JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
November 2021
D-V08

SIGNALMENT (JPC #2018104):  A 7-day-old CD rat.

 

HISTORY:  None

HISTOPATHOLOGIC DESCRIPTION: Small intestine: There is mild to moderate blunting, atrophy, and fusion of 80% of the villi.  Affected villi are lined by attenuated to cuboidal epithelial cells. Enterocytes located at the villous tips are often swollen with abundant, pale eosinophilic, vacuolated cytoplasm (degeneration), and multifocally form syncytia with abundant pale flocculant cytoplasm and up to 15 nuclei. Multifocally, enterocytes are shrunken with hypereosinophilic cytoplasm and a pyknotic nucleus (single cell death). Goblet cells are diffusely moderately reduced in number. The lamina propria is mildly expanded by low numbers of lymphocytes, plasma cells, neutrophils, and eosinophils.

MORPHOLOGIC DIAGNOSIS:   Small intestine: Villar blunting, atrophy, and fusion, diffuse, moderate, with multifocal enterocyte degeneration and viral syncytia, CD rat, rodent.

ETIOLOGIC DIAGNOSIS:   Rotaviral enteritis

CAUSE:   Type B (atypical) rotavirus

CONDITION: Infectious Diarrhea of Infant Rats (IDIR)

 

GENERAL DISCUSSION:

• Type B (atypical) rotavirus is a non-enveloped, icosahedral, double-stranded RNA virus that causes diarrhea in rats less than two weeks of age; older animals (over two weeks of age) are susceptible to infection, but do not show clinical signs of disease
• Family Reoviridae, genus Rotavirus, group B
• Atypical rotaviruses (groups B-G) are morphologically identical to typical and most common rotaviruses (group A) but do not share common capsid antigens
  • Group A rotaviruses are ubiquitous; very host specific
• Heat, pH, and desiccation stable; inactivated by disinfectants
• Initial target sites are villi tips and goblet cells of the superficial one half to two thirds of small intestine villi

PATHOGENESIS:

• Oral ingestion > uptake of virus by mature enterocytes > direct penetration of cell membrane or receptor-mediated endocytosis > replication in cytoplasm > released by cell lysis > villar atrophy (determines severity of disease) > diarrhea
• Pathogenic effects result from three causes (1) malabsorption (2) villus ischemia (3) secretory exotoxin, NSP4
• Viral antigens are present in affected enterocytes; syncytia and viral antigen are present only in the first 18-24 hours; then rapidly decrease in number
• High morbidity, low mortality
• Maternal IgG is protective during the first week of life

TYPICAL CLINICAL FINDINGS:

• Diarrhea 24-36 hours post infection; watery diarrhea for 5-6 days followed by full recovery
• Anorexia, poor growth (runts), weight loss, erythema, cracking and bleeding of the perianal skin
• Rats resistant after 2 weeks of age

TYPICAL GROSS FINDINGS:

• Stomach is usually filled with milk
• Distal small intestine and large intestine contain yellow brown to green fluid, poorly formed fecal pellets, gas, and occasionally mucinous material
• Other organs are not remarkable

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Affects distal small intestine (jejunum and ileum); lesions most significant in ileum
• Villus attenuation, villus epithelial necrosis (luminal one-third of the villi)
• Pathognomonic epithelial syncytia with up to 15 nuclei (only present within the first 24 hours after infection); +/- eosinophilic intracytoplasmic inclusions

ULTRASTRUCTURAL FINDINGS:

• Characteristic “wagon wheel” appearance of cytoplasmic virions (hence “rota”)

ADDITIONAL DIAGNOSTIC TESTS:

• Characteristic gross and microscopic findings and demonstration of rotaviral particles in tissue sections or intestinal contents
• Electron microscopy of epithelial syncytial cells and negatively stained feces or intestinal contents
• Indirect immunofluorescent staining
• PCR has been developed for bovine group B & F rotaviruses

DIFFERENTIAL DIAGNOSIS:

Causes of diarrhea in rats:

• Bacteria: Clostridium piliforme, Salmonella, E. coli, Streptococcus Group D, Campylobacter sp.
• Parasites: Giardia muris, Spironucleus muris, oxyuriasis (Syphacia obvelata, Syphacia muris, Aspicularis tetraptera)

COMPARATIVE PATHOLOGY:

• Group A rotaviruses are far more common and infect humans (mostly infants), laboratory animals, domestic animals, and wildlife:
  • Mice: Cause of epizootic diarrhea of infant mice (EDIM, D-V07); like IDIR, infection possible at all ages with clinical disease apparent only in animals <2 weeks old; highly contagious; effects are transient
  • Rabbits: diarrhea in suckling and weanling animals; often seen in co-infection with enteropathogenic coli or coccidian
  • Cattle: Important cause of diarrhea in beef and dairy neonatal calves >5 days old up to 2-3 weeks old; disease is mild and transient but can be severe when co-infected with coli or coronavirus
  • Pigs: May cause “3-week” or “white” scours in postweaning piglets 2-8 weeks of age; also affects older pigs that are susceptible; clinical signs are similar to, but less severe than, transmissible gastroenteritis
  • Lambs: Diarrhea in neonatal lambs alone or in combination with coli or Cryptosporidium sp.; virus may infect the colon unlike in other species
  • Foals: Diarrhea in foals <3-4 months of age; rare mortality; but, co-infection common with Salmonella and Cryptosporidium spp.
  • Dogs and cats: Rare but can cause diarrhea in puppies and kittens <2 weeks of age
  • Poultry: Subclinical infection or diarrhea in poults and chicks

REFERENCES:

1. Almeida PR, Lorenzetti E, Cruz RS, et al. Diarrhea caused by rotavirus A, B, and C in suckling piglets from southern Brazil: molecular detection and histologic and immunohistochemical characterization. J Vet Diagn Invest. 2018 May;30(3):370-376.
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:37-38, 267-268.
3. Day JM. Rotavirus Infection. In: Swayne DE, ed. Diseases of Poultry. 13th ed., Ames, IA: Iowa State University Press; 2013:281-291.
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; 2017:374-375.
5. Huber AC, Yolken RH, Mader LC, Strandberg JD, Vonderfecht SL. Pathology of infectious diarrhea of infant rats (IDIR) induced by an antigenically distinct rotavirus. Vet Pathol. 1989; 26:376-85.
6. Uzal FA, Platter BL, Hostetter JM. Alimentary System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St Louis, MO: Elsevier; 2016:112,115-117, 151-153.
7. Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:200.

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