JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
November 2021
D-V18

 

Signalment (JPC #1687842):  A sheep

 

HISTORY:  None

 

HISTOPATHOLOGIC DESCRIPTION:  Liver:  There is diffuse, massive lytic necrosis characterized by dissociation of hepatic cord architecture, loss of hepatocytes, and replacement by cellular and karyorrhectic debris, fibrin, edema, and hemorrhage.  Remaining hepatocytes are either individualized and have pale, vacuolated cytoplasm (degeneration) or more frequently are shrunken with hypereosinophilic cytoplasm and pyknotic, karyorrhectic, or karyolytic nuclei (necrotic). Few degenerate hepatocytes contain eosinophilic, often elongate, 5-8 um intranuclear viral inclusion bodies that peripheralize the chromatin. 

 

Gallbladder: The lamina propria and submucosa of the gallbladder is expanded by mild edema, fibrin, and hemorrhage and contains low numbers of viable and degenerate neutrophils, lymphocytes, and plasma cells. The connective tissue surrounding the gallbladder is expanded by clear space, fibrin, hemorrhage, and numerous dilated lymphatics (edema). 

 

MORPHOLOGIC DIAGNOSIS:  1. Liver:  Hepatocellular necrosis, acute, diffuse, massive, severe, with few eosinophilic intranuclear inclusion bodies, breed unspecified, ovine.

2. Gallbladder: Cholecystitis, neutrophilic and lymphoplasmacytic, subacute, diffuse, mild.

 

ETIOLOGIC DIAGNOSIS:  Bunyaviral hepatitis and cholecystitis

 

CAUSE:  Rift Valley fever virus (RVFV) (phlebovirus)

 

CONDITION:  Rift Valley Fever

 

GENERAL DISCUSSION:

• Zoonotic, arthropod-borne disease that results in abortion storms, neonatal mortality, and hepatic necrosis in ruminants
• Family Bunyaviridae, genus Phlebovirus
• ssRNA virus, spherical, 80-100 nm, with host cell-derived bilipid-envelope
• Primarily confined to eastern and southern Africa with rare extensions into Egypt, western Africa, and the Arabian peninsula

 

PATHOGENESIS:

• Transmitted by insect vectors: Primarily mosquitoes (Culex and Aedes ), sand flies, and ticks
• High levels of virus in infected ruminants
• Virus preferentially infects and damages hepatocytes, causing Multifocal progressing to massive hepatic necrosis
• High viral titers occur in aborted fetuses and fetal membranes
• Hemorrhage secondary to consumption of clotting factors

 

TYPICAL CLINICAL FINDINGS:

• Fever, anorexia, collapse, and death within 36 hours; fatal hemorrhagic diathesis common
• Severe leukopenia
• Disease is most severe in sheep: mortality 90-100% in lambs, 10-30% in adults, abortion rates nearing 100%
• Disease is less severe in cattle: mortality 70% in calves, 5-10% in adults, abortion rates high (10-85%)
• Adult sheep, goats, and cattle: Fever, anorexia, vomiting, mucopurulent nasal discharge

 

TYPICAL GROSS FINDINGS:

• Neonatal lambs - Liver is enlarged, yellow-orange, and friable with subcapsular petechial hemorrhages
• Older sheep - Liver is darker with scattered pale foci of necrosis 1-2 mm in diameter
• Marked edema of visceral organs, widespread cutaneous hemorrhages, petechial to ecchymotic hemorrhage on parietal/visceral serosa
• Gallbladder: Edema, hemorrhage and necrosis
• Abomasum and intestine: hemorrhage, hemorrhagic enteritis
• Lymph nodes: Enlargement, edema, hemorrhage, and necrosis
• Kidney: Congestion and hemorrhage
• Hemorrhagic diathesis
• CNS: Attenuated strains are neurotropic and can cause segmental aplasia of the spinal cord, aplasia of the cerebellum, ancephaly, brachygnathia, hydranencephaly, porencephaly, hypoplasia of the spinal cord and cerebellum, and arthrogryposis

