JPC SYSTEMIC PATHOLOGY

DIGESTIVE SYSTEM

November 2024

D-V17

 

Signalment (JPC #2317403): A kudu

 

HISTORY: This animal lived in Kruger National Park, South Africa.

 

HISTOPATHOLOGIC DESCRIPTION: Tongue: The stratum spinosum of the lingual mucosa is expanded by a 5x2mm, well-demarcated vesiculopustule that contains innumerable viable and necrotic neutrophils, occasional sloughed keratinocytes that are either swollen with vacuolated cytoplasm (degeneration) or shrunken and angular with hypereosinophilic cytoplasm and pyknotic to karyorrhectic nuclei (necrosis), abundant eosinophilic fluid, moderate amounts of beaded fibrillary material (fibrin), and mild hemorrhage. The adjacent intact mucosal epithelium contains numerous transmigrating neutrophils in all layers, has prominent intercellular clear spaces with accentuated intercellular bridging (spongiosis), and contains numerous keratinocytes that are swollen and have a single to numerous intracytoplasmic pale vacuoles (hydropic degeneration). The lamina propria subjacent to the vesicle contains a superficial and perivascular inflammatory infiltrate composed of moderate to high numbers of viable neutrophils and fewer macrophages with mild hemorrhage, fibrin, and moderate edema. The blood vessels associated with the lamina proprial inflammatory infiltrates are lined by cuboidal, hypertrophic (reactive) endothelial cells. Additionally, there are few scattered 100x200µm diameter protozoal cysts within the skeletal myocytes that have a prominent, 7 µm-thick, hyalinized cyst wall and contain numerous crescentic, 3 x 15-20 µm bradyzoites. There are numerous filamentous chains and paired cocci within the superficial mucosal stratum corneum.

 

MORPHOLOGIC DIAGNOSES: 1. Tongue: Glossitis, vesiculopustular and neutrophilic, multifocal to coalescing, marked, acute, with marked intramucosal edema, Kudu (Tragelaphus sp.), artiodactyl.

2. Tongue, skeletal muscle: Intrasarcoplasmic protozoal cysts, few.

 

ETIOLOGIC DIAGNOSIS: Aphthoviral glossitis

 

CAUSE: Foot and mouth disease virus (Aphthovirus)

 

CONDITION: Foot-and-mouth disease (FMD)

 

GENERAL DISCUSSION:

• Highly contagious viral infection of all cloven-hoofed animals; cattle, sheep, swine, goats and more than 70 species of wild animals causing high morbidity (100%) and low mortality (1%)
• Non-enveloped ssRNA virus in the genus Aphthovirus, family Picornaviridae; has seven serotypes: A, O, C types, Asia-1, South African Territory (SAT)-1, SAT-2, and SAT-3 with over 70 subtypes with no cross protection
  • Virulence varies with strain (>70 naturally occurring) and species affected
  • Antigenic variation and instability contribute to persistent nature
  • Antigenic drift demonstrated experimentally
• Inactivated at pH <6.0 or >9.0, heat sensitive (>50°C), inactivated by direct sunlight
• Virus survives for months in refrigerated tissues, hides, blood, hay, and other fomites
• Disease spread via movement of infected animals, contaminated animal products, and fomites; can be transmitted up to 250 km by wind

 

PATHOGENESIS:

• Ingestion or aerosol exposure > main port of entry and primary site of viral replication are pharyngeal and pulmonary epithelium > targets lymphoid cells, macrophages, dendritic cells > leukocyte trafficking to regional lymph nodes > replication phase in lymph nodes > systemic spread > lysis of epithelial cells in the stratum spinosum of stratified squamous epithelium
• Virulence factors: 
  1. Capsid proteins (VP1-4): Attachment proteins important in the antigenic & immunogenic properties of virus
  2. α integrins (Vβ1, Vβ3, Vβ6): Receptors on target cells
• Large amounts of virus in vesicular fluid, body secretions/excretions, skin/visceral tissues (esp. pancreas and pituitary gland), exhaled air (esp. pigs), and milk
• Antibody production: Viremia/fever resolve > lesions heal > virus disappears; secondary bacterial infections common
• Carrier state can exist in some species: Water buffalo (only non-domestic species identified) and previously vaccinated cattle
• Sheep and goats are considered to be a frequent inapparent source of dissemination because disease is often mild and lesions are difficult to identify 

