A breakthrough study has revealed that nitisinone, a medication currently used to treat rare genetic disorders, could become a powerful new tool in the global fight against malaria by making human blood lethal to mosquitoes.
Researchers from the University of Notre Dame and Liverpool School of Tropical Medicine have identified that nitisinone has significant potential to suppress mosquito populations and control malaria transmission. The findings, published in the journal Science Translational Medicine, demonstrate a novel approach to vector control by targeting the mosquitoes' ability to digest blood meals.
Mechanism of Action
Nitisinone is primarily prescribed for patients with rare inherited diseases such as alkaptonuria and tyrosinemia type 1, conditions where the body cannot properly break down the amino acid tyrosine. The drug functions by inhibiting 4-hydroxyphenylpyruvate dioxygenase (HPPD), an enzyme involved in tyrosine metabolism.
When mosquitoes ingest blood containing nitisinone, the drug blocks the same HPPD enzyme in their bodies. This inhibition prevents the insects from properly digesting the blood meal, leading to rapid paralysis and death.
"One way to stop the spread of diseases transmitted by insects is to make the blood of animals and humans toxic to these blood-feeding insects," explained Lee Haines, associate research professor of biological sciences at the University of Notre Dame and co-lead author of the study. "Our findings suggest that using nitisinone could be a promising new complementary tool for controlling insect-borne diseases like malaria."
Study Design and Results
The research team conducted their investigation using blood donated by four individuals diagnosed with alkaptonuria who were being treated with nitisinone. This blood was fed to female Anopheles gambiae mosquitoes, the primary vector responsible for malaria transmission in many African countries.
The results were striking. Mosquitoes that consumed blood containing nitisinone exhibited a progressive sequence of symptoms: first losing their ability to fly, then developing full paralysis, and ultimately dying. The drug proved effective against mosquitoes of all ages, including older specimens that are most likely to transmit malaria parasites. Importantly, nitisinone also killed mosquitoes that had developed resistance to traditional insecticides.
Comparative analysis with ivermectin, an anti-parasitic medication currently used for similar purposes, revealed significant advantages for nitisinone. The drug demonstrated a longer active period in human bloodstream and appeared to be more effective at killing mosquitoes across various age groups.
Advantages Over Current Approaches
Current malaria control strategies include the use of ivermectin, which shortens mosquito lifespan when ingested through blood meals. However, researchers note that ivermectin presents several challenges: it can be environmentally toxic, and its widespread use in treating parasitic infections in humans and livestock has led to concerns about resistance development.
Nitisinone could potentially address these limitations. Dr. Haines suggested that alternating between nitisinone and ivermectin might provide an optimal approach to mosquito control.
"In the future, it could be advantageous to alternate both nitisinone and ivermectin for mosquito control," Dr. Haines noted. "For example, nitisinone could be employed in areas where ivermectin resistance persists or where ivermectin is already heavily used for livestock and humans."
Clinical Implications and Future Research
While the initial results are promising, the researchers emphasize that additional studies are necessary to determine optimal dosing regimens for malaria control purposes. The current study focused on blood from patients taking nitisinone for existing medical conditions, but future research will need to establish appropriate dosages specifically for mosquito control applications.
Malaria remains one of the world's most significant public health challenges, particularly in sub-Saharan Africa. According to the World Health Organization, there were an estimated 247 million malaria cases and 619,000 deaths globally in 2021. The emergence of insecticide-resistant mosquitoes and drug-resistant parasites has complicated control efforts, making new approaches like nitisinone particularly valuable.
This research represents a potentially significant advancement in vector control strategies, offering a new mechanism to reduce mosquito populations and interrupt disease transmission cycles. If further studies confirm these initial findings, nitisinone could become an important component of integrated malaria control programs in endemic regions.
