Multi-drug-resistant (MDR) canine hookworms are becoming more prevalent in the United States. Of the three hookworm species typically found in canids, Ancylostoma caninum is the primary concern for domestic dogs. While its potential for zoonotic transmission is lower than that of A. braziliensis (the most common cause of cutaneous larva migrans in humans, often acquired by tourists at the beach), A. caninum can cause a potentially fatal anemia and ill-thrift in puppies infected in the first weeks of life. Over the last 30 years, very effective drugs on the market (including pyrantel, fenbendazole, praziquantel, and moxidectin) meant hookworm infections were straightforward to treat¹. This may not be the case for much longer.

Hookworms all have a similar direct life cycle². Adult female worms in the intestinal tract release up to 10,000 eggs/day. These eggs take anywhere from 2-5 days to hatch and mature into infective third stage larvae (L3) in the environment, where they can last several months if conditions are right. They enter a new host via contact and penetration of the paw pads, or via ingestion. Once in the bloodstream, they migrate to the lungs, up the airway, and down into the gastrointestinal tract, where larvae attach to the intestine wall and mature into adult worms. Alternatively, certain environmental cues encourage larvae to enter muscle tissues and go hypobiotic, where they can remain for years. They slowly leak out when the opportunity arises: immunosuppression, pregnancy, and clearance of adult worms following adulticidal drugs. Larvae can also congregate in a mother’s mammary glands and pass vertically to the newborn puppies when they make contact with the teats. 

Drug resistant populations of A. caninum have been clearly documented arising in imprudently managed populations of racing greyhounds³. Several factors at the facilities typically align in these situations:

• Warm, mild temperatures in Southern States, with no cold season to kill larvae
• Sandy soil covering racetracks, the ideal substrate to maintain newly hatched larvae
• High-density housing with regular movement of animals in and out of the population
• Regular and indiscriminate use of dewormers from birth (often given monthly to all dogs)

As the racing industry continues to decline (Florida made it illegal January 1st, 2021), these same greyhounds are now entering rescues and are adopted into homes across the country. Reports of MDR hookworm infections frequently concern rescued greyhounds, but other breeds are represented.

Recent cases of drug resistant hookworms detected at the AHDC

A 3yo MN greyhound and a 5yo FS greyhound, both adopted from the southeastern US and brought to the northeast, showed signs of persistent hookworm (Ancylostoma caninum) infection despite a history of fenbendazole treatment. Both then received an appropriate multi-drug dose for resistant hookworms (imidacloprid/moxidectin + praziquantel/pyrantel/febantel, i.e.Advantage Multi® + Drontal® Plus) and a fecal egg count reduction test was performed 14 days later. The MN dog went from 42 eggs per gram (epg) to 12 epg, a 71.4% decrease. The FS dog went from 15 epg to 33 epg, a 120.0% increase in fecal egg count indicating hookworm resistance to multiple dewormers. Both dogs were subsequently treated off-label with a 1mg/kg oral dose of emodepside, Profender®⁴, currently only approved as a topical flea medication for cats in the United States. Fourteen days later, the MN dog had 0 epg, a 100% reduction, and the FS dog had 1 epg, a 97% reduction. This appears to have been a successful elimination of infection with multiple-drug resistant hookworms, though further monitoring of the patients is necessary to confirm the infection does not recur. 

Determining hookworm resistance can be done by submitting feces to the AHDC parasitology laboratory for a pre-treatment quantitative Fecal Float (FLOAT), deworming the patient, and then submitting feces for a second quantitative fecal float 14 days after treatment. This follow-up test code is FPCRT for a Fecal Parasite Count Reduction Test. This 2020 report in the Clinician's Brief provides a break down of how to interpret the FPCRT, and which drugs to use, the key points being⁴:

• >95% fecal egg count reduction indicates an effective treatment, your drug is working properly
• 75%-95% fecal egg count reduction, essentially inconclusive, repeat treatment
• <75% indicates resistance to dewormer used

Resistance to a single agent should be followed with triple-combination drug therapy. If this therapy is less than 90% effective, you have established this is a multi-drug resistant population of hookworms, and off label administration of emodepside is warranted. It has been reported effective in the literature and may be the last available drug for the treatment of resistant hookworm populations.

Long term management of hookworm resistance is complicated by the following factors:

• Larval leakage⁵: hypobiotic larvae that have sequestered themselves in muscle tissues slowly emerge to repopulate the GI tract, causing dogs to have intermittent positive fecal flotations 
• Reinfection: a dog with a previously high load of worms may have established a large reservoir of larvae in the environment and gets reinfected
• Density dependent fecundity⁶: there may be a paradoxical increase in egg counts post-treatment. Female worms only use a fraction of their egg laying potential when in dense populations. Once susceptible adult worms die and the intraspecific competition diminishes, surviving adults are free to increase egg production

References

1. SUPERFAMILY ANCYLOSTOMATOIDEA (HOOKWORMS) online access
2. Hawdon, John M., and Kira A. Wise. "Ancylostoma caninum and other canine hookworms." Dog parasites endangering human health. Springer, Cham, 2021. 147-193.
3. Castro, Pablo D. Jimenez, et al. "Multiple drug resistance in hookworms infecting greyhound dogs in the USA." International Journal for Parasitology: Drugs and Drug Resistance 17 (2021): 107-117.
4. Castro, PD Jimenez, R. Kaplan, and DACVM Parasitology DEVPC. "Persistent or suspected-resistant hookworm infections." Clin. Brief (2020): 61-68.
5. Schad, Gerhard A., and Michael R. Page. "Ancylostoma caninum: adult worm removal, corticosteroid treatment, and resumed development of arrested larvae in dogs." Experimental parasitology 54.3 (1982): 303-309.
6. Castro, Pablo D. Jimenez, et al. "Efficacy evaluation of anthelmintic products against an infection with the canine hookworm (Ancylostoma caninum) isolate Worthy 4.1 F3P in dogs." International Journal for Parasitology: Drugs and Drug Resistance 13 (2020): 22-27.