Evidence of resistance to key equine dewormers

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A study in North America has shown conclusively that cyathostomins are developing resistance to the class of deworming drugs that provide the last line of defence against them.

Researchers found that the efficacy of ivermectin and moxidectin was markedly reduced among a group of imported Irish Thoroughbreds in Kentucky, whereas the US-born yearlings on the same farm show no such resistance.

The findings paint a worrying picture of the future of equine parasite control, with no new deworming drugs on the horizon.

Cyathostomins, often referred to as small strongyles or small redworms, are ubiquitous in horses.

Ivermectin and moxidectin belong to the class of dewormers known as macrocyclic lactones and are considered key drugs in the management of parasite burdens in horses.

Equine parasitologist Martin Nielsen and his colleagues, reporting in the International Journal for Parasitology: Drugs and Drug Resistance, say their study is the first in the world to confirm resistance in a population of equine cyathostomins through a series of repeated testing.

The resistance of cyathostomins to two of three available deworming drug classes for horses was first confirmed some years ago.

Despite early predictions of cyathostomins developing resistance to macrocyclic lactones, to date, few reports have been published.

Nielsen, who is with the M.H. Gluck Equine Research Center at the University of Kentucky, stud farm manager Michael Banahan, and parasitologist Ray Kaplan, with the University of Georgia, described current evidence on resistance to macrocyclic lactones among cyathostomins as scarce and mostly inconclusive.

The trio’s research changes that, providing convincing evidence with follow-up confirmation of full-fledged resistance to ivermectin and moxidectin in cyathostomins.

This image of a horse's caecum - the first portion of the large bowel - shows the damage that can be caused by encysted strongyles, also known as cyathostomins. Encysted strongyles are very resilient. ©
This image of a horse’s caecum — the first portion of the large bowel — shows the damage that can be caused by encysted strongyles, also known as cyathostomins. Encysted strongyles are very resilient. © Martin Nielsen

Their research focused on two populations of young Thoroughbreds on a farm in Central Kentucky. One of the groups comprised more than 50 yearlings born on the farm in Kentucky, while the other comprised more than 50 yearlings born in Ireland and imported in October 2019.

The farm diligently followed current guidelines for equine parasite control and employs systematic surveillance of parasite fecal egg counts from all horses present, the researchers said.

The evidence showed that the efficacy of ivermectin and moxidectin was markedly reduced in the Irish imports, whereas the US-born yearlings showed 100% strongyle egg count reduction.

These findings were confirmed through re-treating and re-testing over an eight-month period involving a series of fecal egg count reduction tests — a crucial test in detecting the presence of resistant worms.

In this case, they said, the resistance to ivermectin and moxidectin was imported with the Irish imports.

“This was only discovered due to the meticulous testing protocol in place on this farm, and it allowed the farm manager and staff to take appropriate steps to contain and manage the situation.”

The researchers said the results were remarkable in at least three ways.

“First,” they wrote, “this is the most comprehensive data set demonstrating reduced macrocyclic lactone efficacy against equine cyathostomins reported to date.

“Second, reduced efficacy was demonstrated to both ivermectin and moxidectin, and the suspicion of resistance was confirmed through re-testing.

“Third, the high efficacy of the ivermectin treatments in all three groups of US-bred horses measured concomitantly with the reduced efficacy in the Irish-bred horses demonstrates that the drugs were of high quality, administered correctly by farm personnel, and that the reduced efficacy was not a result of laboratory error.”

The commonest types of worms that infect equids are the small strongyles (also known as cyathostomins).
The commonest types of worms that infect equids are the small strongyles (also known as cyathostomins).

They said the evidence was clear, that cyathostomin populations harbored by the US-bred horses were susceptible to ivermectin, whereas the parasites of the Irish imports were resistant to both ivermectin and moxidectin.

It is also clear, given the circumstances, that the resistant worms were imported to the US from Ireland.

This, they said, demonstrates how resistant parasites can quickly traverse continents and quickly be spread globally.

“Equine operations are strongly encouraged to heed this threat to equine health, and routinely monitor anthelmintic efficacy on a yearly basis,” the trio wrote.

“Only by taking such actions will it be possible to detect cases like these as early as possible and institute appropriate interventions.”

Discussing their findings, Nielsen and his colleagues noted that some of the imported yearlings were sold in September yearling sales this year, while most were retained by the owner and sent away for training.

“Thus, they likely brought their macrocyclic lactone resistant cyathostomins with them and would almost certainly be introducing these to the new facilities.”

The authors noted that the use of dewormers on Kentucky Thoroughbred farms is very intense, with most farms deworming their yearlings six times a year or more.

“Thus, it was always the expectation that macrocyclic lactone-resistant cyathostomins were very likely to eventually occur in the heart of Thoroughbred country in Kentucky.

“In light of this, it is a genuine surprise that the first case of full-fledged macrocyclic lactone resistance was diagnosed in horses imported from Ireland.”

They noted that a recent survey conducted in Ireland documented that parasite control programs adopted by the equine industry there (including Thoroughbred farms) were not following current recommendations, with little or no diagnostic monitoring of parasite presence and treatment efficacy, and frequent use of dewormers and heavy reliance on the macrocyclic lactones.

“Thus, several similar risk factors for the development of ML resistance were also present in Ireland.

“Nonetheless, it is important to note that the Kentucky farm has imported weanlings from Ireland every year for the past several years, and that routine testing in previous years had always demonstrated full macrocyclic lactone efficacy.”

The researchers said the heavy reliance on this class of dewormers for equine strongyle control is obviously problematic, but the industry is left with little choice.

Among cyathostomins, resistance is already widespread to both the benzimidazoles and pyrimidines, often leaving the macrocyclic lactones as the only viable treatment option.

“While macrocyclic lactone resistance has been remarkably slow to progress in cyathostomins, the data presented herein clearly demonstrate that a resistance break-through can happen, and likely is occurring elsewhere as well.”

It is noteworthy, they added, that the degree of parasite egg count monitoring adopted by the farm at the center of the study was well above industry norms.

Other equine operations in the US, Ireland, and elsewhere, most likely already have cyathostomins resistant to this class of dewormer without being aware.

“This case clearly illustrates the importance of quality routine fecal egg count reduction testing, which immediately informed the farm manager of the situation and allowed him to react in time by keeping the populations completely separate, thereby avoiding an introduction of the resistant parasites to the entire facility.”

The authors note that the pharmaceutical industry has not introduced any new anthelmintic classes with new modes of action for equine use since ivermectin almost 40 years ago.

“There are no indications that any new anthelmintic classes will be introduced for horses in the foreseeable future.

“The data presented herein strongly demonstrate that the portfolio of equine anthelmintics is woefully unsatisfactory, leaving end-users with few viable treatment options and almost no alternatives when current options fail.”

 

Importation of macrocyclic lactone resistant cyathostomins on a US thoroughbred farm. M.K. Nielsen, M. Banahan, R.M. Kaplan. International Journal for Parasitology: Drugs and Drug Resistance Volume 14, December 2020, Pages 99-104. https://doi.org/10.1016/j.ijpddr.2020.09.004

The study, published under a Creative Commons License, https://creativecommons.org/licenses/by-nc-nd/4.0/ can be read here.

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