Harvard researchers are now testing experimental malaria bed nets in Burkina Faso and Ethiopia that are designed to target the parasite inside mosquitoes rather than kill the insects. The approach uses antimalarial compounds incorporated into bed-net-like materials and is intended to interrupt Plasmodium falciparum development inside mosquitoes, potentially offering an alternative strategy as insecticide resistance threatens conventional mosquito-control tools.
Researchers at Harvard T.H. Chan School of Public Health and collaborating institutions tested 81 antiparasitic compounds against Plasmodium falciparum, the malaria parasite that causes most malaria cases in Africa and is responsible for most malaria deaths worldwide. They identified two compounds, ELQ-456 and ELQ-331, that interfered with parasite development inside Anopheles gambiae mosquitoes.
The researchers then incorporated the compounds into experimental bed-net materials. Laboratory tests showed that the compounds could kill malaria parasites inside mosquitoes without relying on insecticides to kill the insects themselves. The research has now progressed to field testing in Burkina Faso and Ethiopia.
The findings were published in Nature on May 21, 2025, in a study titled “In Vivo Screen of Plasmodium Targets for Mosquito-Based Malaria Control.”1
Malaria remains a major global health problem. The World Health Organization estimated 263 million malaria cases and 597,000 deaths worldwide in 2023. About 95 percent of malaria deaths occurred in the WHO African Region.2
Mosquito control is an important part of malaria prevention. Insecticide-treated bed nets protect people by reducing contact with mosquitoes and exposing mosquitoes to insecticides. However, resistance to commonly used insecticides has become an increasing challenge in malaria-endemic regions.
The Harvard-led team explored a different approach: instead of making the mosquito the primary target, researchers attempted to make the malaria parasite inside the mosquito the target.
According to co-corresponding author Flaminia Catteruccia, the Irene Heinz Given Professor of Immunology and Infectious Diseases and a Howard Hughes Medical Institute Investigator,
Malaria control desperately needs innovation. This is a momentous step forward in the development of a new mosquito-targeted malaria control strategy, which could lead to a new generation of effective antimalarial bed nets.Flaminia Catteruccia, Professor of Immunology and Infectious Diseases.
The malaria parasite passes through several stages during its life cycle. When an Anopheles mosquito feeds on a person carrying P. falciparum, the parasite enters the mosquito and develops inside it.
For the mosquito to transmit malaria during a later blood meal, the parasite must complete its development inside the insect.
The researchers used this stage of the parasite's life cycle as a point of intervention. They screened 81 compounds representing different mechanisms of action and identified 22 compounds that significantly impaired P. falciparum development in mosquitoes.
Further testing identified ELQ-456 and ELQ-331 as particularly active compounds.1
Mosquito lands on treated net → picks up antimalarial compound → parasite inside mosquito is targeted → the mosquito can survive exposure to the compound while the parasite's development is disrupted, potentially preventing the mosquito from becoming infectious.
Lead author Alexandra Probst, a doctoral student in the Biological Sciences and Public Health program at Harvard T.H. Chan School of Public Health and Harvard Kenneth C. Griffin Graduate School of Arts and Sciences, said,
This new malaria control strategy blocks mosquito-mediated parasite transmission without killing the mosquito and inducing resistance, which could extend the effective lifespan of bed nets.Alexandra Probst, Lead Author
The idea of “curing” mosquitoes is not new. It goes back to research published by the same Harvard-led group in 2019. The study showed that exposing Anopheles mosquitoes to the antimalarial drug atovaquone could block the development of Plasmodium falciparum inside the insects. In laboratory experiments, mosquitoes exposed to atovaquone-coated surfaces for as little as six minutes were prevented from developing transmissible malaria parasites.3
The 2025 study took this concept further. Researchers screened 81 compounds to identify substances that could act against malaria parasites during their development inside mosquitoes. They identified ELQ-456 and ELQ-331 and incorporated the compounds into experimental bed-net materials, demonstrating their activity against the parasite under laboratory conditions.1
By 2026, the research had moved beyond laboratory experiments. Harvard reported that the team was testing the effectiveness of these next-generation bed nets in Burkina Faso and Ethiopia, marking the next stage in evaluating whether the approach can work under field conditions.4
ELQ-456 and ELQ-331 belong to a group of compounds known as endochin-like quinolones.
