Signalment:  

5.65-year-old, female, Indian macaque (Macaca mulatta).Found dead in an outside breeding corral without history of previous illness.

Gross Description:  

The animal was dehydrated with evidence of fecal soiling around the anus. Small intestine and colon were distended with fluid and gas. Contents were blood-tinged and foul smelling. Mesenteric lymph nodes were severely enlarged.

Histopathologic Description:

Small intestine: Small intestinal mucosa contains multiple to confluent areas of necrosis and hemorrhage that in some areas extend to the muscularis mucosa. Necrotic foci are filled with neutrophils forming microabscesses with dense microcolonies of extracellular bacteria. Scattered hyalinized eosinophilic deposits around crypts and vessels in the lamina propria demonstrate apple green birefringence when stained with Congo red and observed with polarized light.

Morphologic Diagnosis:  

1. Enteritis, necrohemorrhagic, suppurative, multifocal, severe, with intra-lesion bacterial colonies. Etiology: Yersinia pseudotuberculosis
2. Amyloidosis, secondary, small intestine and mesenteric lymph node (not submitted)

Lab Results:  

Colonic swab cultures contained Yersinia pseudotuberculosis and Campylobacter coli.

Condition:  

Yersinia enterocolitica; amyloidosis

Contributor Comment:  

Yersinia pseudo tuberculosis is a disease of rodents and birds but has been reported in rabbits, deer, dogs, cats, swine, sheep, goats, chinchillas, horses, non-human primates, man and exotic mammals. In cases where multiple pathogens are isolated, it may be difficult to associate lesions with a specific pathogen. However, necrotizing lesions in the small intestine, obvious bacterial colonization, and severe neutrophilic response are hallmarks of Yersiniosis.(1)

Three species of Yersinia are pathogenic for humans and non-human primates: Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis. Yersinia pestis is transmitted by flea bite, while Y. enterocolitica and Y. pseudotuberculosis are typically self-limiting enteric infections transmitted by ingestion of contaminated food and water. All three organisms contain a virulence plasmid P (approximately 70 kb) that codes for a set of proteins called YOPS (for Yersinia outer membrane proteins) that are actually secreted virulence factors necessary for replication in host cells.(2) Additional plasmids pMT1 and pPCP1 in Y. pestis impart increased virulence.

Yersinia enterocolitica and Y. pseudotuberculosis pass through intestinal M cells, replicate in Peyers patches, and, in rodents, frequently disseminate to mesenteric lymph node, spleen, liver, and lungs. Septicemia is rare in humans and non-human primates. Some literature suggests Yersinia resist phagocytosis by neutrophils and induce apoptosis of macrophages.(4) Recent work suggests that Yersinia can alter antibacterial functions, survive within macrophages, and replicate.(4) Two genes in Y. enterocolitica, ompR and gsrA, controlling response to altered osmolarity and heat shock, are associated with survival in macrophages.(5) Yersinia pseudotuberculosis and Y. pestis may inhibit phagosome acidification,(5) can infect na+�-�ve macrophages, and continue to replicate when exposed to interferon gamma. The latter ability may be conferred by a Pgm (102 kb) segment of the bacterial genome that reduces production of nitric oxide (NO) in infected macrophages.(5)

JPC Diagnosis:  

Small intestine: Enteritis, necrotizing and suppurative, acute, diffuse, marked, with multifocal hemorrhage, microabscesses, amyloidosis, and colonies of coccobacilli.

Conference Comment:  

Some participants noted the presence of fibrin thrombi within the submucosal and mesenteric vasculature; this histologic finding is not present on all slides due to section variability. 

