Study suggests multiple-drug resistance in canine hookworm an emerging problem

Hookworms (A. caninum) in the small intestinal mucosa of a dog. (Image courtesy of the CDC)

Although it’s the most prevalent intestinal nematode parasite in dogs in the United States, Ancylostoma caninum (canine hookworm) has historically been well controlled with the anthelmintic drugs febantel, moxidectin, milbemycin oxime, fenbendazole and pyrantel. However, parasitologists from several U.S. veterinary colleges have reported an uptick in infection recurrence within the past three years—mostly in greyhounds, but in other breeds as well—which suggests the parasite may have become resistant to the drugs typically used to control it. A group of researchers led by Pablo D. Jimenez Castro, DVM, from the University of Georgia College of Veterinary Medicine, set out to study the validity of this hunch.¹

What they did

Dr. Castro and his team obtained fecal samples from three dogs (a greyhound, a miniature schnauzer and a hound mix) being treated for persistent hookworm infections, as well as from two infected dogs with no history of treatment with anthelmintics. Hookworm eggs from these samples were used to infect laboratory beagles and to perform egg hatch assays (to detect resistance to benzimidazoles) and larval development assays (to detect resistance to macrocyclic lactones). These assays were also conducted on eggs taken from the laboratory-infected research dogs.

To detect pyrantel resistance, three of the infected research dogs (representing two isolates) were treated with the anthelmintic drug and then fecal egg count reductions were measured. Finally, using DNA extracted from pools of eggs, third-stage larvae or adults, the researchers used deep amplicon sequencing assays to measure the frequency of nonsynonymous single nucleotide polymorphisms at three different codons (167, 198 and 200) of the A. caninum isotype β-tubulin gene.

What they found

When compared with the dogs with no history of anthelmintic treatments, the A. caninum isolates taken from the three dogs with suspected drug resistance had resistance ratios ranging from 6 to more than 100 for the egg hatch assay and from 5.5 to 69.8 for the larval development assay. As for the two isolates treated with pyrantel, one of the egg counts had no change and the other actually increased. Moreover, a high frequency of resistance-associated single nucleotide polymorphisms was identified at codon 167 in the three resistant isolates.

What this means (for dogs and humans)

According to the researchers, this study’s findings “conclusively demonstrate multiple anthelmintic resistance in multiple independent isolates of A. caninum, strongly suggesting that this is an emerging problem in the United States.” They go on to describe the findings as “important and concerning,” as the rise and spread of canine hookworms that are resistant to the three main anthelmintic classes—the only effective drug classes currently approved for the treatment of canine hookworms in the U.S.—could seriously threaten canine health.

But according to the researchers, dogs aren’t the only animals in danger. The study notes that if anthelmintic resistance can arise in canine hookworms, human medicine should take notice because A. caninum is phylogenetically similar to the hookworm species of humans (A. duodenale, A. ceylanicum and Necator americanus). And as the researchers explain, “the scale-up of mass drug administration for soil-transmitted helminths is now placing similar selection pressures for benzimidazole resistance on human hookworms and reduced efficacies are widely reported.” They offer that the deep amplicon sequencing assay from the study could be used to monitor worldwide benzimidazole resistance in human hookworms.

Reference

1. Jimenez Castro PD, Howell SB, Schaefer JJ, et al. Multiple drug resistance in the canine hookworm Ancylostoma caninum: an emerging threat? Parasit Vectors. 2019;12(1):576.

Sarah Mouton Dowdy, a former associate content specialist for dvm360.com, is a freelance writer and editor in Kansas City, Missouri.