A drug that makes human blood lethal to mosquitoes also acts as a potent contact insecticide absorbed through the feet, providing a promising new approach to combating insecticide resistance.
A new study led by Liverpool School of Tropical Medicine shows that mosquitoes are killed when they feed on blood and then land on a surface sprayed with nitisinone, a drug currently used to treat a rare genetic condition in humans.
The research shows that this is true even when the mosquitoes are highly resistant to existing insecticides, which opens a promising new avenue for formulating nitisinone for indoor spraying or bed nets at a time when resistance poses a significant threat to vector control programs worldwide.
Nitisinone is lethal to mosquitoes as it blocks an enzyme that they need to safely process the protein and amino acids they get from blood.
The new paper, published in Parasites & Vectors , follows on from a study earlier this year that showed that nitisinone is deadly to mosquitoes when they drink the blood from someone on nitisinone therapy. The drug is safe and already approved for widespread human use and is currently the only treatment for the rare genetic disorders tyrosinemia type 1 and alkaptonuria.
In this new study, nitisinone was shown to be mosquitocidal to several mosquito species (Anopheles, Aedes and Culex), including those that transmit malaria, reemerging infections such as dengue and Zika, and emerging viral threats like Oropouche and Usutu viruses.
The research also proved that nitisinone killed mosquitoes regardless of whether exposure occurred before or after a blood meal, tapping into mosquito resting behaviour before or after feeding. Because nitisinone works by disrupting the mosquito's bloodmeal digestion (tyrosine metabolism), which is not a pathway targeted by any of our current insecticides, it could help public health campaigns eliminate mosquitoes where insecticide resistance has made other products fail.
Dr Lee Haines, senior author and Honorary Research Fellow at LSTM said: "Our conclusions are exciting. Working with a drug like nitisinone, and its versatility, bodes well for creating new products to combat mosquitoes. The fact that it effectively kills insecticide-resistant mosquitoes could be a game-changer in areas where resistance to current insecticides is causing public health interventions to fail.
"This project proved how important it is to think outside the box. We don't know yet why nitisinone is absorbed through the mosquito's feet, and why the other similar compounds are not. But it is going to be exciting to solve this mystery!"
Zachary Stavrou-Dowd, Research Assistant and PhD student at LSTM, and lead author on the new paper, said: "Nitisinone acts to clog up the mosquito digestive system. When a mosquito gorges on your arm, that blood contains a massive protein load. What we have shown here is that we can turn that key trait against them. The mosquito can't digest the blood; it becomes overloaded by its own meal; it dies."
The research was part funded by the Jean Clayton Fund for early career researchers at LSTM.
Zachary Stavrou-Dowd said: "Receiving the Jean Clayton Early Career Researcher Award at LSTM was a pivotal moment, it not only helped fund part of this study but also strengthened our application for a Rosetrees Seedcorn Grant. It's a great example of how internal support can catalyse external funding opportunities and boost visibility for early career researchers like me."