Disrupting Mosquito Reproduction and Parasite Development for Malaria Control

• Published in: PLoS pathogens Vol. 12; no. 12; p. e1006060
• Main Authors: Childs, Lauren M, Cai, Francisco Y, Kakani, Evdoxia G, Mitchell, Sara N, Paton, Doug, Gabrieli, Paolo, Buckee, Caroline O, Catteruccia, Flaminia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-12-2016; Public Library of Science (PLoS)
• Subjects: Animals; Anopheles - drug effects; Anopheles - parasitology; Biology and Life Sciences; Control; Disease transmission; Ecdysterone - agonists; Female; Hydrazines - pharmacology; In Situ Nick-End Labeling; Insect Vectors - drug effects; Insect Vectors - parasitology; Insecticide resistance; Insecticide-Treated Bednets; Insecticides - pharmacology; Juvenile Hormones - pharmacology; Life Cycle Stages - drug effects; Malaria; Malaria - transmission; Medicine and Health Sciences; Methods; Models, Theoretical; Mosquito control; Mosquito Control - methods; People and Places; Planning; Population Dynamics; Prevention; Sub-Saharan Africa
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006060

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.