September 15, 2021

Veterinary parasitologists warn that multidrug-resistant hookworms are spreading in the U.S. and that veterinarians should watch for persistent infections.

The Ancylostoma caninum bearing those genetic resistances likely emerged from retired racing Greyhounds and now appear to be spreading within the broader pet dog population, according to parasite researchers and representatives from the American Association of Veterinary Parasitologists. A rise in hookworm shedding also threatens human health because the larvae can infect people through skin contact, causing cutaneous larva migrans.

Some hookworm isolates collected from dogs appear to be resistant to all three anthelmintic drug classes approved in the U.S. for treating hookworm infections. Researchers have found efficacy with emodepside, an anthelmintic approved in Europe for use in dogs, but administering it requires administering a product that is unapproved in the U.S. for use in dogs and that can be dangerous if a dog is coinfected with hookworms and heartworm microfilariae.

Another Food and Drug Administration–approved drug contains emodepside and praziquantel but is labeled only for use in cats, and administering this product to dogs would constitute extralabel use and carry the same heartworm-related concerns.

Antoinette Marsh, PhD, is an associate professor at The Ohio State University College of Veterinary Medicine, president-elect of the AAVP, and chair of the AAVP task force formed, in part, to teach veterinarians that hookworms in the U.S. can be resistant to common treatments and they should follow up on patients to verify the dewormers they prescribe are effective. She said that, until recently, veterinarians who encountered infections that persisted after courses of benzimidazole or pyrantel pamoate could usually rely on a combination course containing moxidectin to treat persistent hookworm shedding in dogs.

“In the last year or so, we’re starting to see slippage—or dogs that are not responding to the moxidectin—and they’re continuing to shed hookworm eggs into the environment, which means that now we have multiple drug-resistant hookworms out there,” Dr. Marsh said. “And we believe that it started in the Greyhound racing population because of the way that drugs were used in the racing Greyhound—maybe misdosing, inappropriate dosing—and just the genetics of the parasites themselves and their reproductive capacity.”

Hookworms can release hundreds of eggs per gram of feces and hundreds of thousands of eggs in a single kennel, Dr. Marsh said. That abundance of genetic material under selective pressure from anthelmintics provides opportunities for strains to emerge with genetic changes that give them the advantage to become the dominant strains in a population.

“If you deworm the dogs and one or two of the strains have had a genetic change which allows them to be drug resistant, they can actually then take over the whole population,” she said.

Dr. Marsh cited study results that indicate dogs with suspected or confirmed drug-resistant hookworms are becoming widespread in the Southeast, and she said they have been documented in the Northeast and California, although the prevalence is unknown as are the genetic markers for resistance. Not all of the isolates are multidrug resistant, she said.

Members of the AAVP task force have been among the authors of scientific articles on the rising threat of multidrug-resistant A caninum. Examples include a December 2019 article in the journal Parasites and Vectors that describes a dramatic increase in recurrent or persistent A caninum infections and tests that demonstrated resistances among independent isolates to anthelmintics from multiple drug classes; an August 2020 Clinician’s Brief article that states that “most, if not all” racing or recently retired racing Greyhounds appear to be infected with multidrug-resistant hookworms; and a 2019 scientific article in the Journal of the American Animal Hospital Association on the use of pyrantel, febantel, and moxidectin in combination to treat nonresponsive or persistent A caninum ova shedding in eight former racing Greyhounds.

Resistance spreading beyond Greyhounds

Dr. Cassan Pulaski is acting director of the Parasitology Diagnostic Laboratory at the University of Georgia College of Veterinary Medicine. She is also a member of the AAVP task force and of the Companion Animal Parasite Council’s board of directors. She said in late July that the volume of laboratory submissions for suspected drug-resistant hookworm infections had multiplied in the prior six months from about one submission every two weeks to one per day.

Dr. Pulaski also noted that the known infections, found through fecal samples submitted to the laboratory, include two hot spots for suspected drug-resistant hookworms in Georgia. One involved at least five dogs at a pet day care near Savannah, and the other involved at least two dogs brought to a dog park near the Georgia-Florida border. The cases near Savannah included at least one Greyhound, and the dog park further south was frequented by Greyhounds.

While she said Greyhounds likely were the initial sources of infection, “it is not a Greyhound-only issue anymore.” Among suspected drug-resistant hookworm submissions received at the UGA laboratory, about half to two-thirds are from Greyhounds, and the rest are largely from dogs with no known contact with Greyhounds.

Dr. Marsh said drug resistance in hookworms likely developed through misuse of anthelmintics that are approved for administration to livestock. Some of those products contain the same active ingredients as prescription anthelmintics intended for dogs but in different formulations and sometimes different routes of administration.

