JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
August 2021
D-B11

 

Signalment (JPC #1947391): 16-month-old African green monkey (Chlorocebus aethiops sabaeus)

 

HISTORY: Found semicomatose with a temperature of 94^oF.

 

HISTOPATHOLOGIC DESCRIPTION:  Colon:  Approximately 20% of the colonic mucosa, often in areas overlying and adjacent to Peyer’s patches, is characterized by multifocal, segmental, well-demarcated, 0.5 to 1.5mm diameter areas of coagulative necrosis characterized by retention of cellular architecture with loss of differential cellular staining.  These foci often extend into the submucosa and are rimmed by lytic necrosis characterized by complete loss of mucosal architecture with replacement by cellular and karyorrhectic debris.  Multifocally within areas of necrosis there are large colonies, up to 2.5mm diameter, of 1-2 um amphophilic coccobacilli. Within the affected areas, there is segmental loss of muscularis mucosa.  The lamina propria and submucosa adjacent to necrotic foci are markedly expanded by viable and necrotic neutrophils, fewer lymphocytes and macrophages, edema, fibrin, and small to moderate amounts of hemorrhage.  Peyer’s patches are often markedly decreased in size with lymphoid depletion.  Multifocally, blood vessels within the submucosa and mesentery are lined by lost, discontinuous, or necrotic endothelium; there is occasional variable occlusion of the lumen by fibrin thrombi with enmeshed neutrophils and lymphocytes; and the tunica media and externa are expanded by fibrin and edema admixed with neutrophils, lymphocytes, necrotic debris, and large colonies of 1-2um coccobacilli that often extend transmurally through vessel walls (necrotizing vasculitis). 

 

Liver:  Multifocally and randomly affecting 10% of the parenchyma are well-demarcated, 100-500um areas of lytic necrosis characterized by loss of normal hepatic architecture and replacement by eosinophilic cellular and karyorrhectic debris admixed with moderate numbers of necrotic neutrophils, fibrin, and large (up to 200 um wide) colonies of 1-2 um amphophilic coccobacilli.  Hepatocytes surrounding areas of necrosis are multifocally dissociated and swollen with pale vacuolated cytoplasm (degeneration) or are shrunken with hypereosinophilic cytoplasm and pyknotic nuclei (single cell death).  Sinusoids multifocally and randomly often contain large, coalescing colonies of 1-2um coccobacilli occasionally accompanied by viable and necrotic neutrophils and macrophages.

 

MORPHOLOGIC DIAGNOSIS: 

1. Colon: Colitis, necrotizing, segmental, acute, severe, with vasculitis, thrombosis, and large colonies of coccobacilli, African green monkey (Chlorocebus aethiops sabaeus), non-human primate.
2. Liver: Hepatitis, necrotizing, random, multifocal to coalescing, moderate, with large colonies of coccobacilli.

 

ETIOLOGIC DIAGNOSIS: Colonic and hepatic yersiniosis

 

ETIOLOGY: Yersinia enterocolitica

 

GENERAL DISCUSSION:

• Gram negative 1 x 3 um facultative intracellular, non-motile, large-colony forming coccobacillus
• Yersiniosis causes enterocolitis, mesenteric lymphadenitis, septicemia, and less commonly hepatitis in domesticated mammals and non-human primates
• Pathogenic Yersinia species: enterocolitica, Y. pseudotuberculosis and Y. pestis
  • Y. enterocolitica and Y. pseudotuberculosis cause enteric and systemic diseases
• Y. enterocolitica can replicate at low temperature and commonly is a cool weather environmental contaminant
• Worldwide significant foodborne pathogen
• Poorly understood epidemiology with shedding by asymptomatic animals and/or birds and rodents
• Non-human primates: Yersiniosis is commonly seen in colonies housed outdoors during wet weather
• Affects cattle, sheep, goat, pig, deer, exotic ungulates, and others world-wide

 

PATHOGENESIS:

• Fecal-oral transmission targeting distal ileum, cecum, and colonic epithelium and M-Cells which overlay Peyer’s patches > large bacterial colonies form in the lamina propria or submucosal lymphoid follicles > recruit neutrophils > result in the destruction of cytoarchitecture, causing necrosis > intestinal mucosa and transmural ulceration > disseminates via lymphatics and hepatic portal system to lymph nodes, liver, and systemic circulation
• Infiltration to the mesenteric lymph nodes can lead to septicemia resulting in necrohemorrhagic lesions in liver, spleen, lungs, and meninges
• Unique virulence factors: invasion of enterocytes and evasion of inflammatory response via plasmid Yersinia virulence (pYV) proteins:
  • Type III secretion system (Ysc T3SS): translocates effector proteins to be injected into host target cells and secrete toxins
  • Yersinia Outer coat Protein (YOPS): interfere with the host cell actin cytoskeleton, blocking phagocytosis, down regulating inflammatory response
  • Low-Calcium Response Virulence (LcrV): aids in the injection of effector proteins, reducing host cell secretion of proinflammatory cytokines, inhibiting neutrophil chemotaxis, interfering with phagocytosis
  • Yersinia Adherence (YadA) protein: provides adherence to target cell integrins, invasion, and resistance to complement
  • Invasin (Inv) protein: binds Beta integrin expressed on the surface of M-Cells, promoting the uptake of Yersinia and chemokine production (IL-8)
  • Attachment Invasion Locus (Ail) protein: confers resistance to complement activity

 

TYPICAL CLINICAL FINDINGS:

• Disease may be gradual in onset, subtle, and chronic
• Gastroenteritis: vomiting, hemorrhagic diarrhea, terminal ileitis
• Lymphadenitis
• Septicemia
• Weight loss, depression, weakness, dehydration
• Hepatomegaly: icterus
• Sudden death in extreme cases

