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© Veterinary Business Development Ltd 2025

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12 Dec 2023

Hookworm drug resistance in US pets: lessons to be learned

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Ian Wright

Job Title



Hookworm drug resistance in US pets: lessons to be learned

Figure 1. Uncinaria stenocephala adult, showing its hook shape.

ABSTRACT

Regular deworming of cats and dogs is a fundamental component of preventive health programmes for UK pets, and has been the focus of helminth control rather than testing. This is because testing is often viewed as unnecessary if routine preventive treatment is used and should, therefore, only be performed in clinical cases or as an alternative to treatme

The recent emergence of multiple anthelmintic drug resistant Ancylostoma caninum hookworms in the US, however, has demonstrated the importance of diagnostic testing in early detection of resistance. Although A caninum is absent or scarce in northern European countries, the potential exists for resistance to emerge in other intestinal roundworms. Surveillance is one of an important range of measures to limit its development and spread.

Keywords:  Diagnosis, testing, Ancylostoma caninum, hookworm, anthelmintic resistance, prevention

Regular deworming of cats and dogs is a fundamental component of preventive health programmes for UK pets.

Treating intestinal roundworms at least four times a year is likely to keep worm burdens low and reduce zoonotic Toxocara species ova output. As a result, it is the minimum treatment frequency for intestinal roundworms recommended by the European Scientific Counsel Companion Animal Parasites (ESCCAP). Monthly treatment, however, is often required to minimise human and animal health risk.

This is the case to prevent Toxocara species shedding in cats and dogs likely to have high worm burdens, or that live with people at high risk of infection. It is also required in dogs whose geographic location and lifestyle puts them at high risk of Echinococcus granulosus or Angiostrongylus vasorum infection.

This frequency of anthelmintic use has led to concerns that anthelmintic drug resistance may develop in cat and dog helminths as it has done in livestock and equine. So far, resistance in intestinal worms of cats and dogs has been slow to develop for a number of reasons.

Large wildlife reservoirs

Foxes have a high prevalence of both hookworm and T canis infection, which are not routinely exposed to anthelmintics. Similarly, hookworms and T cati infections in stray and feral cats will have a diluting effect on the proportion of parasite life stages that have been exposed to anthelmintics.

In addition, Toxocara species infect large numbers of paratenic hosts, including rats and birds, which will not be exposed to anthelmintics.

Arrested larval stages

A proportion of Toxocara species larvae migrating through the body of infected dogs and cats do not reach the intestines and develop into adult worms, but become arrested in the muscles and organs of the host. Periodically, they will reactivate and resume their life cycle – particularly during pregnancy and lactation.

These arrested worms form a population that is relatively protected from anthelmintic exposure and a reservoir of unexposed infection as a result.

Widespread environmental refugia

Resistance is most likely to occur when entire local populations of cat and dog nematodes are exposed to anthelmintic in isolated groups, such as kennelled situations.

The increased movement of cats and dogs around the country with their owners will frequently mix nematodes from different geographic areas, potentially limiting resistance.

It is also common for a wide range of anthelmintics to be used in routine cat and dog deworming.

Low deworming frequency

Despite large numbers of dogs requiring monthly deworming after risk assessment, current deworming frequencies in European surveys rarely exceed an average of three treatments a year.

These factors, however, are not a reason for complacency, as was recently demonstrated by multiple anthelmintic drug resistance (MADR) developing in Ancylostoma caninum hookworms in the US.

Image © Rita Kochmarjova / Adobe Stock.

Hookworm resistance in the US

The canine hookworm, A caninum, is the most prevalent intestinal nematode of dogs in the US, and a significant cause of intestinal disease and anaemia – especially in puppies.

A recent study evaluating more than 39 million faecal samples from 2012 to 2018 found the prevalence of hookworms remained stable between 2012 and 2014, but then rose steadily with an increase of 47% by 2018.

Further evidence of an increase in prevalence was found with a study of 3,006 dog faecal samples collected in 288 dog parks across the US in 2019. This found an A caninum prevalence of 7.1%, significantly higher than previous surveys (Stafford et al, 2020).

