Tyzzer's Disease in Lagomorphs 

Disease Summary

• Tyzzer's disease was first recognised in rabbits in 1965 and is reportedly widespread in rabbit colonies. (B614.8.w8)

Alternative Names (Synonyms)

• Clostridium piliforme infection
• Bacillus piliformis infection 

Disease Type

Infectious/Non-Infectious Agent associated with the Disease

• This is a large pleomorphic, gram-negative, motile, spore-forming, obligate, intracellular bacterium. (B600.10.w10, B601.8.w8, B614.8.w8, J29.9.w1)
• Synonym: Bacillus piliformis was the original name for Clostridium piliforme before the bacterium was reclassified based on the molecular studies of the genome. (B600.10.w10) 
• Aetiology: spores are shed in the faeces and then infection occurs when the animal ingests contaminated material. The organism is thought to initially reside latently in the intestinal tract and then immunosuppressant or stress can precipitate overt disease possibly by facilitating the invasion of the intestinal mucosa and the systemic spread of the bacteria. Infection of the heart occurs by way of the lymphatics whereas infection of the liver occurs via the portal circulation. (B600.10.w10, B614.8.w8)
• Spores remain infectious in the environment for a long time (J29.9.w1); more than a year. (B600.10.w10)

Infective "Taxa"

• Clostridium piliforme

Non-infective agents

Physical agents

References

Disease Author

Referees

Major References / Reviews

Code and Title List

Other References

Code and Title List

Detailed Clinical and Pathological Characteristics

Clinical Characteristics

• Acute onset, short course of one to four days. (J29.9.w1)
• Profuse watery diarrhoea (B600.10.w10, B614.8.w8, J29.9.w1)
• Faecal staining around the perineum (B600.10.w10, B614.8.w8)
• Listlessness/depression. (B614.8.w8, J29.9.w1)
• Dehydration (B600.10.w10, B614.8.w8, J29.9.w1)
• Anorexia (B614.8.w8)
• Death (B600.10.w10). 
  • Death occurs within one to two days of the onset of clinical signs and occurs in around 90% of affected rabbits. (B614.8.w8)
• If rabbits survive the acute infection, they may sometimes develop chronic disease (with small intestinal fibrosis and stenosis); progressive weight loss and ill thrift may be seen. (B601.8.w8, B614.8.w8)

In Sylvilagus floridanus - Eastern Cottontail

• Dysentery is reported to occur in affected cottontails (Sylvilagus floridanus - Eastern Cottontail). (B209.28.w28l)
• In experimentally infected Sylvilagus floridanus - Eastern Cottontail, unformed, tarry stools were passed after three days, the perianal fur was soiled with tarry faeces, and the rabbits died (or were euthanized while moribund) after 4 - 6 days. (J1.12.w14)
  • Greater quantities of unformed stools were passed, and death was sooner, in rabbits treated with corticosteroids at the same time as intragastric inoculation of bacilli. (J1.12.w14)

Incubation

• In Sylvilagus floridanus - Eastern Cottontail, experimentally infected with 10^3.8 ELD₅₀ bacilli intragastrically, clinical signs (tarry faeces) appeared after three days. (J1.12.w14)

Mortality / Morbidity

• HIgh morbidity and mortality, particulary in weanling rabbits. (J29.9.w1)
• This disease usually occurs epizootically in rabbits but may also occur enzootically with large numbers of subclinically infected rabbits and only sporadic clinical cases. (B614.8.w8)
• Mortality rate: may approach 50 % at the peak of an outbreak. (B614.8.w8)
• In Sylvilagus floridanus - Eastern Cottontail, experimentally infected with 10^3.8 ELD₅₀ bacilli intragastrically, all four infected rabbits died. (J1.12.w14)

