JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2017

P-V20

 

Signalment (JPC #1850533):  A lamb

HISTORY:  Fever (105^o F) and mild dyspnea

HISTOPATHOLOGIC DESCRIPTION:  Lung:  Approximately 70% of the section is affected.  There are multifocal to coalescing areas where bronchi and bronchioles (including terminal bronchioles) contain the following changes: marked epithelial hyperplasia with cells piling up to 10 layers thick and occasional mitoses; marked epithelial hypertrophy with cells enlarged 2-8 times normal containing abundant eosinophilic granular cytoplasm and a large, up to 20 um, vesiculate nucleus with a prominent nucleolus (karyomegaly); occasional intraepithelial 10 um basophilic smudgy intranuclear viral inclusion bodies; neutrophils occasionally expanding the submucosa and transmigrating the epithelium; epithelial single cell necrosis; variable amounts of an exudate composed of many viable and degenerate neutrophils, necrotic cellular debris, sloughed epithelial cells,  fewer macrophages and small amounts of fibrin are present within the lumen.  Multifocally adjacent alveoli are filled with many viable and degenerative neutrophils, fewer macrophages and small amounts of fibrin. Alveolar septa are mild to moderately expanded by eosinophilic beaded to fibrillar material (fibrin), few neutrophils, and increased numbers of macrophages and lymphocytes and are occasionally closely approximated (atelectasis).  There is mild to moderate perivascular edema.

MORPHOLOGIC DIAGNOSIS:  Lung:  Bronchopneumonia, subacute, multifocal, severe, with epithelial hyperplasia, necrosis and epithelial basophilic intranuclear viral inclusion bodies, breed unspecified, ovine.

ETIOLOGY:  Ovine Adenovirus

ETIOLOGIC DIAGNOSIS:  Adenoviral pneumonia

GENERAL DISCUSSION: 

• A generally host-specific subclinical infection that causes mild respiratory or enteric disease in a variety of species
• Associated with chronic enzootic pneumonia of sheep along with Mannheimia haemolytica, Pasteurella multocida, PI-3, reovirus, RSV, Chlamydia and Mycoplasma ovipneumoniae
• Unencapsulated, icosahedral, double-stranded DNA virus; 70-90 nm diameter
• Immunodeficiency is normally required in order to produce severe disease
• Seven different ovine viral species; sheep can be infected by bovine adenoviruses

PATHOGENESIS: 

• Virus is epitheliotropic and can be endotheliotropic, especially in ruminants
• Virus attaches to respiratory epithelium and enters cell > viral core migrates to the nucleus > virions produced in the nucleus > virions released by cell lysis
• Respiratory strains can produce necrotizing and proliferative bronchiolitis
• Sloughed and hyperplastic bronchiolar epithelium may cause obstruction of airways leading to atelectasis
• Disruption of bronchiolar epithelium may lead to secondary bacterial infection

TYPICAL CLINICAL FINDINGS: 

• Non-specific respiratory signs: Fever, depression, nasal discharge, mild dyspnea
• Severity worsens with secondary bacterial infection, e.g. Mannheimia haemolytica

TYPICAL GROSS FINDINGS: 

• Cranioventral consolidation +/- atelectasis
• Typically complicated by secondary bacterial infection

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Necrosis and hyperplasia of bronchiolar epithelium with formation of large basophilic intranuclear inclusion bodies
• Variable occlusion of bronchioles by sloughed and hyperplastic epithelium with subsequent atelectasis
• Viral inclusions may be found in the epithelium of the conjunctiva and upper respiratory tract as well as renal pelvis, ureters, urinary bladder, urethra, lacrimal glands, salivary glands and pancreas
• Some viral strains in sheep cause a pronounced cytomegaly and karyomegaly that can be confused with cytomegalovirus infection

ADDITIONAL DIAGNOSTIC TESTS: 

• Virus isolation
• Serology

ULTRASTRUCTURAL FINDINGS:

• Icosahedral array of capsomers; paracrystalline array of virions in nucleus

DIFFERENTIAL DIAGNOSIS: 

Histologic rule-outs:

• Parainfluenzavirus type 3 (Paramyxovirus) – bronchointerstitial pneumonia that produces eosinophilic intracytoplasmic +/- intranuclear inclusion bodies and many multinucleated epithelial syncytial cells
• Suspect adenovirus infection in sheep with bacterial pneumonia

