Richard Musgrove
Dr Richard Musgrove is a zoologist and science journalist. He writes for Cosmos and Double Helix.
Biomedical scientists have successfully dosed bed net material with drugs to kill Plasmodium, the malaria parasite carried by the Anopheles mosquito, before the insect finds a human blood meal and spreads the disease.
Such mosquito disinfection could potentially get around the increasing insecticide resistance problem.
“Insecticide resistance is now extremely common in the mosquitoes that transmit malaria, which jeopardizes many of our most effective control tools,” says Dr Alexandra Probst, lead author of a new paper in the journal Nature.
“By targeting parasites directly in the mosquito, rather than the mosquito itself, we can circumvent this challenge and continue to reduce the spread of malaria.”
Malaria kills more than half a million people each year. It is caused by the single-celled Plasmodium parasite, spread through the bites of infected Anopheles mosquitos. Anti-malarial drugs have been in use since the first gin and tonic — the ‘tonic’ originally included quinine, taken by British soldiers in India in the 1700’s to prevent and combat the disease. Gin was added to counter quinine’s bitter taste.
Treatment has been a constant arms race ever since, battling drug and insecticide resistance by the parasite and its carrier.
The year 2000 saw 896,000 malaria-related deaths, globally. The following two decades showed a decline with 558,000 in 2019, and an uptick to 627,000 in 2021 (WHO Malaria Program 2021). But reductions have stalled in recent years due to insecticide resistance, says lead author Probst. In 2023, there were 263 million new cases of malaria worldwide and 597,000 deaths.
Papua New Guina and the Solomon Islands account for 90% of all cases in the Western Pacific region.
Now a team from Oregan Health and Science University (OHSU) have flipped the approach to the insecticide-treated mosquito nets so often featured in tropical sleeping spaces.
“The best defence against malaria has been insecticide-treated bed nets, but mosquitoes are developing a resistance to those prevention methods. This novel approach targets the source of the disease,” says biomedical researcher and coauthor Dr Mike Rubal, of the Southwest Research Institute, in Texas.
That drug is an ‘ELQ’ an ‘endochin-like quinolone,’ one of a class of experimental antimalarials. These ELQs were synthesised by the OHSU School of Medicine’s Professor Michael Riscoe and tested for their ability to kill the Plasmodium parasite by Professor Flaminia Catteruccia and team at Harvard’s TH Chan School of Public Health.
Eighty-one compounds were tested for their ability to block malaria parasite growth within mosquitos. The two most effective were ELQ drugs from Riscoe’s lab, which even did the job when added to mosquito net material.
Malaria-laden mosquitoes landing on the ELQ-dosed net material were cured of their infections, and the drugs were stable and effective even on insecticide-resistant mosquitoes.
“If an infected mosquito hits or lands on netting containing either of the ELQs, it’s essentially disinfected. It absorbs the treatment via its legs, and that kills the parasites that it’s carrying,” says Rubal.
The team acknowledge that further resistance over time is an issue: “Resistance is always a concern when deploying new chemotherapeutics. Here we used an inhibitor that…could potentially induce mutations that lead to resistance to this prophylactic antimalarial. However, some considerations provide a reason for moderate optimism that parasite resistance would not rapidly emerge when using ELQ combinations. Targeting Plasmodium during a bottleneck in its life cycle would substantially reduce the likelihood of de novo emergence of resistance-conferring mutations.”
Riscoe says, “It was a novel idea by Dr. Catteruccia and her colleagues to incorporate anti-malarial drugs into bed nets and then to see if the mosquitoes would land on the nets and take up the drug. The idea is the drug kills the parasites that cause malaria instead of the mosquitoes, and our data shows this works.”
The team now plans to explore whether the antimalarial ELQs should be included with insecticides in the bed nets or just used alone to reduce disease transmission. Trials with ELQ-impregnated bed nets will begin later this year.
“This work has potential to significantly blunt the transmission of malaria,” Riscoe says. “I think that it will evolve and develop to be a key element in eradicating malaria around the world.”