Nonveterinarians who care for dogs in racing kennels are able to buy such products without prescriptions, she said.

Such misuse can give Greyhounds doses that are ineffective at controlling their infections but sufficient to give resistant worms an advantage over susceptible worms. She said Greyhounds also may metabolize anthelmintics differently than other breeds.

Ohio-based consulting veterinarian Dr. Guillermo Couto, who specializes in Greyhound care and is another task force member, said A caninum had proliferated among racing dogs in the years before all of Florida’s tracks shut down. Most kennels would let dozens of dogs out together for exercise, and hookworms readily spread through feces.

Florida had the majority of the nation’s Greyhound racetracks a few years ago, with 11 tracks as of 2018. In November 2018, about 70% of voters favored amending the state constitution to ban dog racing after December 2020.

The National Greyhound Association now lists five active tracks remaining in the U.S.: two in West Virginia and one each in Arkansas, Iowa, and Texas. But the tracks in Arkansas and Iowa are also scheduled to phase out live racing by the end of 2022.

Dr. Jennifer Ng, who is a companion animal practitioner in Columbia, South Carolina, and a member of the task force, has seen hookworms become more common overall among Greyhounds she fosters and sees through her practice. She performs a mix of paid and volunteer work, including foster care, for the South Carolina–based organization Greyhound Crossroads.

Starting in 2016, Dr. Ng noticed that almost every Greyhound arriving from a track was positive for hookworms upon or soon after arrival, up from an estimated 10%-20% in prior years.

Dr. Ng also saw a rising proportion of those A caninum infections persist after standard treatments, and she has switched her standard protocol to involve one or two combination drugs, depending on the worm burden. But Dr. Ng said some arrivals in the past year have had lower worm burdens, suggesting to her that caregivers on farms and tracks may be improving treatments.

Drugs unapproved in U.S. for use in dogs may help

Dr. Pulaski has consulted about a half dozen veterinarians on the use of anthelmintics approved in Europe for treatment of nematode parasite infections in dogs, especially emodepside. She had yet to see safety or efficacy problems, but she also warned that such use must be the last resort.

If veterinarians prescribe emodepside for dogs, she recommends they first run blood tests for heartworm microfilariae. Those microfiliariae are also vulnerable to emodepside, and their rapid death can cause a fatal anaphylactic reaction in a dog.

In the 2020 Clinician’s Brief article, the authors state that they do not recommend emodepside treatment because they saw limited available data on such use. But the drug is the only potentially effective treatment if a triple combination of approved drugs is ineffective.

The article notes that emodepside with praziquantel is approved by the FDA as a topical solution for cats, but topical administration is ineffective in dogs, and the drug must be administered orally.

In a scientific article published in April 2020 by the International Journal for Parasitology: Drugs and Drug Resistance, researchers describe an A caninum isolate that was resistant to pyrantel pamoate, fenbendazole, and milbemycin oxime but susceptible to an emodepside and praziquantel combination. The study involved tests in Beagles experimentally infected with the isolate, known as Worthy 4.1F3P.

“Based on work in our laboratory, both published and unpublished, as well as frequent communications with veterinarians dealing with cases of persistent hookworm infections, Worthy 4.1F3P appears to be representative of the worms currently circulating in greyhounds,” the article states. “The lack of efficacy demonstrated by the most commonly used products in the U.S. for the treatment of hookworms in dogs therefore portends a very serious situation, and threatens not just canine health, but also human health due to its zoonotic potential.”

Dr. Couto said Greyhounds can have unexpected reactions to drugs commonly prescribed for other breeds, and he recommends only prescribing a drug for use in Greyhounds when data show it’s safe. He has seen, for example, Greyhounds sleep for days after receiving a standard narcotic dose. For that reason, he has not recommended that veterinarians prescribe emodepside.

Follow-up needed

Dr. Marsh urged that veterinarians follow up with clients when they prescribe any dewormers for hookworm infections, and she hopes the AAVP canine hookworm task force will help veterinarians in practice and government learn about the issue. When veterinarians use a dewormer—particularly in a dog with documented infection—it’s important to retest that dog 10-14 days later to ensure the dog is no longer shedding eggs or it has significant reduction in fecal egg counts following deworming. She recommends monitoring as long as shedding persists.

Dr. Pulaski also urged veterinarians to report treatment failures to drug manufacturers, which are obligated to collect data for the FDA on lack of efficacy. And she advocates client education about the risk hookworms present to people and animals and how clients can help prevent infections.