College of Veterinary Medicine Professor's Study Takes the Fight to Drug-Resistant Hookworms

Findings from a new study co-led by Stephanie Martinez, assistant professor of pharmacology in the College of Veterinary Medicine at Utah State University, may help improve the safety of a treatment for dogs infected with drug-resistant hookworms.

Hookworms are parasitic nematodes that infect animals and attach themselves to the gastrointestinal tract, puncturing blood vessels to feed. Their eggs spread through the feces of infected hosts, hatch into larva, and spread to new hosts through contact with contaminated surfaces like soil and sand.

Prolonged infections cause malnutrition and anemia and can be fatal to young or immunocompromised animals.

Hookworms are often particularly tricky to treat, because infections can come in waves. Sometimes, an antiparasitic treatment will kill the adult hookworms living in the gut, but larvae will remain somewhat dormant in the tissues of the body and invade the gastrointestinal tract when they sense the adults are gone.

Parasitologists have been warning of the spread of multidrug-resistant hookworms since at least 2019. In 2021, the news publication of the Journal of the American Veterinary Medical Association (JAVMA News) ran an article outlining how yet another anthelmintic (worm-killing) drug being used to treat the parasitic infection was proving ineffective against some hookworm isolates in lab studies. Now, the three FDA-approved anthelmintic drug classes — benzimidazoles, tetrahydropyrimidines and macrocytic lactones — are proving no match for drug-resistant hookworms.

One drug, emodepside, is showing promise, and the medication in pill form has been approved in Europe for use in dogs. But in the U.S., the Food & Drug Administration has only approved a topical treatment for use in cats.

When all other treatments fail, veterinarians in the U.S. have been blindly giving the FDA-approved feline topical product to dogs by mouth (extralabel use) in hopes that it will be as safe and effective as the pill form available in Europe. But emodepside carries risk of adverse neurological effects in dogs if exposure is too high, and some dog breeds may be susceptible to neurological effects at lower concentrations. It can also be dangerous to use if a dog is also infected with heartworm microfilariae, depending on the stage of infection.

Martinez’ research team aimed to compare total drug exposure of the feline topical solution, when administered orally to dogs, to the safe and effective European pill treatment for dogs.

The study, “Topical and oral emodepside formulations for last-line treatment of multi-anthelmintic drug-resistant hookworms when given orally to dogs are not bioequivalent,” with Martinez as the co-corresponding author, was published online April 4 in the Journal of the American Veterinary Medical Association.

“The idea behind bioequivalence is that if drug exposure is equivalent, we expect a clinically equivalent effect,” Martinez said.

The paper details the crossover study of seven healthy, client-owned dogs tested after being administered the feline topical solution orally, the canine modified-release tablet (only available in Europe), and the feline topical solution, topically.

“Our findings suggest that, if the feline formulation must be given orally to dogs, the dose should be about half of what is currently being used,” Martinez said. “We hope this research can help improve safety in these challenging cases until an FDA-approved canine formulation becomes available.”

Martinez and her co-authors from Auburn University’s College of Veterinary Medicine will appear on a May 2025 episode of the Veterinary Vertex podcast, hosted by the American Veterinary Medical Association, to discuss the study.