JPC SYSTEMIC PATHOLOGY
Signalment (JPC #627741): A six-month old colt
HISTORY: This colt’s mother was immune to African horse sickness. This animal had been vaccinated once against African horse sickness at three months of age.
HISTOPATHOLOGIC DESCRIPTION: Lung: Over 90% of alveoli are filled with abundant pale, eosinophilic, homogenous to fibrillar material (edema and fibrin) admixed with low numbers of macrophages, lymphocytes, and minimal hemorrhage. Diffusely, alveolar septa are expanded up to 3 times normal diameter by fibrin, edema, markedly hypertrophied capillary endothelial cells, and few lymphocytes and macrophages. Diffusely, interlobular septa, perivascular and peribronchial adventitia, subpleural connective tissue, and bronchiole-associated lymphoid tissue are moderately to markedly expanded by edema, fibrin, and low numbers of lymphocytes, plasma cells, and macrophages. Endothelial cells within venules are swollen with vacuolated cytoplasm and large, reactive nuclei. Multifocally bronchi and bronchioles contain moderate amounts of hemorrhage, fibrin, and edema. In less affected areas, occasional alveolar lumina are confluent and lined by shortened alveolar septa with blunt, clubbed ends (emphysema).
MORPHOLOGIC DIAGNOSIS: Lung: Edema, acute, multifocal, severe, with reactive endothelium and mild interstitial pneumonia, breed unspecified, equine.
ETIOLOGIC DIAGNOSIS: Orbiviral pneumonia
CAUSE: African Horse Sickness virus (AHSV)
CONDITION: African Horse Sickness
- African horse sickness virus: genus Orbivirus, family Reoviridae (closely related to bluetongue virus), an infectious, non-contagious, arthropod-borne, peracute to subacute, often fatal disease of Equidae characterized by respiratory distress and/or cardiovascular failure
- AHS is the only OIE-notifiable equine disease: importance due to extreme lethal potential in susceptible horses and very wide distribution of the arthropod vector; concern due to recent spread of related Orbiviral disease (bluetongue virus)
- Horses are most susceptible; mortality rates reach 95% in horses, 80% in mules; South African donkey and zebra are resistant; zebras are likely the natural host and reservoir
- Nine major antigenic types which do not allow for solid immunity between types
- Endemic in Africa, the Middle East, India, and Spain; not found in the US
- Seasonal occurrence because the arthropod vector (primarily Culicoides) thrives in hot, wet conditions; also, AHSV requires an ambient temperature of greater than 15 degrees C to replicate and be transmitted by the vector
- The disease is divided into four different forms based on clinical signs: pulmonary (peracute), cardiac (subacute), mixed (cardiopulmonary), and mild (African horse sickness fever, occurs in resistant species e.g. mules, donkeys, zebras and in horses with immunity to heterologous strains)
- Polyvalent live attenuated vaccine has been shown to reassort and revert to a virulent serotype
- Bite of infected arthropod vector (Culicoides midges) à initial viral replication in regional lymph nodes à viremia (leukocyte trafficking or free) à infection of target organs (tropism for pulmonary and cardiac endothelial cells and, to a lesser extent, dendritic, lymphoid, and monocyte-macrophage cells especially of spleen, lymph nodes, lung, and large intestine) à virally induced endothelial cell dysfunction, endothelial cell lysis, activation of infected macrophages with subsequent cytokine production (IL-1, IL-6, TNFα, IFN-β) à increased vascular permeability à edema, hemorrhage, microthrombosis
- Four different forms may be due to differences in viral tropism for different organs
- Virulence factors:
- The virus has 2 capsid structural proteins VP2 and VP5 that bind to glycosaminoglycans on target cell membranes and facilitate viral attachment and entry
- NS3, a protein inserted in the target cell membrane by the virus, may be cytotoxic (acting as a viroporin), involved in membrane damage and release of virus from infected cells
TYPICAL CLINICAL FINDINGS:
- Pulmonary (peracute) form: most common; short duration fever followed by acute onset severe respiratory distress, rapid death (within a few hours) from pulmonary edema; 3-5 day incubation period
- Cardiac (subacute) form: recurrent fever lasting 3-6 days, then as the fever subsides, subcutaneous and interfascial (cardiogenic) edema develops; mortality as high as 50%, with death due to cardiac failure and pulmonary edema; 7-14 day incubation
- Cardiopulmonary (mixed) form: Mixture of the cardiac and pulmonary form, most of the fatal cases of AHS can be considered of this form; initial mild pulmonary signs followed by characteristic swelling of the head and death due to cardiac failure, or cardiac form followed by marked dyspnea; 5-7 day incubation; death in 3-6 days
- Horse sickness fever (mild form): Fever; minimal clinical signs similar to equine influenza, often transient with full recovery, may go unnoticed in outbreaks, mortality rate is ~70%
TYPICAL GROSS FINDINGS:
- All forms: vascular (endothelial) injury à edema, hyperemia, petechial and ecchymotic hemorrhages, hydrothorax, hydropericardium, ascites, and rhabdomyocytic necrosis
- Pulmonary form:
- Lung: Copious fluid and froth in the airways, pulmonary edema (especially ventral lungs), lungs fail to collapse, hydrothorax
- Other organs: Periaortic and peritracheal edema, diffuse or patchy hyperemia of the glandular fundus of the stomach, hyperemia and petechial hemorrhages of the mucosa and serosa of the small and large intestines, subcapsular hemorrhages in the spleen, renal cortex congestion, lymph node enlargement and edema, variable hydropericardium, petechial hemorrhages of the pericardium
- Cardiac form:
- Heart: Massive hydropericardium (often >2L fluid); epicardial and endocardial ecchymoses
- Other tissues: Edema of the subcutaneous, subfascial, subserous, and intermuscular tissues of the head and neck (especially palpebral and supraorbital tissues, nuchal ligament) +/- lower neck, brisket, shoulders; lungs typically normal to slightly engorged; diffuse gastrointestinal submucosal edema; terminally, petechial hemorrhages usually occur on the conjunctiva and ventral surface of the tongue
- Mixed form: Any combination of the above lesions
- Mild form: No significant gross lesions
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Endothelial degeneration and necrosis, edema, +/- hemorrhage, +/- infarction
- Lung: Interstitial, alveolar, subpleural, and perivascular edema; alveolar exudate composed of fibrin, protein rich fluid, and few mixed inflammatory cells; venule endothelial cells swollen with vacuolated cytoplasm and large reactive nuclei (direct viral cytotoxicity); fibrinous microthrombi; capillary congestion
- Heart: Myocardial, epicardial, and endocardial hemorrhage, myocardial edema, multifocal myocardial necrosis with inflammation
- Subcutis, intramuscular tissue, lymph nodes, gastrointestinal tract: Edema
- Icosahedral; approximately 60-80nm in diameter; paracrystalline arrays
- Vascular endothelium: hypertrophy, alterations in intercellular junctions, subendothelial deposition of cellular debris/fibrin, or loss
ADDITIONAL DIAGNOSTIC TESTS:
- Diagnosis requires viral isolation, virus identification (e.g. PCR, in-situ hybridization, immunohistochemistry), or serology
- Equine viral arteritis (Arterivirus): Fibrinoid vasculitis, interstitial pneumonia, ventral and lower limb edema, serous nasal discharge, widespread hemorrhage, pulmonary edema, hydrothorax, and hydroperitoneum
- Hendra virus (Paramyxoviridae): Alveolar edema, vasculitis, endothelial syncytial cells; pulmonary and visceral edema
- Equine infectious anemia (Lentivirus): immune mediated (C3 complement) hemolysis, edema, petechia, hepatosplenomegaly, erythroid hyperplasia
- Purpura hemorrhagica (post streptococcal leukocytoclastic vasculitis): severe widespread hemorrhage and edema (face and limbs)
- Babesia caballi, equi (Equine Babesiosis/Piroplasmosis): Fever, anemia, supraorbital edema; intraerythrocytic protozoa evident during acute phase
- Equine viral rhinopneumonitis (Herpesvirus, EHV-1): bronchointerstitial pneumonia with interlobular septal edema, eosinophilic intranuclear inclusions in bronchial and alveolar epithelium
- Equine encephalosis virus (Orbivirus): facial swelling, CNS signs especially loss of control or incoordination of hindquarters
- Surra (Trypanosoma evansi), other trypanosomes ( congolense, T. vivax, T. brucei brucei): fatal in horses, camel, and dogs, transmitted by tsetse and other flies, results in intermittent fever, anemia, and weight loss
- Anthrax (Bacillus anthracis): diffuse hemorrhage, edema, large intravascular bacilli
- Dogs: The pulmonary form of infection (severe respiratory distress, high mortality) can occur following ingestion of infected horseflesh; infective viral dose is very high
- Zebras are the natural host and reservoir, rarely exhibit clinical signs.
- AHS has been experimentally induced in goats, guinea pigs, mice, ferrets, and rats
- AHS is reported in elephants, camels, and other wildlife in sub-Saharan Africa
Orbiviruses: Vasculitis-induced lesions
- Equine: African Horse sickness virus, Equine encephalosis virus (facial swelling, pelvic limb incoordination)
- Ruminants: Bluetongue virus
- Cattle: Ibaraki virus
- Deer: Epizootic hemorrhagic disease virus
- Lopez A, et al. Respiratory system, mediastinum and pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016: 526.
- Miller LM, Gal A. Cardiovascular system and lymphatic vessels. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016: 603-604.
- Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier; 2016:72-74.
- Weyer C, Grewar JD, Burger P, Rossouw E, Lourens C, Joone C, et al. African horse sickness caused by genome reassortment and reversion to virulence of live, attenuated vaccine viruses, South Africa, 2004–2014. Emerg Infect Dis. 2016;22(12):2087-2096.
- Zachary JF. Mechanisms of microbial infections. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016:212-214.