 

TYPICAL CLINICAL FINDINGS:

• Initially salivation, nasal discharge, lameness; lethargy, fever, decreased milk production, and blanching of coronary bands may precede vesicles 
• Pregnant animals may abort
• Sudden death in young animals with no typical vesicular lesions from viral myocarditis – mainly interventricular septum
• Sequelae: Hoof deformation, decreased milk production, chronic mastitis, failure to thrive, diabetes mellitus

 

TYPICAL GROSS FINDINGS:

• Gross lesions alone cannot differentiate the vesiculoulcerative entities 
• Early: Hyperemic foci on oral mucosa, udder (especially teats of lactating animals), and feet along coronary band 2-7 days post infection > develop into vesicles (epidermal vesicles are the hallmark of disease) > coalesce to form bullae > rupture leaving raw ulcers; shreds of epithelium may adhere to edges
• Lesions develop primarily in areas of friction or trauma; oral mucosa, tongue, interdigital cleft, and teats of lactating animals; foot lesions occur in the majority of cases and hooves may slough
  1. Less frequent locations: Vulva, prepuce, conjunctiva, esophagus, forestomaches, intestines, trachea, and bronchi may be involved
• Malignant form of the disease: Gray/yellow myocardial streaking (“tiger heart”) in animals less than 6 months of age; similar lesions may be present in skeletal muscle

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Epithelium: Early swelling, necrosis, and lysis of affected deep keratinocytes; extensive spongiosis of stratum spinosum > necrosis of overlying keratinocytes; rupture of vesicles to form erosions/ulcers > +/- secondary bacterial overgrowth
  1. Mild leukocytic infiltration around erosions 
  2. Microscopic vesicles in haired skin of brisket, abdomen, neck, carpus, and perineum
• “Dry” lesions in oral mucosa in which edema seeps through stratum corneum; now vesicles; mucosa appears necrotic
• Mammary gland: Acinar necrosis 
• Heart and skeletal muscle: Hyaline degeneration, necrosis, and calcification 
  1. Mononuclear & necrotizing myocarditis and myositis in young animals
• Pancreas: Loss of pancreatic islets, acinar necrosis, and regeneration

 

ADDITIONAL DIAGNOSTIC TESTS:

• Viral antigen and nucleic acid detection
• Virus isolation
• Serology
• Reverse transcriptase PCR
  1. FMD virus detectable in body fluids (primarily milk and less so in saliva, nasal secretions, and blood serum), skin, and oral mucosa; not detected in mammary gland (Suchowski, J Vet Diagn Invest, 2021)
• Nonstructural proteins are detected with commercial ELISA tests in endemic areas during post-outbreak serosurveillance (Browning, J Vet Diagn Invest, 2020)

 

DIFFERENTIAL DIAGNOSIS in cattle:

• Gross (oral lesions):
  • Vesicular stomatitis (rhabdovirus), vesicular exanthema of swine (genus vesivirus; family calicivirus), and swine vesicular disease (genus enterovirus; family picornaviridae): Indistinguishable from FMD
  • Bovine viral diarrhea (BVD)/mucosal disease (bovine pestivirus): Not vesicular, linear esophageal ulcers, Peyer’s patch necrosis 
  • Infectious bovine rhinotracheitis (bovine herpesvirus 1): Not vesicular, fibrinonecrotic rhinotracheitis   
  • Malignant catarrhal fever (alcelaphine herpesvirus-1, ovine herpesvirus-2): Not vesicular, corneal edema (“blue eye”), conjunctivitis, profuse mucopurulent nasal discharge
  • Rinderpest (morbillivirus): No vesicle, necrotic stomatitis, enteritis, Peyer’s patch; eradicated 
• Gross (foot lesions):
  • Contagious foot rot of ruminants (Dichelobacter nodosus): No oral lesions, not vesicular, +/- Fusobacterium necrophorum
  • Hairy heel warts, foot warts, strawberry foot, raspberry heel, papillomatous digital dermatitis (Treponema spp.): No oral lesions, not vesicular
  • Chemical burns or trauma to hooves: No oral lesions, not vesicular
  • Vesicular stomatitis, vesicular exanthema of swine, and swine vesicular disease: Indistinguishable from foot-and-mouth disease
  • BVD: Not vesicular, chronic digital dermatitis

 

COMPARATIVE PATHOLOGY:

FMD in other species:

• Cloven-hoofed animals especially susceptible & natural infection has been reported in domestic & wild ruminants, camelids, elephants, and swine, as well as hedgehogs; cattle are indicator hosts; infections have also been documented in captive Asian black bears and sun bears
• Sheep/goats less susceptible than cattle; dental pad common site of erosions; lameness may be prominent in acute outbreaks; carrier state exists; maintenance host
• Pigs: foot lesions more common than oral lesions; carrier state not observed in swine; abortion and stillbirth reported; swine are amplifier hosts 

 

Other 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	Senecavirus	--	+	--

 

REFERENCES:

1. Agnew D, Nofs S, Delaney MA, et al. Xenartha, Erinacoemorpha, some Afrotheria, and Phloidota. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:527-528.
2. Browning CFJ, Di Nardo A, Henry L, Pollard T, Hendry L, Romey A, Relmy A, Eble P, Brocchi E, Grazioli S, King DP, Ludi AB. Inter-laboratory comparison of 2 ELISA kits used for foot-and-mouth disease virus nonstructural protein serology. J Vet Diagn Invest. 2020;32(6):933-937.
3. Dill V, Eschbaumer M. Reliable detection, sequencing, and transfection of foot-and-mouth disease virus RNA from badly preserved vesicular epithelium. J Vet Diagn Invest. 2019;31(5):778-782.
4. Gal A, Castillo-Alcala F. Cardiovascular System, Pericardial Cavity, and Lymphatic Vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:687.
5. Jimenez Martinez, MA, Gasper DJ, Carmona Mucino MdC, et al. Suidae and Tayassuidae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:214.
6. Jones MEB, Gasper DJ, Mitchell E. Bovidae, Antilocapridae, Giraffidae, Tragulidae, Hippopotamidae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:128-129.
7. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:242-243.
8. Landolfi JA, Terrell SP. Proboscidae. In: Terio KA, McAloose D, St. Leger J ed. Pathology of Wildlife and Zoo Animals. Cambridge, MA: Elsevier Inc. 2018:424.
9. Seoke L, Fosgate GT, Opperman PA, Malesa RP, Lazarus DD, Sirdar MM, Heath L. Optimization of a foot-and-mouth disease virus Southern African Territories-specific solid-phase competitive ELISA for small ruminant serum samples. J Vet Diagn Invest. 2024;36(2):192-204.
10. Spagnoli ST, Gelberg HB. Alimentary system and the Peritoneum, Omentum, Mesentery, and Peritoneal Cavity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:418-419, 464.
11. Stanton JB, Zachary JF. Mechanisms of Microbial Infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:248-249.
12. Suchowski M, Eschbaumer M, Teifke JP, 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.
13. 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; 2016:117-119.
14. Valentine BA. Skeletal Muscle. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1007.e1.
15. Yuan X, Lv J, Lin X, Zhang C, Deng J, Wang C, Fan X, Wang Y, Xu H, Wu S. Multiplex detection of six swine viruses on an integrated centrifugal disk using loop-mediated isothermal amplification. J Vet Diagn Invest. 2019;31(3):415-425.

 

 

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