JPC SYSTEMIC PATHOLOGY
RESPIRATORY SYSTEM
October 2023
P-V03 (NP)
Signalment (JPC #2359302): Tissue from a common bottlenose dolphin (Tursiops truncatus)
HISTORY: Found stranded on the shoreline
HISTOPATHOLOGIC DESCRIPTION: Lung: There are multifocal to coalescing areas of consolidation affecting approximately 40% of the pulmonary parenchyma. In these areas, bronchiolar and alveolar lumina are expanded by an exudate composed of eosinophillic cellular and karyorrhectic necrotic debris admixed with numerous foamy macrophages, viral syncytial cells, viable and necrotic neutrophils, lymphocytes, plasma cells, fibrin, hemorrhage, and edema. Predominantly in consolidated areas and to a lesser extent in less affected pulmonary parenchyma, alveolar septa are expanded by fibrin, edema, increased macrophages and lymphocytes, and small amounts of necrotic debris. Multifocally alveoli are lined by hyperplastic type II pneumocytes, and bronchiolar epithelium often coalesces to form viral syncytial cells with up to 20 nuclei. Bronchiolar epithelial cells, type II pneumocytes, syncytial cells, alveolar macrophages, and rarely fibroblasts contain round to oval, 2 – 4 µm diameter, eosinophilic, intracytoplasmic and intranuclear viral inclusion bodies. Multifocally peribronchiolar, perivascular, and subpleural interstitia are expanded up to 5 times normal by increased clear space and ectatic lymphatics (edema). Focally, a bronchiole is markedly distended by cross and tangential sections of an adult intraluminal metastrongyle nematode surrounded by sloughed epithelial admixed with eosinophillic karyorrhectic debris. The nematode is 200 µm in diameter, has a 5-8 µm thick, smooth, hyalinized cuticle, polymyarian-coelomyarian musculature, a pseudocoelom, lateral chords, an intestine lined by few multinucleated cells, and reproductive structures.
MORPHOLOGIC DIAGNOSIS: 1. Lung: Pneumonia, bronchointerstitial, necrotizing, histiocytic, and neutrophilic, subacute, focally extensive, moderate, with type II pneumocyte hyperplasia, viral syncytial cells, and eosinophilic intranuclear and intracytoplasmic viral inclusion bodies, bottlenose dolphin (Tursiops truncatus), cetacean.
2. Lung: Intrabronchiolar adult metastrongyle nematode, with minimal neutrophilic and histiocytic inflammation, etiology consistent with Halocercus lagenorhynchi.
ETIOLOGIC DIAGNOSIS: Morbilliviral pneumonia
CAUSE: Dolphin morbillivirus (DMV); cetacean morbillivirus (CeMV); pilot whale morbillivirus
GENERAL DISCUSSION:
- Cetacean morbillivirus (CeMV) is the common name of the morbillivirus that affects cetaceans (porpoises, dolphins and whales) as well as pinnipeds (seals); at least six distinct strains that are associated with a particular cetacean species, divided into two groups:
- CeMV-1:
- Pilot whale morbillivirus (PWMV)
- Porpoise morbillivirus (PMV)
- Dolphin morbillivirus (DMV)
- Beaked whale morbillivirus (BWMV)
- CeMV-2:
- Strains recovered from Guiana dolphin (GDMV) and Indo-Pacific bottle-nose dolphins
- GDMV more closely related to terrestrial mammal morbilliviruses than other CeMV strains
- Strains recovered from Guiana dolphin (GDMV) and Indo-Pacific bottle-nose dolphins
- CeMV-1:
- Highly-contagious, pantropic, single-stranded, negative-sense RNA virus of the family Paramyxoviridae that is lymphotropic, epitheliotropic, and neurotropic
- CMV is closely related to ruminant morbilliviruses: Rinderpest virus (RPV) and Peste-des-petits ruminants virus (PPRV)
- Recently classified into 4 main presentations:
- Acute systemic
- Subacute systemic
- Chronic systemic
- Chronic localized encephalitis
- Associated with cyclic epidemics (mass mortality events) and interepizootic presentations
- Secondary infections occur with bacteria (Streptococcus phocae, Photobacterium damselae), virus (herpesvirus), Toxoplasma gondii and fungi (Aspergillus fumigatus)
PATHOGENESIS:
- Routes of transmission include aerosol as well as by direct contact, including between mother and calf/fetus; migratory behavior and close association of pods facilitates transmission
- Proposed pathogenesis: Inhalation or direct contact -> replication in lymphoid tissue (lymphotropic) -> viremia 5-12 days post-infection -> lymphocytolysis and lymphoid depletion -> dissemination to multiple tissues, including respiratory, GI tract, CNS -> immunosuppression -> increased susceptibility to secondary infections (fungal, bacterial, protozoal) -> death
- Viral excretion may occur through skin, urinary, and fecal routes, but transmission via these routes is less likely due to viral dilution in seawater
- Pantropic virus, entry receptor on immune cells is CD 150 (SLAM), epithelial receptor is PVRL4 (nectin-4)
