JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1687842): A sheep
HISTOPATHOLOGIC DESCRIPTION: Liver and gallbladder: Diffusely affecting all of the section of liver there is massive lytic necrosis characterized by dissociation of hepatic cord architecture, loss of hepatocytes and replacement by cellular and karyorrhectic debris, fibrin, and hemorrhage. Remaining hepatocytes are shrunken, individualized and have pale, vacuolated cytoplasm (degeneration) or are condensed with hypereosinophilic cytoplasm, pyknotic, karyorrhectic or karyolytic nuclei (necrotic) admixed with cellular debris and fibrin. Few degenerate hepatocytes contain eosinophilic, often elongate, 5-8 um intranuclear viral inclusion bodies that periphalizes chromatin. The connective tissue surrounding the gallbladder is loosely arranged and expanded by clear space, fibrin, hemorrhage and numerous dilated lymphatics (edema). The lamina propria and submucosa of the gallbladder is expanded by mild edema and hemorrhage and contains low numbers of viable and degenerate neutrophils, lymphocytes, and plasma cells.
- Liver: Hepatocellular necrosis, acute, diffuse, massive, severe with few eosinophilic intranuclear inclusion bodies, breed unspecified, ovine.
- Gallbladder: Cholecystitis, neutrophilic and lymphoplasmacytic, subacute, diffuse, mild, with fibrin, hemorrhage and edema.
ETIOLOGIC DIAGNOSIS: Bunyaviral hepatitis and cholecystitis
CAUSE: Rift Valley fever virus (RVFV) (phlebovirus)
CONDITION: Rift Valley Fever
- Zoonotic, arthropod-borne disease of Africa 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
- 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 and high viral titers occur in aborted fetuses and fetal membranes
- Multifocal hepatic necrosis progressing to massive necrosis
- Hemorrhage secondary to consumption of clotting factors
TYPICAL CLINICAL FINDINGS:
- Fever, anorexia, collapse and death within 36 hours
- Most severe disease in sheep: mortality 90-100% in lambs, 10-30% in adults, abortion rates nearing 100%
- Less severe in cattle: mortality 70% in calves, 5-10% in adults, abortion rates 10-85%
- Abortion rates in both species is very high
- Fatal hemorrhagic diathesis common
- Adult sheep, goats and cattle: Fever, anorexia, vomiting, mucopurulent nasal discharge
- Severe leukopenia
- Humans develop similar signs; some develop a hemorrhagic fever
TYPICAL GROSS FINDINGS:
- Neonatal lambs - Liver is enlarged, yellow-orange, and friable with subcapsular petechial hemorrhages
- Older sheep - Liver is darker, scattered pale foci of necrosis 1-2 mm in diameter
- Widespread cutaneous hemorrhages, petechial to ecchymotic hemorrhage on parietal/visceral serosa, and hemorrhagic enteritis
- Gallbladder: Edema, hemorrhage and necrosis
- Abomasal and intestinal hemorrhage
- Lymph nodes: Enlargement, edema, hemorrhage and necrosis
- Kidney : Congestion and hemorrhage
- Hemorrhagic diathesis
- 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:
- Early focal hepatic necrosis ranging from centrolobular to massive 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
- Necrosis in germinal centers of lymph node and spleen
- Renal glomerular hypercellularity and necrosis; acute renal tubular injury (in some cases may be most signficant lesion)
- Encephalitis characterized by neuronal necrosis and perivascular inflammation late in infection
- Minimal cholestasis; not as prominent as in Wesselsbron disease and an important diagnostic feature to differentiate the diseases
- Anterior uveitis in experimentally infected lambs
- 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
- Wesselsbron disease (Flaviviridae, flavivirus): 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): Massive hepatic necrosis
- Mycotoxicosis (aflatoxin): Megalocytosis, focal necrosis, biliary hyperplasia
- Copper poisoning: Acute periacinar necrosis, biliary fibrosis, pigment
- Chlamydophila, rickettsia-like organisms (Colesiote conjunctivae), Mycoplasma sp., Neisseria sp. are rule outs for keratoconjunctivitis in sheep
- Highly pathogenic in sheep, cattle, goats, and zoonotic; Humans are often infected by aerosol from aborted fetuses and fetal membranes
- Affects monkeys, camels, rodents, dogs, cats, horses
- Field investigations of wildlife have confirmed their importance in the natural ecology of RVF and 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: Abortion; CNS lesions (hydranencephaly, microencephaly, cerebellar hypoplasia) and arthrogryposis with fetal infection
- Akabane virus: Similar lesions to Cache Valley fever virus
- 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.
- 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.
- 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.
- Odendaal L, Clift SJ, Fosgate GT, Davis AS. Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Adult Sheep. Vet Pathol. 2018 Oct 21:3000985818806049. [Epub ahead of print].
- 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 Jan;26(1):49-60.
- Reperant LA, et al. Companion Animals as a Source of Viruses for Human Beings and Food Production Animals. J Comp Pathol. 2016 Jul;155(Suppl 1):S41-53.
- 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.