JPCSYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

October 2024

D-V11

 

Signalment (JPC #1210479): An ox

 

HISTORY: None. 

 

HISTOPATHOLOGIC DESCRIPTION: Superficial oral mucosa: Diffusely, the stratum spinosum is markedly expanded and fragmented by numerous coalescing, variably sized (up to 500µm diameter) vesicles and pustules. Vesicles contain homogenous, pale eosinophilic fluid, amorphous eosinophilic cellular debris, basophilic karyorrhectic debris (necrosis), and beaded fibrillar material (fibrin). Pustules additionally contain moderate numbers of viable and degenerate neutrophils, fewer lymphocytes and plasma cells, and eosinophils that infiltrate into the adjacent stratum spinosum. The remaining stratum spinosum epithelium multifocally exhibits intracellular edema (hydropic degeneration) or variable cytoplasmic hypereosinophilia with nuclear pyknosis (necrosis). Multifocally, there are chains of cocci, filamentous bacilli, and plant material adhered to or within the surface epithelium.

 

MORPHOLOGIC DIAGNOSIS: Oral mucosa: Stomatitis, vesicular and necrotizing, acute, diffuse, severe, breed not specified, bovine.

 

ETIOLOGIC DIAGNOSIS: Rhabdoviral stomatitis

 

CAUSE: Vesicular stomatitis virus (rhabdovirus)

 

CONDITION: Vesicular stomatitis (VS)

 

GENERAL DISCUSSION:

• Family Rhabdoviridae, genus Vesiculovirus; enveloped single-stranded RNA virus
• Two distinct serotypes in the Americas:

• VS New Jersey serogroup (VSV-NJ): One subtype; more common and virulent; responsible for most epizootics
• VS Indiana serogroup (VS-IV): Three subtypes

• Two other viruses are known to cause disease:

• VS Alagoas virus (VSV-AV): Formerly Indiana 3
• Cocal virus: Formerly Indiana 2 

• Primarily affects horses, cattle, pigs, mules, swine and South American camelids; Can also affect white-tailed deer, raccoons, feral swine, and some rodents (incl. hamsters); disease does not occur in sheep and goats
• Zoonotic; human disease is characterized by a severe influenza-like syndrome (nonfatal)
• The only vesicular disease that affects and/or naturally occurs in horses
• Grossly indistinguishable from foot and mouth disease (FMD), but this disease only affects cloven-hoofed animals (such as cattle and pigs)
• Enzootic in Central and South America; sporadic in North America 
• Seasonal occurrence during warmer weather
• Cattle: Morbidity near 100%; clinical signs in 5-60%; mortality negligible
• Economically important; decreases production in dairy herds 
• Young animals rarely show clinical signs
• Self-limiting disease lasting 1-5 weeks
• Secondary infections are common and delay healing; coronary band lesions may

take a long time to heal

 

PATHOGENESIS:

or vesicular fluid; biting insects feeding on lesions (sand flies and black flies serve as reservoirs), non-biting insects and fomites act as mechanical carriers

• Virus enters through breaks in the skin or oral mucosa (intact skin/mucosa is resistant to infection) > viral replication in tonsils > viral shedding to oral cavity > epithelial cell destruction and intercellular edema > separation from underlying tissue > local vesiculation and epithelial denudation > spread by local extension to lymph nodes of the head > healing is usually rapid and complete due to neutralizing antibodies and local immunity
• Viremia reported in swine, laboratory animals, and bats
• Virus cannot be cultured from blood, but has been ID’d experimentally in horses in inoculation sites within oral cavity, retropharyngeal lymph nodes, and tonsils
• The majority of viral replication occurs in the epithelium (stratum spinosum)
• A single surface glycoprotein (G protein) protrudes from the envelope and is the

major antigen enhancing viral infectivity and inducing neutralizing antibody

 

TYPICAL CLINICAL FINDINGS:

• Incubation period 24-48 hours; lesions occur mainly on ORAL MUCOSA 
• Initially starts as vesicle formation 
• Excessive salivation and vague signs of depression in horses 
• Lesions in the mouth lead to salivation, grinding of teeth (bruxism), reluctance

to eat, and weight loss

claws/hooves

 

TYPICAL GROSS FINDINGS:

mouth, coronary bands, and teats

• Can lead to extensive sloughing of the epithelium
• Oral lesions: Tongue, lips, oral commissures, gingiva, hard palate, and nostrils

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Intercellular edema (spongiosis) and acanthosis of stratum basale and spinosum 
• Cells dissociate and become necrotic > forming enlarging coalescing vesicles that

fill with transudate

• Neutrophil and macrophage infiltration in response to necrosis
• Ruptured vesicles leave erosions
• No inclusion bodies
• Microscopic findings alone are not enough to diagnosis VS! 

