) is applied to Anopheles gambiae females, which are the dominant malaria mosquito vector in Sub Saharan Africa, it substantially shortens lifespan, prevents insemination and egg production, and significantly blocks Plasmodium falciparum development, three components that are crucial to malaria transmission. Modeling the impact of these effects on Anopheles population dynamics and Plasmodium transmission predicts that disrupting steroid hormone signaling using 20E agonists would affect malaria transmission to a similar extent as insecticides. Manipulating 20E pathways therefore provides a powerful new approach to tackle malaria transmission by the mosquito vector, particularly in areas affected by the spread of insecticide resistance.
Highlights
Despite recent progress in combating the malaria parasite, nearly 200 million infections and around 500,000 deaths are caused by malaria annually, mostly in young children in sub-Saharan Africa [1, 2]
Current mosquito control methods are severely threatened by the rapid spread of insecticide resistance in anopheline mosquito populations that transmit the malaria-causing Plasmodium parasites
When we model the impact of steroid hormone agonists on malaria transmission, we predict that these compounds would provide an important new tool against malaria, in regions of widespread insecticide resistance
Summary
Despite recent progress in combating the malaria parasite, nearly 200 million infections and around 500,000 deaths are caused by malaria annually, mostly in young children in sub-Saharan Africa [1, 2]. Of the four classes of insecticides available for malaria control, pyrethroids are the only compounds approved for use on long-lasting insecticideimpregnated bed nets (LLINs), due to their relatively low toxicity, and they are heavily used in indoor residual spray (IRS) programs [5]. This is a major limitation, as the increased application of both interventions over the last decade has inevitably led to the emergence and spread of insecticide resistance in natural mosquito populations. Other aspects of adult mosquito biology that determine vectorial capacity, such as host preferences for blood-feeding, susceptibility to parasite development, and reproductive fitness, have not yet been fully exploited for malaria control
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