Pathology

Gross pathology

• General: 
  • Perineal faecal soiling and dehydration. (B614.8.w8)
• Gastrointestinal tract: 
  • Intestinal wall oedema. (B601.8.w8)
  • Necrotic lesions in the caecum and the adjacent intestine. (B614.8.w8, J29.9.w1)
  • In the caecum there may be ecchymotic and petechial haemorrhages on the serosal surface; thickened and oedematous wall; patchy areas of necrosis in the mucosa. (B614.8.w8)
  • The lesions that are seen in the caecum frequently extend to the adjacent proximal colon and distal ileum. (B209.28.w28l, B614.8.w8)
  • The intestinal contents may be fluid. (B209.28.w28l)
  • In chronic cases stenosis of the intestine due to fibrosis at the areas of previous necrosis. (B600.10.w10, B601.8.w8, B614.8.w8)
• Liver:
  • Necrotic lesions are seen in the liver; however these lesions may be absent in peracute cases. (B614.8.w8)
    • Numerous pinpoint white foci approximately 2 to 3 mm (or less) in diameter throughout the parenchyma. (B209.28.w28l, B614.8.w8)
• Heart: 
  • This organ is frequently spared but necrotic lesions may be present and seen as white streaks of pale foci most commonly in the left ventricle and the septum. (B614.8.w8, J29.9.w1)
    • Myocardial lesions are not found in peracute disease. (B600.10.w10)

• In Sylvilagus floridanus - Eastern Cottontail, experimentally infected with 10^3.8 ELD₅₀ bacilli intragastrically. (J1.12.w14)
  • Perineal fur soiled with tarry faeces.
  • Increased, straw-coloured peritoneal fluid.
  • GIT: Terminal 15 cm of the ileum, plus the caecum and colon, showed conspicuous ulceration of the mucosa. 
  • Hepatic: few miliary white spots.
  • Cardiac: in one individual (the longest survivor), a 1 x 5 mm white band in the left ventricular myocardium.

Histopathology

• Gastrointestinal tract: 
  • Haemorrhages in the caecal submucosa. (B209.28.w28l, B614.8.w8)
  • Submucosal oedema and mucosal necrosis in the caecum and the adjacent intestine. (B209.28.w28l, B614.8.w8)
  • Mucosal necrosis may sometimes spread into the submucosa and the muscularis. (B614.8.w8)
  • Clostridial piliformis organisms may be seen in the epithelial and muscle cells. (B209.28.w28l)
• Liver:
  • Focal necrotic areas which are usually close to the portal areas. (B209.28.w28l; B614.8.w8)
  • Polymorphonuclear leucocytes may surround the necrotic foci and they may also be seen in the hepatic sinusoids. (B614.8.w8)
  • Chronic lesions may be calcified and surrounded by fibrosis and multinucleated giant cells. (B209.28.w28l; B614.8.w8)
  • Clostridiaum piliforme organisms may be seen in intact hepatocytes at the edge of the acute lesions. However, they may be absent in chronic lesions. (B209.28.w28l, B614.8.w8)
    • Using the Warthin-Starry stain, the bacteria are seen as light brown to black rods. (B614.8.w8)
• Heart:
  • Linear or focal areas of necrosis close to myocardial blood vessels. There is sometimes a moderate inflammatory cell response in association with these necrotic areas. (B614.8.w8)
    • Myocardial lesions generally occur in the left ventricle and septum. (B600.10.w10)
    • Myocardial lesions are not found in peracute disease. (B600.10.w10)
• In Sylvilagus floridanus - Eastern Cottontail, experimentally infected with 10^3.8 ELD₅₀ bacilli intragastrically, all four infected rabbits died. (J1.12.w14)
  • GIT: lower GIT, focal necrosis epithelial cells.
  • Hepatic: focal necrosis of hepatocytes.
  • Cardiac: occasional necrosis of myocardial cells.

Human Health Considerations

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

• A serological survey of Oryctolagus cuniculus domesticus - Domestic European rabbits from fifteen research or breeding facilities in Japan revealed antibodies to Bacillus piliformis [Clostridium piliforme] in rabbits from nine facilities. In the positive facilities around 15 % of the tested rabbits had detectable antibodies. [1991] (B614.8.w8)
• Complement-fixing antibodies to Bacillus piliformis [Clostridium piliforme] were detected in 9/14 (64%) sera from wild Sylvilagus floridanus - Eastern Cottontail in Maryland, USA. (J1.12.w14)
• Experimental disease in Sylvilagus floridanus - Eastern Cottontail. (J1.12.w14)
• In pet rabbits in the USA, serology suggested infection (mainly asymptomatic) in 47%. (B600.10.w10)

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" volume 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

• Oryctolagus cuniculus domesticus - Domestic European rabbit
• Sylvilagus floridanus - Eastern Cottontail

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

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

• Complement-fixing antibodies to Bacillus piliformis [Clostridium piliforme] were detected in 9/14 (64%) sera from wild Sylvilagus floridanus - Eastern Cottontail in Maryland, USA. (J1.12.w14)

Further information on Host species has only been incorporated for species groups for which a full Wildpro "Health and Management" volume 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

• Sylvilagus floridanus - Eastern Cottontail

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

General Information on Environmental Factors/Events and Seasonality

• The vegetative form of Clostridium piliformis is unstable outside the host. (B614.8.w8)
• Spores will be killed by heating them at 80 °C for thirty minutes. (B614.8.w8)

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

• Seen in rabbits in Japan, USA. (B600.10.w10, B614.8.w8, J1.12.w14)

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

• --

General Information on Investigation / Diagnosis

• Presumptive diagnosis 
  • Typical gross and microscopic lesions. (B614.8.w8)
    • Intestinal wall oedema is characteristic. (B601.8.w8)
  • Organisms are visible on histopathological examination of the liver. (B600.10.w10)
• Definitive diagnosis: 
  • Demonstration of characteristic intra-cellular bacteria in the affected tissues via histopathology. The tissue needs to be prepared with special stains: the Warthin-Starry silver stain is the most effective but Giemsa or periodic acid-schiff stains can also be used. Immunofluorescence can be useful in identifying the organisms if they are not evident in the specially stained preparations. (B614.8.w8)

• Environmental Assessment
• History & Documentation
• Physical Examination of Mammals
• Necropsy of Mammals
• Imaging in Lagomorph Diagnosis and Treatment
• Clinical Pathology of Lagomorphs
• Chapter 2 - B36 Field Manual of Wildlife Diseases - Specimen Collection and Preservation
• Chapter 3 - B36 Field Manual of Wildlife Diseases - Specimen shipment
• Appendix A - B36 Field Manual of Wildlife Diseases - Sample specimen history form

Similar Diseases (Differential Diagnosis)

• Similar clinical signs and lesions to those seen with Tyzzer's disease in rabbits have been seen in laboratory rabbits in which Escherichia coli was the only bacterium found (Colibacillosis). (J240.37.w1)

Specific Medical Treatment

"There is no treatment known to be of value for clinically ill rabbits". (B614.8.w8)

• Antibiotic treatment yields poor results possibly due to the intracellular location of the organism limiting the efficacy of the medication. (B614.8.w8)
• Chlortetracycline, streptomycin, penicillin and erythromycin were shown to be only partially inhibitory of the growth of this organism in embryonated eggs, and sulfamethazine and chloramphenicol were reported to be completely lacking in inhibitory properties. (B614.8.w8)
• Oxytetracycline 50 mg/kg orally every 12 hours may assist in suppressing an outbreak. (J29.9.w1)
• Although antibiotics are not effective in clinical cases, anecdotal evidence suggests antibiotics may be of value in limiting the epizootics: 
  • In one outbreak of Tyzzer's disease, oxytetracycline was used in the drinking water and the epizootic ended in thirty six hours (1971). (B614.8.w8)
  • In another case, clinical disease was reported to be eliminated from a mouse colony after tetracycline was added to the drinking water. (B614.8.w8)

• Treatment and Care

General Nursing and Surgical Techniques

• Treatment and Care - Fluid Therapy

Preventative Measures

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• Preventative Medicine for Mammals

Environmental and Population Control Measures

Lagomorphs

Reduce exposure of the animals to spores by:

• Regular cage cleaning. (B614.8.w8)
• Prevention of crowding. (B614.8.w8)
• Dust control (B614.8.w8)

Inactivate spores by:

• 0.3% sodium hypochlorite solution. (B614.8.w8, J29.9.w1) or
• Heating to 80 °C for thirty minutes. (B614.8.w8)

• Screening for serum antibodies against this organism can be a useful means of rabbit colony surveillance. Subclinically infected animals will produce antibodies which persist for long periods, possibly throughout life. Indirect fluorescent antibody assay or the enzyme-linked immunosuppressant assays can be used for detection of antibodies. (B614.8.w8)
• Animals testing positive should be removed. (B614.8.w8)

• Environmental and Population Management