Veterinary drug could curb malaria and Zika outbreaks

Calibr researchers look at a class of drugs called isoxazolines with an eye toward human use

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LA JOLLA, Calif.—Medicines given to household pets to kill fleas and ticks might be effective for preventing outbreaks of malaria, Zika fever and other dangerous insect-borne diseases that infect millions of people worldwide, according to a new study led by scientists at Calibr, a non-profit drug discovery institute closely affiliated with Scripps Research, and TropIQ Health Sciences, a Dutch social enterprise.
The researchers found that a class of drugs called isoxazolines, sold in veterinary products such as fluralaner (Bravecto) and afoxolaner (NexGard) to protect pets from fleas and ticks, also kill species of disease-carrying mosquitos that feed on human blood.
The research team, led by TropIQ’s Dr. Koen Dechering and Calibr’s Dr. Matt Tremblay, determined via experimental studies on mosquitoes and computer modeling that giving isoxazoline drugs to less than a third of the population in areas prone to seasonal outbreaks of insect-borne diseases could prevent up to 97 percent of all cases of infection. The results of the study were published recently in the Proceedings of the National Academy of Sciences (PNAS).
“Insect-borne infectious diseases remain primary causes of severe illnesses and fatalities worldwide, and new approaches to preventing outbreaks of these diseases are critically needed,” said Dr. Peter Schultz, CEO of Calibr and Scripps Research. “Our findings suggest that isoxazolines might be effective at controlling outbreaks of diseases carried by mosquitoes and other insects in regions with limited medical infrastructure.”
Millions of people each year contract malaria, Zika fever and other insect-borne diseases that are particularly prevalent in tropical and sub-tropical regions. In 2016, an estimated 216 million people contracted malaria worldwide and 445,000 died from the disease (mostly children in the African Region), according the U.S. Centers for Disease Control and Prevention. Zika, a mosquito-borne disease that can cause birth defects in infants born to infected mothers, has spread rapidly around the planet in recent years and is now found in 90 countries.
“Research on insect-borne diseases has predominantly focused on control of insect populations through use of insecticides and prevention of bites through distribution of bednets, but these approaches have not been fully effective in controlling outbreaks,” says Koen Dechering, CEO of TropIQ Health Sciences. “Vaccines are largely lacking for most diseases and drugs to treat people who have contracted the disease are losing efficacy because of emerging resistance.”
The international research team investigated a new strategy, the possibility of giving humans isoxazolines to block transmission of diseases by insect vectors.
When administered orally, the drugs are absorbed into the bloodstream and spread throughout the animal’s body, where they remain active for up to three months. While well tolerated in dogs and cats, the drugs kill blood-sucking fleas and ticks that feed on the blood of treated animals by damaging the insects’ nervous systems.
The Calibr and TropIQ scientists and their collaborators tested two of the drugs, fluralaner and afoxolaner, and found they also kill species of disease-carrying mosquitos and sand flies that feed on human blood infused with the insecticides. The drugs also were effective against insect strains that are resistant to common insecticides.
Based on existing data from studies of the drugs in animals, the researchers estimated that a single human dose of the drugs would convey an insecticide effect against mosquitos and sand flies lasting 50 to 90 days.
“In many regions where seasonal outbreaks are endemic, medical infrastructure is such that delivery of medical care is on an intermittent basis,” said Tremblay, chief operating officer of Calibr and Scripps Research and a senior author on the PNAS paper. “Isoxazolines could be administered prior to the beginning of seasonal disease outbreaks to convey protection until the threat diminishes at the end of the season.”
The drugs may not work as vaccines, since a treated person could still contract a disease from an insect bite. But an insect that bites an infected person taking the drugs would die before it could transmit the disease to other people, an effect that, when multiplied over a large population, would reduce the overall number of infections.
Based on safety studies of isoxazoline use in animals, the drugs have a good chance of being safe if repurposed for human use, according to Calibr. The research team is planning to evaluate the efficacy of the drugs in humans, and anticipates that these studies will take around two years.

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