JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V14 (NP)

 

Signalment (JPC #2286754): 4-month-old female mink.

 

HISTORY: Four mink with history of dyspnea and a mild serous nasal discharge were submitted from a mink farm that was experiencing losses in the current kit crop.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: The section of lung is diffusely consolidated. Alveolar septa are expanded up to 10 times normal by macrophages, fewer lymphocytes and plasma cells, edema, and variable amounts of necrotic cellular debris. Alveoli are often lined by cuboidal epithelium (type II pneumocyte hyperplasia) which rarely contain variably sized (up to 12um diameter), homogenous, indistinct, amphophilic intranuclear viral inclusion bodies. Alveolar lumina are variably filled with an exudate composed of increased numbers of foamy alveolar macrophages, eosinophilic fibrillar material (fibrin), and sloughed necrotic debris. Diffusely, perivascular, peribronchiolar, and subpleural connective tissue is expanded by moderate numbers of plasma cells and lymphocytes with edema and dilated lymphatics. Bronchioles and bronchi contain variable amounts of fibrin with few macrophages, plasma cells, and lymphocytes. The pleura is multifocally mildly thickened up to twice normal by fibrous connective tissue.

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, necrotizing and histiocytic, diffuse, marked, with type II pneumocyte hyperplasia, peribronchial and perivascular lymphoplasmacytic infiltrates, and rare amphophilic viral intranuclear inclusion bodies, mink (Mustela vision), mustelid.

 

ETIOLOGIC DIAGNOSIS: Parvoviral pneumonia

 

CAUSE: Aleutian mink disease virus (ADV, AMDV)

 

GENERAL DISCUSSION:  

• Single-stranded DNA virus; family Parvoviridae, genus Amdoparvovirus (previously Amdovirus), species Carnivore amdoparvovirus 1; there are several strains with variable virulence 
• Typically a disease of farm-raised mink; a disease of financial importance worldwide

• Disease signs vary with the age and coat color of mink, as well as strain of virus

• 4 viral strains recognized: Utah-1, Ontario, Montana, and Pullman
• Coat color: Mink homozygous for the Aleutian gene (blue coat color) are especially susceptible, heterozygous individuals are less severely affected, and mink lacking this gene are susceptible but may carry and excrete the virus for years without clinical signs 

• The Aleutian gene is linked to a gene responsible for a lysosomal abnormality  (Chediak-Higashi syndrome) of granulocytes, which inhibits destruction of phagocytized immune complexes
• Chediak-Higashi syndrome is presumed to be a defect in the lysosomal trafficking gene (LYST) that results in defective melanosomes, lysosomes, platelet-dense granules, and cytolytic granules in many cell types, including melanocytes, neutrophils, monocytes, natural killer lymphocytes, and platelets

 

PATHOGENESIS:  

• In general, all parvoviruses are dependent on the S-phase of the host cell cycle for virus replication, and therefore induce greatest cytolytic disease in tissues with a high mitotic rate, including lymphoid tissues undergoing antigenic stimulation; virus localization is limited to certain cell types that bear the appropriate viral receptors
• Virus is shed in saliva, urine, and feces; transmission is via inhalation or ingestion; vertical transmission is mainly responsible for maintaining the virus in a population in the wild (mink are normally solitary animals) 
• Virus replicates and becomes sequestered in macrophages and dendritic cells; abundant viral antigen usually found in Kupffer cells and lymphoid organs
• In adults, strong humoral immune response is elicited à increased gamma globulins; with persistent infection, persistent antigenic stimulation à antigen-antibody complex deposition (type III hypersensitivity)à clinical signs (e.g. immune-complex glomerulonephritis and arteritis); in older mink, death is attributed to glomerulonephritis or secondary infection following immunosuppression
• In young animals (kits), virus has cytocidal effect on pneumocytes and disease manifests as an acute interstitial pneumonia

 

TYPICAL CLINICAL FINDINGS:  

• Kits: Acute pneumonia à lethargy, increasingly labored breathing, unconsciousness, death
• Adults: Hypergammaglobulinemia (usually >20% of total serum protein), plasmacytosis, lethargy, anorexia, cachexia, polydipsia, fever, blood exuding from the mouth and anus; in persistently infected mink, infertility and abortion

 

TYPICAL GROSS FINDINGS:  

• Kits: Noncollapsing, patchy to diffusely red lungs; hepatomegaly, splenomegaly
• Adults: Splenomegaly and/or splenic congestion; lymphadenopathy; hepatomegaly and/or hepatic chronic passive congestion; gingivitis; oral ulcers; multiple hemorrhages; arteritis; enlarged pale yellow kidneys with petechiae, pitting, or atrophy

