JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

December 2024

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 (karyolytic) 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 5-10µm 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 (edema).

MORPHOLOGIC DIAGNOSIS: Liver: Necrosis, massive, subacute, diffuse, with stromal collapse and hepatocellular intranuclear and 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
Enveloped RNA Flavivirus transmitted by Aedes mosquitoes
Causes abortion outbreaks and perinatal death in sheep
High mortality in new-born lambs and kids and subclinical infection in adults
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
- Moderate mortality within 72 hours
Adult sheep, goats, cattle, and calves:
- Generally non-fatal; biphasic fever; clinically inapparent infection; jaundice
- Outbreaks of abortion and perinatal death in ruminants

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 (more prominent than in Rift Valley fever)
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: (Zoonotic) 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:

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.
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.
Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:252.
Van Wettere AJ, Brown DL. Hepatobiliary System and Exocrine. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:530.