JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
November 2021
D-V06

Signalment:  (JPC# 1782647):  Two-day-old piglet

 

HISTORY:  This piglet had profuse, watery feces and vomited milk curd.

 

HISTOPATHOLOGIC DESCRIPTION:  Small intestine:  Diffusely and circumferentially the intestinal wall is thin due to a loss of normal intestinal mucosal architecture characterized by villi that are severely blunted, shortened, and fused as well as marked crypt loss, reducing the villus height to crypt depth ratio to less than 1:1.  The mucosal lining is reduced to a single layer of attenuated basophilic enterocytes, and remaining crypts are lined by either flattened, attenuated epithelium or hypertrophic epithelial cells that occasionally pile up and contain a moderate amount of foamy basophilic cytoplasm and a large, irregularly ovoid nucleus with finely stippled chromatin and one prominent nucleolus, and there are occasional mitotic figures (regeneration).  Multifocally, remaining crypt lumina contain small amounts of eosinophilic cellular and karyorrhectic debris (necrosis) and few macrophages, lymphocytes, and plasma cells (crypt abscesses). Diffusely, the lamina propria is moderately expanded by lymphocytes and plasma cells. The intestinal lumen is dilated.

 

Mesentery: Perimeter vascular plexus (perimesenteric plexus) is present (normal porcine structure).

 

MORPHOLOGIC DIAGNOSIS:  Small intestine:  Villar necrosis and loss, diffuse, acute, severe, with multifocal crypt regeneration and crypt abscesses, breed unspecified, porcine.

 

ETIOLOGY:  Porcine coronavirus (alphacoronavirus 1)

ETIOLOGIC DIAGNOSIS:  Coronaviral enteritis

 

CONDITION:  Transmissible gastroenteritis (TGE)

 

GENERAL DISCUSSION:

• Coronaviruses are enveloped, single-stranded RNA viruses that are sensitive to sunlight and resistant to freezing
• TGE is a highly contagious disease in piglets <10-14 days of age characterized by near 100% morbidity, vomiting and profuse diarrhea; may cause diarrhea and villous blunting in susceptible pigs of all ages, although the youngest are most severely affected (i.e. neonates/nursing/suckling) and severity of clinical signs decreases with age, mild or in apparent signs in sows
• Seasonal, usually winter and spring; also seems to affect chilled piglets
• A cause of porcine periweaning failure-to-thrive syndrome (PFTS)

 

PATHOGENESIS:

• Virus ingestion > infection of mature differentiated columnar epithelial cells of intestinal villi > loss of disaccharidase activity (enterocytes are source of these enzymes) > undigested lactose (from milk) in intestinal lumen > osmotic diarrhea
• Virus destroys villi > loss of intestinal surface area > malabsorption diarrhea
• Virus does not infect undifferentiated cells of the crypts > as infected villus cells are shed, crypt epithelium proliferates > migrates up and lines shortened villi > altered sodium transport across undifferentiated epithelium lining shortened villi > accumulation of electrolytes and water in the lumen
• Several mechanisms account for the age-dependent susceptibility to TGE:
• Neonates:
  • Have tall villi (villus height:crypt depth is 7-9:1) lined by mature differentiated enterocytes and short, inactive crypts of undifferentiated epithelium > large population of susceptible cells and crypts that are slow to repair
  • Inherently susceptible to dehydration, electrolyte imbalances, hypoglycemia
  • Gastric secretions are not as acidic as in older animals (virus is acid labile), and milk buffers gastric acid, protecting the virus
• Piglets older than 3 weeks are more resistant due to:
  • Virus production in enterocytes of older pigs is less efficient, possibly due to the onset of the immune response or the inability of these regenerating cells to support virus growth
  • Crypt epithelium is actively proliferative so mucosa can regenerate faster

 

TYPICAL CLINICAL FINDINGS:

• < 2 weeks of age
  • Vomiting and profuse yellow watery diarrhea, rapid weight loss
  • Pronounced dehydration, hypoglycemia, metabolic acidosis
  • Near 100% mortality within 2 - 5 days
• > 2 weeks of age
  • Transient vomiting and diarrhea
  • Dehydration, unthrifty condition
  • Likely to recover
• Feeder pigs and sows
  • Inapparent or mild fever, inappetance, diarrhea
  • Agalactia in affected sows

 

TYPICAL GROSS FINDINGS:

• External: Dehydration, perineum stained with fluid feces
• Stomach: May contain milk curd
• Small intestine: Flaccid, walls thin and transparent, distended with gas and yellow frothy fluid with flecks of mucus

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Small intestinal villous atrophy and epithelial cell necrosis (but not pathognomonic for TGE); decrease in villus height:crypt depth [7 or 9:1 à 1:1]
• Hypertrophy of crypts (prominent regeneration)
• Mixed submucosal inflammatory cell infiltrate if secondary invaders are present

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunofluorescence (IFA) or immunoperoxidase staining
• Virus isolation
• Serology

 

DIFFERENTIAL DIAGNOSIS:  (For diarrhea in piglets; note age of piglet affected)