In addition, empirical evidence has been emerging over the past few years of persistent hookworm infections that were not responding to anthelmintic therapy.

Of these, infections in retired racing greyhounds were over-represented. MADR was suspected to be at work in at least some of these cases (Jimenez Castro et al, 2019).

A US-based laboratory was able to establish one of these A caninum isolates from an adopted retired racing greyhound and, in a controlled efficacy study, confirmed high levels of resistance to all classes of anthelmintic approved for treatment of hookworm in dogs (Jimenez Castro et al, 2020).

This resistance has appeared to have developed due to intensive indiscriminate anthelmintic treatment of individual groups of greyhounds on breeding farms. Greyhound racing in the US has been in steep decline in recent years, leading to many greyhounds in intensive breeding and racing establishments being rehomed to domestic situations.

Within the past few years, A caninum genetic markers for benzimidazole drug resistance have become available and been used to evaluate the distribution of A caninum fenbendazole resistance in US dogs. This demonstrated that anthelmintic resistance had been disseminated throughout homes in the US, both in greyhounds and now in a range of pet dog breeds (Jimenez Castro et al, 2021).

Additionally, multi-drug resistant hookworms in 21 dogs of different breeds were identified within the same south-eastern US kennel, suggesting that intensively dewormed kennelled dogs are the source of MADR (Jimenez Castro et al, 2023).

Case reports continue to suggest that these MADR hookworms continue to be moved around via rehomed dogs, leading to domestic drug resistant populations.

A caninum infection is largely absent from northern Europe, so why should we care?

This MADR outbreak may feel a long way away from our UK shores. The hookworm Uncinaria stenocephala (Figure 1) is our predominant UK hookworm, with A caninum being rare and absent. In addition, no anthelmintic resistance has been observed in helminths of UK cats and dogs.

A number of reasons, however, reveal why this US development should be deeply concerning for UK veterinary professionals and pet owners.

Figure 1. Uncinaria stenocephala adult, showing its hook shape.

Similar anthelmintic resistance could develop in the UK under similar circumstances in a variety of intestinal roundworms

Although A caninum is thought to be absent from most or all of the UK, the hookworm U stenocephala is prevalent and T canis widespread.

Although both parasites have large wildlife reservoirs, it is entirely possible that intensive deworming in breeding, kennelled or even domestic household situations could lead to the development of resistance.

MADR worms could arrive in the UK via relocated dogs from the US

Natural disasters such as Hurricane Katrina have led to the relocation of many dogs within the US by rescue charities, but some are also relocated abroad. This creates a small, but significant risk that MADR worms could establish in the UK.

We have very little routine testing protocols in practice to detect MADR in UK cats and dogs

The lack of routine faecal testing of cats and dogs in the UK means any resistance developing would potentially go undetected for a long time, allowing it to spread.

This means the potential exists for MADR to develop and spread in intestinal helminths of UK cats and dogs. A recent survey showed that 97% of UK dogs and 68% of UK cats have a relevant risk factor that would make monthly deworming necessary (McNamara et al, 2018).

Concerns regarding over-treatment, the development of anthelmintic resistance and environmental contamination have led to the question of whether regular testing of pets and only treating positive pets could replace preventive treatment.

This approach is also endorsed by ESCCAP and adopted in a number of northern European countries.

It does, however, have a number of drawbacks which need to be recognised.

Avoiding the treatment of animals with zero worm burdens does not decrease the risk of resistance

The risk of resistance is only reduced if significant numbers of parasites not exposed to anthelmintics are released into the environment to create refugia. This is not achieved by not treating pets with no parasites.

An argument exists for deworming at a frequency that allows some shedding of ova and larvae into the environment to limit resistance, but this is hard to justify where significant human health risk from worms exists, such as E granulosus and Toxocara species.

Pets are already exposed to infection before employment of an anthelmintic

If treatment is employed only when positive animals are identified, then shedding of infectious stages has already occurred.

While desirable for decreasing resistance, this means that zoonotic and pet disease risk has already occurred.

Diagnosis of parasites is often more expensive to the client than treatment

On a practical level, it can be difficult to justify the expense of frequent diagnostic testing for parasitic infection when simple, cheap prophylactic measures are available. That is now being countered as diagnostic tests for some parasites become simpler and cheaper.