 

ULTRASTRUCTURAL FINDINGS:

outer membrane with glycoprotein projections

• Virions bud from cytoplasmic membrane into the dilated intercellular spaces
• Submembranous vacuolation; focal separation of the apposed cell surfaces;

lysis of desmosomes occur at sites of virion formation

 

ADDITIONAL DIAGNOSTIC TESTS:

• Virus isolation from vesicular fluid and associated mucosa from the tongue
• Serum neutralization, complement fixation, fluorescent antibody tests, IgM-IgG ELISA, PCR
• Titers can persist for years but have a limited protective effect
• Next-generation sequencing can be used to ID various equine pathogens, including different strains of vesicular stomatitis virus in horses (Anis, J Vet Diagn Invest, 2021)
• Definitive diagnosis achieved through either viral isolation in tissue culture or embryonated eggs, fluorescent antibody techniques, complement fixation, PCR, or inoculation of suckling mice

 

DIFFERENTIAL DIAGNOSIS: 

Vesicular diseases of cattle:

affects only cloven-hoofed animals –FMD serotype A can be shed in bovine milk following nasopharyngeal infection without associated mastitis (Suchowsky, J Vet Diagn Invest, 2021)

 

Vesicular diseases of pigs:

• Vesicular stomatitis
• Foot and mouth disease
• Vesicular exanthema of swine (Caliciviridae, Vesivirus)
• Swine vesicular disease (Picornaviridae, Enterovirus)
• Senecavirus A (Picornaviridae, Senecavirus)

 

Erosive diseases of cattle:

• Infectious bovine rhinotracheitis (Bovine herpesvirus 1)
• Bovine viral diarrhea (Flaviviridae, Pestivirus)
• Bluetongue (Reoviridae, Orbivirus)
• Rinderpest (Morbillivirus)
• Malignant catarrhal fever (gammaherpesvirus)
• Trauma
• Photosensitization (lightly pigmented skin on the face and muzzle)

 

COMPARATIVE PATHOLOGY:

• VS is the only vesicular disease that affects horses
• Sheep and goats often seroconvert; clinical signs are rare
• Deer mouse: Systemic infection in intranasally infected deer mice; disseminated

CNS infection in juveniles infected intradermally; viremia in nestling mice infected by black fly bite; may play a role as a potential reservoir or amplifying host for VSNJV

• Guinea pigs, mice and monkeys can be infected experimentally
• Wildlife: Serologic evidence of viral exposure in numerous species, including

white-tailed deer, elk, raccoons, rodents, and opossums

• Pigs: Senecavirus A (SVA) presents with similar characteristics; mild clinical lesions and signs; cutaneous vesicles that rupture to form ulcers on lips, snout, tongue and feet
• Vesicular stomatitides:

Disease	Cause	Ruminant	Swine	Horse
Foot-and-mouth disease	Aphthovirus	+	+	--
Swine vesicular disease	Enterovirus	--	+	--
Vesicular stomatitis	Rhabdovirus	+	+	+
Vesicular exanthema of swine	Calicivirus	--	+	--
Seneca virus disease	Senecavirus	--	+	--

 

 

REFERENCES:

1. Anis E, Ilha MRS, Engiles JB, Wilkes RP. Evaluation of targeted next-generation sequencing for detection of equine pathogens in clinical samples. J Vet Diagn Invest. 2021;33(2):227-234.
2. Maia C. Sand fly-borne diseases in Europe: epidemiological overview and potential triggers for their emergence and re-emergence. J Comp Path. 2024;209:6-12.
3. Spagnoli ST and Gelberg HB. Alimentary system and the peritoneum, omentum, mesentery and peritoneal cavity. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Mosby; 2022:418-419. 
4. Stanton JB and Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:244-246, 
5. Suchowski M, Eschbaumer M, Teifke JP, and Ulrich R. After nasopharyngeal infection, foot-and mouth disease virus serotype A RNA is shed in bovine milk without associated mastitis. J Vet Diagn Invest. 2021;33(5):997-1001. 
6. 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; 2015:117-158.

 

 

 

 

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