JPC SYSTEMIC PATHOLOGY
Signalment (JPC #N93-1 10): 1-day-old thoroughbred foal
HISTORY: This foal was weak from birth and showed an elevated respiratory rate and effort. Mucous membranes were hyperemic and icteric. Supportive care and treatment, including positive pressure ventilation, were pursued without success. The foal developed pulmonary hemorrhage and edema terminally and died within one day of its birth.
HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally bronchiolar architecture is effaced by abundant necrotic debris and fibrin, and there are multifocal, patchy areas of hemorrhage and consolidation throughout the section. Diffusely, bronchial and bronchiolar epithelium is often sloughed, lost and/or necrotic with shrunken hypereosinophilic cytoplasm and pyknotic nuclei, or is degenerate with swollen cytoplasm and loss of cilia. Multi-nucleated viral syncytial cells of the epithelium are frequent. Epithelial and syncytial multifocally contain 4um eosinophilic intranuclear inclusion bodies that marginate the chromatin. The bronchiolar submucosa is expanded by necrotic debris, infiltrating neutrophils and macrophages, fibrin, hemorrhage, and edema. Multifocally, alveolar septa are necrotic and thickened by neutrophils and macrophages and covered by a brightly eosinophilic 7um thick hyaline membrane composed of polymerized fibrin. Fibrin, hemorrhage, and edema with scattered necrotic debris and neutrophils are within alveolar lumina. The subpleural space, intralobular septa and perivascular areas are markedly expanded up to 500um by abundant hemorrhage, fibrin, and edema and few macrophages, neutrophils, and lymphocytes.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, bronchointerstitial, fibrinonecrotic, acute, diffuse, marked, with subpleural hemorrhage, alveolar hyaline membranes, epithelial syncytial cells, and intraepithelial intranuclear viral inclusion bodies, Thoroughbred, equine.
ETIOLOGIC DIAGNOSIS: Equine herpesviral pneumonia (in utero infection)
CAUSE: Equine herpesvirus-1 (EHV-1)
CONDITION: Equine viral rhinopneumonitis
- Member of the alphaherpesvirus subfamily: fast growing, cytocidal viruses, linear double stranded DNA virus. 2 subtypes with subtype 1 more pathogenic
- Virus is endotheliotropic, epitheliotropic, and neurotropic, but NOT neurovirulent
- Three forms have been described: abortigenic, respiratory, and neurologic:
- Abortigenic form is characterized by late term abortion, stillbirth, or the birth of weak foals that die shortly after parturition (See Systemic R-V01)
- Respiratory form is generally considered nonfatal, mostly involving foals, characterized by rhinitis, tracheitis, and bronchiolitis; upper respiratory infections may be caused by EHV-1 or EHV-4
- The neurologic form is characterized by ischemic myeloencephalopathy secondary to EHV-1–associated vasculitis
- Two subtypes have been described: Subtype 1 causes more severe respiratory disease and more commonly isolated from aborted foals; Subtype 2 is isolated from mild respiratory disease
- Infects, remains quiescent (in trigeminal ganglion) and causes recurrent disease in adult primary hosts
- Cause serious disease during immune deficiencies, when transmitted to susceptible secondary hosts, or when complicated by secondary bacterial infection
- Pregnant mares and mares nursing foals are over-represented
- The virus is pantropic in the fetus, affecting predominately the respiratory epithelium and endothelial cells
- Typically, EHV-1 causes late gestational abortions (9 and 11 months) or the birth of stillborn and weak neonatal foals
- Fetuses infected with the virus in utero at or near term may be born alive but do not survive due to severe respiratory disease and secondary bacterial septicemia
- Inhalation of infected droplets > infects epithelial cells of nasopharynx > infects lymphocytes and monocytes > leukocyte trafficking > infects endothelial cells in several tissue and pregnant uterus > inflammation > thrombo-occlusive necrotizing vasculitis
- Gross and histologic lesions are related to vasculitis
- Virus attaches and replicates in the nasal, pharyngeal and/or tonsilar epithelium
- Replication occurs in the nucleus; envelope acquired by budding through nuclear and cell membrane
