Signalment:  

4-months-old male calf (Bos primigenius taurus)The animal is from a dairy farm and presented for necropsy in October 2009. Clinical signs included fever and bloody diarrhea. Antibiotic treatment was attempted but the animal died after two days from the onset of the clinical signs. Vaccination history was unknown and the animal tested negative for Bovine Viral Diarrhea virus as required by the eradication program. (October 2009).

Gross Description:  

A general poor body condition was noted at necropsy. The small and large intestines contained a large amount of fibrino-hemorrhagic exudates. The mucosa was edematous and hyperemic with multifocal, pinpoint areas of necrosis more evident at the level of the Peyers patches with occasional wider foci of ulceration.

Histopathologic Description:

Small and large intestine sections: The lymphoid follicles at the level of the Peyers patches contain large areas of necrosis characterized by hypereosinophilic cellular debris mixed with fibrinous exudate. Lymphocytolysis is evident in the more preserved lymphoid follicles. Numerous intranuclear, basophilic to amphophilic, completely or partially filling the nuclei, round to oval inclusion bodies are present in the endothelial cells of mucosal and submucosal small blood vessels. Multifocally the mucosa shows loss of tissue architecture and cellular detail; replaced by hypereosinophilic cellular debris (coagulative necrosis) mixed with fibrin and extravasated erythrocytes (hemorrhage). Moderate edema is present in the submucosa adjacent to the lymphoid tissue. Multifocally, few crypts are markedly dilated and filled with necrotic epithelial cells, viable and degenerate neutrophils and, occasionally mucinous material (crypt abscesses). In some places this is associated with the herniation of the overlying mucosal glands into the necrotic lymphoid centers. Few foci of granulation tissue are present around some lacunar spaces filled with neutrophilic exudates in the submucosa (cecum). In the new-formed blood vessels of the granulation tissue are visible the intranuclear inclusion bodies. Distended lymphatic vessels (edema) are scattered throughout the muscular layer. Bacterial colonies (not present in all sections) are associated with the necrotic mucosa and present within the inflamed herniated cystic glands.

Morphologic Diagnosis:  

1) Enterocolitis, multifocal, necrotizing and fibrino-hemorrhagic, severe, acute with severe Peyers patch necrosis and intranuclear inclusion bodies (adenoviral type). 
2) Colitis, multifocal, submucosal, neutrophilic, chronic moderate with granulation tissue formation and intralesional bacterial colonies.

Lab Results:  

Bacteriology for Salmonella spp. was negative. Virology for BVDV (Ag ELISA method) was negative.

Condition:  

Bovine adenovirus 10

Contributor Comment:  

After human and fowl adenoviruses, bovine adenoviruses (BAdVs) present the third largest group of adenoviruses originating from one host species(7). They have been classified into two separate genera: Atadenovirus (namely types 4-8) and Mastadenovirus (types 1-3 and 9). The most recently described, BAdV 10, is the cause of a well-defined disease in cattle, particularly in calves, characterized by acute severe fibrinous, necrotizing and hemorrhagic enterocolitis of worldwide occurrence(1, 6, 7). Another uncommon characteristic of this virus is the variation in the genome size of various isolates, which justifies its classification as a separate BAdV species(1, 4). Electron microscopical examination showed the densely stained virus particles measured 70 to 75 nm in diameter (1, 6).

Microscopic lesions were found in the respiratory (bronchiolitis and bronchopneumonia) and intestinal tract (necrosis, fibrinous exudates, hemorrhage, mild infiltration with mononuclear cells and granulocytes) whereas the basophilic or amphophilic vascular inclusion bodies were identified in the lung, kidney, liver, abomasum, small intestine and colon(2,4). Necrosis preferentially affected Peyers patches with extension to the overlying mucosa. In the described cases the pathologic findings were related to the primary vascular damage produced by the virus, supported by the absence of other enteric pathogens(3,4,5). Bacteria, when present, are considered secondary opportunists, but potential contributors to the ultimate pathologic process(3). The vessels sometimes contained thrombi with many leukocytes and neutrophils present in the walls(3). However further experimental studies are needed to determine the virulence of BAdV and to establish if its presence in the vascular endothelium is a cause or a consequence of a co-existing enteric disease(5).

