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In the ongoing battle against malaria, effectively managing mosquito populations plays a vital role.
Various strategies are employed to curb mosquito numbers and minimize the risk of malaria transmission. Among these methods is the use of ivermectin, an antiparasitic medication. When mosquitoes consume blood containing ivermectin, it significantly reduces their lifespan, thus helping to lower the malaria transmission rates.
Despite its effectiveness, ivermectin presents challenges. It poses environmental hazards and raises concerns over potential resistance development due to its widespread application in treating human and animal parasite infections.
A recent study published in Science Translational Medicine highlights an alternative medication that could aid in mosquito population suppression and mitigate malaria spread. Researchers discovered that when patients are administered nitisinone, their blood becomes lethal to mosquitoes.
“One potential method to impede the spread of insect-borne diseases is to render the blood of humans and animals toxic to these blood-feeding insects,” stated Lee R. Haines, an associate research professor at the University of Notre Dame and co-lead author of the study. “Our research indicates that nitisinone could serve as a promising additional tool for combatting diseases like malaria that are transmitted by insects.”
Nitisinone is typically prescribed for individuals with rare genetic disorders, such as alkaptonuria and tyrosinemia type 1, which hinder their ability to metabolize the amino acid tyrosine. This medication acts by inhibiting the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD), preventing the accumulation of harmful metabolic byproducts in the body. When mosquitoes feed on blood containing nitisinone, the drug disrupts the function of HPPD in the mosquitoes as well, impairing their ability to digest the blood and leading to their demise.
The research team conducted an evaluation of the necessary nitisinone concentrations for effectively killing mosquitoes, comparing its efficacy against ivermectin, which is considered the benchmark in ectoparasitic treatments.
“We aimed to establish that nitisinone could outperform ivermectin in this context,” noted Álvaro Acosta Serrano, a professor of biological sciences at Notre Dame and co-corresponding author of the study. “In fact, nitisinone demonstrated excellent performance; it possesses a significantly longer half-life in human blood compared to ivermectin, which means its ability to kill mosquitoes remains effective for an extended period. This aspect is essential for field applications related to safety and cost-efficiency.”
To test the effect of nitisinone on female Anopheles gambiae mosquitoes, the leading species of malaria transmitters in various African regions, the research team partnered with the Robert Gregory National Alkaptonuria Centre at the Royal Liverpool University Hospital. The center was conducting trials on nitisinone among individuals diagnosed with alkaptonuria, who donated blood for the study. The results revealed that participants on nitisinone had blood lethal to mosquitoes, which Haines characterized as possessing a “hidden superpower.”
Data pertaining to the metabolism of nitisinone in human blood was collected, enabling the researchers to refine their modeling and validate the pharmacological potential of nitisinone as a strategy for mosquito population control.
The study confirmed that nitisinone not only has a longer duration of action than ivermectin in the bloodstream, but it also has the capacity to kill mosquitoes at all life stages, particularly the older ones most likely to transmit malaria, including those resistant to conventional insecticides.
“In the future, it may be beneficial to utilize both nitisinone and ivermectin interchangeably for mosquito management,” Haines added. “For instance, nitisinone might be particularly useful in regions facing issues with ivermectin resistance or where ivermectin usage is already prevalent in livestock and human treatments.”
The next phase for the research team involves conducting semi-field trials to identify the dosages of nitisinone that optimize its effectiveness as a mosquito repellent.
“Nitisinone is a flexible compound that can also function as an insecticide. Its specific targeting of blood-sucking insects makes it an environmentally sustainable option,” Acosta Serrano elaborated.
Moreover, expanding the application of nitisinone as a vector control tool could inadvertently boost the drug’s production and lower its cost for patients afflicted with rare genetic disorders associated with tyrosine metabolism.
The study was supported by various organizations, including the UK Medical Research Council, the Biotechnology and Biological Sciences Research Council, and the Wellcome Trust Institutional Strategic Support Fund, among others.
Alongside Acosta-Serrano and Haines, contributors to the study include Anna Trett, Jeremy Burrows, Clair Rose, Natalia García, Giancarlo Biagini, Ghaith Aljayyoussi, Dagmara McGuinness, Clément Regnault, Michael Barrett, Didier Leroy, and others affiliated with several institutions dedicated to malaria and genetic research.
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