title: Disrupting Mosquito Reproduction and Parasite Development for Malaria Control.
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.
authors.affiliation: 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.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Childs
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Francisco Y
authors.identifier: http://orcid.org/0000-0003-4718-9632
authors.initials: FY
authors.lastname: Cai
authors.affiliation: 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.
authors.forename: Evdoxia G
authors.initials: EG
authors.lastname: Kakani
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Sara N
authors.identifier: http://orcid.org/0000-0002-7926-1881
authors.initials: SN
authors.lastname: Mitchell
authors.affiliation: 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.
authors.forename: Doug
authors.identifier: http://orcid.org/0000-0001-7508-7559
authors.initials: D
authors.lastname: Paton
authors.affiliation: 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.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gabrieli
authors.affiliation: 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.
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Buckee
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Flaminia
authors.initials: F
authors.lastname: Catteruccia
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects* / Q000469:parasitology*; D004441:Ecdysterone / Q000819:agonists; D005260:Female; D006834:Hydrazines / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007303:Insect Vectors / Q000187:drug effects / Q000469:parasitology; D057148:Insecticide-Treated Bednets; D007306:Insecticides / Q000494:pharmacology*; D007605:Juvenile Hormones / Q000494:pharmacology*; D008018:Life Cycle Stages / Q000187:drug effects; D008288:Malaria / Q000635:transmission*; D008962:Models, Theoretical; D009032:Mosquito Control / Q000379:methods*; D011157:Population Dynamics
chemical_list: D006834:Hydrazines; D007306:Insecticides; D007605:Juvenile Hormones; D004441:Ecdysterone; C406712:methoxyfenozide