JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
October 2024
D-P29 (NP)
Signalment (JPC #2316934): Young adult male cynomolgus monkey (Macaca fasicularis)
HISTORY: This lesion was an incidental finding at the terminal necropsy of a subacute toxicity study. Gross finding was a single, 0.5 cm diameter, dark green raised area within the wall of the cecum at necropsy.
HISTOPATHOLOGIC DESCRIPTION: Large intestine: Multifocally expanding the submucosa and the tunica muscularis are granulomas that are up to 4.5 mm in diameter and centered on multiple cross sections of adult strongyle nematodes. These nematodes are admixed with a central core of eosinophilic cellular and karyorrhectic debris (lytic necrosis), brown granular pigment (hemosiderin), canary yellow angular hematoidin, abundant hemosiderin-laden macrophages, and fewer eosinophils. This core is surrounded by epithelioid macrophages, multinucleated giant cell macrophages, fewer lymphocytes, plasma cells, and eosinophils, which are further surrounded by a variably thick band of fibrous connective tissue. Inflammatory cells infiltrate multifocally into the tunica muscularis, muscularis mucosa, and lamina propria. Adult nematodes are 350 µm in diameter, with a prominent, 2-4 µm, smooth, eosinophilic cuticle, platymyarian-meromyarian musculature, vacuolated lateral cords, an intestine lined with few multinucleated cells with a dense microvillar layer, and a reproductive tract. The lamina propria is infiltrated by low numbers of eosinophils and lymphocytes. The intestinal lumen contains cellular debris, plant material, bacilli, colonies of coccobacilli, and occasional free, spherical, 60-75 µm, ciliated protozoal trophozoites (likely Balantidium coli).
MORPHOLOGIC DIAGNOSIS: Large intestine, submucosa and tunica muscularis: Granulomas, eosinophilic, chronic, multifocal, moderate, with adult Strongyle nematodes, Macaca fasicularis, non-human primate.
ETIOLOGIC DIAGNOSIS: Colonic oesophagostomiasis
CAUSE: Oesophagostomum spp
GENERAL DISCUSSION:
- Nodular nematode of the “true strongyles”
- In non-human primates:
- Most common nematode in Old World monkeys and great apes, in the family Strongylidae; considered potentially zoonotic
- 4th stage larvae form pyogranulomatous nodules in the submucosa of the colon; occasionally found in ectopic locations such as the peritoneum, mesentery, and kidney
- Potentially zoonotic; worldwide distribution
- Mild disease except in heavy infectious or if the nodules rupture on the serosal aspect causing peritonitis
- In nonhuman primates, the species most frequently mentioned include O. apiostomum, O. bifurcum, O. aculeatum, O. stephanostumum, and O. blanchardi
- In NHPs, Oesophagostomum spp larvae release a low molecular weight product that is chemotactic for neutrophils; may contribute to pyogranulomatous nodule formation
- In sheep, cattle, and swine:
- In sheep, O. columbianum is important in warm temperate to tropical regions and low burdens can be pathogenic, causing anorexia, mucoid diarrhea, and ill-thrift
- Nodules similar to those seen in NHPs seen in the large intestine are encysted 4th stage larvae; adults found within the mucus layer in colon
- Deeper nodules may project on serosal surface, termed pimply gut
- In cattle, O. radiatum causes similar disease with loss of appetite, reduced productive efficiency, anemia, hypoproteinemia, and diarrhea
- Hemorrhage seen at sites of larval emergence can lead to anemia
- In swine, disease is usually subclinical
LIFE CYCLE:
- Direct life cycle: Begins with the passing of eggs in the animal feces >eggs develop into stage one larvae > molts twice (approximately one week to become infectious stage three larvae) > host ingests stage three larvae > migrate to intestine, unsheath, and penetrate the intestinal wall to form firm, encapsulated nodules > these rupture in 5-8 days> worms released in intestinal lumen and mature > copulate> eggs from the female are then deposited in the feces
TYPICAL CLINICAL FINDINGS:
- NHPs are usually asymptomatic unless severely infected
- Unthrifty, weight loss, and diarrhea
- Submandibular edema ("bottle jaw") in ruminants
- "Thin sow syndrome" - a chronic infection with periodic acute flare-ups
- Rarely causes peritonitis via perforation or rarely migrate to the skin and cause cutaneous nodules
- High mortality with heavy infections (calves, lambs)
TYPICAL GROSS FINDINGS:
- Granulomas (elevated, smooth, 2-4 µm in diameter, firm) within the mesentery, small intestine, or colon
- Elevated firm nodules on the serosal surface of the large intestine, cecum, and mesentery; may also be in ectopic sites such as kidney, peritoneal wall, small intestinal mesentery, omentum, liver, lungs, and/or diaphragm
- Lesions with hemorrhage may be brown or black and older lesions may mineralize
- Ulcers can form in mucosa where larval penetrated in and migratory tract can contain caseous exudate
- Nodular rupture can lead to peritonitis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Granuloma or granuloma-like structure with eosinophils, central necrotic debris, and nematode within intestine wall or in serosa – young nodules may contain viable worms, while older nodules will contain dead worms surrounded by caseous material +/- foci of mineralization
- Parasites approximately 300 μm in diameter with a thick cuticle
- Platymyarian musculature
- Low lateral chords
- Pseudocoelom
- Triradiate esophagus
- Large intestine lined by a few multinucleated cells with a prominent brush border
- Reproductive tract
ADDITIONAL DIAGNOSTIC TESTS:
- Occasional fecal float will be positive – eggs look like other Strongylidae
- ID of larvae via stool culture; occasionally, adults will pass in feces and can be ID’d
DIFFERENTIAL DIAGNOSIS:
- Mesenteric lymphadenitis
- Mycobacterium bovis
COMPARATIVE PATHOLOGY:
- Reported in cattle, sheep, goats, wild pigs, and primates; humans are accidental hosts
- Sheep and goats in North America: Oesophagostomum columbianum
- Cattle all over the world: Oesophagostomum radiatum
- Pigs: Oesophagostomum dentatum
REFERENCES:
- Gardiner CH, Poynton SL. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology;1999:8,24.
- Strait K, Else JG, Eberhard ML. Parasitic disease of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research. Vol 2. Diseases. 2nd ed. San Diego, CA: Elsevier, Inc. 2012: 232-233.
- 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. St. Louis, MO: Elsevier Ltd; 2016:115-116, 215.