JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V21 

 

Signalment (JPC #1954709): 5-month old, female Irish setter.

 

HISTORY: Presented with pulmonary signs, incomplete antibiotic therapy response .

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Bronchiolar and to a lesser extent bronchial epithelium is multifocally necrotic characterized by shrunken, angular, epithelial cells with hypereosinophilic cytoplasm and karyorrhectic nuclei that are occasionally sloughed into the lumen, or epithelium is mildly to moderately hyperplastic, piling up to 6 cell layers thick. Multifocally, bronchiolar epithelial cells and less often bronchial epithelial cells, type II pneumocytes, and alveolar macrophages contain a single 3-10µm diameter, amphophilic, smudgy, intranuclear viral inclusion body that fills the nucleus. Diffusely, the lumina of bronchi, bronchioles, and to a lesser extent peribronchiolar alveoli are expanded by an exudate composed of abundant viable and necrotic neutrophils and fewer macrophages and lymphocytes admixed with occasional sloughed epithelial cells, moderate necrotic debris, hemorrhage, fibrin, and edema. The peribronchiolar and parabronchial interstitium is expanded by low to moderate numbers of lymphocytes and macrophages with fewer plasma cells. This inflammatory infiltrate extends into the peribronchiolar alveolar septa, expanding the septa up to 5 times normal. Alveolar septa are infrequently lined by type II pneumocytes. The peribronchial and perivascular interstitium is moderately expanded by clear space with numerous dilated lymphatics (edema). Occasional alveoli are collapsed (atelectasis).

 

Spleen: No significant findings. 

 

MORPHOLOGIC DIAGNOSIS: Lung: Bronchiolitis and bronchitis, necrotizing and proliferative, multifocal, subacute, moderate, with multifocal lymphohistiocytic inflammation and numerous amphophilic intranuclear inclusions, Irish setter, canine.

 

ETIOLOGIC DIAGNOSIS: Canine adenoviral pneumonia 

 

CAUSE: Canine adenovirus type 2 (CAV-2)

 

GENERAL DISCUSSION: 

• Family Adenoviridae; dsDNA; related to, but distinct from, Canine adenovirus type 1; limited to the respiratory tract and intestinal epithelium; immunity to CAV-1 is protective against CAV-2 and vice versa (Day, 2020)
• CAV-2 vaccination reduces morbidity and shedding, but does not prevent infection; vaccinated dogs can shed vaccine strain virus to other dogs for improved community protection (Day, 2020)
• Endemic worldwide; wild carnivores and marine mammals (Day, 2020)
• Part of the canine infectious respiratory disease (CIRD) complex; naturally occurring infections are rare and usually associated with immunosuppression
  1. Note: PBVD states that infection is common, but that disease is transient
  2. Other CIRD entities: Bordetella bronchiseptica, Streptococcus zooepidemicus, Mycoplasma, canine parainfluenza virus, canine influenza virus, canine respiratory coronavirus, canine distemper virus, canine herpesvirus-1

 

PATHOGENESIS: 

• Inhalation of infected aerosols -> replication in upper respiratory epithelial cells, mucous cells in the trachea and bronchi, non-ciliated bronchiolar epithelial cells, and type II pneumocytes 
• Experimentally, reinfection may lead to hyperreactive airways that cause the bronchial mucosa to become highly “responsive” to irritation; occurrence undetermined in natural infections 

 

TYPICAL CLINICAL FINDINGS:

• Mild fever, oculonasal discharge, coughing, and poor weight gain
• Clinically mild unless complicated by secondary bacterial infection or co-infection with other viruses (i.e. canine distemper virus)

 

TYPICAL GROSS FINDINGS: 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Amphophilic to basophilic intranuclear inclusions in alveolar macrophages, type II pneumocytes, and airway epithelium
• Bronchiolar epithelial necrosis with suppurative exudation; alveolar spaces contain macrophages, neutrophils, and fibrin
• Peribronchiolar and interstitial lymphocyte infiltration; not prominent
• Common co-infections:
  1. Canine distemper virus: Morbilliviral syncytial cells and intracytoplasmic and intranuclear inclusions in various tissues with adenoviral inclusions in the lungs
• Brain: Hemorrhage in the brainstem and caudate nuclei

 

ULTRASTRUCTURAL FINDINGS:

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

• Canine adenovirus-1 (D-V19): Primarily affects hepatobiliary system (centrilobular necrosis with intranuclear inclusions and gallbladder edema); may also affect respiratory system, kidney, central nervous system, eyes (granulomatous iridocyclitis and corneal edema- “blue eye”)
• Canine herpesvirus-1: Necrosis, intranuclear inclusion bodies (eosinophilic Cowdry type A) and lesions elsewhere in the body in addition to the respiratory system
• Canine distemper virus (P-V01): Multisystemic; more interstitial component, eosinophilic intracytoplasmic & intranuclear inclusions and syncytial cells 
• Canine parainfluenza virus-2: Commonly affects the upper respiratory tract (larynx and trachea); bronchitis and bronchiolitis
• Bordetella bronchiseptica: No inclusions and peribronchiolar lymphoid nodules

