JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
December 2021
D-V28

 

Signalment (JPC# 2100531): Yearling steer

 

HISTORY: This animal was inoculated intradermally with an infectious agent. The animal became very depressed, had bloody diarrhea, and was euthanized seven days post-inoculation.

 

HISTOPATHOLOGIC DESCRIPTION: Colon: There is diffuse mucosal erosion with multifocal ulceration characterized by loss of superficial enterocytes with replacement by a mat of degenerate neutrophils, fibrin, hemorrhage, necrotic cellular debris and a mixed population of bacteria (pseudodiphtheritic membrane). Crypts are multifocally decreased in number and separated by moderate numbers of lamina proprial lymphocytes, plasma cells, and neutrophils. Multifocal crypts are characterized by one of the following changes: crypts are lined by hyperplastic epithelial cells which pile up to 3 layers thick and have vesiculate nuclei and increased mitotic figures (regeneration), or are ectatic, lined by attenuated epithelium, and lumina contain abundant necrotic debris, degenerate neutrophils, and foamy macrophages (crypt abscesses). Numerous enterocytes contain an eosinophilic, 4-7 µm, intranuclear viral inclusion body that marginates the chromatin and is surrounded by a clear halo and/or one or more, 4-9 µm, eosinophilic, intracytoplasmic viral inclusions. Affected enterocytes often form viral syncytial cells with up to ten nuclei, which multifocally contain intranuclear viral inclusions. There is multifocal, marked crypt herniation deep into severely depleted submucosal lymphoid germinal centers, which exhibit lymphocytoloysis and replacement by increased numbers of macrophages and plasma cells. Macrophages and lymphocytes often contain previously described intranuclear inclusions. Small vessels in the submucosa, tunica muscularis, and serosa are surrounded by few lymphocytes and occasional plasma cells. The serosa is mildly expanded by edema and fibrin.

 

MORPHOLOGIC DIAGNOSIS: Colon: Colitis, erosive and necrotizing, subacute, diffuse, moderate, with lymphoid depletion, crypt herniation, and enterocytic, lymphocytic, and histiocytic eosinophilic intranuclear and intracytoplasmic viral inclusion bodies and viral syncytial cells, breed not specified, bovine.

 

ETIOLOGIC DIAGNOSIS: Morbilliviral colitis

 

CAUSE: Bovine morbillivirus (Rinderpest virus)

 

CONDITION: Rinderpest (RP)

 

SYNONYMS: Cattle plague

 

GENERAL DISCUSSION:

• Officially declared eradicated by the World Organisation for Animal Health (OIE) in 2011
• Acute to subacute, highly contagious viral disease of domestic cattle, buffalo, and yaks; small ruminants, wild ungulates, and pigs are variably susceptible
• Key features include fever, oral erosions, diarrhea, lymphoid necrosis, and high morbidity and mortality
• Family: Paramyxoviridae, genus: Morbillivirus
• Enveloped, ssRNA, 120-300 nm, relatively fragile, highly pleomorphic

 

PATHOGENESIS:

• Transmission via direct or close indirect contact with entry via nasopharyngeal mucosa
• Virus excreted in urine, feces, nasal/oral secretions, and milk
• Infected animals start shedding virus 1-2 days prior to the onset of clinical signs
• RPV has envelope and hemagglutinin/fusion surface glycoproteins used for attachment and fusion
• Wildtype virus binds to host SLAM (CD150) found on activated T cells, B cells, and dendritic cells
• Affinity for lymphoid tissue with replication in monocytes, lymphocytes of tonsils, mandibular and pharyngeal lymph nodes followed by viremia in 48-72 hrs
• Further replication in nasal, oral, and alimentary mucosal cells, causing focal necrosis, erosion, and fibrinous exudation, especially near lymphoid tissue
• Destroys lymphoid tissue; mesenteric lymph nodes, gut associated lymphoid tissue
• Immunodeficiency with invasion by other viruses or opportunistic bacteria
• Death from severe dehydration and occasionally from secondary infections
• Survivors develop lifelong immunity

 

TYPICAL CLINICAL FINDINGS:

• Incubation 3-5 days
• Dehydration, emaciation
• Prodromal phase: Acute high fever, anorexia, decreased milk yield, and lacrimation
• Mucosal phase: Nasal/ocular mucopurulent discharge and occasionally hyperemia of vaginal mucosa and swelling of vulva
• Diarrhetic phase: Severe bloody diarrhea, prostration, dehydration, shock, death
• Convalescence may take many weeks
• Profound leukopenia, hemoconcentration, hypoproteinemia, and hypochloremia