In other domestic species like horses and pigs, enteric adenovirus infection targets the epithelial cells, yielding to villus atrophy, epithelial sloughing and mild diarrhea. This differs from what seen in calves in which the intestinal pathology is associated with primary infection of blood vessels resulting in necrosis of the mucosa and lymphoid tissue.

The disease must be differentiated from common causes of fibrinous and hemorrhagic enterocolitis, including coccidiosis, bovine viral diarrhea, salmonellosis and bovine malignant catarrhal fever. There is very limited information available on the prevalence of BAdVs, particularly BAdV 10 infection within cattle populations(5). At present, adenoviral infection of cattle with enteric disease is probably underdiagnosed especially because there is no test suitable for diagnosis of the disease in live animals and, second, because diagnostics require histopathologic or immunocytochemical examination of the intestine(4, 5). It has been speculated that the sporadic cases of fatal BAdV 10 infection can be the result of some type of immunological incompetence(2). Further confirmation through electron microscopy, in situ hybridization or virus isolation in tissue cell cultures was not possible at that time.

JPC Diagnosis:  

Small intestine: Enteritis, necrotizing, multifocal to coalescing, severe, with villar blunting, crypt herniation, lymphoid depletion, and endothelial intranuclear viral inclusions.

Conference Comment:  

The contributor does an excellent job of summarizing and describing the lesions associated with BAdV 10. Although difficult to reflect in the morphologic diagnosis, the lesions in this case are most severe within and directly overlaying the necrotic Peyers patches. There are two different gross lesion presentations associated with BAdV 10 infection. The first includes hemorrhagic bands along the serosa, while the second is a more generalized hemorrhagic enteritis overlain by a fibrinous exudate and with associated Peyers patch necrosis(1,4). Other gross lesions occasionally associated with BAdV 10 infection include pulmonary edema and abomasal ulceration(4).

The use of the term crypt abscess to describe the material filling the crypts is considered by some to be a misnomer as the material is often composed of necrotic epithelial and inflammatory cells within a crypt lumen, rather than suppurative inflammation of the crypt epithelium. The moderator prefers cryptitis as a more descriptively accurate term for the lesions in this case. Crypt abscess would more appropriately describe the lesions associated with ulcerative colitis where a suppurative inflammatory process of the epithelium predominates; however, the term crypt abscess is widely used by veterinary pathologists and is generally understood.

References:

1. Adair BM, McKillop ER, Smyth JA, Curran WL, McNulty MS: Bovine adenovirus type 10: properties of viruses isolated from cases of bovine haemorrhagic enterocolitis. Vet Rec 138: 250-252, 1996
2. Lehmkuhl HD, Cutlip RC, DeBey BM: Isolation of a bovine adenovirus serotype 10 from a calf in the United States.J Vet Diagn Invest 11: 485-490, 1999
3. Orr JP: Necrotizing Enteritis in a calf infected with adenovirus. Can Vet J 25: 72-74, 1984
4. Smyth JA, Benk+�-� M, Moffett DA, Harrach B: Bovine Adenovirus Type 10 identified in fatal cases of adenovirus-associated enteric disease in cattle by in situ hybridization. J Clin Microbiol 34: 1270-1274, 1996
5. Smyth JA, Moffett DA, Garderen E, Orr JP: Examination of adenovirus-types in intestinal vascular endothelial inclusions in fatal cases of enteric disease in cattle, by in situ hybridization. Vet Microbiol 70: 1-6, 1999
6. Thompson KG, Thomson GW, Henry JN: Alimentary tract manifestations of bovine adenovirus infections. Can Vet J 22: 68-71, 1981
7. Ursu K, Harrach B, Matiz K, Benk+�-� M: DNA sequencing and analysis of the right-hand part of the genome of the unique bovine adenovirus type 10. J Gen Virol 85: 593-601, 2004