 

COMPARATIVE PATHOLOGY:

Adenoviruses occur in many animal species: Necrotizing and proliferative bronchiolitis is the most pronounced feature in pneumotropic strains; infection usually associated with immunodeficiency

• Horses: Equine adenovirus 1 & 2; most common in Arabian foals with severe combined immunodeficiency (SCID); bronchopneumonia and generalized disease; amphophilic intranuclear inclusion bodies in swollen superficial epithelial cells
• Cattle: Bovine adenovirus-3 (BAdV); causes mild respiratory disease
• Sheep/goats (P-V20): Ovine adenovirus serotype 7 (OAdV) [P-V20] and goat adenovirus 1 (GAdV-1); Usually asymptomatic or mild upper respiratory disease
• Deer: Odocoileus adenovirus 1 (OdAdV-1); closely related to bovine adenovirus 7, goat adenovirus 1, and ovine adenovirus 7; can cause local or systemic disease; endotheliotropic, with vasculitis most notable in the lung (with pulmonary edema) and GI tract (with intraluminal intestinal hemorrhage); mule deer most susceptible
• Camelids: Several reports of adenovirus-associated enteritis
• Avian adenovirus genera (previously associated group): 
  1. Aviadenovirus (Group I): Inclusion body hepatitis (many avian species), quail bronchitis virus, hydropericardium syndrome virus, gizzard erosions
  2. Siadenovirus (Group II): Hemorrhagic enteritis (turkeys), marble spleen disease (pheasants), avian adenovirus splenomegaly (broilers)
  3. Atadenovirus (Group III): Egg drop syndrome (chickens), ducks
• Guinea pigs: Guinea pig adenovirus (GPAdV-1); usually asymptomatic; necrotizing bronchitis and bronchiolitis resulting in a high mortality, low morbidity
• Mice: Murine adenovirus-1 (experimental infections); murine adenovirus-2 (enterotropic; runting in neonates)      
• Non-human primates: Simian adenovirus; cause mild to moderately severe respiratory, enteric disease, keratitis/conjunctivitis and necrotizing pancreatitis 
• Pinnipeds: Stellar sea lions have antibodies to CAV-1 and CAV-2; single report of endothelial infection in the lung, lymph nodes, and eye in one California sea lion
• Other: Adenovirus reported in wild canids (endemic in gray wolves in US); Elasmobranchs (dusty smoothhounds); reptiles (snakes, lizards, chelonians), ostriches; and birds of prey

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4^th ed. Ames, IA: Iowa State Press; 2016:218.
2. Boulianne M. Avian Disease Manual. 8th edition. Jacksonville, FL: OmniPress; 2019:20-2.
3. Caswell JL, et al. The respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol 2, 6th ed. St. Louis, MO: Elsevier; 2016:542, 557, 569, 577. 
4. Colegrove KM, Burek-Huntington KA, Roe W, et. al.   Pinnipediae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:577-8.
5. Day MJ, Carey S, Clercx C, et. al. Aetiology of canine infectious respiratory disease complex and prevalence of its pathogens in Europe. J Comp Pathol. 2020;176:86-108.
6. Howerth EW, Nemeth NM, Ryser-Degiorgis M-P.  Cervidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:157-8.
7. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:634-635.
8. Origgi FC.  Lacertilia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:881.
9. Ossiboff RJ.  Serpentes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:908.
10. Rodríguez CE, Duque AMH, Steinberg J, et al.  Chelonia. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:840.
11. Smith DA.  Palaeognathae: Apterygiformes, Casuariiformes, Rheiformes, Struthioniformes; Tinamiformes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:641-2.
12. Stedman NL, Garner MM.   Chondrichthyes. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:1012.
13. Tamukai K, Minami S, Kurihara R, et. al. Molecular evidence for vaccine induced canine distemper virus and canine adenovirus 2 coinfection in a fennec fox. J Vet Diagn Invest. 2020;32(4):598-603.
14. 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. St. Louis, MO: Elsevier; 2016:116,143-145.
15. Wachtman L, Mansfield K. Viral diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, Morris T, eds. Nonhuman Primates in Biomedical Research: Diseases, Vol 2.   London, UK: Academic Press; 2012:287-30.
16. Wünschmann A, Armién AG, Höfle U, et al.   Birds of prey. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:729-31.

 

 

Click the slide to view.

---