Gross rule-outs: Viral pneumonias of sheep

• Parainfluenzavirus Type 3 – see above
• Maedi (small ruminant lentivirus/ovine progressive pneumonia) – severe interstitial pneumonia of older (>2 yrs) animals
• Jaagsiekte (ovine retrovirus) – low-grade bronchioalveolar carcinoma with considerable nasal discharge

COMPARATIVE PATHOLOGY: 

Four genera:

• Mastadenovirus
  • Canine adenovirus type 1: Infectious canine hepatitis
  • Canine adenovirus type 2: Produces bronchointerstitial pneumonia with necrotizing bronchiolitis; clinical disease is usually a consequence of immunosuppression
  • Bovine: Associated with respiratory and enteric disease in calves but not considered the primary pathogen in either syndrome (bovine mastadenoviruses A-C; bovine adenovirus 1, 3 and 10)
  • Equine adenovirus types 1 and 2: Mild respiratory disease except in SCID Arabian foals where adenoviral infection leads to severe bronchiolitis and atelectasis (equine mastadenovirus A and B)
  • Porcine: Associated with encephalitis and diarrhea (porcine mastadenoviruses A-C; porcine adenoviruses 1-5)
  • Guinea pig: Adenoviral pneumonitis (Guinea pig adenovirus (GPAdV))
  • Non-human primates: Mild to moderately severe respiratory and enteric disease as well as keratitis/conjunctivitis
  • Sheep: Ovine mastadenoviruses A and B (includes ovine adenoviruses 1-5, bovine adenovirus 2 and goat adenovirus 2)
• Atadenovirus
  • Wildlife: Cervine adenovirus (Odocoileus hemionus deer adenovirus 1 (OdAdV-1) – proposed to be cervid atadenovirus A; cervid adenovirus 1) causes Adenovirus Hemorrhagic Disease of Deer present in Oregon and California; in deer it produces pulmonary edema and erosions, ulcerations, hemorrhage or abscesses in the oral cavity (similar to Bluetongue virus and Epizootic Hemorrhagic Disease (orbiviruses)) with widespread vasculitis and endothelial intranuclear inclusions
  • Snakes and lizards: Subclinical or produces hepatitis, esophagitis, enteritis, splenitis and encephalopathy (lizard atadenovirus A, snake atadenovirus A)
  • Chickens, ducks, geese: Egg drop syndrome (duck atadenovirus A; duck adenovirus 1)
  • Goats and sheep: Mild to no clinical disease (ovine atadenovirus D; goat adenovirus 1 and ovine adenovirus 7)
• Aviadenovirus
  • Chickens:
    • Inclusion body hepatitis (fowl aviadenovirus D and E; fowl adenovirus 2 (FAdV2), FAdV8, FAdV11))
    • Hepatitis-hydropericardium syndrome virus (fowl aviadenovirus C; FAdV4)
    • Gizzard erosion (fowl aviadenovirus A; FAdV1)
  • Quail bronchitis virus (fowl aviadenovirus A)
  • Turkey aviadenovirus B (turkey adenovirus 2 (TAdV2))
• Siadenovirus:
  • Frog siadenovirus A
  • Raptor siadenovirus A
  • Turkey siadenovirus A (TAdV3)
    • Hemorrhagic enteritis (turkeys)
    • Marble spleen disease (pheasants)
    • Avian adenovirus splenomegaly (broilers)
  • Psittacine adenovirus 2
  • Budgerigar adenovirus 1
  • Gouldian finch adenovirus 1
  • Silawesi tortoise adenovirus 1

REFERENCES:

1. Caswell JL, Williams KJ. Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. New York, NY:Elsevier Limited; 2016:542,557,569,577.
2. Fitzgerald SD, Hess M, Smyth JA, Pierson FW, Reed WM, Jack SW. Adenovirus infections. In: Swayne DE, ed. Diseases of Poultry. 13th ed. Ames, IA: John Wiley & Sons, Inc; 2013: 289-331.
3. Lopez A, Martinson SA. Respiratory system, mediastinum and pleurae. In: Zachary JF ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:489,546.
4. MacLachlan NJ, Dubovi EJ. Adenoviridae. In: MacLachlan NJ, Dubovi EJ, eds. Fenner’s Veterinary Virology. 5th ed. San Diego, CA: Elsevier/Academic Press; 2017:217-227.
5. Ojkic D, Brash ML, Jackwood MW, Shivaprasad HL. Viral diseases.  In: Bouliannw M, ed. Avian Disease Manual. 7th ed. Jacksonville, FL:American Association of Avian Pathologists; 2013:10-17.
6. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. New York, NY:Elsevier Limited; 2016:144-146.

 

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