Both compounds interfere with the malaria parasite's mitochondrial electron transport chain, a system involved in producing the energy the parasite needs to develop. However, they act at different sites of the parasite's cytochrome bc1 complex.
This complex plays a role in the parasite's energy-producing processes. Interfering with it can prevent the parasite from developing normally inside the mosquito.1
The researchers incorporated the compounds into polyethylene materials designed to resemble bed-net materials. In laboratory experiments, the treated materials exposed mosquitoes to the parasite-targeting compounds.
The researchers found that the experimental compounds could kill malaria parasites inside mosquitoes without needing to kill the mosquito.
In the laboratory experiments, the compounds were active at low concentrations. The compounds retained activity after a year on the bed-net-like materials and remained effective when mosquitoes encountered them up to four days before becoming infected. 4
The researchers also tested the approach in mosquitoes resistant to conventional insecticides. The parasite-targeting compounds continued to act against P. falciparum in these mosquitoes.
Co-corresponding author Dyann Wirth, Richard Pearson Strong Professor of Infectious Diseases, commented: Resistance to insecticides has compromised mosquito control efforts, particularly in Africa. One great advantage of this strategy is that it is focused on killing the parasite rather than the mosquito.
This distinction is important because the strategy does not depend on the same mosquito-killing mechanism used by conventional insecticides.1
Conventional insecticide-treated nets primarily target mosquitoes. Their effectiveness can therefore be affected when mosquito populations become resistant to the insecticides used on the nets.
The experimental approach changes the target. The mosquito can survive exposure to the treated material, but the malaria parasite developing inside it is exposed to the antimalarial compound.
If the parasite cannot complete its development, the mosquito may not become capable of transmitting malaria to another person.
The researchers therefore describe the approach as a mosquito-based malaria-control strategy that aims to block parasite transmission without relying on mosquito mortality.4
The laboratory findings suggest that targeting malaria parasites during their development inside mosquitoes can prevent or reduce parasite transmission.
In the mosquito experiments, ELQ-456 completely inhibited detectable parasite infection under the study conditions, while ELQ-331 reduced infection prevalence by 69.3%.
The researchers also found evidence that the two compounds act at different sites within the parasite's mitochondrial electron transport chain.
The findings also raise the possibility that resistance to these compounds could come with a biological cost to the parasite. In the study, parasites carrying certain resistance-associated mutations showed impaired development during the mosquito stage, although this does not establish that resistance would not emerge in field populations. 1
However, these findings do not yet demonstrate that the experimental bed nets can reduce malaria transmission in human populations.
The study provides evidence for a different strategy for malaria vector control: targeting the parasite while it is inside the mosquito rather than relying exclusively on killing the mosquito.
The researchers suggested that parasite-targeting compounds could potentially be incorporated into existing bed-net infrastructure. Future studies will need to establish whether this approach can work outside laboratory conditions and how it could be combined with existing malaria-control measures.4
For now, the research represents an experimental strategy for interrupting malaria transmission at the mosquito stage of the parasite's life cycle. It does not replace currently recommended malaria prevention methods.
1. Probst, Alexandra S., Douglas G. Paton, Federico Appetecchia, et al. 2025. “In Vivo Screen of Plasmodium Targets for Mosquito-Based Malaria Control.” Nature 643: 785–793. https://doi.org/10.1038/s41586-025-09039-2.
2. World Health Organization. 2024. World Malaria Report 2024. Geneva: World Health Organization. World Malaria Report 2024
3. Paton, Douglas G., Lauren M. Childs, Maurice A. Itoe, et al. 2019. “Exposing Anopheles Mosquitoes to Antimalarials Blocks Plasmodium Parasite Transmission.” Nature 567: 239–243. https://doi.org/10.1038/s41586-019-0973-1.
4. Harvard T.H. Chan School of Public Health. 2026. “Malaria is gaining ground, but researchers are developing promising new solutions.” June 3, 2026. Harvard T.H. Chan School of Public Health
5. Nature. 2025. “Research briefing: In vivo screen of Plasmodium targets for mosquito-based malaria control.” May 21, 2025. Nature Research Briefing
(Rh/SS/MSM)