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Diseases / List of Viral Diseases / Disease description:

European Brown Hare Syndrome

INDEX - INFORMATION AVAILABLE

GENERAL INFORMATION

SUSCEPTIBILITY, DISEASE CHARACTERISTICS & DIAGNOSIS

TREATMENT & CONTROL

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THE FOLLOWING INFORMATION IS HELD ON THE INFECTIOUS AGENT INFORMATION PAGE
Caliciviridae- European Brown Hare Syndrome Virus  :
 

  • Virus Structure and Identification
  • Associated Host Species of Virus (Animal Types Affected) and Hazard / Risk
  • Virus Life Cycle, Transmission and Effects of Chemicals
  • Transmission and Biogeographical / Climatic Range for Virus

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General and References

Disease Summary

-This viral disease has been observed in Lepus europaeus - Brown hares and Lepus timidus - Mountain hares in several European countries. It is a highly fatal disease that is similar to Rabbit Haemorrhagic Disease and is characterised by haemorrhages in the lungs and the trachea, pulmonary oedema and necrotic hepatitis. (B614.9.w9, J514.1.w1)

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Alternative Names (Synonyms)

  • EBHS
  • Leporid calicivirus hepatitis
  • Infectious necrotic hepatitis of Leporidae
  • Viral hepatitis of hares
  • Fältharesjuka
  • Acute hepatosis
  • Acute necrotising hepatitis
  • Leverdystrophie
  • Syndrome hémorrhagique du lièvre

(B209.16.w16, J3.125.w4, J514.1.w1, J604.58.w1)

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Disease Type

 Viral

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Infectious/Non-Infectious Agent (directly associated with the Disease)

European brown hare syndrome is caused by European Brown Hare Syndrome Virus, a calicivirus. 

Species/Taxa

Chemical

  • --

Physical

  • --

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References

Disease Author

Dr Debra Bourne MA VetMB PhD MRCVS (V.w5)

Referee

Dolores Gavier-Widen DVM MS PhD (V.w151)

References

Detailed references are provided attached to specific sections.

ORGANISATIONS-

  • --

ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

 

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Epidemiology and Host Susceptibility Factors

Incubation Period, Time Course and Persistence of Disease

General Editorial Description The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
1) INCUBATION PERIOD
  • Experimentally, the incubation period is usually two to three days, but a longer period (six days) to first signs was noted in a hare which survived experimental infection.
2) DISEASE DURATION (TO RECOVERY OR DEATH) IN INDIVIDUAL ANIMALS
  • Generally EBHS has a short disease duration, ranging from peracute to subacute disease, with deaths as soon as 62 hours post infection and peaking at 72-90 hours post infection with experimental infection, and clinical signs lasting five hours to two days; death can also occur without any prior clinical signs, while death at five to six days after exposure is typical of the subacute form. Chronic disease can also occur: the presence of EBHSV has also been confirmed in hares with chronic liver damage.
3) TIME COURSE / PERSISTENCE OF DISEASE IN A SUSCEPTIBLE POPULATION
  • Epidemics in free-living populations may last from a few weeks to several months. Outbreaks may be superimposed on a background of epizootic disease. On hare farms, outbreaks may last a few days to a few weeks.
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Mortality / Morbidity / Susceptibility / Life stage affected

General Editorial Description The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
1) NUMBER OF DEATHS
  • In wild hares, the exact mortality rate is not known, but declines in hare numbers have been recorded after this disease arrived in an area. A study in Sweden, 1980-1989, found that overall, 14% of Lepus europaeus - Brown hare and 3% of 958 Lepus timidus - Mountain hare died of EHBS. Very high mortality, up to 90 or 100%, has been recorded in some outbreaks in farmed hares, but more usually it is lower, averaging 30%. In areas where EBHS is endemic, lower mortality occurs.
2) NUMBER OF ANIMALS AFFECTED
  • Morbidity can be high, reaching 100% in some outbreaks, but in outbreaks in farmed hares, morbidity as low as 30% has also been seen.
3) EFFECTS OF AGE, SEX AND REPRODUCTIVE STATUS
  • This is a disease of adult hares with juveniles being unaffected; hares of two to three months of age may become infected but do not develop clinical signs. Survivors have long-lasting protective immunity. Neonates may have antibodies, indicating passive transfer of immunity.
4) EFFECTS OF BODY CONDITION AND OTHER DISEASES
  • [No data]
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Clinical & Pathological Characteristics, and Diagnosis

Clinical Signs (by physiological system)

Overall Clinical Presentation The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.

Peracute:

  • With peracute disease, hares may die without showing any prior clinical signs

Acute/subacute:

  • With acute or subacute disease, a variety of neurological signs may be seen including abnormal behaviour such as loss of fear of humans/dogs, jumping into the air, incoordination, blindness, running in circles, hind limb paralysis, and convulsions. It is thought these reflect hepatic encephalopathy.
  • One wild hare was reported to have slow pupillary reflexes and reaction to touching of whiskers, while pain proprioception was limited.
  • Depression or dullness is common.
  • Anorexia may be noted.
  • Epistaxis sometimes occurs. 
  • Dyspnoea has been reported and serous or mucopurulent nasal discharge has been seen in experimentally infected hares.
  • Jaundice may develop in hares surviving several days.