- Viral envelope glycoproteins B, C, and D are used to attach to a variety of target cells by binding to an array of receptors such as herpesvirus entry medator A, nectin-1, nectin-2 (herpesvirus entry proteins C and B), and 3-O-sulfated herapin sulfate
TYPICAL CLINICAL FINDINGS:
- Systemic disease in live-born neonates
- Late-term abortion, stillbirth, or birth of weak foal
- Mare may have an inapparent infection, although a history of mild upper respiratory tract infection may have been noticed a few weeks earlier
- Respiratory system infection in neonatal foals: Dyspnea, increased respiratory rate, fever, congestion of mucous membranes, serous to mucopurulent nasal discharge, +/- coughing
TYPICAL GROSS FINDINGS:
- Aborted foals: Little to no autolysis due to late-term abortion, icterus, meconium staining
- Lung: Heavy, diffuse rubbery-firm texture and multiple white foci of necrosis
- Severe interlobular/pulmonary edema are the most consistent gross lesions in aborted fetuses, non-collapsing lung lobes, rib impressions, pale yellow to white foci of necrosis measuring 2-4 mm in diameter, petechiae on the pleural surfaces, and fibrin casts in trachea/bronchi (considered almost pathognomonic)
- Liver, spleen, and adrenal glands: Multifocal necrosis with prominent lymphoid follices in spleen
- Brain and spinal cord: Not always apparent but may include random, multifocal areas of hemorrhage and necrosis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Bronchointerstitial pneumonia with interlobular septal edema
- Eosinophilic intranuclear inclusions of the bronchial and alveolar epithelium are specific; may also be in hepatocytes
- +/- syncytial cells in the respiratory epithelium, endothelial cells, and usually in the hepatocytes peripheral to areas of necrosis
- Lesions of fetal stress: necrosis of germinal centers occurs in spleen and in other lymphoid tissues, including thymus; inclusions also may be present
- CNS: Characteristic lesion is nonsuppurative necrotizing vasculitis and thrombosis
- Normal placenta
- Enveloped, 150 nm diameter virions with a 100 nm icosahedral nucelocapsid
- Envelopes vary in size
- Capsid surrounded by "tegument" enclosed by a lipoprotein envelope
- Envelope covered by small glycoprotein peplomers (heparan sulfate proteoglycan)
ADDITIONAL DIAGNOSTIC TESTS:
- Immunofluorescent antibody, virus isolation
- ELISA (differentiates EHV-1 from EHV-4)
- Viral respiratory infections in foals:
- Equine arteritis virus (Arterivirus, Arteriviridae) - rapidly progressive bronchointerstitial pneumonia and intestinal necrosis in foals and yearlings; no inclusions
- Equine adenovirus (Mastadenovirus, Adenoviridae) in SCID foals - bronchiolitis and pneumonia, pancreatic and salivary gland necrosis; basophilic INIB
- EHV-2 (Equine Cytomegalovirus, Gammaherpesvirus) - purulent nasal discharge and lymphadenopathy
- EHV-3 (Equine coital exanthema, Alphaherpesvirus) - subclinical respiratory infection in yearling horses
- EHV-4 (Equine rhinopneumonitis, Alphaherpesvirus) - acute respiratory disease in foals > 2 months, weanlings and yearlings; less common and sporatic
- EHV-5 (Equine multinodular pulmonary fibrosis, Gammaherpesvirus) – multinodular pulmonary fibrosis
- Equine paramyxoviral pneumonia (Hendra virus; family Paramyxoviridae, genus Henipavirus) - Marked pulmonary edema with gelatinous sub-pleural lymphangiectasia; diffuse alveolar edema with vasculitis, capillary thrombosis, ectatic lymphatics, fibrinous exudate, hemorrhage, and syncytial cells within vessels
- African horse sickness (Orbivirus; family Reoviridae) – Massive pulmonary edema
- Herpesviral Respiratory Diseases:
- Infectious Bovine Rhinotracheitis (Bovine Herpesvirus 1, Alphaherpesvirus)
- Caprine Herpesvirus (Caprine Herpesvirus 1, Alphaherpesvirus)
- Pseudorabies (Suid Herpesvirus 1, Alphaherpesvirus)
- Canine Herpesvirus (Canine Herpesvirus 1, Alphaherpesvirus)
- Feline Herpesvirus (Feline Herpesvirus 1, Alphaherpesvirus)
- Avian Infectious laryngotracheitis (Gallid Herpesvirus 1, Alphaherpesvirus)
- Porcine Cytomegalovirus (Porcine Herpesvirus 2, Betaherpesvirus)
- Malignant Catarrhal Fever (Alcelaphine Herpesvirus 1, Gammaherpesvirus)
- Bovine Herpesvirus (Bovine Herpesvirus 4)
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