JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

September 2024

D-B11

 

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

 

HISTORY: Found semi-comatose 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 µm amphophilic coccobacilli. 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, 100-500µm 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 µm wide) colonies of 1-2 µm 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 1-2µm 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:

• In Old and New World monkeys, Y. enterocolitica and Y. pseudotuberculosis are the two most common causes of bacterial yersiniosis 
• Gram negative 1 x 3 µm facultative intracellular, non-motile, large-colony forming coccobacillus            
• Monkeys are found dead without clinical signs of disease, yersiniosis causes enterocolitis, mesenteric lymphadenitis, septicemia, and less commonly hepatosplenomegaly in domesticated mammals and non-human primates 
• Pathogenic Yersinia species: Y. 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 cold, 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 contributing to bacterial survival in the host
  • Invasin (Inv) protein: Binds Beta integrin expressed on the surface of M-Cells, promoting the uptake of Yersinia spp. and chemokine production (IL-8)

 

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 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 Y. pseudotuberculosis 
• Swine oral fluid deposits on pen can be used as a culture source. 

 

DIFFERENTIAL DIAGNOSIS:

Bacteria that form large colonies in tissue (YAACSS):

• Yersinia sp.
  • 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
  • Y. 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 sp. (gram-positive): Caseous lymphadenitis 
• Actinobacillus sp. (gram-negative): Fibrinonecrotic pneumonia
• Corynebacterium sp. (gram-positive): Necrosuppurative embolic pneumonia 
• Staphylococcus sp. (gram-positive): Necrosuppurative inflammation in multiple organs
• Streptococcus sp. (gram-positive): Causes fibrinopurulent exudate 
• Trueperella pyogenes (gram-positive): Abscesses

 

Hemorrhagic enterocolitis in non-human primates:

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

 

COMPARATIVE PATHOLOGY:

• Yersinia pseudotuberculosis is zoonotic and a facultative intracellular bacteria 
• Foals: (Yersinia sp.) Sporadic pneumonia and septicemia
• Freshwater fish: Y. ruckeri causes “Red Mouth”, a hemorrhagic inflammation of the perioral subcutis of (especially rainbow trout)
• Sheep, Goats, and Cattle: (Y. enterocolitica, predominantly Y. pseudotuberculosis) Placentitis with abortion, perinatal mortality, epididymitis-orchitis, mastitis, and “pyemic hepatitis.”
• Pathogenic Yersinia spp. may also affect cattle, sheep, goat, pig, deer, red deer, water buffalo, and exotic ungulates
• Rodents may serve as carriers of both Y. enterocolitica, Y. pseudotuberculosis, but mice, voles, beavers, muskrats, and agoutis may be susceptible to fatal characteristic hepatitis, splenitis, and fibronecrotizing and ulcerative enterocolitis lesions
• Captive lions are susceptible to Y. pseudotuberculosis due to predation of rodent and avian wildlife reservoirs 
• Lagomorphs, fruit bats, passerine birds and toucans are susceptible to Yersiniosis, infected via ingestion of contaminated foodstuffs, and demonstrate characteristic hepatic and splenic lesions
• Galliformes, Columbiformes: Yersinia pseudotuberculosis creates a chronic infection (Pseudotuberculosis) with granulomas in organs and skeletal muscle, resembling Avian mycobacteriosis. Vaccine-associated sarcoma reaction reported in village weaver birds after routine vaccination for Y. pseudotuberculosis. 

 

 

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. Crespo R, Franca MS, Fenton H, Shivaprasad HL. Galliformes and Colubriformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:741-768. 
3. Cullen JM, Stalker MJ. Liver and Biliary System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:258-352. 
4. Day CE, Stidworthy MF, Cian F, Barrows M. Injection-Site Sarcoma in Three Village Weaver Birds (Ploceus cucullatus) Associated with Autogenous Yersinia pseudotuberculosis Vaccination. J Comp Pathol. 2022;199:43-50.
5. Delaney MA, Treuting PM, Rothenburger JL. Rodentia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:499-516.
6. Delaney MA, Treuting PM, Rothenburger JL. Lagomorpha. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:481-498. 
7. Fulton RM, Boulianne M. Bacterial Diseases. In: Boulianne M ed. Avian Disease Manual. 8^th ed. Jacksonville, FL: Omnipress; 2019.
8. Farina LL, Lankton JS. Chiroptera. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:607-632. 
9. Foster RA, Premanandan C. Female Reproductive System and Mammae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1263-1307.
10. Lane LV, Yang PJ, Cowell RL. Selected Infectious Agents. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:45-65. 
11. Matz-Rensing K, Lowenstine LJ. New World and Old World Monkeys. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:343-374. 
12. Noga EJ. Fish Disease: Diagnosis and Treatment. 2nd ed. Ames, IA: Wiley Blackwell; 2010:197-199. 
13. Spagnoli ST, 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; 2022:396-485. 
14. Schmidt R, Reavill DR, Phalen DN. Liver. In: Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015L103, 184-185.
15. Schott F, Hoffmann K, Sarno E, et al. Evaluation of oral fluids for surveillance of foodborne and zoonotic pathogens in pig farms. J Vet Diagn Invest. 2021;33(4):655-663. 
16. 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. 
17. Trupkiewicz J, Garner MM, Juan-Salles C. Passeriformes, Caprimulgiformes, Coraciiformes, Piciformes, Bucerotiformes, and Apodiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:793-818. 
18. 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.
19. Valli VEOT, Kiupel M, Bienzle D, Wood RD. Hematopoietic System. In: Maxie MG, ed. Jubb, Kennedy & Palmer's Pathology of Domestic Animals. Vol 3. 6th ed. St. Louis, MO: Elsevier; 2016:102-268. 
20. Womble M, Cabot ML, Harrison T, Watanabe TTN. Outbreak in African lions of Yersinia pseudotuberculosis infection, with aberrant bacterial morphology. J Vet Diagn Invest. 2022;34(2):334-338.

Click the slide to view.

---