JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

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 less often 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:

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 sp., 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: Lapine rotavirus group A causes variably severe diarrhea in suckling and weanling animals; gross and histo lesions similar to those seen in piglets
    • Part of “rabbit enteritis complex”: includes Clostridium spiriforme, C. piliforme, E. coli, Lawsonia intracellularis, and Eimeria species.
    • Infection with bovine rotavirus also reported
  • 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 E. 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
    • Rotavirus C associated with diarrhea outbreaks and asymptomatic infections (Flores, J Vet Diagn Invest. 2021)
    • Rotavirus H is an emerging pathogen; detected in pigs with and without diarrhea (Flores, J Vet Diagn Invest. 2021)
    • Rotaviruses have zoonotic potential – concern for infection of agricultural workers and for viral reassortment (Flores, J Vet Diagn Invest. 2021)
    • Porcine astrovirus-associated enteritis often confounded by rotavirus infection (Opriessnig, J Comp Path. 2020)
    • Dashboard developed for real-time tracking of swine rotavirus in Ontario, Canada (Petukhova, J Vet Diagn Invest 2023)
  • Lambs: Diarrhea in neonatal lambs alone or in combination with E. coli or Cryptosporidium sp.; virus may infect the colon unlike in other species 
  • Foals: Disease most often seen in 5-35 day-old foals, but can occur in foals between 2-160 days old; most severe disease (and potentially death) occurs in foals under 2 weeks of age (Uzal, J Vet Diagn Invest 2022)
    • Novel equine rotavirus group B identified in foals with diarrhea in Kentucky (with no concurrent pathogens detected); 96% homology with ruminant group B rotaviruses suggests ruminant origin
    • Season and geographic location not found to affect detection rate of equine rotavirus in ≥ 6-mo-old horses in the United States (Willette, J Vet Diagn Invest 2022)
  • 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
    • Rotavirus may be one of several enteric viruses at least partially responsible for runting stunting syndrome (RSS) in commercial chickens, however Gallivirus (a picornavirus) was the only virus statistically associated with RSS in recent study (de Oliveira Vet Pathol 2021)
  • Turkeys: Rotavirus is one of several enteric viruses associated with poult enteritis complex
  • Pet and aviary birds: rotavirus has been implicated as a cause of viral enteritis; may cause villar atrophy
  • White-tailed deer: Rotavirus most often identified pathogen in enteritis/enterocolitis cases in captive deer necropsy cases from Wisconsin Veterinary Diagnostic Laboratory from 2009-2021 (Clarke J Vet Diagn Invest 2023)
  • Camels: Rotavirus infections common cause of enteritis in young and neonatal camelids

REFERENCES:

1. Agnew D. Camelidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:197. 
2. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:37-38, 129, 267-268.
3. Clarke LL. Postmortem diagnoses and factors influencing diagnoses in captive white-tailed deer in Wisconsin, 2009-2021.
4. 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; 2018:491. 
5. De Oliveira LB, Stanton JB, Zhang J, et al. Runting and Stunting Syndrome in Broiler Chickens: Histopathology and Association With a Novel Picornavirus. Vet Pathol. 2021;58(1):123-135.
6. Fletcher OJ, Abdul-Aziz T. Chapter 7: Alimentary System. In: Abdul-Aziz T, Fletcher OJ, Barns HJ, eds. Avian Histopathology. 4th ed. Madison, WI: Omnipress; 2016: 274.
7. Flores PS, Costa FB, Amorin AR, Mendes GS, Rojas M, Santos N. Rotavirus A, C, and H in Brazilian pigs: potential for zoonotic transmission of RVA. J Vet Diagn Invest. 2021;33(1):129-135.
8. Opriessnig T, Xiao CT, Halbur PG. Porcine Astrovirus Type 5-Associated Enteritis in Pigs. J Comp Path. 2020;181:38-46.
9. Petukhova T, Spinato M, Rossi T, et. al. Development of interactive dashboards for monitoring endemic animal pathogens in Ontario, Canada: Ontario interactive animal pathogen dashboards. J Vet Diagn Invest. 2023;35(6):727-736.
10. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:78-79.
11. 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; 2022:447-448. 
12. Uzal FA, Arroyo LG, Navarro MA, Gomez DE, Asin J, Henderson E. Bacterial and viral enterocolitis in horses: a review. J Vet Diagn Invest. 2022;34(3):354-375.
13. 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.
14. Willette JA, Kopper JJ, Kogan CJ, Seguin MA, Schott HC. Effect of season and geographic location in the United States on detection of potential enteric pathogens or toxin genes in horses ≥ 6-mo-old. J Vet Diagn Invest. 2022;34(3):407-411.
15. 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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