JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
August 2018
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:  Multifocally affecting approximately 20% of the colonic mucosa, there are well-demarcated segmental areas of coagulative and lytic necrosis of the mucosa, ranging in size from 0.5 to 1.5mm, characterized by retention of cellular architecture with loss of differential cellular staining, and/or complete loss of mucosal architecture with replacement by cellular and karryorectic debris, which extends into the submucosa.  Within the affected areas, there are segmental loss of muscularis mucosa, and the adjacent lamina propria and submucosa are markedly expanded by viable and degenerating neutrophils, with fewer lymphocytes and macrophages, edema, fibrin, and hemorrhage.  Areas of necrosis are overlying Peyer’s patches and Peyer’s patches are decreased in size with lymphoid depletion.  Multifocally vessels within the submucosa and adjacent mesenteric adipose tissue have lost, disrupted or necrotic endothelium with occasional occlusion of the lumen by fibrin thrombi with enmeshed neutrophils and lymphocytes;  the tunica media and externa are thickened by fibrin and edema, admixed with neutrophils, lymphocytes, necrotic debris, and large colonies of 1-2um coccobacilli that often extend transmurally thru vessel walls (necrotizing vasculitis).  Multifocally within areas of necrosis there are large (up to 2.5mm wide) colonies of 1-2 um amphophilic coccobacilli that extend into the submucosa.

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 degenerate neutrophils, fibrin, and large  (up to 200 um wide) colonies of 1-2 um amphophilic coccobacilli.  Hepatocytes surrounding areas of necrosis multifocally are hypertrophed, and occasionally dissociated with pale vacuolated cytoplasm (degeneration).  Randomly in the sinusoids are individual large coalescing bacterial colonies accompanied by viable and degenerate neutrophils and macrophages.

MORPHOLOGIC DIAGNOSIS: 

1. Colon: Colitis, necrohemorrhagic, 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
  • enterocolitica and Y. pseudotuberculosis are enteric and systemic diseases
• enterocolitica can replicate at low temperature and commonly as 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 effectors 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 cells secretion of proinflammatory cytokines, inhibiting neutrophils 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 intestinal 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 an 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

• Usually mild with abnormally fluid intestinal content, and
• 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:

• Microcolonies of bipolar staining gram-negative amphophilic coccobacilli forming 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: 

• Diagnosed in tissue section by finding characteristic microcolonies of coccobacilli in microabscesses
• Isolation (culture) and identification required for confirmation diagnosis

DIFFERENTIAL DIAGNOSIS:

• Bacteria that form large colonies in tissue (YAACSS):
  • 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
  • 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

• Hemorrhagic enterocolitis in non-human primates:
  • Shigella (gram-negative): lesions limited to large intestine; colonic edema, hemorrhage and ulcers and/or pseudomembrane; no large bacterial colonies
  • Campylobacter (gram-negative): similar to shigellosis but also affect 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 spp. 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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