 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Liver:
  • Multifocal, random necrotizing hepatitis ranging from centrilobular to massive; necrosis is more severe and widespread in young animals and aborted fetuses
  • Eosinophilic intranuclear inclusion bodies (often elongated) in hepatocytes
  • +/- Fibrinous vasculitis and thrombosis
  • Fibrin in sinusoids
  • Mineralization of necrotic hepatocytes
  • Minimal cholestasis; not as prominent as in Wesselsbron disease and an important diagnostic feature to differentiate the diseases
• Lymphoid organs: Necrosis in germinal centers of lymph node and spleen; lymphocytolysis
• Kidney: Renal glomerular hypercellularity and necrosis; acute renal tubular injury (in some cases may be most signficant lesion)
• Brain: Encephalitis characterized by neuronal necrosis and perivascular inflammation late in infection
• Placenta: necrosis of trophoblasts and endothelial cells within the cotyledonary and intercotyledonary chorioallantois
• Eye: Anterior uveitis in experimentally infected lambs

 

ULTRASTRUCTURAL FINDINGS:

• Condensation/apoptosis of hepatocytes
• Sinusoidal lining cells not damaged
• Intranuclear inclusions composed of fibrillar rods; viral particles within cytoplasm

 

ADDITIONAL DIAGNOSTIC TESTS

• Virus isolation/virus neutralization
• Viral antigen immunofluorescence
• ELISA detection of IgM, IgG
• RT-PCR assays
• IHC in liver, spleen, kidney, lung, skin

 

DIFFERENTIAL DIAGNOSIS:

Hepatic necrosis in sheep:

• Wesselsbron disease (Flaviviridae, flavivirus) (D-V29): One of the primary differential diagnoses for clinical signs, gross and histological lesions; random small foci of hepatocellular necrosis, active reaction of the sinusoidal lining cells, and more obvious cholestasis and icterus
• 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

 

Keratoconjunctivitis in sheep:

• Chlamydia
• rickettsia-like organisms (Colesiote conjunctivae)
• Mycoplasma
• Neisseria

 

COMPARATIVE PATHOLOGY:

RVFV in other species:

• Highly pathogenic in sheep, cattle, goats
• Affects monkeys, camels, rodents, dogs, cats, horses
• Zoonotic: Humans are often infected by aerosol from aborted fetuses and fetal membranes; develop similar signs; some develop a hemorrhagic fever
• Wildlife are important in the natural ecology of RVF and are potential maintenance hosts

 

Other select bunyaviruses of veterinary and human medical importance:

• Hantavirus: Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans
• Cache Valley fever virus: Fetal infection results in abortion, CNS lesions (hydranencephaly, microencephaly, cerebellar hypoplasia), and arthrogryposis
• Akabane virus: Similar lesions to Cache Valley fever virus

 

REFERENCES:

1. Brown DL, Van Wettere AJ, Cullen JM. Hepatobiliary system and exocrine pancreas. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier, Inc; 2017:457.
2. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Louis, MO: Elsevier, Inc; 2016:281.
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. St. Louis, MO: Elsevier, Inc; 2016:312-313.
4. Duncan, M. Perissodactyls. In: Terio K, McAloose D, Leger J, eds. Pathology of Wildlife and Zoo Animals, San Diego, CA: Elsevier 2018: 451.e5.
5. Odendaal L, Clift SJ, Fosgate GT, Davis AS. Ovine Fetal and Placental Lesions and Cellular Tropism in Natural Rift Valley Fever Virus Infections. Vet Pathol. 2020;57(6):791-806.
6. Odendaal L, Davis AS, Fosgate GT, Clift SJ. Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Young Lambs. Vet Pathol. 2020;57(1):66-81. 
7. Odendaal L, Clift SJ, Fosgate GT, Davis AS. Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Adult Sheep. Vet Pathol. 2019;56(1):61-77.
8. Odendaal L, Fosgate GT, Romito M, Coetzer JA, Clift SJ. Sensitivity and specificity of real-time reverse transcription polymerase chain reaction, histopathology, and immunohistochemical labeling for the detection of Rift Valley fever virus in naturally infected cattle and sheep. J Vet Diagn Invest. 2014;26(1):49-60.
9. Reperant LA, Brown IH, Haenen OL, et al. Companion Animals as a Source of Viruses for Human Beings and Food Production Animals. J Comp Pathol. 2016;155(1 Suppl 1):S41-53.
10. Schlafer DH, Foster RA Female Genital System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Louis, MO: Elsevier, Inc; 2016:439-440.

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