Mosquitoes beware – your next meal could be your last
Nitisinone is already used to slow the effects of tyrosinemia type 1, a hereditary condition that can cause severe liver disease and kidney failure, and other diseases.
But it also makes any mosquitoes that ingest it unable to digest the blood they feed on, killing them rapidly, research led by the Liverpool School of Tropical Medicine (LSTM) found.
The study, published in Science Translational Medicine this week, showed that the drug blocks an essential enzyme mosquitoes need to break down their food.
Tests showed a small amount of the drug was even able to kill mosquitoes that have developed the ability to resist conventional insecticides – an increasingly widespread problem that has slowed efforts to combat malaria and other mosquito-borne diseases.
'What makes nitisinone so exciting is its novel mode of action against blood-feeding insects like mosquitoes,' said Dr Lee Haines, an Honorary Fellow at LSTM and one of the authors of the study.
'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.'
The study followed earlier research which first validated the theory that nitisinone could be used to kill insects that feed on blood. It proved highly effective at killing tsetse flies that spread sleeping sickness.
While the drug does not prevent a feeding mosquito from infecting someone with a virus, it could provide a new tool to combat the spread of disease by thinning out their populations, the researchers believe.
Several insecticides are already widely used in this way, such as ivermectin, a medicine usually used to treat parasitic infections in animals and people and which shortens the lifespan of any insect that ingests it.
But ivermectin, while abundant, is toxic in the environment and insects can also develop resistance to it when it is overused.
'Billions of doses have been given to people for the worming campaigns,' said Professor Álvaro Acosta Serrano, another of the study's co-authors. 'Ivermectin is obviously a very popular veterinary drug, so in farms it is polluting the soil and that has some ecological issues.'
As well as being much less harmful to other insects or animals in the ecosystem, nitisinone has the added advantage of lasting much longer in the body, he told The Telegraph.
'Nitisinone, because it has a much longer half life in blood – 54 hours compared to Ivermectin which is only 18 hours max – it has much better performance.'
As well as helping to suppress mosquito populations by killing those that unwittingly feed on humans carrying nitisinone, the drug could be used against mosquitoes in numerous other applications.
It could be used in the sugar-based bait traps currently being tested around the world which lure in mosquitoes and poison them, or it could be sprayed on to bed netting and buildings to get into mosquitoes that way.
The researchers are already planning to investigate whether the drug could be given to cows and other livestock animals to turn them into unwitting reservoirs of death for the insects that feed on them.
'This is a very versatile molecule,' Prof Acosta Serrano said.
Because it was originally developed to be a herbicide, it has many properties that make it ideal for use in these kinds of applications, including good resistance to UV light, he added.
Before all this though the researchers say more work is needed, including safety studies looking at different dosages. They are also yet to study how the drug interacts with antimalarials.
Another major challenge is cost.
While ivermectin has been produced cheaply by generic drug manufacturers for decades and has been donated in vast quantities to tackle diseases like river blindness, nitisinone – despite being off-patent – remains expensive.
'We need to convince a company to drop the prices because, for vector control use, interventions have to be really cost effective,' said Prof Acosta Serrano.
And while nitisinone promises to provide another tool with which to combat mosquito-borne disease, we are still waiting for scientific breakthroughs before we will be able to beat malaria.
'It's important to know that there is not a silver bullet to control any of the vector borne diseases, especially malaria,' he said. 'We still need to come out with better drugs. There is a huge problem with parasites that become drug resistant. We still don't have a completely efficacious vaccine available.'
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