A two-year-old Dutch Warmblood gelding presented with extreme weight loss and diarrhoea in December. The horse had been at pasture with seven others for the last three months with daily supplementary hay. The horse was rugged and had not been closely examined for six weeks however had been observed eating on a daily basis. On the day of admission to the hospital the horse had been seen standing alone, in-appetent with severe diarrhoea.
On arrival to the hospital the horse was quiet, alert and responsive, body condition score 1/9 (284kg bwt). There was faecal staining down the hindquarters and tail. The heart rate and respiratory rate were elevated (76 beats per minute and 20 breaths per minute). Mucus membranes were pink and moist with a capillary refill time of 2seconds. Gastrointestinal sounds were increased. Skin tent was extremely prolonged, indicating significant dehydration. Abdominal ultrasound revealed a fluid filled colon and caecum with good SI motility and no evidence of bowl thickening. Although no abnormalities were detected per rectum, upon completion of the examination a large number of cyathostome larvae were visible on the rectal sleeve. Faecal analysis was negative for strongyle eggs.
The significant clinicopathological abnormalities are presented below:
Fibrinogen 6.3g/L (1.8-3.7g/L)
Serum Amyloid A (SAA) 180mg/L (<10mg/l) Haematocrit (HCT) 45.1% (24-44%) Albumin 15g/L (31-38g/L) Blood lactate 3.1mmol/L (0.2-0.7mmol/L)
Acute weight loss
Poor body condition
Differential diagnosis for diarrhoea
Infectious: Samonellosis, Clostridium perfringens, Clostridia difficile, Lawsonia intracellularis,
Parasitic: Strongylosis, larval cyathostomiasis
Miscellaneous: carbohydrate overload, sand enteropathy
Due to the horse’s age, number of horses at pasture and poor worming history the most likely diagnosis was a larval cyathostomosis. Although the faecal worm egg count was negative this does not take into account the encysted burden of worms and therefore cannot rule out infection. The presence of red worm larvae on the rectal sleeve following rectal examination indicates the presence of larvae.
An intravenous catheter was placed and maintainance fluids were administered to rectify the dehydration. 4L of plasma (Hypermune, Veterinary Immunogenics) was also given to provide anti-endotoxic and colloidal support. Dexamethasone (Dexadresson, Intervet) 0.05mg/kg IV every other day was administered initially. The horse was also started on fenbendazole (FBZ) (Panacur Guard) 7.5mg/kg SID for 5days.
Additional supportive therapy included free access to palatable feed and fresh water.
The following day, the horse was quiet with a moderate appetitite. Faeces became more watery so treatment with di-tri-octahedral smectite (Biosponge, Platinum Performance)1g/kg q6hrs per nasogastric tube and codeine phosphate (Codeine Phosphate, Crescent Pharma) 1mg/kg PO TID was started and adjusted daily according to faecal consistency.
On day 3 the horse appeared slightly colicky and appetite reduced. Treatment with a single dose of flunixin meglumine (Finadyne, MSD Animal Health) 1.1mg/kg improved signs of abdominal pain.
The following day the horse was brighter and appetite improved. The intravenous fluids were discontinued. At this point dexamethasone was replaced by oral prednisolone (Equisolon, Boerhinger Ingleheim) 1mg/kg PO SID. The diarrhoea improved over the following two days and on day 6 the codeine and biosponge were also discontinued.
On day 7 of hospitalisation the horse was given moxidectin (MOX) (Equest, Pfizer) 0.4mg/kg to treat any parasites resistant to the fenbendazole therapy.
A further blood sample on day 10 revealed improvement in HCT, fibrinogen and SAA. The albumin remained low at 15g/L but considering the horse’s dehydration on admission, this was slightly improved and would be expected to take weeks to return to a normal range. The horse was discharged. At this point the horse had a good appetite, was very bright and was passing normal droppings. Weight had increased from 284kg on admission to 305kg.
Strongylid round worm, subfamily Cyathostominae, and infestation may affect up to 100% of pastured animals (Tolliver et al, 1987, Lyons et al, 1999, Lind et al, 2003). In adult horses, the disease is usually asymptomatic or observed in sub-clinical forms however in horses, which have not been treated, treated infrequently or are on heavily grazed pasture can reach hundreds of thousands (Chapman et al, 2003, Gasser et al, 2004). The most common clinical manifestation of cyathosome infection is associated with acute larval cyathostomosis (Murphy et al, 1997). The poor worming history, minimal pasture management and heavily grazed pasture in this case indicated that this was likely.
As with this case larval cyathostomosis is usually diagnosed in horses of 1-3years of age and is most commonly associated with severe weight loss, weakness, acute or chronic diarrhoea, subcutaneous oedema, pyrexia and colic (Lyons et al, 2000). In the UK age (<5years), season (winter) and the time since last deworming (<2weeks) were all identified as risk factors for the occurrence of this disease (Reid et al, 1995).
