Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission

Nature. 2019 Mar;567(7747):239-243. doi: 10.1038/s41586-019-0973-1. Epub 2019 Feb 27.

Abstract

Bites of Anopheles mosquitoes transmit Plasmodium falciparum parasites that cause malaria, which kills hundreds of thousands of people every year. Since the turn of this century, efforts to prevent the transmission of these parasites via the mass distribution of insecticide-treated bed nets have been extremely successful, and have led to an unprecedented reduction in deaths from malaria1. However, resistance to insecticides has become widespread in Anopheles populations2-4, which has led to the threat of a global resurgence of malaria and makes the generation of effective tools for controlling this disease an urgent public health priority. Here we show that the development of P. falciparum can be rapidly and completely blocked when female Anopheles gambiae mosquitoes take up low concentrations of specific antimalarials from treated surfaces-conditions that simulate contact with a bed net. Mosquito exposure to atovaquone before, or shortly after, P. falciparum infection causes full parasite arrest in the midgut, and prevents transmission of infection. Similar transmission-blocking effects are achieved using other cytochrome b inhibitors, which demonstrates that parasite mitochondrial function is a suitable target for killing parasites. Incorporating these effects into a model of malaria transmission dynamics predicts that impregnating mosquito nets with Plasmodium inhibitors would substantially mitigate the global health effects of insecticide resistance. This study identifies a powerful strategy for blocking Plasmodium transmission by female Anopheles mosquitoes, which has promising implications for efforts to eradicate malaria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Africa / epidemiology
  • Animals
  • Anopheles / drug effects*
  • Anopheles / growth & development
  • Anopheles / parasitology*
  • Antimalarials / administration & dosage
  • Antimalarials / pharmacology*
  • Atovaquone / administration & dosage
  • Atovaquone / pharmacology
  • Cytochromes b / antagonists & inhibitors
  • Female
  • Insecticide-Treated Bednets
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / prevention & control*
  • Malaria, Falciparum / transmission*
  • Models, Biological
  • Mosquito Control / methods*
  • Mosquito Vectors / drug effects*
  • Mosquito Vectors / parasitology
  • Plasmodium falciparum* / drug effects
  • Plasmodium falciparum* / pathogenicity
  • Time Factors

Substances

  • Antimalarials
  • Cytochromes b
  • Atovaquone