A novel strategy targets malaria-causing Plasmodium parasites in mosquitoes
The fight against malaria may someday include ridding mosquitoes themselves of the parasites that cause the disease.
In the lab, treating female mosquitoes with an antimalarial drug stopped parasites from developing inside the insects. Mosquitoes were exposed to the treatment when they landed on a drug-coated glass surface for as little as six minutes, comparable to how long mosquitoes stop on protective bed nets as they hunt for a meal, researchers report online February 27 in Nature.
“People have been exploring ways to control insect pests for an awful long time,” says Joshua Yukich, a malaria epidemiologist at Tulane University in New Orleans who was not involved in the research. A strategy that kills malaria-causing parasites in mosquitoes “is pretty exciting.” It may be possible to make insecticide-treated bed nets even more effective by adding antimalarial compounds, he says.
Malaria, caused by Plasmodium parasites and spread by the bites of Anopheles mosquitoes, is a flulike illness with high fever and chills. Without treatment, it can be fatal: In 2017, there were 219 million cases of malaria worldwide, mostly in Africa, and 435,000 deaths, mainly in children.
Since 2000, an international effort to combat malaria in Africa has prevented an estimated 663 million cases, researchers say, largely thanks to insecticide-treated bed nets. The nets kill mosquitoes and help protect sleepers from bites. But that progress has been threatened with the emergence of insecticide-resistant mosquitoes.
To test whether targeting the parasites in mosquitoes could work, Flaminia Catteruccia, a molecular entomologist at the Harvard T.H. Chan School of Public Health, and colleagues treated a glass surface with the antimalarial drug atovaquone. Mosquitoes landed on the surface and absorbed the drug through their legs. The compound then made its way to the insects’ gut, where it prevented the parasite Plasmodium falciparum from developing, the team found.
The strategy worked whether insects were infected with the parasites before or after the drug treatment. An “autopsy” of the mosquitoes seven to nine days after an infectious blood meal found the insects were parasite free after treatment with certain doses of the drug, the researchers say.
Atovaquone, which is used to treat malaria in people, kills Plasmodium parasites by inhibiting a protein in the mitochondria, the energy factories inside cells. But it’s possible using antimalarial drugs to treat mosquitoes could result in the parasites becoming resistant to the drugs, endangering crucial therapies. So Catteruccia and her colleagues would like to test other compounds that can kill the parasites in mosquitoes.
There are already options out there, Catteruccia says, including antimalarial drugs that have shown effectiveness against the parasites in tests but didn’t pass muster as treatment, because of problems with how they were taken up in the human body or other issues. “In a way, we can repurpose drugs that are not good enough for human use,” she says.
As for the mosquitoes, developing resistance shouldn’t be a concern, Catteruccia says. In the study, treatment with atovaquone didn’t shorten the insects’ life spans or interfere with mosquitoes’ ability to reproduce. “The mosquito doesn’t care at all about picking up this drug,” she says.
Along with finding suitable drugs, it would also be necessary to develop formulations that can remain active on bed nets for perhaps a few years, Yukich says. Long-lasting insecticide-treated nets, for example, keep their insect-killing power for three years or so, even with daily use and washing.
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