The blood results in this case alongside the diarrhoea and weight loss indicated a protein losing enteropathy. A decrease in total protein levels, particularly albumin, and neutrophilia are common presentations of horses infested with cyathostomes (Steinbach et al, 2006). The synchronous reactivation of the encysted larvae (EL3) into the gut lumen can cause extensive bowl inflammation which can not only result in enteral protein loss and impaired nutrient absorption, but also entrance of bacterial toxins into the tissues (Abbot, 1998, Giles et al, 1985 and Reid et al, 1995). This can be fatal in up to 50% of cases (Love et al, 1999). The plasma administered in this case aimed to provide colloidal support due to the reduced albumin, and act as an anti-endotoxic agent (Tennant-Brown, 2011).
The debilitated condition the horse was in in this case led to consideration of the most appropriate treatment. There is a concern over worsening of a horses condition following administration of anthelmintics, however there is a balance between this and a delay in treatment leaving sufficient time for recovery following anthelmintic treatment (Johns, 2014). Johns (2014) describes the potential for using fenbendazole in severely emaciated horses.
The concern with determining treatment is that the mucosal stages constitute the major cyathostomin burden, which is not particularly susceptible to most anthemintics (Love and Mckeand 1997). Chemotherapeutic strategies are not always successful in severe cases however the main two drugs licensed treatments for encysted larvae are FBZ or MOX.
The initial treatment used in this case was Fenbendazole 7.5mg/kg bwt administered daily for 5 consecutive days. It has been shown to provide >95% efficacy vs. total mucosal larvae, including >91% efficacy against inhibited EL3 (Duncan et al, 1998). A single dose of moxidectin 0.4 mg/kg bwt was administered on day 7. This has been shown to have a persistent effect and be effective against all life cycle stages, including 90.8% efficacy against EL3 (Reinemyer et al, 2003). There have been limited reports of resistance and as such is recommended for the treatment of larval cyathostominosis (Reinemyer et al, 2003 and Molento et al, 2008). The reason for this follow treatment with moxidectin is due to the world wide prevalence of FBZ resistance, and even 5day courses at 7.5 or 10mg/kg bwt cannot overcome this resistance (Tarigo-Martinie et al, 2001).
Although there is little research to support it, clinicians often choose to treat larval cyathostomes with a 5day course of fenbendazole followed by moxidectin. Reasoning behind this maybe due to FBZ killing larvae at a slower rate and therefore avoids a severe anaphylactic reaction associated with larval death. Also due to the resistance seen with fenbendazole, it leads to a ‘belt and braces’ approach to remove the encysted parasites.
A concern with moxidectin is the risk of toxicity in severely-debilitated horses. Because of its highly lipophilic nature, moxidectin can become highly concentrated in the serum of animals with little body fat, such as this case, which increases the risk of neurotoxicity as it able to cross the blood-brain barrier, which is described in the literature (Johnson et al, 1999 and Muller et al, 2003).
In many reported cases clinical signs have been evident following treatment of affected horses, a syndrome thought to be due to the inflammatory reaction associated with parasite death. A study performed by Steinbach et al, (2006) found a five-day course of fenbendazole caused extensive inflammation and ulceration of the intestinal wall associated with parasite death. However moxidectin treatment led to disintegration of larvae without the severe inflammatory response which supports the use of the latter drug in treatment of clinical cases, and questions the treatment protocol used in this case (Steinbach et al, 2006).
Anthelmintic treatment is often administered alongside steroid therapy, which is important if heavy larval loads are suspected as with this case. The inflammatory reaction created by parasite death is often managed with corticosteroid treatment. Often treatment is started prior to larvicidal medication particularly if heavy larval loads are suspected. This aims to prevent acute exacerbation of the disease by rapid death of encysted larvae (Church et al, 1986). Church et al (1986) found that the administration of steroids alongside the anthelmintics lead to a synergistic drug effect. The corticosteroid lessens the immune mechanisms contributing to larval arrestment allowing the mucosal larvae to resume maturation and therefore more susceptible to the action of anthelmintics (Church et al, 1986). Although there has been no further evidence for its use, in clinical practice there appears to be a therapeutic advantage with cyathostomosis cases in giving oral corticosteroid concurrently with anthelmintics (Love and McKeand, 1997). As this was a concern in this case corticosteroid treatment was used alongside anthelmintic therapy.
Codeine Phosphate although not licensed in horses, was used in this case to provide symptomatic relief of diarrhoea. It works by reducing gastrointestinal secretions and delaying intestinal transit. There was improvement seen in faecal consistency after 48hours and the dose was altered accordingly (Murphy et al, 1997).
Studies are currently underway to develop a diagnostic assay to allow the detection and quantification of mucosal cyathostomes to allow for targeted treatment (Proudman and Matthews, 2000). FEC underestimate the true parasite burden when larval populations predominate and luminal adult burdens are low (Dowdall et al, 2002). This was seen in this case where the FEC was negative however the clinical signs and presence of larval on the rectal sleeve all suggested larval cyathstomiasis.
The successful outcome in this case supported the treatment protocol used. However after consideration of the literature it would be prudent to question whether moxidectin alongside corticosteroid therapy would provide less intestinal inflammation, reducing the severity of clinical signs alongside ensuring the death of the encysted parasites.