Scientists want to poison mosquitoes to fight malaria – with human blood

 

Using low doses of a drug approved to treat rare genetic conditions in humans kills mosquitoes – and leaves them very dead. Scientists say it could be a valuable new tool in the fight against the disease.

Female Anopheles gambiae mosquitoes transmit malaria parasites to humans. This particular female glows green due to a diet containing fluorescein, a substance that appears green under ultraviolet light, revealing the mosquito's hemolymphatic system.Malaria causes more than 600,000 deaths each year and is just one of several deadly human diseases spread by mosquitoes. What if we could make our blood poisonous to the parasites that crave it ?

Although it sounds like science fiction, the idea is not that far-fetched.

In a recent study published in the journal Science Translational Medicine , scientists reported that a drug known as nitisinone can make human blood toxic to mosquitoes , which died within hours of feeding on blood samples from patients who received relatively small doses of the drug. What's more, the drug remains effective for up to 16 days after the initial dose is administered.

It is important to note that nitisinone does not protect against malaria infections . However, since it kills mosquitoes before they lay eggs, it may reduce disease-carrying mosquito populations to the point where the chain of infection is broken.

Similar to a vaccine that relies on herd immunity, the premise is not to be individually immune to malaria, but to work together as a community to control an outbreak.

While the researchers say the tool cannot completely eradicate mosquito-borne diseases, it could be useful when used in conjunction with other strategies, including insecticide-infused bed nets, malaria prevention drugs and vaccines . The new tool could prove particularly effective in areas where mosquitoes have already developed resistance to other treatments.

The interesting thing here is that we are using a drug that the United States Food and Drug Administration (FDA) has already approved because it is used to treat rare genetic diseases,” says Álvaro Acosta Serrano , a parasitologist, vector biologist and co-author of the study.

A drug with an interesting history

Inspired by a toxin from the bottlebrush (a plant in the genus Callistemon ), nitisinone was originally designed for use as a herbicide and worked by acting on an essential amino acid known as tyrosine .

A family of rare genetic disorders, such as tyrosinemia type I and alkaptonuria , occur when the body fails to properly metabolize this same amino acid. Researchers discovered that nitisinone could be an effective treatment , and the U.S. FDA approved its use in humans in 1992.

“This is the only thing that keeps kids with tyrosinemia type 1 alive,” Acosta Serrano says. “It’s not a perfect solution, but there is no alternative.” Because nitisinone causes a range of side effects in patients with these disorders, he says they often need much larger amounts of the drug than would be needed for effective mosquito control.

In 2016 , a pair of Brazilian researchers named Marcos Sterkel and Pedro Oliveira discovered that blood-feeding insects, such as fleas, flies, and mosquitoes, have evolved the ability to rapidly process tyrosine , which floods their bodies after a blood meal.

More importantly, they also found that the insect dies if they can affect this process .

Knowing that Acosta Serrano’s lab at the Liverpool School of Tropical Medicine in the United Kingdom was working with another blood-sucking, disease-carrying parasite known as the tsetse fly , the researchers contacted him to see if nitisinone might play a role in their research. Soon after, the team expanded the scope of their work to examine nitisinone’s effect on mosquitoes.

And that's how nitisinone went from killing plants to saving children and potentially fighting a deadly disease .

There are no silver bullets for malaria

Because nitisinone has already passed several rigorous safety tests, repurposing the drug to combat mosquito-borne diseases would require fewer approvals , says Acosta Serrano, who is now at the University of Notre Dame. For example, nitisinone is already approved for use in newborns and young children, and there have been no reported harmful effects in pregnant people . That’s one reason the results are promising.

“I think the study is very interesting,” says George Dimopoulos , a molecular biologist specializing in mosquito-borne diseases at the Johns Hopkins Bloomberg School of Public Health. For starters, the idea that nitisinone might be useful in combating mosquito-borne diseases is entirely new, he says. It’s also intriguing that the side effects appear to be less than those of ivermectin, a drug that can be used to prevent malaria transmission —and more effectively.

Of course, Dimopoulos pointed out several disadvantages.

“Malaria is a disease of poverty,” says Dimopoulos. “Anything that becomes expensive or burdensome is not going to work, especially with a method of intervention like this, where we are not protecting the individual per se, but the population.”

The rarity of the diseases treated with nitisinone means the drug is still too expensive for widespread use. However, Acosta Serrano hopes that increased interest will lead to a reduction of up to 80 percent in the cost of nitisinone.

The indirect nature of prevention could also be a hurdle. “It’s always hard to convince people to take a drug that doesn’t protect them,” says Dimopoulos.

However, he believes it may be possible to combine nitisinone treatment with an anti-malaria drug in the future. Furthermore, the treatment may be more effective if given to livestock living near a population , which would effectively act as a sort of mosquito decoy.

Similarly, since mosquitoes also rely on nectar as a food source, scientists have experimented with creating insecticide-laced nectar sacs that attract mosquitoes without exposing other pollinators to the poison .

“So in theory, we can use this drug to expose mosquitoes through this technology,” Dimopoulos says. “We don’t necessarily have to give it to humans.”

Resistance is another concern with any mosquito control method . However, only time will tell if the creatures can evolve to tolerate the toxin.

Whatever role nitisinone plays in the future, Acosta Serrano and Dimopoulos agree that the drug will be most effective if it is integrated into a multifaceted approach tailored to each population .

“In some places, drugs mixed with vaccines might work best. In others, insecticides and new technologies like genetically modified mosquitoes, for example, might be more effective,” Dimopoulos says. “It’s a bit like personalized medicine .”

“There are no silver bullets for malaria,” he says. “And I don’t think there ever will be any silver bullets.”