 

TYPICAL GROSS FINDINGS:

• Emaciated carcass
• Erosions, ulcerations, and hemorrhagic lesions affecting the oral cavity
• Initial lesions on inner surface of lower lip, adjacent gum, cheeks, ventral tongue
• Rarely observe lesions in the rumen, reticulum
• Hemorrhagic, necrotic, edematous Peyer’s patches
• Hemorrhage and congestion of cecum, colon, rectum (zebra stripes)
• Congestion, swelling, and erosion of vulval and vaginal mucosa

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lymphoid necrosis with loss of mature lymphocytes and replacement by plasma cells and macrophages
• Focal mucosal necrosis just above basal layer, extending to the surface; in stratified squamous epithelium lesions start in stratum spinosum where infected cells undergo degeneration and necrosis (and may have inclusion bodies), resulting in formation of erosions and ulceration
• Necrosis of intestinal crypts with resultant erosions and ulcers
• Syncytia (oral mucosal epithelium)
• Intracytoplasmic and intranuclear eosinophilic inclusion bodies in infected epithelial cells and lymphoid cells
• Intestinal lesions most severe over Peyer’s patches
• Minimal inflammation

 

ULTRASTRUCTURAL FINDINGS:

• Virions are enveloped, covered with peplomers, and have a “herringbone-shaped” helically symmetrical nucleocapsid, 660-800 nm x 18 nm.

 

ADDITIONAL DIAGNOSTIC TESTS:

• Clinical diagnosis considered sufficient in endemic areas
• Virus isolation from tissues of mucosal lesions or lymph nodes
• Virus neutralization and enzyme immunoassays available
• Immunohistochemistry and in situ hybridization

 

DIFFERENTIAL DIAGNOSIS:

For gastrointestinal ulceration in bovines:

• Bovine viral diarrhea/mucosal disease (bovine pestivirus): Linear esophageal ulcers; swollen and necrohemorrhagic Peyer's patches; inclusions in RP are distinctive (D-V09)
• Malignant catarrhal fever (Herpesviridae, gammaherpesvirus, ovine herpesvirus-2 or alcelaphine herpesvirus-1): Similar gross findings plus conjunctivitis and corneal edema; lymphoblastic and lymphocytic necrotizing vasculitis (D-V15)
• Infectious bovine rhinotracheitis (alphaherpesvirus, bovine herpesvirus-1): Similar gross findings; epithelial necrosis, eosinophilic intranuclear inclusions (R-V02)
• Foot-and-mouth disease (Picornaviridae, aphthovirus): Vesicles, affects coronary bands and interdigital areas (D-V17)
• Vesicular stomatitis (Rhabdoviridae, vesiculovirus): Vesicles; affects coronary bands (D-V11)
• Salmonella (D-B01)
• Johne’s disease (Mycobacterium avium subsp. paratuberculosis) (D-B09)
• Arsenic poisoning (D-T14)

 

COMPARATIVE PATHOLOGY:

Rinderpest in other species:

• Infections tend to be mild or subclinical in sheep, more severe in goats

 

Other morbilliviral diseases:

• Peste-des-petits-ruminants: Sheep and goats; very similar to rinderpest (P-V04)
• Canine distemper: Footpad hyperkeratosis, thymic atrophy, bronchopneumonia, intranuclear and intracytoplasmic inclusion bodies in multiple cell types (astrocytes, neurons, lymphocytes, multiple epithelia), syncytia (I-V12, N-V11, P-V01, U-V07)
• Measles: Humans, non-human primates; highly infectious exanthematous disease (P-V02)
• Phocine and cetacean morbilliviruses: respiratory disease; broncho-interstitial pneumonia with syncytia (P-V03)

 

REFERENCES:

1. Foreign Animal Diseases “The Gray Book”. Committee on Foreign Animal Diseases of the United States Animal Health Association. St. Joseph, MO; 2008: 377-382.
2. Spickler AR, Roth JA, Gaylon J, Lofstedt J, eds. Emerging and Exotic Diseases of Animals. 4th ed. Ames, IA: Iowa State University, 2010: 216-219, 248-251, 349-352, 358-359, 268-271.
3. 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: 128-130.
4. Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier, 2017: 200-203.

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