 

TYPICAL GROSS FINDINGS:

• Usually mild with an abnormally fluid intestinal content
• Raised nodules up to 5 mm in diameter with ulcerative fibrinohemorrhagic enterocolitis with visible foci or confluent masses of caseous necrotic debris
• Caseous lymphadenitis and/or lymphadenopathy
• Hepatomegaly, splenomegaly with multifocal abscesses and necrosis
• Mild fibrinous cholecystitis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Diagnosed in tissue section by finding characteristic microcolonies of coccobacilli in microabscesses; bipolar staining, gram-negative, amphophilic coccobacilli; abscesses in the lamina propria, often over or adjacent to Peyer’s patches
• Intense local infiltrate of inflammatory cells, mainly neutrophils forming small abscesses (> 300 um) around the bacteria, with multinucleated giant cells
• Congestion of adjacent blood vessels containing fibrin thrombi
• In fulminant Yersinia infection in all species, there is fibrinous or fibrinohemorrhagic enterocolitis

ADDITIONAL DIAGNOSTIC TESTS: 

• Isolation (culture) and identification required for confirmation diagnosis to differentiate from pseudotuberculosis

 

DIFFERENTIAL DIAGNOSIS:

Bacteria that form large colonies in tissue (YAACSS):

• Y. Yersinia
  • Y. pseudotuberculosis: affects a wide range of species including primates; acute septicemia; granulomatous nodules in the spleen, liver, lymph nodes, and lung occur in the chronic form; in primates, there is acute, severe, fibrinonecrotic enteritis and mesenteric lymphadenitis with necrosis in the liver, lung, and spleen; it can cause abortions in cattle, sheep, and goats; histologically there is a necrotic core surrounded by large numbers of epithelioid macrophages but no giant cell macrophages; differentiation from Y. enterocolitica requires culture
  • T. pestis (plague): transmission occurs by direct contact with infected carcasses, bodily excretions or by flea bites; the organism enters through mucous membranes or broken skin; the organism is killed in neutrophils but can survive and replicate within macrophages, with spread to regional lymph nodes and/or bacteremia; the organism uses host-derived proteins to produce an envelope that is resistant to host phagocytosis, allowing rapid replication and causing sudden death
• Actinomyces (gram-positive): caseous lymphadenitis
• Actinobacillus (gram-negative): fibrinonecrotic pneumonia
• Corynebacterium (gram-positive): necrosuppurative embolic pneumonia
• Staphylococcus (gram-positive): necrosuppurative inflammation in multiple organs
• Streptococcus (gram-positive): causes fibrinopurulent exudate
• Trueperella pyogenes (gram-positive): abscesses

 

Hemorrhagic enterocolitis in non-human primates:

• Shigella (gram-negative): lesions limited to the large intestine; colonic edema, hemorrhage and ulcers and/or pseudomembrane; no large bacterial colonies
• Campylobacter (gram-negative): similar to shigellosis but also affects the small intestine; necrosis, edema, hemorrhage, villus blunting and fusion
• Salmonella (gram-negative): fibrinonecrotic enteritis, typhlitis and colitis; no large colonies
• Enteropathogenic coli causes hemorrhagic gastroenteritis and ulcerative colitis; no large colonies
• Balantidium coli can cause ulcerative colitis

 

COMPARATIVE PATHOLOGY:

• Foals: (Yersinia) sporadic pneumonia and septicemia
• Freshwater fish: ( ruckeri) causes “Red Mouth”, a hemorrhagic inflammation of the perioral subcutis of (especially rainbow trout)
• Sheep and Goats: ( enterocolitica, Y. pseudotuberculosis) placentitis with abortion, perinatal mortality, epididymitis-orchitis, and mastitis
• Pathogenic Yersinia may also affect cattle, sheep, goat, pig, deer, red deer, water buffalo, and exotic ungulates

 

REFERENCES:

1. Brady AG, Carville AL. Digestive System Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. 2nd ed. St. Louis, MO: Elsevier; 2012: 602.
2. Uzal FA, Platter BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Philadelphia, PA: Elsevier; 2016: 71, 176-177.
3. Green CE. Yersiniosis. In: Greene CE, eds. Infectious Diseases of the Dog and Cat. 4th ed. St Louis, MO: Elsevier; 2012: 390.
4. Gelberg HB. Alimentary System and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:380.
5. Hirsch DC. Enterobacteriaceae: Yersinia. In: Hirsch DC, MacLachlan NJ, Walker RL, eds. Veterinary Microbiology. 2nd ed. Ames, IA: Blackwell Publishing; 2004: 79-80.
6. Oda S, Kabeya H, Sato S, et al. Isolation of Pathogenic Yersinia enterocolitica 1B/O:8 from Apodemus Mice in Japan. J Wildl Dis. 2015: 51(1): 260-264.
7. Simmons J, Gibson S. Bacterial and Mycotic Diseases of Nonhuman Primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases. 2nd ed. St. Louis, MO: Elsevier; 2012: 138-140.
8. Songer JG. The Genus Yersinia. In: Songer JG, Post KW, eds. Veterinary Microbiology Bacterial and Fungal Agents of Animal Diseases. St. Louis, MO: Elsevier; 2005: 141-142.
9. Soto E, Griffin M, Verma A, Castillo-Alcala F, Beierschmitt A, Beeler-Marfifi J, et al. An Outbreak of Yersinia enterocolitica in a Captive Colony of African Green Monkeys (Chlorocebus aethiops sabaeus) in the Caribbean. Comp Med. 2013: 63(5): 439-444.

 

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