22 Nov 2010
Rachael Conwell
Job TitleRachael Conwell discusses the life cycle, clinical signs and treatment options for an intestinal nematode that has a dire effect on equine patients
CYATHOSTOMINS (small redworms) are the most important intestinal nematodes responsible for disease in equids1. Large burdens can be difficult to diagnose, and anthelmintic resistance complicates both treatment and control of cyathostomins.
The cyathostomin life cycle is direct and non-migratory. Eggs are passed in the faeces, which hatch as L1 and develop to L2 and L3 on pasture. This takes a minimum of two weeks. L3 are ingested from the pasture and penetrate the wall of the caecum and colon, where they encyst and develop to late L3 and L4. They then emerge into the gut lumen and develop to L5 and adults1.
Alternatively, the early L3 can inhibit, remaining within the mucosal wall for prolonged periods (months to years)2.
This inhibition is thought to be triggered by the parasite in response to the environment, such as cold conditioning of L3 on pasture prior to ingestion, but it involves numerous factors, including the host immune response and the numbers of parasites already present in the intestinal wall and lumen1,3.
Mucosal stages can account for up to 99.5 per cent of the total worm burden and, once inhibited in the intestinal mucosa, they have low susceptibility to anthelmintics. Therefore, horses treated previously with anthelmintics can still carry very large and even life-threatening larval burdens4. Horses do not acquire 100 per cent immunity to this parasite, necessitating appropriate lifelong management and treatment1.
Diagnosis of larval burdens can be problematic. The majority of the cyathostomin burden in autumn and winter is likely to be mucosal, and can involve several million larvae. However, the faecal egg count (FEC) will be low or even negative1.
Larval cyathostominosis can occur due to the presence of large numbers of larvae in the mucosa and associated inflammation, or as a result of sudden mass emergence. Reasons for reactivation are not known, but they can have severe consequences and a high fatality rate1.
Clinical signs include chronic weight loss, inappetence, lethargy, hypoalbuminaemia, oedema, colic and mild-to-profuse diarrhoea1,5. Inflammation within the intestinal mucosa may also cause altered motility, predisposing to caecocaecal and caecocolic intussusceptions3. Multifocal non-strangulating intestinal infarction has also been reported as a consequence of larval cyathostomins6. Any age can be affected, although disease is most commonly reported in young horses and aged ponies2,6.
Eosinophilia and neutrophilia are non-specific findings in larval cyathostominosis cases7,8. Hypoalbuminaemia occurs due to enteral protein loss from the inflamed bowel wall, but this may be transient rather than persistent. Serum globulins alter at different stages of infection and are not uniform, with alpha, beta and/or gamma globulins being variably increased7,9.
Diagnosis is, therefore, often made based on seasonality (autumn or winter), history, recent anthelmintic treatment and a high index of suspicion. Treatment relies on fluid therapy, minimising the gut inflammation and removal of the larvae with appropriate anthelmintics.
Severe diarrhoea can result in substantial fluid loss, and the priority is to stabilise fluid, electrolyte and protein losses. Large volumes of intravenous polyionic crystalloids may be required and plasma and/or synthetic colloids, such as hetastarch or pentastarch, are often used.
Oral codeine phosphate at 1.0mg/kg to 3mg/kg three times daily has been shown to be effective, but is not licensed as a veterinary product10.
Oral corticosteroids are often advocated for use concurrently with anthelmintic treatment to minimise the inflammatory response.
The prognosis for the survival of clinical cases has been given as 40 per cent, with two to three months for the recovery period – delayed treatment has a poorer prognosis10.
Anthelmintics are used as part of the treatment for larval cyathostominosis – the risk of disease is also reduced by effective control of the parasite.
Over the past 20 years, cyathostomin resistance to benzimidazoles has developed and become widespread, reaching levels of 100 per cent in some areas when the single dose is used1. The fiveday fenbendazole course, which has good efficacy against the mucosal stages, is also unlikely to be effective when benzimidazole resistance is present. Resistance is inherited, and thus passed from one generation of worms to the next, and resistant worms are spread by the movement of horses between studs and yards1. Resistance can develop quickly following first exposure to an anthelmintic, and reversion to susceptibility does not occur, even when a particular drug class is not used for many years.
Pyrantel and ivermectin are effective adulticides, but have little effect against the mucosal (especially early L3) stages. Resistance to pyrantel has developed very slowly in comparison to the benzimidazoles. However, it has been identified in the UK11. Reduced efficacy to ivermectin has been identified in Germany, as shown by a reduced egg reappearance period1.
Moxidectin was introduced in the late 1990s, and is licensed for high efficacy versus all stages, particularly the early L3. It is imperative to preserve the efficacy of this drug for as long as possible by appropriate targeted use, and by using the correct dose and formulation. The mechanism of resistance to the macrocyclic lactones is complex and multi-factorial, but this will merely prolong the time taken for resistance to develop, rather than prevent it. Multi-drug resistance has already been reported in horses in Brazil1.
Some horses may show signs of larval cyathostominosis shortly after anthelmintic administration, and clinical cases may worsen when anthelmintic treatment is instigated. With five-day fenbendazole, the parasites are enclosed by granulomas, causing extensive inflammation and ulceration of the intestinal wall by day 14 post-treatment8.
Moxidectin causes larvae to disintegrate and be resorbed without stimulating a severe inflammatory response8. Therefore, it may be more appropriate for clinical cases, or when high burdens are suspected. However, moxidectin should be used with care in debilitated and thin horses. It is highly lipophilic, reaching high concentrations in serum in horses with little body fat. It also potentially causes neurological signs12.
To maintain drug efficacy for as long as possible, selection pressure on the nematodes should be reduced by minimising the frequency of anthelmintic exposure and maintaining a refugium (a percentage of parasites not exposed to a drug at each treatment, thus they remain susceptible). A refugium is the most important factor in determining the rate of anthelmintic resistance development, and can be maintained by leaving some animals untreated and by only treating horses when high levels of pasture contamination are present.
A small number of horses within a group will carry the majority of the worm burden, and individual FECs should be regularly monitored in the whole population at peak periods of parasite transmission (spring/ summer). A decision to treat with adulticides during this time should be made, based on FECs (greater than 200epg), with low-FEC animals left untreated.
Given the problem of anthelmintic resistance, FEC reduction tests should be performed, ideally yearly, to ensure the adulticide used is efficacious. FECs indicate individual potential for pasture contamination due to the adult burden, but are not accurate for estimation of the larval small redworm burden, particularly in the autumn and winter1.
Larvicidal treatments are indicated in late autumn/early winter (five-day fenbendazole if it is known to be sensitive on a particular yard, or moxidectin where fenbendazole resistance is present or status is not known).
New horses should be quarantined and treated with moxidectin prior to turnout. Regular removal of faeces from the pasture is an additional management factor that will also help to reduce the potential worm burden.
To effectively bring about sustainable anthelmintic use, vets need to be more involved in worm control programmes, as once anthelmintic failure is identified, resistance is already present1. Horse owners recognise the importance of nematodes on horse health, but often have poor interpretation of FECs and will worm regardless, even when low counts are obtained, taking little action to delay resistance development11.
Research efforts have focused on investigating the biology of the mucosal stages and the host immune response5. Understanding the molecular mechanism of resistance may enable anthelmintic control to remain effective. No test is available for assessing mucosal larval burden, but research is under way to develop an ELISA-based test to detect infection levels1.
Rachael Conwell
Job Title