Subclinical:

  • Some infected hares develop only subclinical infection.

Chronic

  • Hares with chronic disease may remain in poor body condition.

(References are available in the detailed literature reports below)

CLICK THE LINKS FOR Literature Reports on Specific Clinical Characteristic Descriptions available
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Clinical Pathology (Testing Samples incl. Serology)

Overall Clinical Pathology findings The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
  • In hares with fatal infection, a severe leucopaenia develops by 24 hours post infection, while in hares that survive, a more modest temporary reduction occurs.
  • There is a marked rise in serum alanine aminotransferase and aspartate aminotransferase about four days after infection in fatally infected hares, but a more moderate, transient, increase in hares that survive.
  • Haematological and biochemical values return to normal by ten days post inoculation in surviving hares.
  • Antibodies may be detected as early as four or five days post infection.

(References are available in the detailed literature reports below)

Sampling

  • Blood should be taken for serology and may be used for haematology and biochemistry analysis.

See also:

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Pathological Findings (by anatomical system)

Overview The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
GROSS PATHOLOGY
  • Most hares dying from EBHS are in good condition, with plenty of food in the stomach, although some are in poorer condition. Jaundice is a variable finding, seen in hares which have died after subacute disease, rather than in hares with peracute disease. 
  • The tracheal and nasal mucosa are commonly be dark red (congested), there is usually bloody froth in the trachea and the lungs generally show oedema, congestion and/or haemorrhage; sometimes there is a bloody nasal exudate. 
  • There is often liver pathology; the liver may be pale and yellowed, with obvious demarcation of lobular structure, or may be congested; sometimes it is slightly enlarged, and it may be friable. However, gross liver pathology is not always obvious.
  • Moderate splenomegaly and congestion is common; massive splenomegaly is seen occasionally. 
  • Gastric haemorrhages and enteritis have been noted sometimes, as has mucoid colitis. 
  • The kidneys are sometimes congested; yellowing of the kidneys and a notable cortico-medullary boundary have been recorded in some cases. 
  • Conjunctivitis may be noticed. 
  • Other findings are variable.
  • Note: In many infected hares there are no gross lesions. 
HISTOPATHOLOGY
  • Necrotic hepatitis is a consistent finding in hares dying from acute EBHS. There is usually diffuse acute coagulative hepatocellular necrosis of hepatic periportal and midzonal areas (sometimes the whole lobule may be affected) along with formation of acidophilic bodies and commonly granular accumulation of calcium in hepatocytes. Sinusoidal congestion and haemorrhage are common, and in many cases there is also microvacuolar fatty degeneration in the liver. Inflammatory cell infiltration may be absent or minor in acute cases, but there may be portal infiltration by macrophages, lymphocytes and a few heterophils, and there may be granulocytes infiltrating into the parenchyma. In hares in which the clinical course lasted longer than three to four days, there is less extensive hepatocellular necrosis, but the fatty change is more pronounced, there are more inflammatory changes and there is also proliferation of bile ducts.
  • Pulmonary hyperaemia, oedema and haemorrhage are common findings, as well as tracheal hyperaemia, sometimes oedema, and sometimes submucosal haemorrhages.
  • Splenic congestion is commonly noted together with a variable degree of lymphoid follicular depletion, although follicular hyperplasia has been seen in some individuals.
  • Around one third of affected hares have renal tubular necrosis and calcification, hyperaemia and haemorrhage are common, and proteinaceous casts are often noted in the tubules. Nephrosis is found in the peracute form.
  • There may be changes in other organs associated with terminal circulatory failure and haemorrhage.
  • Hepatic fibrosis may be present in hares which survive the acute infection. 
  • Electron Microscopy: 
    • With transmission electron microscopy, cells show changes of severe degeneration and necrosis of hepatocytes. Rarely, virus-like particles are seen in the cytoplasm of hepatocytes.
    • With negative stain electron microscopy, characteristic calicivirus-type viral particles, icosahedral, 30 - 40 nm diameter may be seen, although structural detail may be lacking.
    • Using immuno-electron microscopy, aggregations of viral particles may be demonstrated.
  • Immunohistochemistry:
    • Viral antigens have been detected using immunohistochemistry in various cells including in the liver (hepatocytes and macrophages; in one study in endothelial cells), in the lungs and kidneys (epithelial cells, one study), in the spleen (macrophages/mononuclear cells) and in lymph nodes (mononuclear cells). 

