Conference 11 - 2014 Case: 01 20141203

Signalment:

1-year-old male Thoroughbred equine, Equus ferus caballus. Submitted was a 299 kg yearling Thoroughbred colt that lived on pasture with about ten other yearlings. He presented on emergency to the Equine Surgery Service at the Veterinary Medical Teaching Hospital (VMTH) at UC Davis on 28 Jan 2010 for colic of approximately 3 hours duration. The colt was initially found down and rolling in his pasture. His pasture mates were also yearlings. One pasture mate had presented with colic on the previous day and the others were clinically normal. The colt and pasture mates were fed a sweet feed and alfalfa twice daily. He was dewormed on 1 Dec 09 with ivermectin, and then on 1 Jan 10 with fenbendazole.

On presentation at the teaching hospital, the colt was depressed to obtunded. He continually attempted to lie down and exhibited severe discomfort regardless of analgesia administration. Mucous membranes were hyperemic and tacky, and the horse was tachypnic. Reduced borborygmi were ausculted in dorsal left quadrant, with excessive borborygmi in all other quadrants. Dried feces were pasted to the perianal area. Serum chemistry abnormalities included albumin 1.7 g/dL (reference: 2.7-4.2 g/dL), total protein 4.8 g/dL (reference 5.8-8.7 g/dL), neutrophils 17,313 /uL (reference: 2600-6800 /uL), fibrinogen 700 mg/dL (reference: 100-400 mg/dL).

Nasogastric intubation resulted in no net reflux. Cloudy fluid was obtained via abdominocentesis and characterized by 19,880 total nucleated cells (89% neutrophils) and a lactate of 5.5 mg/dL. Due to unrelenting pain, immediate surgery was recommended and preparations were begun, but euthanasia was ultimately selected due to financial concerns.

Gross Description:

The colt was in good post mortem and body condition. The oral mucosa was generally dull red, with a distinctive darker red-purple line along the gingiva of the maxillary incisors. The sclera of both eyes were injected. The haircoat was dirty and patches of hair were matted with mud. Approximately 5 L of yellow, cloudy fluid filled the peritoneal cavity. The serosal surface of the large colon was gray-purple and the colic arteries and veins were prominent and distended. The mesenteric lymph nodes associated with the large colon, most notably along the intercolonic mesothelium, were turgid, dark red, and embedded in edematous connective tissue. The large colon and cecum contained abundant green, liquid fluid ingesta with fewer than 100 free floating tapeworms. The mucosal surface of the large colon (ventral>dorsal) and cecum was thickened (up to 1.5 cm in width), pale pink to tan, and finely corrugated. Innumerable, pinpoint to 0.1 cm diameter, dark flecks cover the mucosal surface ("salt and pepper colon") and visualized by the dissecting scope, correspond to encysted larval worms. The apex of the cecum was inverted, extending proximally from the apical tip, with approximately 14 cm present beyond the ceco-colic junction and within the lumen of the right ventral colon. The base of the cecum was gas distended. The serosal surface of the intussusceptum was deep dark red, dull, and friable, and the associated mucosal surface was diffusely dark red, thickened to 1 cm, and oozed serosanguinous fluid on cut section. The lumen of the cecum near this intussusception within the base contained thick, mucoid, yellow material. The stomach contained abundant semi-dry, packed feed.

Histopathologic Description:

Multiple sections of large intestinal mucosa were examined in which abundant cyathostome larvae were present. The majority of the cysts were embedded within the tubular glands of the mucosa, where curled single larvae resided in dilated glandular crypts either freely or surrounded by a thin fibrous capsule. Occasionally, the cysts penetrated beneath the basement membrane and submucosa where the larvae were surrounded with a more prominent fibrous capsule, and a variably dense circumferential band of inflammation. The lamina propria was expanded by edema, congested submucosal blood vessels, and an inflammatory infiltrate comprised of neutrophils, plasma cells, lymphocytes, and histiocytes. The number of eosinophils varied among sections of the colon. Multifocally, the superficial mucosal epithelium was eroded, and luminal contents included acellular eosinophilic material. Submucosal arteries had moderate medial hyperplasia and scattered foci of intimal mineralization (intimal bodies).

Morphologic Diagnosis:

1. Cecum: Apical cecal intussusception with acute infarction.
2. Large colon and cecum: Mucosal larval cyathostomiasis.
3. Peritoneum: Moderate peritoneal effusion.

Lab Results:

Cecal contents submitted for parasitology analysis revealed two endoparasites via flotation: filariform nematode larvae, consistent with the 3rd/4th stage of cyathostome larvae and adult Anoplocephala sp. tapeworms. No ova were found on flotation.

