JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1214032): Juvenile rhesus monkey (Macaca mulatta)
HISTORY: This monkey had intractable diarrhea.
HISTOPATHOLOGICAL DESCRIPTION: Colon: Diffusely, and most severe over Peyer’s patches, there is partial to full thickness mucosal necrosis with abundant hemorrhage, fibrin, eosinophilic cellular and karyorrhectic debris, degenerate neutrophils, and scattered superficial colonies of bacteria. Occasionally, remaining intestinal crypts are ectatic, lined by attenuated epithelium, and contain sloughed epithelial cells admixed with degenerate neutrophils(crypt abscesses). Multifocally, blood vessels in the lamina propria and submucosa are variably occluded by finely fibrillary to polymerized/hyalinized eosinophilic fibrin admixed with enmeshed degenerative inflammatory cells(fibrin thrombi). Diffusely, the submucosa is moderately expanded by increased clear space with ectatic lymphatics (edema) and finely beaded eosinophilic fibrin admixed with moderate numbers of degenerate neutrophils and fewer numbers of lymphocytes and plasma cells, and multifocal mild hemorrhage. The mucosa associated lymphoid tissue (MALT) contains decreased numbers of lymphocytes and increased numbers of tingible body macrophages admixed with necrotic debris (lymphoid depletion).
MORPHOLOGIC DIAGNOSIS: Colon: Colitis, necrohemorrhagic, acute, diffuse, severe, with fibrin thrombi, lymphoid depletion and edema, Rhesus monkey (Macaca mulatta), nonhuman primate.
ETIOLOGIC DIAGNOSIS: Colonic shigellosis
ETIOLOGY: Shigella spp.
CONDITION: Bacillary dysentery
- Gram-negative, nonmotile, non-spore forming, aerobic and facultative anaerobic rod-shaped bacteria
- Shigella spp. cause severe hemorrhagic enteritis (dysentery) in non-human primates and in humans
- Four serogroups:
- One of the most common enteric infection in NHPs
- S. flexneri and S. sonnei are endemic & cause majority of all infections in humans and NHPs; S. dysenteriae is the most pathogenic (Shiga toxin)
- Few organisms are required to cause disease
- Fecal-oral transmission > enter M cells through a phagosome > lyse phagosome and proliferate intracellularly > transmigrate into lymphoid follicles > phagocytized by macrophages > macrophage apoptosis > induction of IL-8 > neutrophil recruitment and mucosal inflammation > inflammatory response damages integrity of epithelial lining > luminal bacteria directly invade epithelial cells > bacterial invasion of enterocytes at basolateral surface (preferred invasion site) > bacterial replication in the cytoplasm of enterocytes > spread via F-actin microfilaments (intracellular) and pseudopods (extracellular) > widespread colonic epithelial damage
- Both chromosomal and plasmid encoded gene expression required for full virulence expression; delivered via a type III secretion system that injects bacterial proteins directly into host cell cytoplasm
- S. dysenteriae – Shiga toxin (highly cytotoxic via inhibition of protein synthesis)
- Damages endothelium in microvasculature of colon and glomeruli
- Can lead to hemolytic-uremic syndrome in humans
- S. flexneri – produces cytotoxin (kills host cell) and enterotoxin (fluid secretion by small intestine)
- All Shigella spp. produce Shigella toxin (binds to a membrane glycolipid receptor)
TYPICAL CLINICAL FINDINGS:
- Incubation of 1-4 days
- Watery and/or mucoid, bloody diarrhea, lethargy, dehydration, edema of face and neck, and weight loss
- Most commonly associated with reactive arthritis (stifle, elbow, coxofemoral and interphalangeal joints)
- Acute cases are often fatal
- Asymptomatic carriers/shedders important in propagation of disease; animals can be chronically re-infected
TYPICAL GROSS FINDINGS:
- Affects terminal ileum, cecum, colon and rectum
- Necrohemorrhagic colitis, +/– ulceration with pseudomembrane formation
- Ulceration; mesenteric lymphadenopathy; edema
- Possible sequela includes small intestinal intussusception or rectal prolapse
- May cause necrohemorrhagic periodontitis/gingivitis and arthritis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Mucosal edema, congestion, hemorrhage, necrosis, with possible ulceration and pseudomembrane formation, often over or adjacent to Peyer’s Patches
- Blood vessels in mucosa and submucosa are congested and may contain fibrin thrombi
- Large numbers of neutrophils and fewer lymphocytes, plasma cells, and macrophages invade mucosa
- Mucosal crypt abscesses may be present
- Free and intravacuolar bacteria in the cytoplasm of enterocytes, macrophages, and M cells
ADDITIONAL DIAGNOSTIC TESTS:
- Isolation and identification (culture) for confirmation
Gross and microscopic findings:
- Campylobacter fetus ssp. jejuni and E. coli affect both small and large intestine; lesions are less severe than those of Shigella spp.; both are associated with chronic colitis of macaques
- Salmonella enteritidis or typhimurium causes necrotizing, suppurative enterocolitis and can cause septicemia
- Yersinia enterocolitica and Y. pseudotuberculosis produce submucosal microabscesses with large colonies of bacteria
- Enteropathogenic (or enteroinvasive) E. coli causes hemorrhagic gastroenteritis and ulcerative colitis
- Balantidium coli can cause ulcerative colitis
- Stress, dietary changes, and inflammatory bowel disease
- Primarily NHP and human disease
- High zoonotic potential
- Dogs can be transient excreters due to coprophagia
- Dogs and cats have not shown disease
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