A drug used to treat rare genetic disorders also makes human blood lethal to mosquitoes, new research led by Liverpool School of Tropical Medicine shows.
Nitisinone, a medication already used to treat rare genetic disorders like tyrosinemia type 1, blocks an essential enzyme mosquitoes need to digest their blood meal, resulting in rapid death.
The new findings build on Liverpool School of Tropical Medicine’s (LSTM) groundbreaking 2021 research that validated nitisinone's effectiveness against tsetse flies.
Published in Science Translational Medicine this week, this new LSTM-led study reveals nitisinone's remarkable ability to kill both insecticide-susceptible and resistant mosquito strains at far lower doses than initially thought possible.
These findings represent a major advancement in the fight against malaria, offering a promising new vector control strategy at a critical time when growing insecticide resistance threatens global disease management progress.
Dr Lee Haines, first author, Honorary Fellow at LSTM and currently Associate Research Professor at the University of Notre Dame, said: “What makes nitisinone so exciting is its novel mode of action against blood-feeding insects like mosquitoes. Unlike conventional insecticides that target the mosquito’s nervous system, nitisinone targets an entirely different biological pathway in mosquitoes, which offers a new option for managing the growing problem of insecticide resistance”.
Nitisinone acts much faster and remains effective for longer than ivermectin, another proven mosquitocidal drug, and successfully kills older mosquitoes that typically carry malaria parasites.
Professor Álvaro Acosta-Serrano, study lead at LSTM and now at the University of Notre Dame, USA, said: “We thought that if we wanted to go down this route, nitisinone had to perform better than ivermectin. Indeed, nitisinone’s performance was fantastic; it has a much longer half-life in human blood than ivermectin, which means its mosquitocidal activity remains circulating in the human body for much longer. This is critical when applied in the field for safety and economic reasons.”
Dr Anna Trett, co-first author, PhD graduate from LSTM in 2025 and now working for the Clinton Health Access Initiative, said: "Older female mosquitoes are the primary transmitters of the malaria parasite. These mosquitoes are often more resistant to insecticides, so finding a treatment effective against them is a major advancement in the search for novel vector control tools to address residual and outdoor malaria transmission."
Further safety studies at various dosing levels are now required, particularly in healthy populations from malaria-endemic countries, as well as into how the drug interacts with antimalarial drugs to see if it could genuinely be repurposed for malaria control.
Professor Giancarlo Biagini, Pro Vice-Chancellor for Research & Innovation at LSTM and co-author on the paper, said: "This innovative study exemplifies LSTM’s commitment to translational, interdisciplinary research that drives real-world impact. We are now embarking on follow-on clinical studies to evaluate nitisinone’s safety and efficacy as a complementary tool to existing malaria transmission control strategies, leveraging LSTM’s extensive network of pre-clinical and clinical platforms and partnerships. While these findings are highly promising, further rigorous evaluation is essential before nitisinone can be implemented in public health programmes."
The study was conducted by scientists from LSTM, including co-corresponding author Dr Ghaith Aljayyoussi, and an international team from Universidad Nacional de La Plata in Argentina, the University of Glasgow, and Medicines for Malaria Venture.
The study was also made possible due to the quality collaboration with the Royal Liverpool University Hospital and its National AKU Centre.