JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-P17

Signalment (JPC #1505439): Adult gibbon (Hylobates sp.)

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Small intestine: Diffusely, the villi are blunted and fused with mucosal epithelial erosion and multifocal individual enterocyte necrosis. Intestinal crypt epithelium is diffusely hyperplastic, piling up to 3 cell layers thick with large vesiculate nuclei and increased mitotic figures extending up the villi. Crypts are moderately dilated, often lined by attenuated epithelium, and contain numerous intraepithelial and luminal cross and tangential sections of adult nematodes, developing larvae, and eggs. Adult nematodes are 20-25 µm in diameter, with a smooth cuticle, platymyarian-meromyarian musculature, and intestinal and reproductive tracts within a pseudocoelom. Larvae are 10 µm in diameter and contain closely packed basophilic cells and an esophagus with a distinct corpus, isthmus, and bulb (rhabditiform). Eggs are 20-25 µm, thin-shelled, ovoid, eosinophilic to magenta, multicellular (morulated), and lobulated. The lamina propria and to a lesser extent the superficial submucosa are expanded by moderate numbers of lymphocytes, plasma cells, eosinophils, and neutrophils admixed with fibrin and edema.

 

MORPHOLOGIC DIAGNOSIS: Small intestine: Enteritis, lymphoplasmacytic and eosinophilic, chronic-active, diffuse, moderate, with crypt hyperplasia, villus blunting, fusion, and erosion, and numerous rhabditoid nematode adults, eggs, and larvae, etiology consistent with Strongyloides sp., gibbon (Hylobates sp.), nonhuman primate.

 

ETIOLOGIC DIAGNOSIS: Intestinal strongyloidosis

 

CAUSE: Strongyloides sp.

 

GENERAL DISCUSSION:

• Rhabditoids: Small nematodes, the most common genera include Strongyloides, Rhabdias, Pelodera, and Halicephalobus
• Strongyloides spp. parasitize all species of domestic animals, and infect the small intestine of most species
• These nematodes are unique in having free-living and parasitic forms:
  • Parasitic parthenogenic adult females asexually produce larvae capable of direct infection of the host; adult females and larvae are found in the gastrointestinal tract, migrating larvae can be found in the lungs and other parenchymous organs, there are no parasitic males
  • Free-living males and females reproduce sexually

 

PATHOGENESIS:

• Filariform L3 larvae penetrate skin, or less commonly are ingested (e.g. in colostrum or milk) with probable subsequent penetration of gastrointestinal mucosa, or in utero transmission à larval migration primarily through naso-frontal region to bloodstream à carried to lungs (granulomatous to eosinophilic pulmonary migration tracts) à larvae migrate to airways à larvae carried up the mucociliary escalator and swallowed à adults parasitize small intestine (most species)
• Autoinfection may occur in some species (e.g. S. stercoralis in apes or dogs): eggs hatch within intestinal lumen à filariform larvae reinvade intestinal (colonic) wall à larval migration, hyperinfection

 

TYPICAL CLINICAL FINDINGS:

• Nonspecific clinical signs include diarrhea, hypoproteinemia, weight loss, dehydration
• Disease in gibbons: 

• Diarrhea is the most common clinical sign, and may be hemorrhagic or mucoid
• Other common signs include: dermatitis, urticarial, anorexia, depression, listlessness, debilitation, vomiting, emaciation, reduced growth rate, dehydration, constipation, dyspnea, cough, prostration, death, paralytic ileus

 

TYPICAL GROSS FINDINGS:

• Parasitic adult females may be visible grossly 
• Larval migration is often asymptomatic; may see mild cough or bronchial

Irritation or acute alveolar inflammation in hypersensitive animals

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Organism: Mucosa contains numerous parasites, most of which larvae establish and persist within tunnels in the epithelium at the base of villi or in upper crypts (adults may be at the surface epithelium)
  • Larvae: 15-20 µm diameter; esophagus with corpus, isthmus, and bulb (“rhabditiform”); double lateral alae; and a notched tail
  • Adults: Female only, typically 2-6mm long, 25-30 µm diameter, have smooth cuticle, platymyarian-meromyarian musculature, low cuboidal uninucleate intestinal cells, anterior cylindrical esophagus, retroflexed ovaries, and paired amphidelphic (folded on themselves) uteri which fill the posterior 2/3 of the body, absence of ovojectors
  • Eggs: Comparatively large (55x35 µm), may be retained in epithelial tunnels 
• Epithelial destruction may result in villus atrophy and blunting, crypt hyperplasia, indistinct brush border, +/- squamous metaplasia and/or erosions, and mixed eosinophilic to lymphocytic inflammation of the lamina propria if sufficient numbers of parasites are present
• Larval invasion of the submucosal and serosal lymphatics may result in severe granulomatous endolymphangitis
• In gibbons: catarrhal to hemorrhagic, erosive to ulcerative, or necrotizing enterocolitis +/- secondary peritonitis; pulmonary hemorrhage is the most common extraintestinal lesion