Condition:

Cyathostomes

Contributor Comment:

The Cyathostominae, or small strongyles, are a subfamily of the class Nematoda that include four main genera. It is the larvae, typically, that are clinically significant, mainly in equid hosts.(2) Larval stages (L3) migrate into the deep mucosa or submucosa of the large bowel (mainly cecum and ventral colon) from the gut lumen and enter the glands to molt and develop, before emerging into the lumen to molt again and mature. If larvae undergo a period of arrested development, most anthelmentics are ineffective.(4) If arrested larvae synchronously emerge from these cysts (hypobiosis), edema, rupture of the muscularis mucosa and ulceration of the overlying mucosa may occur. Alternatively, larvae can complete development in the cecum and colon lumen, and shed eggs into the feces.(2)

It is postulated that cyathostomes have become resistant to certain anthelmintic drugs.(4) A combination of lack of penetration of anthelmintics during the encysted stage along with current inconsistent deworming practices practiced by horse owners and managers has likely led to these new resistant populations, which in turn has led to an increase in incidence of infection over the last 10 years.(4,5) As a result, cyathostomes are considered the primary parasitic pathogen of horses.(6)

Cyathostomiasis has been associated with non-specific clinical signs of colic and chronic diarrhea, and more specifically with cecocecal intussusceptions.(6) Disrupted intestinal motility, which has been experimentally induced by infection with cyathostomes,(6) could contribute to both diarrhea and/or cecocecal intussusception. Given the large number of potential motility disorders in the horse, it is puzzling that cecocolic intussusception is commonly associated with only a limited number of etiologies. Some blood chemistry and hematology aberrations that have been associated with cyathostomiasis include neutrophilia and hypoalbuminemia.(6) Histopathological changes associated with cyathostome larvae infection of the colonic mucosa include a fibroblastic reaction to penetrating larvae, which results in distension and distortion of the glands as the larvae grow. Goblet cell hyperplasia and hypertrophy and a modest, predominantly lymphocytic, inflammatory infiltrate are associated with the encysted larvae.(6)

This colt had numerous clinical signs, hematologic changes, and post mortem findings characteristic of cyathostomiasis. The striking cecocolic intussusception was the probable source of colic and unrelenting pain that ultimately led to euthanasia. An additional sign supportive of intestinal dysmotility was pasting of feces in the perianal area, suggestive of diarrhea. Changes suggestive of cyathostomiasis in blood work parameters were found, including hypoalbuminemia and neutrophilia. Post mortem exam revealed abundant larvae encysted in the mucosa, with mucosal changes described above that are characteristic of cyathostomiasis.

JPC Diagnosis:

Colon: Colitis, histiocytic and lymphoplasmacytic, diffuse, moderate, with numerous mucosal small strongyle larvae.

Conference Comment:

This is an excellent case illustrating the severe reaction and associated clinical gastrointestinal problems which may ensue following a mass emergence from hypobiosis of the most pathogenically significant nematode of horses. The contributor highlights the important aspects of the Cyathostome spp. lifecycle and how it relates to anthelmintic resistance, an increasing problem among many domestic animals and their parasitic inhabitants. Conference participants agreed that the histologic lesions in this case are more acute than chronic, with little evidence of fibrosis and only 3rd stage and 4th stage larvae identified. This is consistent with a simultaneous, massive eruption of larvae in spite of recent anthelmintic treatment just over two weeks prior to presentation.

Adult small strongyles are essentially nonpathogenic; rather, it is the mass emergence of previously arrested larvae in a short period of time which causes clinical disease. The development of arrested larvae more often occurs from late winter to early summer, and the host and/or environmental factors which influence it are poorly understood.(1) Some evidence suggests the presence of luminal worms provide negative feedback to mucosal larvae,6 which may correlate with their emergence after anthelmintic treatment and elimination of adults, as likely occurred in this case. Interestingly, arrested development of larvae has been documented for periods extending over two years.(6)

Histologic classification of nematodes is often possible when organisms are well preserved like in the current case. The characteristic large intestine with few multinucleated cells is readily identifiable and is indicative of one of three strongyle subgroups. Cyathostomes are part of the subgroup Trichostrongylus, and all are found with platymyarian musculature and longitudinal ridges along their external cuticle.(3) The ridges are faintly visible on some cross sections in this case as small and evenly-spaced. True strongyles also have platymyarian musculature, thick smooth cuticle and often vacuolated lateral chords. The third group, Metastrongylus, are the only strongyles with coelomyarian musculature.(3) Also important to speciation in this example is the presence of numerous organisms, as small strongyles often occur in large numbers.

Conference participants discussed the absence of fibrin thrombi within vessels in the affected area and how that relates to intestinal diseases of displacement such as an intussusception, which often do not cause endothelial damage. This is in contrast to infectious diseases such as Clostridium spp. or Salmonella spp., where fibrin thrombi are commonly observed.

References:

1. Brown CC, Baker DC, Barker IK. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmers Pathology of Domestic Animals. 5th ed. Vol. 2. Philadelphia, PA: Elsevier Saunders; 2007:248-249.

2. Corning S. Equine cytahostomins: a review of biology, clinical significance and therapy. Parasites & Vectors (2009) 2 (Suppl 2):S1-6

3. Gardiner CH, Poynton SL. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: American Registry of Pathology; 1999:22.

4. Peregrine AS, McEwen B, Bienzle D, Koch TG, Weese JS. Larval cyathostominosis in horses in Ontario: An emerging disease? Can Vet J (2006) 47:80-82

5. Kaplan RM, Klei TR, Lyons ET, Lester G, Courtney CH, French DD, Tolliver SC, Vidyashankar AN, Zhao Y. Prevalence of anthelmintic resistant cyathostomes on horse farms. JAVMA, (2004) 225:903-910.

6. Love S, Murphy D, Mellor D. Pathogenicity of cyathostome infection. Vet Parasitol (1999) 85:113121.