Ending malaria by killing mosquitoes that bite humans: a promising tool for combating the disease

A drug that injects malaria-carrying mosquitoes with poison into the bloodstream. This idea—of using the human body itself to kill these malaria vectors and thus reduce transmission— is behind a new study published Wednesday night in The New England Journal of Medicine . This is the BOHEMIA clinical trial , the largest study to date examining the potential of the drug ivermectin as a complementary tool for malaria control.

The project, coordinated by the Barcelona Institute for Global Health (ISGlobal) in collaboration with the Manhiça Health Research Centre and the KEMRI-Wellcome Trust Research Programme, and funded by Unitaid , demonstrated that ivermectin combined with the use of mosquito nets reduced new malaria infections by 26%. This antiparasitic drug, used to treat neglected tropical diseases such as onchocerciasis and lymphatic filariasis , has been shown to reduce malaria transmission by killing mosquitoes that feed on people treated with the drug.

The clinical trial administered 400 micrograms per kilogram of this drug once a month for three months to 28,932 children between the ages of 5 and 15 in Kwale, a coastal county in Kenya with a high malaria burden. The trial administered more than 56,000 treatments at the start of the rainy season . “That's the time when mosquitoes reproduce exponentially, but if you manage to catch them at the beginning, you can break that upward curve and then decrease transmission,” explains Carlos Chaccour, BOHEMIA co-principal investigator and ISGlobal researcher at the time of the study, in a video interview. After three months, the results were promising: the children who received ivermectin showed a 26% reduction in malaria incidence compared to those who received albendazole, the control drug used in the study.

Children who received ivermectin had a 26% reduction in malaria incidence compared to those who received albendazole, the control drug used in the study.

The scientist, who currently works at the University of Navarra's Center for International Development, explains that between 2000 and 2015, initiatives such as insecticide-treated bed nets and indoor spraying significantly reduced malaria mortality. However, progress has since stalled due to reasons such as the emergence of chemical resistance , changes in insect behavior , and declining funding . According to the latest report from the World Health Organization (WHO) , 263 million new cases and 597,000 deaths from this disease will be recorded in 2023, 95% of them in Africa.

“That's why something that allows you to kill mosquitoes, regardless of the time or place they bite, is interesting as a mass distribution strategy,” he says. The researcher adds that this method “is not a silver bullet,” but rather an additional tool that also has the advantage of being able to be worn. “You can get infected; there's no individual protection. But the mosquitoes that bite me don't bite my children. The individual benefit comes from an improvement in malaria in my community,” he explains.

The analysis also concludes that the use of ivermectin has other direct benefits for the population, in addition to its traditional use in treating onchocerciasis and lymphatic filariasis , as it significantly reduces scabies and head lice, is good for intestinal parasites, and kills bed bugs. "This research has the potential to transform the future of malaria prevention, especially in endemic regions where current tools are losing effectiveness," concludes Regina Rabinovich, principal investigator at BOHEMIA and director of the Malaria Elimination Initiative at ISGlobal, in a statement.

Among the limitations, Chaccour mentions that this is a study conducted only in children and also under clinical trial conditions. “Therefore, you're constantly monitoring people and making sure everyone takes [the drug]. We still need to know how it works from an operational standpoint: if you launch it in one country and distribute it worldwide,” he explains.

This research has the potential to transform the future of malaria prevention, especially in endemic regions where current tools are losing effectiveness.

Regina Rabinovich, principal investigator at BOHEMIA and director of ISGlobal's Malaria Elimination Initiative

Furthermore, the original idea was to conduct two clinical trials simultaneously: one in Kenya and one in Mozambique, in the rural district of Mopeia. However, their implementation was severely impacted in 2022 by Cyclone Gombe and a subsequent cholera outbreak, which significantly disrupted operations. The Mozambique study is now under review, but, as Chaccour explains, its findings are not interpretable because the goal was to reach 64% of the population and only halfway there, and other logistical issues slowed down the process. “[The results] are useful for knowing which are the key variables that need to be addressed at the population level. But it is not a study that supports its use, nor one that says it is useless, which would also be useful,” the researcher summarizes.

Chaccour explains that now "the priority" is to conduct a second study that demonstrates its efficacy, thus enabling the WHO to recommend the use of ivermectin as a public health strategy for malaria control. He also considers it interesting to conduct operational research, that is, to see what happens if, instead of giving three doses, five are given, or if, instead of giving one dose of 400, one dose of 600 is given. He also notes what would happen if ivermectin were combined with the malaria vaccine or with mass administration of antimalarials. "Another thing that interests me a lot is the One Health approach (a comprehensive approach whose objective is to balance and optimize the health of people, animals, and ecosystems). Because we have given the drug to people, but the mosquitoes that transmit malaria often bite animals as well. This isn't relevant for malaria because there is no parasite transmission, but it does give them free blood," the researcher mentions.

"For diseases that affect the poor, we always take a long time to do things. I think we need to take the possibilities much more seriously and try to speed up the timeline."

Carlos Chaccour, co-principal investigator of BOHEMIA

Regarding the future of malaria research, in these times of funding cuts that threaten progress in the fight against this disease, Chaccour believes that these cuts "are felt everywhere" and that the decrease will require researchers to be much more responsible in the quality of the data they generate. He also believes it is an opportunity for countries to pursue their own initiatives. "And also for integrative tools like ivermectin. Because if I now have a malaria program, one for scabies, another for onchocerciasis, one for lymphatic filariasis , someone might come and say, 'Look, with this single tool you can treat five or six different diseases,'" he mentions.

Finally, he emphasizes that we must find ways to accelerate the generation of evidence. “The proof of concept for [this study] is something I did in 2008: killing mosquitoes that feed on treated people. It's been 17 years. For diseases that affect the poor, we always take a long time to do things. I think we need to take the possibilities much more seriously and try to speed up the timeline.”