In seropositive but apparently healthy hares:

  • Hepatic vacuolar degeneration, hepatosis or hepatitis (small scattered mononuclear cell foci).
  • Hyperplasia of splenic follicles.
  • Tracheitis (mononuclear cell infiltration) [one description].
VIRUS ISOLATION
  • The virus cannot be isolated in tissue culture, therefore confirmation of virus identity generally relies on analysis of products from RT-PCR. See below for further details

(References are available in the detailed literature reports below)

CLICK THE LINKS FOR Literature Reports on Specific Pathological Findings Descriptions available
CLICK THE LINKS FOR Editorial Overviews Available

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Diagnostic Criteria

General Indicative Signs
  • An acute onset disease with high mortality is indicative. (B22.30.w17)
  • Tentative diagnosis is possible in individuals with abnormal behaviour. (B209.16.w16)
  • Note: Diagnosis may be suspected from the post mortem examination, but gross pathological changes of shock, such as lung oedema and multiple organ hyperaemia, are not specific to EBHS, while liver lesions may not be macroscopically visible, therefore confirmatory tests are required. (B209.16.w16, J64.10.w10, V.w151)
Definitive Diagnosis Detailed information on clinical-pathological findings, necropsy findings and laboratory tests for antigen or antibody are provided in the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
  • Definitive diagnosis is based on recognition of characteristic microscopic liver lesions and/or demonstration of virus. (B22.30.w17), B209.16.w16, J1.29.w20, J64.10.w10)
  • The virus or viral antigen may be identified in liver (highest titre) or other tissue using haemagglutination, ELISA, negative staining electron microscopy (EM), immune EM, or RT-PCR. (B22.30.w17, B209.16.w16, J1.29.w20, J1.41.w7, J1.41.w9)
    • Viral antigen is consistently detected in the liver of infected hares. (J1.29.w20)
    • Immunohistochemistry may be carried out for detection of viral antigens in sections of liver or spleen. (B209.16.w16, J26.31.w3, J64.10.w5, J307.34.w1)
  • Serological tests include haemagglutination inhibition and ELISA (B209.16.w16); ELISA is preferred. (B614.9.w9)
CLICK THE LINKS FOR Specific Technique Reports
CLICK THE LINKS FOR Specific Clinical Pathology Findings (Sample Results)
CLICK THE LINKS FOR Specific Pathological Findings 
Similar Diseases The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
CLICK THE LINKS FOR Specific Similar Disease Reports Literature Reports for Similar Diseases (Disease Reports)
CLICK THE LINKS FOR OVERVIEWS of management techniques available

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Treatment and Control

Specific Medical Treatment (Antiserum, Antidote, Anti-(viral/bacterial/fungal) etc.)

Specific Medical Treatment The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
ANTISERUM
  • Antiserum (from convalescent or hyperimmunised hares) may prevent death if given during the incubation phase of the disease.
ANTIVIRAL DRUGS
  • There is no specific medical treatment (no antiviral drugs) for EBHS. 
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  • No specific techniques described

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General Nursing and Surgical Techniques

Nursing and Supportive Care The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
  • No effective treatment is known.
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Surgical Treatment
  • Not applicable for this disease.

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Vaccination & Prophylactic Treatment

Vaccination The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
  • No vaccines are commercially available.
  • In the event of an outbreak on a hare farm, autogenous killed vaccine can be prepared from the livers of hares dying early in the outbreak, and used to immunise hares which are not yet showing signs of disease.
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Prophylactic Treatment The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
Antiviral drugs:
  • There is no specific medical treatment (no antiviral drugs) for EBHS. 
Passive immunisation:
  • Antiserum (from convalescent or hyperimmunised hares) may prevent death if given during the incubation phase of the disease.
CLICK THE LINKS FOR Literature Reports
CLICK THE LINKS FOR OVERVIEWS of management techniques available

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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
  • Steps should be taken to prevent indirect infection of captive hares via contaminated hay or grass (from excreta of wild hares), contaminated footwear, clothing etc.
  • Sodium hydroxide or formaldehyde can be used for disinfection.
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CLICK THE LINKS FOR Technique Descriptions, if available
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Population Control Measures

The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.

  • A colony with EBHS should be quarantined.
  • Depopulation could be carried out.
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CLICK THE LINKS FOR Technique Descriptions, if available
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Isolation and Quarantine The following editorial comment summarises detailed information given within the LITERATURE REPORTS. Links to the LITERATURE REPORTS are provided at the bottom of this box.
  • Hares should not be translocated from an infected area to an area free of EBHS.
  • Hares entering a hare farm or colony should be quarantined and tested serologically, with only seronegative hares allowed to enter.
  • Captive hares should be kept isolated from wild hares (as well as predators) using appropriate fencing.
CLICK THE LINKS FOR Literature Reports
CLICK THE LINKS FOR Technique Descriptions, if available
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CLICK THE LINKS FOR OVERVIEWS of management techniques available
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Authors & Referees

Authors Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referee Dolores Gavier-Widen DVM MS PhD (V.w151)

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