Journal Article

Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission

Paton, Douglas G., Holmdahl, Inga E., Catteruccia, Flaminia, Itoe, Maurice A., Buckee, Caroline O., Childs, Lauren M.

2019

Overview

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 malaria 1 . However, resistance to insecticides has become widespread in Anopheles populations 2 – 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. Treatment of female Anopheles gambiae mosquitoes with atovaquone causes arrest of the Plasmodium falciparum parasite in the midgut, and this holds promise for malaria eradication in areas with insecticide-resistant mosquito populations.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/417 / 631/326/417/1716 / 631/601/1466 / 692/699/255/1629 / Adulticides / Africa - epidemiology / Animals / Anopheles / Anopheles - drug effects / Anopheles - growth & development / Anopheles - parasitology / Antimalarials / Antimalarials - administration & dosage / Antimalarials - pharmacology / Antiparasitic agents / Aquatic insects / Atovaquone / Atovaquone - administration & dosage / Atovaquone - pharmacology / Blocking effects / Computer simulation / Control / Culicidae / Cytochrome / Cytochrome b / Cytochromes / Cytochromes b - antagonists & inhibitors / Disease control / Disease transmission / Environmental aspects / Erythrocytes / Female / Global health / Humanities and Social Sciences / Infections / Inhibitors / Insect bites / Insecticide resistance / Insecticide-Treated Bednets / Insecticides / Letter / Low concentrations / Malaria / Malaria, Falciparum - epidemiology / Malaria, Falciparum - prevention & control / Malaria, Falciparum - transmission / Mass distribution / Midgut / Mitochondria / Models, Biological / Mosquito Control - methods / Mosquito Vectors - drug effects / Mosquito Vectors - parasitology / Mosquitoes / multidisciplinary / Nets / Parasites / Parasitic diseases / Permethrin / Pesticide resistance / Physiological aspects / Plasmodium (Protozoa) / Plasmodium falciparum / Plasmodium falciparum - drug effects / Plasmodium falciparum - pathogenicity / Public health / Pyrimethamine / Science / Science (multidisciplinary) / Time Factors / Tropical diseases / Vector-borne diseases