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

Diarrhea in nonhuman primates:

• Bacterial diarrhea (Campylobacter, Shigella, Salmonella, E. coli, Yersinia): Culture
• Balantidium, Giardia, Candida: Smears, floats, or histopathology
• Rotavirus: Self-limiting, no infectious agents in fecal floats
• Stress, inflammatory bowel disease, dietary changes

 

COMPARATIVE PATHOLOGY:

Strongyloides spp. parasitize all species of domestic animals; selected spp. of importance:

• Cattle: S. papillosus can cause diarrhea and occasional death in suckling ruminants; there is an associated syndrome of sudden death caused by cardiac failure of undetermined pathogenesis
• Sheep: Strongyloides may affect lambs up to several months; even confined lambs
• Horses: S. westeri in foals is associated with diarrhea that can be fatal in heavily infected animals; it has been hypothesized (unproven) that skin penetration by L3 larvae can permit entry of Rhodococcus equi
• Swine: Mainly S. ransomi, causes diarrhea in suckling piglets including wild boar piglets; infection is asymptomatic in adults; vertical transmission occurs during suckling; larval migration may cause pulmonary lesions 

• Rotavirus is often associated with other causes of diarrhea: E. coli, coccidiosis, adenoviral infection, and Strongyloides 
• Wild Boars: Infects the intestine of wild boars; pathogenic to suckling piglets; vertical transmission occurs; adult infection is asymptomatic

• Piglets: Blood loss, anemia, and diarrhea 

• Dogs: S. stercoralis can undergo autoinfection (repeated parasitic generations develop in the same host individual, which can result in rapid expansion of parasitic populations, typically in association with severe immunosuppression), commonly fatal in 2-3 month old puppies in kennel environments; causes duodenal villus atrophy and lamina propria mononuclear inflammation, and larvae may incite granulomas in the lamina propria and submucosa; larval migration may cause pulmonary lesions; also affects some other species including humans (zoonotic potential in immunocompromised humans, humans are the natural host, see discussion on apes below)
• Cats: 

• S. felis may cause mild focal granulomatous to eosinophilic interstitial pneumonia due to larval migration, and may cause focal crypt hyperplasia near nematodes in the small intestine; diarrhea is uncommon
• S. planiceps (formerly S.catti) 
• S. stercoralis (small intestine) 
• S. tumefaciens (colon) has rarely been associated with chronic diarrhea; different from other Strongyloides spp. because it causes proliferation of submucosal glands of the colon resulting in formation of nodules in which the worms are found (unknown cause/effect)

• Apes: Important, sometimes fatal disease of captive young apes, Strongyloides sp. eggs are commonly found on fecal exams; disease has been reported in detail in Gibbons

• S. fuelleborni: Old World monkeys and apes are the natural host; eggs are shed in feces
• S. stercoralis: Humans are the natural host; eggs hatch within the intestinal lumen, larvae shed in feces, but larvae may directly penetrate colon wall instead of being shed into feces (autoinfection à hyperinfection, especially in young orangutans); larvae may be found in the lung associated with acute interstitial pneumonia

• New World Monkeys: S. cebus
• Old World Monkeys: S. fulleborni, S. simiae, S. pappilosus
• Snakes: Rhabdias and Strongyloides are the important rhabditoid nematodes of snakes; Rhabdias spp. remain in the lung to mature into adults; Strongyloides spp. complete their maturation in the intestines

• Strongyloides: May result in proliferative enteritis

• Macropodid: Strongyloides occur in regions of the cardiac glandular mucosa; heavily infected kangaroo may have erythematous gastric mucosa; fatal infections are due to severe infections and are only documented in captive animals 
• Anurans: Strongyloides spp. cause proliferative enteritis in both free-ranging and captive animals 

 

REFERENCES:

1. Gardiner CH, Poynton SL. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology;1999:14-16.
2. Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:458.
3. Graham EA, Los Kamp EW, Thompson NM, Tillis SB, Childress AL, Wellehan JFX, Walden HDS, Ossiboff RJ. Proliferative strongyloidiasis in a colony of colubrid snakes. Vet Pathol. 2024;61(1):109-118.
4. Higgins D, Rose K, Spratt D. Monotremes and Marsupials. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London, England: Elsevier; 2018:473. 
5. Lowenstine LJ, McManamon R, Terio KA. Apes. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London, England: Elsevier; 2018:398-399.
6. Martinez MAJ, Gasper DJ, Mucino MCC, Terio K. Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London, England: Elsevier; 2018:220.
7. Ossiboff RJ. Serpentes. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London, England: Elsevier; 2018:914.
8. Strait K, Else JG, Eberhard ML. Parasitic diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases, Vol. 2. 2nd ed. Waltham, MA: Academic Press; 2012:222-231.
9. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier Saunders; 2016:113-115, 152, 211-212.

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