JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
December 2021
D-V29 (NP)

 

Signalment (JPC #2469833):  Merino lamb

 

HISTORY:  This animal was from a flock where a few abortions and neonatal deaths had occurred.  There were no floodwater pools on the farm, but there were increased numbers of mosquitoes when compared to the previous 4-5 years.

 

HISTOPATHOLOGIC DESCRIPTION:  Liver:  There is nearly diffuse loss of 95% of hepatic parenchymal architecture characterized by dissociation of hepatic cords with stromal collapse and replacement by abundant eosinophilic cellular and basophilic karyorrhectic debris admixed with hemorrhage, fibrin, and edema (panlobular/massive necrosis), and frequent remaining hepatocytes are shrunken and angular with hypereosinophilic cytoplasm and faded (karyolitic) to fragmented (karyorrhectic) nuclei (single cell death).  The few remaining viable hepatocytes are often swollen with pale, vacuolated cytoplasm (degenerate), and scattered viable hepatocytes also contain a single to few 5-10um diameter, eosinophilic, intranuclear inclusion bodies with minimal chromatin peripheralization and/or variably sized, irregularly round, eosinophilic intracytoplasmic inclusions.  The periportal connective tissue contains few macrophages, lymphocytes, and plasma cells, and several dilated lymphatics (suggestive of edema).

 

MORPHOLOGIC DIAGNOSIS:  Liver:  Necrosis, massive, subacute, diffuse, with stromal collapse and hepatocellular eosinophilic intranuclear viral inclusion bodies and eosinophilic intracytoplasmic inclusion bodies, Merino sheep, ovine.

 

ETIOLOGIC DIAGNOSIS:  Flaviviral hepatitis

 

CAUSE:  Wesselsbron virus (flavivirus)

 

CONDITION:  Wesselsbron’s disease

 

GENERAL DISCUSSION:

• Wesselsbron’s disease is an acute, zoonotic, arthropod-borne flavivirus infection of sheep, goats, cattle, and birds in southern Africa
• Causes abortion outbreaks and perinatal death in sheep
• High mortality in new-born lambs and kids and subclinical infection in adults
• Enveloped RNA virus transmitted by Aedes mosquitoes
• Outbreaks occur during and after heavy rains and end abruptly with first frost; lower prevalence in dryer regions
• Zoonotic

 

PATHOGENESIS:

• 2-5 day incubation period
• Hepatotropic (newborn lambs) and neurotropic (embryonic and fetal tissue in pregnant ewes)
• Mosquito bite à blood vessel penetration or deposition in vascularized extracellular matrix à virus enters monocytes (blood) or Langerhans cells and trafficking tissue macrophages (extracellular matrix) à lymphatic vessels à lymph nodes à other lymphoid tissues (spleen, liver) à hepatocytes and Kupffer cells (targets cells; monocyte-macrophage system)
• During epizootics, infection via other biting insects may also occur
• Direct transmission between animals has not been reported

 

TYPICAL CLINICAL FINDINGS:

• Newborn lambs:
  • Fever, anorexia, listlessness, weakness, tachypnea
  • 18-27% mortality rate in newborns: Death within 72 hours
• Adult sheep, goats, cattle, and calves:
  • Generally non-fatal; biphasic fever; clinically inapparent infection; jaundice
  • Abortion or fetal mummification in ruminant species

 

TYPICAL GROSS FINDINGS:

• Acute: Widespread petechiae and gastrointestinal hemorrhage in the abomasal mucosa; digested blood in abomasum
• Chronic:
  • Yellow-orange liver with hepatomegaly, patchy congestion, friability, and moderate to severe jaundice
  • Splenomegaly
  • Congested, edematous lymph nodes; lymphadenomegaly

 

TYPICAL MICROSCOPIC FINDINGS:

• Random foci of hepatocellular necrosis of individual or small groups of hepatocytes (less extensive than Rift Valley fever)
• Irregular eosinophilic intranuclear viral inclusion bodies occasionally within degenerate hepatocytes; chromatin is not well marginated
• Scattered pigmented macrophages and mononuclear inflammation in portal regions and sinusoids
• Hydropic degeneration of less affected hepatocytes
• Kupffer cell proliferation
• Bile duct proliferation
• Canalicular cholestasis
• Spleen and lymph nodes: Lymphocyte necrosis and lymphoblast stimulation

 

ADDITIONAL DIAGNOSTIC TESTS:

• Virus isolation from a variety of tissues
• Serology
• IHC for viral antigen localization within tissue
• Hemagglutinin inhibition: high degree of cross reactivity with other flaviviruses
• ELISA: More sensitive and less cross-reactive than hemagglutination inhibition

 

DIFFERENTIAL DIAGNOSIS:

Hepatic necrosis in sheep:

• Rift Valley Fever (family Bunyaviridae, genus Phlebovirus) (D-V18): More extensive periacinar to midzonal or massive necrosis and hemorrhage; high morbidity and mortality; affects fetus through adult sheep; canalicular cholestasis is less prominent
• Phytotoxicosis (blue green algae) (D-T11): Massive hepatic necrosis
• Mycotoxicosis (aflatoxin) (D-T03): Megalocytosis, focal necrosis, biliary hyperplasia
• Copper poisoning (D-T05): Acute periacinar necrosis, biliary fibrosis, pigment

 

Abortions in sheep (viral):

• Rift Valley Fever (family Bunyaviridae, genus Phlebovirus) (D-V18): Rapid onset and high mortality in lambs; abortion rate approaches 100%; hepatic necrosis prominent in the fetus
• Border disease virus (family Flaviviridae, genus Pestivirus): Wide variety of tissues affected; hairy shakers; dysmyelination or hypomyelination within the fetal CNS
• Bluetongue virus (family Reoviridae, genus Orbivirus) (D-V16): Necrotizing encephalopathy if infected between 50 and 80 days of gestation; fetus often absorbed if infected prior to 50 days
• Orthobunyaviruses (Simbu serogroup)
  • Cache valley virus, Schmallenberg virus, Akabane virus, Aino virus: Hydranencephaly, scoliosis, and/or arthrogryposis common

 

COMPARATIVE PATHOLOGY:

• Humans: Severe flu-like symptoms, fever, headache, blurred vision, myalgia, and arthralgia
• A reported cause of high mortality in a flock of juvenile ostriches
• Subclinical infection in horses, pigs, a camel and a Namaqua gerbil
• Other flaviviruses present in southern Africa but causing little morbidity in livestock: Yellow fever virus, West Nile virus, Spondweni virus (most closely related virus to Zika virus), Uganda S and Banzi viruses (Uganda S serocomplex), Israel turkey meningoencephalitis, Usutu (belongs to Japanese encephalitis complex), and Ntaya and Bagaza viruses (Ntaya serocomplex)

 

REFERENCES:

1. Brown DL, Van Wettere AJ, Cullen JM. Hepatobiliary system and exocrine pancreas. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017: 457-458.
2. Constable PD, Hinchcliff KW, Done SH, Grunberg W, eds. Veterinary Medicine, A Textbook of the Diseases of Cattle, Horses, Sheep, Pigs, and Goats. 11th ed. St. Louis, MO: Elsevier; 2017:2084-2086.
3. Cullen JM, Stalker MJ. Liver and biliary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2016:426-7, 428-9, 430-1, 437-40.
4. Schlafer DH, Foster RA. Female genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier; 2016:312.
5. Zachary JF. Mechanisms of microbial infections. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:206-207.

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