Disrupting Mosquito Reproduction and Parasite Development for Malaria Control

PLoS Pathogens

Lauren M. Childs¹  Francisco Y. Cai²  Evdoxia G. Kakani²  Caroline O. Buckee³  Sara N. Mitchell³  Paolo Gabrieli³  Doug Paton⁴  Flaminia Catteruccia⁴ 

[1] Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America;Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America;Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America;Dipartimento di Medicina Sperimentale, Universita' di Perugia, Perugia, Italy

关键词: Mosquitoes;    Malaria;    Insecticides;    Death rates;    Malarial parasites;    Blood;    Plasmodium;    Steroid hormones;   

DOI  :  10.1371/journal.ppat.1006060

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY