Diseases / List of Bacterial Diseases / Disease description:

Tularemia in Lagomorphs with notes on Hedgehogs and Bears

INFORMATION AVAILABLE

GENERAL INFORMATION

CLINICAL CHARACTERISTICS & PATHOLOGY

INVESTIGATION & DIAGNOSIS

TREATMENT & CONTROL

SUSCEPTIBILITY & TRANSMISSION

ENVIRONMENT & GEOGRAPHY

..

 

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General and References

Disease Summary

Tularemia is an acute bacterial septicaemic disease which can occur in many vertebrate species, but particularly rabbits and hares (Leporidae - Rabbits and Hares (Family)) and Rodentia - Rodents (Order) (mainly Muridae - Rats, mice, voles, gerbils etc. (Family) and Sciuridae - Squirrels, Marmots etc. (Family)).
Lagomorphs Tularemia is a common plague-like disease of wild lagomorphs but is rarely seen in the domestic rabbit. (B58.18.w18, B527, B614.8.w8)

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Alternative Names (Synonyms)

  • Plaguelike disease of rodents
  • Plaguelike lymphadenitis
  • Conjunctivitis tularensis
  • Francis's disease
  • Deerfly fever
  • Rabbit fever
  • Rabbit disease
  • Cattle-fly fever
  • Pahvant Valley fever
  • Pahvant Valley plague
  • Glandular type tick fever
  • Yato-byo
  • Ohara's disease
  • La Tularemie
  • die Tularemie

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Disease Type

Bacterial Infection

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Infectious/Non-Infectious Agent associated with the Disease

Francisella tularensis
  • A gram-negative, aerobic, non-motile, coccobacillary bacterium. (B614.8.w8)
  • This organism is widely distributed in nature; it has been isolated from over one hundred species of wildlife including birds, mammals and biting insects. (B614.8.w8)
  • There are two major biovars:
    • Type A strains Francisella tularensis tularensis:
      • highly virulent to humans as well as wildlife
      • was thought to be only found in North America, but has been found in arthropods in Europe.
      • lagomorphs (rabbits and hares) are the principle wildlife vectors.
    • Type B strains 
      • less virulent to humans than the tularensis biovar, but cause high mortality in wildlife
      • Francisella tularensis holarctica (Francisella tularensis palaearctica): found in the Americas and Eurasia (Nearctic and Palearctic) in hares and rodents;
      • Francisella tularensis mediaasiatica: in rodents and hares in Central Asia
      • Francisella tularensis novicida in North America and Australia. Closely linked to waterborne transmission, principle wildlife hosts unknown.
    (B527, B614.8.w8)
    • For further discussion of different biovars, see B527 - Tularemia - full text included.
Synonyms
  • Bacterium tularense (B614.8.w8)
  • Pasteurella tularensis
History
  • 1818 in Japan, 1890 or earlier in Norway, possibly as early as 1653, disease in humans now considered to be probably tularemia.
  • 1911 - Tularemia was described as a plaque-like disease that occurred in ground squirrels (Citellus beecheyi) in California.
  • 1912 - The organism was isolated and named after Tulare County in California: Bacterium tularense.
  • 1914 - The first human cases of tularemia in North America supported by laboratory diagnosis were reported (retrospectively, cases in North America as early as 1904). 
  • Mid 1920s - Dr Edward Francis recognised the importance of the association of the human cases of tularemia with the exposure to rabbits. He also studied the aetiology and pathogenesis of the disease.
    • The aetiologic agent was subsequently renamed Francisella in his honour. 
  • 1930s - 1940s - average more than 1,000 cases per year in the USA.
  • World War II -  thousands of cases in Soviet and German soldiers on the Eastern European front.
  • 1950s to present -  declining numbers of cases in the USA, human outbreaks e.g. in Spain (1997), Kosovo (1999 - 20000) and southern Sweden (2000).

    (B527, B614.8.w8)

A variety of invertebrates, particularly Ixodidae - Hard ticks (Family) are important both as vectors and in maintenance of the disease in the environment. Various mosquitoes and other biting flies may be important vectors in localised areas. (B527)

  • Bloodsucking arthropods including mites, ticks, flies, midges, mosquitoes, fleas and lice. (B58.18.w18)

Infective "Taxa"

Non-infective agents

--

Physical agents

-- Indirect / Secondary

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References

Disease Author

Debra Bourne MA VetMB PhD MRCVS (V.w5); Nikki Fox BVSc MRCVS (V.w103); 
Click image for main Reference Section

Referees

William Lewis BVSc CertZooMed MRCVS (V.w129); Richard Saunders BVSc BSc CertZooMed MRCVS (V.w121)

Major References / Reviews

Code and Title List

B58.18.w18, B209.18.w18, B228.9.w9, B282.18.w18, B527 - full text included

In Hedgehogs
B228.9.w9

In Lagomorphs
B614.8.w8
J1.11.w14, J1.13.w18, J1.24.w14, J1.26.w15, J40.57.w1, J64.11.w9

Other References

Code and Title List

In Bears
J1
.16.w12, J64.17.w1, J497.20.w1, P18.6.w1

In Lagomorphs
J497.20.w1

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Clinical Characteristics and Pathology

Detailed Clinical and Pathological Characteristics

General Tularemia is an acute bacterial septicaemic disease. (B614.8.w8)

Clinical Characteristics

  • Sudden death is the most frequent presentation of tularaemia in affected animals; however, depression, anorexia, and ataxia may be seen. (B614.8.w8)
  • Depression and fever; sometimes also local inflammation or ulceration a the site of entry of the organism, and enlarged local/regional lymph nodes. (B209.18.w18)
  • In humans, usually the ulceroglandular form is seen, with one, less commonly several ulcerated skin lesions, and enlarged lymph nodes. Other syndromes affect the eyes, oropharynx or lungs; systemic disease also occurs. (B527)
  • In highly susceptible species, often only mild apathy is noted before death. (B209.18.w18)
  • In sheep, laboured breathing, lagging behind the flock, diarrhoea, rigid gait, frequent urination. (B527)
  • In cats, depression and enlarged lymph nodes. (B527)
Hedgehogs
  • Illness associated with infection in hedgehogs has been reported. (B228.9.w9) "septicaemia with an enlarged spleen and multiple necrotic foci in the spleen and liver". (B228.9.w9)
Lagomorphs Sudden death is the most frequent presentation of tularaemia. However, other clinical signs that may be observed include:
  • Depression (B209.18.w18, B527, B614.8.w8)
  • Wild lagomorphs may become tame or easy to catch. (B58.18.w18, B527)
  • "Tularemic hares and cottontails have been observed to behave oddly, to run slowly, and to be captured easily." (B58.18.w18)
  • Exhaustion. (B527)
  • Stupor. (B527)
  • Rubbing the nose and forefeet into the ground. (B58.18.w18, , B527)
  • Failing to raise the head properly or carry the forefeet properly. (B58.18.w18, B527)
  • Anorexia (B614.8.w8)
  • Ataxia/staggering (B58.18.w18, B527, B614.8.w8)
  • Recurrent tonic spasms. (B58.18.w18, B527)
  • Fever. (B209.18.w18)
  • In Lepus timidus - Mountain hare and Lepus europaeus - Brown hare experimentally infected with Francisella tularensis biovar palaearctica, mild depression was noted for several days, but no other signs occurred and infection was not fatal. (J1.24.w14)
  • In Lepus europaeus - Brown hare, a brief period of severe apathy may be seen before death. (J1.39.w8)

Asymptomatic infection of Francisella tularensis is thought to occur frequently because there is a high prevalence of antibody in wild rabbits and also this organism is occasionally isolated from apparently healthy animals. (B614.8.w8)

Incubation

--
Hedgehogs --
Lagomorphs

Mortality / Morbidity

  • In humans, 5 - 15% mortality prior to the use of antibiotics in cases in North America; more recently less than 2%. However, if untreated there can be systemic infection with high mortality. In other regions, with biovars of lower pathogenicity to humans, mortality usually under 1%. (B527)
Hedgehogs -- 
Lagomorphs

Pathology

  • "Inflammation and necrosis in lymph nodes and scattered foci of coagulation necrosis in lever, spleen, bone marrow, and lungs." (B209.18.w18)
Gross

Acute disease in sensitive species

  • Abdominal cavity: sometimes fibrin strands.
  • Pulmonary: usually congestion and oedema.
  • Hepatic: pale necrotic foci.
  • Splenic: enlarged spleen with pale necrotic foci.
  • Lymph nodes: caseous necrotic foci.
  • Bone marrow: pale necrotic foci.
  • Blood vessels: congestion, thrombosis.

(B209.18.w18)

Chronic disease

  • Poor body condition.
  • Granulomatous lesions in the lungs, liver, spleen, lymph nodes, kidneys.

(B209.18.w18)

Histopathology

Acute disease in sensitive species

  • Spleen, liver, lymph nodes, lungs, bone marrow: multifocal coagulative necrosis. (B209.18.w18)

Chronic disease

  • Spleen, liver, lymph nodes, lungs, kidneys: granulomatous lesiosn. Central necrosis with surrounding vacuolated macrophages, giant cells and epitheliod cells. (B209.18.w18)
Hedgehogs Lesions of "septicaemia with an enlarged spleen and multiple necrotic foci in the spleen and liver". (B228.9.w9)
Lagomorphs The extent of the lesions is dependent on the duration of the disease; lesions may be minimal or absent in peracute cases. (B614.8.w8)

In Lepus timidus - Mountain hare:

  • Liver, spleen and bone marrow: focal coagulative necrosis and congestion. (B614.8.w8, J1.24.w14, J64.11.w9)
  • Gastrointestinal tract: haemorrhagic enteritis and typhlitis, particularly in hares with tularemia in the winter months. (J1.24.w14)

In Lepus europaeus - Brown hare with more chronic disease. (P18.6.w1)

  • Kidneys and lungs: granulomatous lesions. (P18.6.w1)

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Human Health Considerations

Tularemia is a zoonotic disease. (B614.8.w8)
  • Infection with Francisella tularensis results in an acute febrile disease. A skin ulcer may be seen as the primary lesion, followed by inflammation of regional lymph nodes - this is called the ulceroglandular form of the disease. Fever and weakness are common clinical signs and in severe cases the disease may progress to septicaemia and pneumonia. Ulcerative conjunctivitis has also been reported. (B614.8.w8)
Incidence of tularemia in humans
  • The incidence of this disease in the USA peaked in 1941 with 2291 cases but declined to around 10% of that level in the early 1990s. (B614.8.w8)
Species involved in transmitting the disease to humans

Of the species which harbour Francisella tularensis, about half have reportedly transmitted tularemia to humans; rabbits and hares are the most frequently incriminated species. (B614.8.w8)

  • Rabbits:
    • Up to 90% of cases of tularemia in humans have been linked to exposure to lagomorphs; rabbits of the Sylvilagus genus are reported to present the greatest risk in North America. (B614.8.w8)
    • N.B. "There have been no reported cases of tularemia acquired from Oryctolagus cuniculus". (B614.8.w8)
    • In North America, more human cases are associated with tick-borne tulareaemia of rabbits than with water-borne tularaemia of rodents. (J64.11.w9)
  • Arthropods may also transmit the infection to humans. (B614.8.w8)
  • In Central Europe and Western Europe, human cases are commonly associated with direct contact with dead or sick hares. (J64.11.w9)
  • In Sweden, human cases usually are associated with transmission by mosquitoes. (J64.11.w9)

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Susceptibility / Transmission

General information on Susceptibility / Transmission

Susceptibility
  • A wide variety of mammals and some birds are reported to be susceptible to infection. Infection has been reported less commonly in reptiles, amphibians, fish, crustaceans, molluscs and annelids.(B527)
  • In most carnivores, infection does not generally cause bacteraemia or clinical disease. However, domestic cats may develop illness, sometimes fatal. (B527)
  • Cattle and camels are reported to be moderately susceptible, sheep highly susceptible, goats and water buffalo have low susceptibility, and pigs and horses have intermediate susceptibility. (B527)
  • Rodents, including Muridae - Rats, mice, voles, gerbils etc. (Family) and Sciuridae - Squirrels, Marmots etc. (Family) are very important hosts in many areas. (B527)
Transmission
  • Transmitted by a variety of ectoparasites, by direct contact and by indirect contact (via environmental contamination). (B58.18.w18)
    • In North America, transmission is mainly via ticks, particularly Dermacentor variabilis, Dermacentor andersoni, Dermacentor parampertis, Dermacentor occidentalis, Haemaphysalis leporis-palustris, Amblyomma americanum and Ixodes dentatus. (B209.18.w18)
    • In Eurasia, Dermacentor marginatus, Dermacentor pictus, Ixodes ricinus and Rhipicephalus rossica are important species. (B209.18.w18)
    • In Japan, Haemaphysalis flavis, Ixodes japonensis and Ixodes nipponensis are known vectors. (B209.18.w18)
  • Via the skin or conjunctiva:
    • Francisella tularensis will usually enter the host via these routes either by penetrating intact epithelium or via a wound. This may occur by: 
      • Direct contact
      • Arthropod bite
        • Ticks
        • Mosquitoes

      (B614.8.w8)

  • Ingestion of infected water. (B614.8.w8)
  • Ingestion of infected meat/carcasses. (B209.18.w18, B614.8.w8)
  • Inhalation of infected aerosols (airborne infection). (B209.18.w18, B614.8.w8)
Lagomorphs
Susceptibility 
Transmission
  • Tularaemia is transmitted via arthropods, particularly ticks, via contaminated water and by direct contact with infected animals. (J64.11.w9)
  • In North America, transmission is mainly via ticks, particularly Dermacentor variabilis, Dermacentor andersoni, Dermacentor parampertis, Dermacentor occidentalis, Haemaphysalis leporis-palustris, Amblyomma americanum and Ixodes dentatus.  (B209.18.w18)

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Disease has been reported in either the wild or in captivity in:

Occurrence in Hedgehogs
  • Infection reported in Erinaceus europaeus - West European Hedgehog. (B58.18.w18, B282.18.w18)
  • Infection reported in hedgehogs. (B16.13.w13)
  • Experimental infection reported. (B58.18.w18, B282.18.w18)
  • Hedgehogs are a natural host in the CIS. (B228.9.w9)
  • Serological evidence of recent infection has been recorded in a hedgehog in Iran. (B228.9.w9)
Occurrence in Bears
Occurrence in Lagomorphs

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

(List does not contain all other species groups affected by this disease)

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Disease has been specifically reported in Free-ranging populations of:

Occurrence in Hedgehogs
Occurrence in Bears
Occurrence in Lagomorphs

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" module has been completed (i.e. for which a comprehensive literature review has been undertaken). Host species with further information available are listed below:

Host Species List

(List does not contain all other species groups affected by this disease)

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Environment/Geography

General Information on Environmental Factors/Events and Seasonality

  • In Lepus timidus - Mountain hare in Europe, large epidemics in occur mainly in late summer to early autumn. (B209.18.w18)
    • A study of tularemia in Lepus timidus - Mountain hare in Sweden found that most cases were diagnosed in autumn with few in winter and none in spring.  (J1.24.w14)
  • In a study of a semi-isolated population of Sylvilagus floridanus - Eastern cottontail in southern Illinois1982 - 1988 deaths from tularemia occurred from spring 1988 to winter 1990. (J40.57.w1)
  • Seasonality of infection in humans varies, e.g. in summer from tick bites, in winter among fur trappers. (B209.18.w18)

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Regions / Countries where the Infectious Agent or Disease has been recorded

  • Type A strains Francisella tularensis tularensis:
    • highly virulent to humans as well as wildlife
    • was thought to be only found in North America, but has been found in arthropods in Europe.
    • lagomorphs (rabbits and hares) are the principle wildlife vectors.
  • Type B strains 
    • less virulent to humans than the tularensis biovar, but cause high mortality in wildlife
    • Francisella tularensis holarctica (Francisella tularensis palaearctica): found in the Americas and Eurasia (Nearctic and Palearctic) in hares and rodents;
    • Francisella tularensis mediaasiatica: in rodents and hares in Central Asia
    • Francisella tularensis novicida in North America and Australia. Closely linked to waterborne transmission, principle wildlife hosts unknown.
(B527, B614.8.w8)

In Europe, tularaemia is widespread but appears not to be found in the UK, Ireland, Spain and Portugal. (B209.18.w18)

  • For further discussion of different biovars in different geographical areas, see B527 - Tularemia - full text included.

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Regions / Countries where the Infectious Agent or Disease has been recorded in Free-ranging populations

  • Type A strains Francisella tularensis tularensis:
    • highly virulent to humans as well as wildlife
    • was thought to be only found in North America, but has been found in arthropods in Europe.
    • lagomorphs (rabbits and hares) are the principle wildlife vectors.
  • Type B strains 
    • less virulent to humans than the tularensis biovar, but cause high mortality in wildlife
    • Francisella tularensis holarctica (Francisella tularensis palaearctica): found in the Americas and Eurasia (Nearctic and Palearctic) in hares and rodents;
    • Francisella tularensis mediaasiatica: in rodents and hares in Central Asia
    • Francisella tularensis novicida in North America and Australia. Closely linked to waterborne transmission, principle wildlife hosts unknown.
(B527, B614.8.w8)
  • For further discussion of different biovars in different geographical areas, see B527 - Tularemia - full text included.

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General Investigation / Diagnosis

General Information on Investigation / Diagnosis

  • Necropsy: the typical lesions seen at necropsy are suggestive of tularemia. However, identification or isolation of the organism is necessary for definitive diagnosis. (B209.18.w18, B614.8.w8, J64.11.w9)
  • Impression smears of liver, spleen, kidney, lung or bone marrow, or tissue sections: Gram-negative bacteria, very small, usually in large numbers. (B209.18.w18)
    • Indirect or direct fluorescent antibody techniques for confirmation. (B209.18.w18)
  • Identification / isolation of the organism
    • Fluorescent antibody techniques can be used to identify the organism in fixed tissue. (B209.18.w18, B614.8.w8)
    • Culture: blood enriched cysteine heart agar or glucose-cysteine agar can be used to culture Francisella tularensis by inoculating the agar plates directly with necropsy or clinical specimens and incubating them aerobically for 48 to 96 hours at 37 °C. NB. standard laboratory media are not suitable for growth of this organism. (B209.18.w18, B614.8.w8)
  • Serological screening may be used including:
    • Tube agglutination test
    • Rapid slide test for agglutination antibodies;
    • ELISA
    (B209.18.w18, B614.8.w8)
Lagomorphs See the general information above.
Related Techniques
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Similar Diseases (Differential Diagnosis)

Depends on the species. In general, "any disease producing necrotizing, suppurative, or granulomatous lymphadenitis, multifocal hepatitis and splenitis, and/or autopsy findings compatible with Gram-negative bacterial septicaemia." (B209.18.w18)
  • Pseudotuberculosis
  • Mycobacterial infection
  • Staphylococcus infection
  • Salmonellosis
  • Tyzzer's disese
  • Systemic herpesvirus infections
  • Parasites encysting in the liver. 

(B209.18.w18)

Lagomorphs
  • --

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Treatment and Control

Specific Medical Treatment

Antibiotics
  • Streptomycin is the drug of choice. (B58.18.w18, B209.18.w18, B282.18.w18)
    • Some strains are resistant. (B282.18.w18)
  • Gentamicin is an alternative. (B209.18.w18)
  • Tetracyclines and chloramphenicol are less effective; these are bacteriostatic, not bacteriocidal, therefore when treatment is stopped, recrudescence of the disease may occur. (B209.18.w18, B282.18.w18)
Lagomorphs
  • Streptomycin or another aminoglycoside should be effective. (B614.8.w8)
    • NB. tetracycline can be used but when therapy is stopped recrudescence of the disease may occur. (B614.8.w8)
Related Techniques

 

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General Nursing and Surgical Techniques

--
Lagomorphs --
Related Techniques
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Preventative Measures

Vaccination A modified live vaccine can be used in individuals that are at exceptionally high risk. (B614.8.w8)
Lagomorphs --
Prophylactic Treatment

 

Lagomorphs --
Related Techniques
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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection To prevent spread of disease to domestic animals or humans:
  • Minimise contact with biting insects and animal carcases. (B282.18.w18, B614.8.w8)
  • Meat from wild-caught lagomorphs in infected areas should be thoroughly cooked. (B614.8.w8)

Lagomorphs

  • --
Population Control Measures
  • Control of this disease in wild animal populations has apparently not been attempted. (B614.8.w8)
Lagomorphs --
Isolation, Quarantine and Screening --
Lagomorphs
  • Translocation of wild lagomorphs from endemic areas should be avoided or carried out with care. (B209.18.w18)
Related Techniques
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