Each of the three species of Yersinia mentioned by the contributor (Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica) produces a distinct syndrome in various species of animals. Yersinia pestis may infect cats in the southwestern United States following consumption of infected rodents. The disease syndrome in cats, like humans, can be bubonic, septicemic and pneumonic; the bubonic form is associated with the lowest mortality rate. In cats the bubonic form occurs most frequently, and affected animals are febrile, dehydrated, have lymphadenomegaly and hyperesthesia. Suppuration of lymph nodes may result in draining fistulous tracts. Delay or failure to treat infected animals increases the risk of developing the septicemic form via lymphatic or hematogenous spread. Histologically, there is marked suppurative and necrotizing lymphadenitis with hemorrhage.(3) The septicemic form results in involvement of nearly all organs and clinical signs of septicemic shock and dissemination intravascular coagulation (DIC); death typically occurs in 1-2 days. The pneumonic form occurs as a primary infection through direct inhalation, or can occur secondary to either the bubonic or septicemic forms. Of the three forms, the pneumonic form carries the worst prognosis, with nearly a 100% fatality rate.(3)

Yersinia pseudotuberculosis produces caseonecrotic foci in mesenteric lymph nodes, spleen and liver of susceptible animals, of which there are many. There is marked necrosis, parenchymal collapse and vasculitis in the liver in addition to multiple pyogenic granulomas visible grossly as variably sized white foci. The spleen and lymph nodes have similar foci, and these organs are enlarged by lymphoid and histiocytic hyperplasia.(7) The organism is also linked to abortions in cattle, sheep and goats; the bacteria localize in the caruncle with passage to the chorioallantois and fetus. The lesions are typically that of placentitis of the cotyledons observed histologically as villar necrosis with granulocytic and histiocytic infiltration of the chorioallantois, and fibrinoid necrosis of the media in placental vessels with mononuclear and neutrophilic infiltrates. Septal vessels in the caruncles are thrombosed, resulting in necrosis and hemorrhage with marked neutrophilic and mononuclear infiltrates. The fetus is often delivered in a good state of preservation, with thoracic and abdominal effusion and foci of hepatic necrosis admixed with granulocytic and mononuclear infiltrates. The myocardium, lymph nodes and conjunctiva may have similar inflammatory infiltrates.(6)

Yersinia enterocolitica is known to cause disease in sheep, cattle, goats, deer and pigs in addition to humans and non-human primates. Gross lesions vary with the severity of infection, with fluid intestinal contents and congestion in mild cases, and edema to hemorrhage, ulceration and fibrin exudation in more severe cases. Histologic lesions include large colonies of coccobacilli in the lamina propria and villi in the distal small intestine and marked neutrophilic infiltration with microabscessation, ulceration, hemorrhage, and occasional pyogranulomas. In addition to enteritis, Y. enterocolitica is also associated with caseous mesenteric lymphadenitis.(1)

References:

1. Brown CC, Barker DC, Barker IK The alimentary system. In: Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed., vol. 2. Philadelphia, PA: Elsevier Ltd; 2007:204-206.

2. Cornelis GR, Boland A, Boyd AP, et al. The virulence plasmid of Yersinia, an antihost genome. Microbiol Molec Bio Rev. 1998;62(4):1315-1352.

3. Macy D. Plague. In Greene CE, ed. Infectious Diseases of the Dog and Cat. Saint Louis, MO: Saunders Elsevier; 2006:439-445.

4. Monack DM, Mecsas J, Bouley D, Falkow S. Yersinia induced macrophage apoptosis in vivo aids in the establishment of systemic infection in mice. J Exp Med. 1998;188(11):2127-2137.

5. Pujol C, Bliska JB. Turning Yersinia pathogenesis models inside out: subversion of macrophage function by intracellular yersiniae. Clin Immunol. 2005;114:216-226.

6. Schlafer DH, Miller RB. Female genital system. In: Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed., vol. 3. Philadelphia, PA: Elsevier Ltd; 2007:500.

7. Valli VEO: Hematopoietic system. In: Maxie MG, ed. Jubb, Kennedy and Palmers Pathology of Domestic Animals. 5th ed., vol. 3. Philadelphia, PA: Elsevier Ltd; 2007:298-299.

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