         

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Large basophilic to amphophilic intranuclear inclusion bodies are common
• Kits: Acute interstitial pneumonia with type II pneumocyte hyperplasia, hyaline membrane formation, and amphophilic intranuclear inclusion bodies
• Adults (U-V05): Immune-complex glomerulonephritis and arteritis; plasma cell infiltrates in the renal interstitium, hepatic portal areas, and red pulp of the spleen; bile duct proliferation; multifocal lymphocytic infiltrates are common and tentatively diagnostic

 

ULTRASTRUCTURAL FINDINGS:  

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Counter-immunoelectrophoresis (CIEP) testing remains the gold standard for AMDV diagnosis, especially in large captive facilities
• PCR, in-situ hybridization, IFA, radioimmunoassay, complement fixation, ELISA

 

DIFFERENTIAL DIAGNOSIS:  

Interstitial pneumonia:

• Canine distemper virus (P-V01): Eosinophilic intracytoplasmic and intranuclear inclusions
• Orthomyxovirus (influenza): Inclusions are rare

Other Parvoviruses:

• Mink enteritis virus: Viral isolation may be necessary to differentiate
• Feline panleukopenia: Closely-related to mink enteritis virus; destruction of lymphocytes and leukocyte progenitors in bone marrow; younger animals more severely affected 

 

COMPARATIVE PATHOLOGY:  

Amdoparvoviruses in other species:

• First discovered in mink, later in domestic ferrets and wild mustelids (striped skunk); novel amdoparvoviruses have been identified in foxes, raccoon dogs, and red pandas as well.
• Ferrets: 

• Ferret-derived strains are different from mink-derived strains; although the mink strains of ADV can infect ferrets, there are several strains that are more commonly found in ferrets that are of lower virulence in mink
• Disease is similar but more insidious (chronic, progressive) than in mink 
• Other reported disease presentations include: Liver failure, intestinal disease including melena, and central nervous system disease

• Striped skunks (Alex, Vet Pathol 2023): Skunk amdoparvovirus (SKAV) 

• Multisystemic lymphoplasmacytic inflammation (interstitial nephritis, myocarditis, hepatitis, meningoencephalitis, pneumonia, splenitis); do not exhibit glomerulonephritis as do mink
• Immune complex deposition: Multiorgan arteritis +/- fibrinoid necrosis
• Neurologic disease: Encephalomalacia with cerebral microangiopathy

• Red pandas (Alex, Vet Pathol 2023): Red panda amdoparvovirus (RPAV)

• Gross: Peritoneal and pericardial effusion; duodenal serosal petechiation; segmental small intestinal thickening
• Histo: Perivascular cuffing of histiocytes, lymphocytes, plasma cells, and neutrophils within the mesentery, serosal surface of intestines, urinary bladder, and pancreatic interlobular septal vessels, myocarditis, nephritis, interstitial pneumonia
• Long-term virus shedding (6 years) documented in one red panda pair
• No strong evidence linking age (young) to pneumonia, but sample size was small

 

References:   

1. Ackermann MR. Inflammation and Healing. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:106. 
2. Alex CE, Kvapil P, Busch MDM, et al. Amdoparvovirus-associated Disease in Red Pandas (Ailurus fulgens). Vet Pathol. 2023 :1-10.
3. Alex CE, Watson KD, Schlesinger M, et al. Amdoparvovirus-associated Disease in Striped Skunks (Mephitis mephitis). Vet Pathol. 2023 ;60(4) :438-442.
4. Church ME, Terio KA, Keel MK. Procyonidae, Viverridae, Hyenidae, Herpestidae, Eupleridae, and Prionodontidae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:30. 
5. 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; 2022:659.
6. Gola, C, Kvapil P, Kuhar U, et al. Fatal Cerebrovascular Accident in a Captive Red Panda (Ailurus fulgens) with Concurrent Amdoparvovirus Infection. J Comp Pathol. 2023;205 :11-16.
7. Snyder PW. Diseases of Immunity. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:320, 337. 
8. Uzal FA, Plattner BL, Hostetter JM.  Infectious and Parasitic Diseases of the Alimentary Tract.  In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals.  Vol 2. 6th ed. St. Louis, MO: Elsevier; 2016:153-158.
9. Williams BH, Burek Huntington KA, Miller M. Mustelids. In: Terio KA, McAloose D, St. Leger J. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:296.

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