• Porcine epidemic diarrhea (Alphacoronavirus)
  • Similar disease presentation and pathologic changes as TGEV, but antigenically distinct so can be distinguished with diagnostic testing (i.e. PCR, etc.)
  • Type I causes diarrhea in pigs up to 4-5 weeks of age
  • Type II causes diarrhea in pigs of all ages
  • Similar signs as TGE but less severe
  • Even though the disease is less severe, animals are productively infected, and can continue to shed the virus long term
  • Most commonly reported in Asia and Europe but caused a 2013-2014 U.S. epidemic
• E. coli (enteric colibacillosis) (D-B13)
  • Profuse diarrhea in piglets < 10 days of age (peak incidence at 3 days of age)
  • No vomiting, may have mild villous atrophy
  • Presence of bacilli adherent to brush border of enterocytes
• Rotavirus enteritis (D-V07, V08)
  • Disease in suckling and weaned pigs (1 - 5 weeks of age)
  • High morbidity and low mortality
  • Villous atrophy less severe than in TGE
• Clostridium perfringens type C (clostridial enterotoxemia) (D-B02)
  • Affects newborn piglets less than one week of age
  • Bloody diarrhea, mucosal hemorrhage and necrosis, rapid death
• Hemagglutinating encephalomyelitis virus (Betacoronavirus):
  • Affects piglets under 10 days of age
  • Vomiting is characteristic; wasting disease; acute encephalomyelitis may occur
  • Diarrhea may occur but is not severe
• Coccidiosis (Isospora suis) (D-P01)
  • Diarrhea without blood in piglets 5-15 days of age (peak incidence 7-10 days of age)
  • Clinical signs precede production of oocysts.
• Porcine Deltacoronavirus
  • Similar condition to PEDV and TGE but distinguishable
  • Diarrhea and vomiting in all age groups, mortality in young piglets
  • In a recent study, mesenteric lymph node and small intestine were the main sites of virus detection via IHC (Vitosh-Stillman, J Vet Diagn Invest. 2016)

 

COMPARATIVE PATHOLOGY:

• Antigenically related coronaviruses:
  • Porcine respiratory coronavirus (PRCV): A deletion mutant of TGE with tropism for the respiratory system; causes mild respiratory disease
  • Canine coronavirus (D-V03): Enteritis
  • Feline infectious peritonitis virus (S-V03, U-V06, P-V15): Peritonitis, pneumonia, meningoencephalitis, panophthalmitis
  • Feline enteric coronavirus: Diarrhea in kittens
• Other selected coronaviruses not antigenically related to TGE:
  • Porcine hemagglutinating encephalomyelitis virus: Vomiting, wasting, encephalomyelitis
  • Porcine epidemic diarrhea virus: Gastroenteritis
  • Mouse hepatitis virus [lethal intestinal virus of infant mice (LIVIM)] (D-V04): Hepatitis, enteritis, encephalomyelitis
  • Sialodacryoadenitis virus in rats (D-V05, S-V02): Necrosis of salivary and nasolacrimal glands
  • Bovine coronavirus: Winter dysentery
  • Bluecomb virus of turkeys: Enteritis, cyanosis of skin of head and neck

 

REFERENCES:

1. Constable PD, Hinchcliff KW, Done SH, Grunberg W. Veterinary Medicine A Textbook of the Diseases of Cattle, Horses, Sheep, Pigs, and Goats. 11^th Vol. 1. St. Louis, MO: Elsevier; 2017:391.
2. Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery and peritoneal cavity. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby; 2017:401-402.
3. Kawaguchi H, Horie M, Onoue K, et al. Development of a Model of Porcine Epidemic Diarrhea in Microminipigs. Veterinary Pathology. 2019;56(5):711-714.
4. Kenney SP, Wang Q, Vlasova A, Jung K, Saif L. Naturally Occurring Animal Coronaviruses as Models for Studying Highly Pathogenic Human Coronaviral Disease. Vet Pathol. 2021 May;58(3):438-452.
5. Ha Y, Lee YH, Ahn KK, Kim B, Chae C. Reproduction of postweaning multisystemic wasting syndrome in pigs by prenatal porcine circovirus 2 infection and postnatal parvovirus infection or immunostimulation. Vet Pathol. 2008; 45(1):842-848.
6. Madson DM, Arruda PH, Magstadt DR, Burrough ER, et al. Characterization of porcine epidemic diarrhea virus isolate US/Iowa/18984/2013 infection in 1-day-old cesarean-derived colostrum-deprived piglets. Vet Pathol. 2016; 53(1):44-52.
7. Niederwerder MC, Nietfeld JC, Bai J, Peddireddi L, et al. Tissue localization, shedding, virus carriage, antibody response, and aerosol transmission of Porcine epidemic diarrhea virus following inoculation of 4-week-old feeder pigs. J Vet Diagn Invest. 2016; 28(6):671-678.
8. Saif LJ, et al. Coronaviruses. In: Zimmerman JJ, Karriker LA, Ramirez A, Schwatz KJ, Stevenson GW eds. Diseases of Swine. 10th ed. Ames, IA: Wiley-Blackwell; 2012: 503-514.
9. Stevenson GW, et al. Emergence of Porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences. J Vet Diagn Invest. 2013; 25(5):649-54.
10. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, eds. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. St. Louis, MO: Elsevier; 2015:113-115, 147-153.
11. Vitosh-Stillman S, Loy JD, Broderson B, Kelling C, et al. Experimental infection of conventional nursing pigs and their dams with Porcine Deltacoronavirus. J Vet Diagn Invest. 2016; 28(5):486-497.
12. Zachary JF. Mechanisms of microbial disease. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby; 2017:203-205.

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