As a small container of blood is affixed to the top of a mesh enclosure housing mosquitoes, the hungry insects take notice. They begin flying toward the canister.
I’m in Galvin Life Science Center, standing inside an insectary — a room where insects are kept and studied — with Notre Dame biologists Lee Haines and Álvaro Acosta Serrano. The insectary resembles a large walk-in refrigerator without the chill in the air: The constant 80 degrees and 80 percent humidity mimic the tropical environments where mosquitoes thrive in the wild. The climate control system is noisy, drowning out the high-pitched buzz of the insects’ flapping wings.
Within each mesh-enclosed cage, the mosquitoes have plenty of food, water and space to lay eggs. The cages allow scientists to study disease transmission, test mosquito control methods and observe mosquito behavior. A tightly wrapped translucent sleeve provides the only means for the researchers to slip an arm inside a cage without letting inhabitants escape.
Haines and Acosta Serrano have been studying the drug nitisinone with colleagues in several countries for nearly a decade. Recently, their team has discovered that blood containing the drug, developed to treat rare, hereditary metabolic disorders, is deadly to mosquitoes — including Anopheles gambiae, a malaria-spreading vector found primarily in sub-Saharan Africa. The finding makes nitisinone a potential game-changer when it comes to killing mosquito populations and reducing the incidence of malaria and the other deadly diseases such insects transmit.
Although this research started exclusively with human blood, the Notre Dame scientists have adapted the protocol to use sheep blood instead, because it is less expensive and is easy to obtain. The activity of nitisinone appears to remain the same whether it is mixed with human, horse or sheep blood, Haines says.
These latest results were published in March in Science Translational Medicine, a biomedical journal published by the American Association for the Advancement of Science, and soon drew headlines around the world in popular magazines and newspapers including National Geographic, The Independent and Discover.
Nitisione offers a potential alternative for battling vector-borne disease in those regions of the globe where mosquitoes have developed a resistance to the insecticides or drugs already in use, says Haines, an associate research professor of biological sciences at Notre Dame and a co-lead author of the study. As a medical entomologist, she studies how insects spread diseases.
The drug kills mosquitoes and other blood-feeding vectors, such as ticks, bedbugs and fleas, says Acosta Serrano, a molecular parasitologist and vector biologist and co-corresponding author of the study.
Approved for human use by the U.S. Food and Drug Administration in 2002, nitisinone kills the mosquitoes without harming butterflies or other insects that do not feed on blood. If this use of the drug is approved, its administration in regions where malaria is endemic and difficult to fight could significantly reduce the population of the mosquitoes that carry the malaria parasite.
Female mosquitoes bite and feed on the blood of humans and other animals. Males do not. The blood provides the protein the females need to lay their eggs, and they must bite to ingest the blood — they aren’t able to simply drink it. They require blood that is “warm like a human, tastes like a human and smells like a human,” Haines explains. If it doesn’t, “they won’t feed.”
To mimic skin, the container of blood in the mesh cage is covered with a thin cellulose membrane. During my visit, graduate student Stephanie Morgan carefully transfers a vial of sheep’s blood into a container. Once the container is sealed, she balances it on her wrist for several minutes to warm it to body temperature and to transfer her scent.
Various methods are currently used to kill mosquitoes and reduce the risk of malaria. One tool is ivermectin, an antiparasitic medication discovered in the 1970s and given to children in some parts of the world to treat worms. The drug has the side benefit of being deadly to mosquitoes that feed on the blood of children who take it. But ivermectin has drawbacks. It’s toxic to some aquatic organisms, it lingers in the environment, it is not approved for use by pregnant mothers or infants, and its overuse leads to resistance among targeted insect populations. Meanwhile, nitisione, even at low, therapeutic doses, appears to outperform ivermectin as a preventative.
Nitisinone may even be applied as an insecticide. When sprayed on walls and other surfaces, it can permeate the mosquito’s exoskeleton and kill it that way, Acosta Serrano says.
That outcome applies even to mosquito populations that have become resistant to standard insecticides, Haines adds — though the scientists note that more research is required on the drug’s use as an insecticide.
Nitisinone was developed for patients who have rare, inherited diseases — alkaptonuria and tyrosinemia type 1 — that make it difficult for humans to metabolize the amino acid tyrosine. The medicine works by blocking an enzyme called 4-hydroxyphenylpyruvate dioxygenase. It also blocks that enzyme in mosquitoes, whose resulting inability to digest blood causes them to die within about 24 hours. They first lose the ability to fly, then rapidly progress to full paralysis and death.
The research on nitisinone as a protection against mosquitoes and the diseases they carry isn’t finished. Further field trials will assess safety and efficacy.
Nor is the potential advancement a malaria cure. But deployed in conjunction with other tools, such as insecticide-laced bed nets and malaria-prevention drugs and vaccines — nitisinone could greatly reduce mosquito populations and illness rates. “It’s another tool in the toolbox,” Haines says.
Haines, a Canadian citizen, and Acosta Serrano, who is Venezuelan-British, joined the Notre Dame faculty two years ago, recruited from their former positions at the Liverpool School of Tropical Medicine in Great Britain. The nitisinone research was funded through grants provided by nonprofit foundations in Britain and by the Seattle-based Gates Foundation.
The researchers collaborate with pharmacological modelers who “told us what concentration of the drug should be in human blood if you were taking this drug,” Haines says. They also worked with the Robert Gregory National Alkaptonuria Centre in Liverpool. People using nitisinone for alkaptonuria donated the blood used in the initial part of the study.
Haines and Acosta Serrano are affiliated with Notre Dame’s Eck Institute for Global Health, which supports interdisciplinary faculty and student researchers whose work addresses health disparities around the world. The institute views health as a human right and promotes research, training and service to improve health standards for all people, especially the residents of resource-poor countries who may be disproportionately impacted by preventable diseases.
Mosquitoes transmit diseases such as malaria, yellow fever, dengue fever and the Zika virus and kill more people than any other creature: an estimated 1 million people die each year from these illnesses; more than 600,000 from malaria alone.
Nitisinone is currently expensive — at least $31.67 per capsule in the U.S., according to pharmacychecker.com — because relatively few people take it. But if it becomes a common treatment to kill mosquitoes, much more would need to be made. That, Haines notes, would drive down the price. Eventually, nitisinone could become standard issue for travelers or military personnel heading to regions where malaria and other insect-borne diseases are widespread. It could also save lives in refugee camps, she says.
Were the World Health Organization to approve nitisinone for such voluntary mass distribution in tablet form, people would have to be educated about its ability to kill mosquitoes and consider their role in limiting mosquito numbers and reducing mosquito-borne diseases.
Taking the medication “would be an altruistic act,” Haines says.
While malaria is a deadly concern outside the U.S., where the disease was eradicated in 1951, climate change assures its eventual return. “You have a lot more adverse weather events like hurricanes coming through. Way more mosquito habitats have been created here,” Haines says. “There are going to be huge mosquito problems and mosquito-borne diseases here in the U.S.”
In 2023, public health officials identified seven locally acquired cases of malaria in Florida. “With climate change, it’s not if, it’s when,” Acosta Serrano affirms.
Malaria aside, other serious, mosquito-related diseases such as Eastern equine encephalitis and West Nile virus are already a domestic threat and are getting more attention every year.
“It’s wise to think about what [has] happened globally,” Haines says, “because that gives us a hint as to what we are going to face in the near future.”
Margaret Fosmoe is an associate editor of this magazine.