JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

October 2023

P-V22 (NP)

 

Signalment (JPC #1737276): Dairy cows, breed unspecified.

 

HISTORY: A number of dairy cows from a herd in the Republic of South Africa were reluctant to move and walked with a stiff gait. Several cows developed severe respiratory signs and died in a matter of hours. Tissue presented is from one of the dead cows.

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocal to coalescing areas involving approximately 40% of the alveolar lumina are filled with homogenous eosinophilic fluid (edema) mixed with variable amounts of fibrin, occasional mild hemorrhage, low numbers of neutrophils, macrophages, lymphocytes, and sloughed pneumocytes. Multifocally, alveolar septa are thickened up to 3 times normal by edema, variable amounts of fibrin, few neutrophils, lymphocytes, and macrophages. Adjacent peribronchial and peribronchiolar connective tissue is mildly expanded by a similar inflammatory infiltrate. There is diffuse marked interstitial emphysema with compression of adjacent alveoli and multifocal mild paraseptal emphysema. The tunica media and adventitia of several blood vessels are expanded by edema and infiltrated by low numbers of lymphocytes, neutrophils, and macrophages. Adjacent lymphatics are moderately ectatic. Multifocally the lumina of bronchi and bronchioles contain an exudate composed of moderate numbers of viable and necrotic neutrophils, streaming leukocyte nuclei, sloughed epithelial cells, and necrotic cellular debris. These inflammatory cells multifocally extend into the adjacent peribronchial connective tissue.   

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, subacute, multifocal, moderate, with diffuse marked interstitial emphysema and moderate pulmonary edema, breed unspecified, bovine.

 

ETIOLOGIC DIAGNOSIS: Rhabdoviral pneumonia

 

CAUSE: Bovine ephemeral fever virus

 

CONDITION: Bovine ephemeral fever (BEF)

 

SYNONYMS: Three-day sickness, bovine epizootic fever, three-day stiff sickness, dragon boat disease

 

GENERAL DISCUSSION: 

• A member of the viral genus Ephemerovirus; family Rhabdoviridae
• A noncontagious epizootic vector-borne viral disease of cattle and water buffalo characterized by sudden onset of fever, stiffness, and lameness
• High morbidity and low mortality with rapid spontaneous recovery in uncomplicated cases within 3-4 days of the onset of clinical signs
• Disease of economic concern due to decreased milk production, prolonged infertility, and late-term abortions
• Range: Endemic in tropical regions (Africa, Asia), epidemics in summer/autumn in subtropical and temperate areas (Africa, Asia, Middle East, Australia); never reported in Europe, North or South America
• Disease is sporadic, seasonal, and correlated with rainy periods and wet summer months (spread is influenced by wind movement)

 

PATHOGENESIS:

• Transmitted by mosquitoes and biting midges of the Culicoides genus
• Incubation period is 2-4 days and rarely up to 9 days
• Exact pathogenesis is poorly understood; virus may replicate in endothelial cells and alveolar macrophages
• BEFV alpha-1 protein expressed in infected cells is similar to a viroporin, which may facilitate virus replication
• Cellular damage is due to massive interferon production
• Occlusion of bronchioles by inflammatory exudate causes rupture of alveoli and bronchioles, giving rise to interstitial and subcutaneous emphysema
• Vasculitis results in serofibrinous polyserositis
• Postinfection, animals have lifelong immunity

 

TYPICAL CLINICAL FINDINGS:

• Extremely variable clinical signs from imperceptible to death
• Biphasic to multiphasic fever with peaks of 40-51.5°C (104-107^oF) 12-18 hours apart 
• Acute phase: 50% drop in milk production for remainder of lactation

• High titers of Interferon-α, interleukin 1, and tissue necrosis factor

• Second febrile phase: Anorexia, oculonasal discharge, muscle tremors, lameness, stiffness, recumbency, patchy edema of the face, rumen stasis, diarrhea or constipation, late-term abortions, temporary infertility (bulls)
• Severe cases: Limb paralysis, inability to swallow, coma, death
• Whether the disease is mild or severe, recovery commences suddenly and is complete in up to 97% of uncomplicated cases, hence “ephemeral fever”
• Clinical signs are worse in old, fat, bulls and heavily lactating cows i.e. top producers
• Early neutrophilia (with left shift), lymphopenia, hyperfibrinogenemia, and hypocalcemia 

• Hypocalcemia may contribute to anorexia, decreased ruminal and intestinal motility, muscle fasciculations and recumbency

• Clinical signs observed in an epizootic are usually diagnostic

 

TYPICAL GROSS FINDINGS:  

• Serofibrinous polyserositis as a result of increased vascular permeability
• Fibrin-rich fluid in the pleural, peritoneal and pericardial cavities +/- joint cavities
• Joints may be surrounded by brown, gelatinous fluid that extends along fascial planes
• Pulmonary emphysema, edema, and congestion
• Focal skeletal muscle necrosis (due to recumbency)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Edema with neutrophilic infiltrates +/-  hyperemia and hemorrhage
• Vascular changes: Endothelial swelling and hyperplasia, fibrinoid necrosis of arterioles, perivascular fibroplasia, vascular thrombosis in muscle
• Pulmonary changes: Congestion and edema, accumulation of inflammatory cells, fibrin and necrotic debris in small airways leading to occlusion and interstitial emphysema

 

ULTRASTRUCTURAL FINDINGS:  

• Negative sense single-stranded RNA virus with 5 nonstructural proteins
• Bullet shaped virions approximately 70 x 170 nm

 

ADDITIONAL DIAGNOSTIC TESTS: 

• ELISA, viral isolation, RT-qPCR (Gao, JVDI, 2020)
• Serology is not recommended (cross-reacts with arbovirus Kimberley virus)

 

DIFFERENTIAL DIAGNOSIS:

• Bovine respiratory syncytial virus (P-V06, Paramyxovirus) - Syncytial cells and intracytoplasmic inclusion bodies
• Parainfluenza type 3 (Paramyxovirus) – Few syncytial cells and intracytoplasmic inclusion bodies
• 3-Methylindole intoxication (P-T01) - Hyaline membranes and type II pneumocyte hyperplasia
   
   

COMPARATIVE PATHOLOGY:

• Clinical BEF only affects cattle and water buffalo but neutralizing antibodies can be found in Cape buffalo and various species of deer and antelope
• Rhabdoviridae family:
  •  Lyssavirus genus – All cause rabies or rabies like symptoms

• Rabies 
• Mokola virus
• Lagos bat virus
• European and Australian bat lyssaviruses

• Vesicular stomatitis virus (cattle, horses, pigs)
• Pike fry virus (grass carp rhapdovirus) – Visceral hemorrhage
• Spring viremia of carp – Visceral hemorrhage

• Bovine ephemeral disease – Rapid onset fever and lameness

 

References:

1. Bowen RA. Rhabdoviridae. In: MacLachlan NJ, Dubovi EJ, eds. Fenner’s Veterinary Virology. London, UK: Elsevier Inc; 2011:338-9.
2. Gao S, Du J, Tian Z, et al. A SYBR green I-based quantitative RT-PCR assay for bovine ephemeral fever virus and its utility for evaluating viral kinetics in cattle. J Vet Diagn Invest. 2020;32(1):44-50.
3. Hamblin C. Bovine ephemeral fever. In: Foreign Animal Diseases. 7th ed. Boca Raton, FL: United States Animal Health Association;2008: 175-83.
4. Robinson WF, Robinson NA. Cardiovascular system. In: Maxie ME, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 3. Philadelphia, PA: Elsevier; 2016:79-80.

 

 

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