Shedding of parasitic stages in the faeces is often intermittent

Infection with zoonotic potential may be present and diagnostic tests will still be negative. A caninum, for instance, may also cause life-threatening disease in dogs without patent infection being present.

Resistance may still be generated by small groups of cats or dogs being treated intensively

The MADR outbreak in the US appears to have come from groups of commercial dogs and then spread, rather than from the domestic pet population. These arguments mean that for testing to replace monthly treatment in high-risk groups, it would need to be performed at least quarterly and ideally monthly to avoid prolonged human exposure to zoonotic life stages, and harm to pets through exposure to pathogenic nematodes.

The opportunity exists to include these strategies as an alternative to routine treatment on practice health plans to make them more affordable and to promote them to clients where compliance with routine deworming is likely to be poor.

To effectively limit anthelmintic resistance, however, other strategies are needed, including the following.

Accurate dosing

Under-dosing through animal weights not being up to date or a deliberate measure to save money will promote resistance through fitness selection.

Rotation of active ingredients

Although large population study evidence is missing from cat and dog populations, rotation of anthelmintic classes may help to limit resistance in a similar way to livestock and horse nematodes.

Treatment with multiple classes?

In a similar way to drug class rotation, use of multiple classes of anthelmintic (for example, pyrantel with moxidectin or febantel) may also slow resistance, although, again, evidence in cats and dogs is lacking.

Maximising compliance

Making treatment as convenient and easy to apply as possible will reduce mis-dosing and under-dosing, leading to increased efficacy in the short term and reduction of anthelmintic resistance in the long term. Owner preference for tablet or spot-on formulations should be taken into account.

Demonstrating how to give tablets or apply spot-on preparations is also useful in improving client confidence and understanding.

Responsible removal of faeces

To prevent resistant parasite life stages entering the environment. This is especially important in closed systems such as kennels and breeding establishments.

Routine testing alongside treatment

This has a number of benefits to practices, both in terms of reinforcing good practice among pet owners, identifying which parasites are present in a local area and, crucially, to detect signs of drug resistance. It can be performed at annual wellness checks, six-monthly or quarterly heath checks. More economical and flexible testing options have become available for faecal testing in cats and dogs. Faecal flotation allows faeces to be efficiently examined by concentrating ova present in the faeces in small volumes of liquid while eliminating debris.

This technique may still have diagnostic sensitivities as low as 60% for some roundworm ova such as Toxocara species and has poor sensitivity for tapeworm egg detection, depending on the method used (Wolfe et al, 2001). Sensitivity increases with pooled samples over three days. It is important to know whether dogs are coprophagic prior to testing, as this can lead to false positive results.

Strongyle eggs in ruminant and horse faeces will pass through the digestive tract of cats and dogs unchanged, giving the impression the pet is infected with hookworm (Figure 2).

Figure 2. Horse strongyle egg from dog faeces.

Similarly, T cati eggs may be found in dogs that have eaten cat faeces. Copro-antigen testing detects antigens of some parasites in faeces, including intestinal roundworms. Highly sensitive and specific tests are commercially available for intestinal roundworms, whipworms and hookworms. These tests allow infections to be detected when ova shedding is not occurring and avoids false positive results due to coprophagia.

Conclusions

Traditionally in the UK, routine treatment for worms has been the focus of worm prevention in cats and dogs, and plays an important role both in animal health and limiting zoonotic risk.

Treatment and testing, however, are not mutually exclusive and routine testing alongside anthelmintic use has many benefits, including early detection of possible drug resistance. The hookworm resistance outbreak in the US demonstrates the importance of testing for early detection. Strategies in livestock and equine production that maintain refugia are difficult for companion animal parasite management due to the zoonotic risk.

Early detection is, therefore, our best defence, so that positive cats and dogs can be treated with alternative drug classes and measures put in place to prevent geographic spread.

Other lessons can be learned from equine and livestock parasitology, such as the potential benefits of anthelmintic rotation, appropriate removal of faeces and accurate dosing.

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