- Virus has attachment protein, called viral H protein, and fusion protein, called viral F protein, that allow attachment to cell receptors
- F proteins are involved with penetration into cell, cell-to-cell spreading, and formation of syncytia
- Unlike other paramyxoviruses, morbilliviruses lack neuraminidase activity
- Neuraminidase is a surface attachment molecule that cleaves sialic acid on the infected cell surface and inhibits the virus from attaching to already-infected cells; also plays a role in releasing virions from the cell
- Can be used to distinguish morbilliviruses from other paramyxoviruses
- Neuraminidase is a surface attachment molecule that cleaves sialic acid on the infected cell surface and inhibits the virus from attaching to already-infected cells; also plays a role in releasing virions from the cell
TYPICAL CLINICAL FINDINGS:
- Often found dead or stranded moribund in poor body condition
- Neurologic signs including abnormal behavior, trouble swimming, circling, ataxia, and incoordination
- Compromised buoyancy
- Respiratory distress, tachycardia, muscle tremors
- Skin lesions and erosions of buccal mucosa
- Heavy ecto-/endoparasite burden
TYPICAL GROSS FINDINGS:
- Varies; gross lesions may be widespread or absent in brain-only form. Systemic lesions may include:
- Exudative pneumonia with atelectasis, subpleural emphysema, and failure of lungs to collapse
- Lymphadenopathy of lung-associated nodes
- Ulceration of skin and buccal mucosa
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Varies; lesions may be widespread or localized to brain
- Systemic lesions:
- Respiratory system:
- Necrotizing bronchointerstitial pneumonia with type II pneumocyte hyperplasia
- Syncytia (bronchial, bronchiolar, alveolar)
- Intracytoplasmic and intranuclear viral inclusions in respiratory epithelium, bronchiolar gland epithelium, and syncytial cells
- Fibroplasia of alveolar septa if chronic
- Lymphoid tissues:
- Lymphoid depletion and lymphocytolysis in the spleen, lymph nodes, thymus
- Respiratory system:
- Syncytia, which often contain inclusions, in cortex of lymph nodes in both Systemic and brain-only presentations:
- Central nervous system:
- Severe non-suppurative encephalitis, prominent perivascular cuffs
- Intracytoplasmic and intranuclear viral inclusions in degenerate and necrotic neurons, glial cells, and syncytia
- Central nervous system:
ADDITIONAL DIAGNOSTIC TESTS:
- Examination of smears of conjunctival, nasal, buccal, vaginal, preputial, urethral mucosa, or peripheral leukocytes for morbilliviral inclusions
- Immunohistochemistry (PDV, CDV) or immunofluorescence
- ELISA, PCR, virus isolation, paired serology
DIFFERENTIAL DIAGNOSIS:
In dolphins, diseases that cause:
- Respiratory signs – Influenza, lungworm infection, coccidiomycosis, cryptococcosis
- Enteric signs – Salmonellosis
- CNS signs – Cryptococcosis, Toxoplasmosis
- Skin lesions:
- Erysipelothrix rhusiopathiae: Lethargy, anorexia, cough, diarrhea, cutaneous lesions in dolphins (short, gram-positive rods on histo)
- Calicivirus (San Miguel sea lion virus)
- Paracoccidioides brasiliensis (I-F09, formerly thought to be Lacazia [Loboa] loboi): Fungal infection causes granulomas on head, dorsal fin, flukes
- Poxvirus (causes “ring”, “pinhole” or “tattoo” lesions)
COMPARATIVE PATHOLOGY:
- CeMV isolated in a monk seal with concurrent Toxoplasma gondii infection; not similar in sequence to phocine distemper virus
- Other morbilliviruses:
- Canine distemper virus (CDV) (P-V01): Affects numerous species including terrestrial carnivores, Baikal seals, etc. – respiratory, CNS, epithelium primarily affected
- Rinderpest virus: Primarily large ruminants – erosions of upper GI and respiratory tract, diarrhea, necrotic Peyer’s patches; eradicated in 2011 per OIE
- Peste-des-petits ruminants virus: Small ruminants – respiratory signs, oral mucosal erosions, diarrhea, necrotic Peyer’s patches
- Measles virus: Non-human primates—respiratory, GI, skin, CNS lesions
- Phocine distemper virus (PDV) is closely related to canine distemper virus
- Harp seal thought to be reservoir of PDV; also affects Sea Otters, especially populations in coastal Alaska
- Viral excretion via respiratory (most important), urinary, fecal, and ocular routes
- Possible transmission by hematophagous arthropods
- Resembles distemper in dogs: Fever, oculonasal discharge, conjunctivitis, keratitis, coughing, dyspnea, diarrhea, abortion, neurologic signs
- Subcutaneous emphysema of cervical and thoracic areas -> increased buoyancy -> difficulty diving
- Polar bears: Infections with CDV, PDV and DMV have been documented
References:
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