Clostridial Enteritis and Enterotoxaemia in Rabbits 

Disease Summary

• This condition is mainly seen in colony-kept rabbits but is occasionally seen in the individual pet rabbit. (B600.10.w10)
• Young, weaning-aged rabbits from five to eight weeks old are particularly susceptible to this condition because they may have incomplete enteric colonisation by commensal bacteria which allows rapid colonisation by Clostridium spiriforme from the environment. This results in either a profuse watery diarrhoea or a mucoid diarrhoea with caecal colonisation. It is an acute, severe disease and death usually occurs within one to three days. (B609.2.w2)
• Older rabbits may suffer from this condition if they are subjected to predisposing factors that allow enteric colonisation of clostridial species including stress, inappropriate antibiotic use, and inappropriate diet. Colonisation may result in either an acute, frequently fatal, disease or a milder form that is more amenable to treatment. (B609.2.w2)

Alternative Names (Synonyms)

• Clostridial enterotoxicosis
• Clostridium spiroforme-mediated diarrhoea

Disease Type

Infectious/Non-Infectious Agent associated with the Disease

Clostridial spiroforme

• Clostridial spiroforme is the major pathogen involved in this disease. (B600.10.w10, B614.8.w8)
• This microorganism is a gram-positive, spore-forming, non-mobile, anaerobic bacterium that is capable of producing potent enterotoxins. (B600.10.w10, B614.8.w8)
• The curved or coiled shape distinguishes it from most other species of Clostridia. Long chains of linked Clostridium spiroforme produce the coiled shape. (B614.8.w8)
• This species can be found in the faeces of healthy humans. (B614.8.w8)
• In lagomorphs: 
  • practically all rabbit isolates of Clostridial spiroforme are toxigenic. The toxin is cytotoxic. (B614.8.w8)

Other clostridial species

• In lagomorphs: 
  • In rare cases, other clostridial species may be involved, e.g. Clostridium perfringens or Clostridium difficile. (B600.10.w10, B614.8.w8)
  • Clostridium cocleatum has also been reported in rabbits. It is similar to Clostridium spiroforme but its ability to ferment galactose differentiates it from this species. (B614.8.w8)

Pathogenesis of clostridial enterotoxaemia in lagomorphs

• A change in the normal flora in the gastrointestinal tract usually precedes enterotoxaemia and this change will allow colonisation and proliferation of Clostridium spiroforme. (B614.8.w8)
• Coliforms will also proliferate in this environment but this is thought to be incidental and not critical for enterotoxaemia development. (B614.8.w8)
• The caecum of healthy rabbits contains a variety of microorganisms including small gram-negative rods, large anaerobic metachromatically staining bacilli, and ciliated protozoa. However, Clostridium spiroforme is usually absent. (B614.8.w8)
• Predisposing factors
  • Conditions that can alter the normal gut flora and favour the colonisation and proliferation of Clostridial spiroforme include:
    • Weaning
    • Abrupt diet change
    • Parturition and lactation
    • Illness
    • Antibiotic administration
  • The feeding of high energy and low fibre diets to weanlings is one of the most important predisposing factors of enterotoxaemia. This feeding practice favours the disruption of caecal flora by causing caecal hypomotility and increasing the availability of simple carbohydrate substrates, e.g. glucose, that are required by pathogenic microorganisms. (B614.8.w8)
• Clostridium spiroforme is usually absent from the gastrointestinal of healthy rabbits so exposure to the organism is necessary for disease to occur. In adults, exposure to this organism does not produce disease unless the normal gut flora is first disrupted. However, in weanlings, exposure is sufficient for the induction of disease and this is probably due to the unstable caecal flora that is characteristic of this age. (B614.8.w8)

Infective "Taxa"

• Clostridium (Bacteria Genera):
  • Clostridial spiroforme 
  • (Clostridium difficile, Clostridium perfringens)

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

• An acute watery diarrhoea.
• A chronic intermittent diarrhoea.
• A serious life-threatening disease that is associated with enterotoxaemia.

(B609.2.w2)

Clinical history 

• An acute watery diarrhoea: this is the most common history with depression, listlessness and anorexia. The diarrhoea is often described as foul smelling. (B609.2.w2)
• Mucoid enteritis: weaning-aged rabbits may be presented with an acute onset of mucoid diarrhoea with anorexia and depression. (B609.2.w2)
• Soft and sticky diarrhoea; mucous covered diarrhoea; or watery diarrhoea: in adults. This may be intermittent. (B609.2.w2)
• There may be a history of recent stress, antibiotic use or inappropriate diet in adults (B609.2.w2), see the Susceptibility / Transmission section below for more information

Clinical findings

• Anorexia, depression and brown, watery diarrhoea, sometimes with blood and mucus. (B602.16.w16)
• Anorexia: this may occur at the same time as diarrhoea; sometimes diarrhoea is preceded by a six to twelve hour period of anorexia during which Clostridial spiroforme can be recovered from the faecal contents. (B614.8.w8)
• Development of hypothermia; death in 24 - 48 hours. (B602.16.w16)
  • Affected rabbits will rapidly become hypothermic and moribund with subsequent death twenty four to forty eight hours later. (B614.8.w8)
  • Occasionally a rabbit may survive for several days. (B614.8.w8)
  • In rare cases rabbits may recover. (B614.8.w8)
• Acute onset watery brown diarrhoea which soils the perineal area. (B602.16.w16, B614.8.w8)
  • Sometimes containing blood and mucus. (B602.16.w16)
• Occasionally enterotoxaemia may occur without concomitant diarrhoea either as:
  • a chronic disease that is manifested by anorexia and weight loss or:
  • a peracute fatal illness.
  • (B614.8.w8)
• Mild to moderate diarrhoea
  • Abdominal discomfort and fluid-filled or gas-filled intestines or caecum. (B609.2.w2)
  • Perineal faecal staining may be present. (B609.2.w2)
  • Abdominal pain: hunched posture, bruxism or reluctance to move. (B609.2.w2)
• Acute, severe diarrhoea; enteric shock
  • Abdominal distension; tympanic abdomen. (B609.2.w2)
  • Dehydration (B609.2.w2)
  • Depression (B609.2.w2)
  • Tachycardia or bradycardia (B609.2.w2)
  • Tachypnoea (B609.2.w2)
  • Hypovolaemic shock: weak pulses, pale mucous membranes and decreased capillary refill time. (B609.2.w2)
  • Hypothermia:
    • If the rabbit is in shock the body temperature will usually be low. (B609.2.w2)
    • False low temperature reading: this may occur if the thermometer is not completely inserted into the rectum (approximately 3 cm). (B609.2.w2)

CBC, biochemistry, urinalysis

• In cases of mild to moderate diarrhoea:
  • usually normal. (B609.2.w2)
• With acute severe diarrhoea:
  • there may be haemogram abnormalities that are consistent with acute inflammation and shock / haemoconcentration. (B609.2.w2)
  • electrolyte abnormalities and acid-base alterations. (B609.2.w2)

Incubation

• --

Mortality / Morbidity

• --

• Clostridial enteritis is a common disease in the domestic rabbit. (B609.2.w2)
• This is often a fatal disease in weanling rabbits. (B609.2.w2)
• Enterotoxaemia may occur sporadically, but epizootics are common. One report in 1987 documented the death of 47 % of weanling rabbits over a one year period in a barrier-maintained rabbit colony. (B614.8.w8)

EXPECTED COURSE AND PROGNOSIS 

• Most rabbits with mild to moderate disease will respond well to treatment. (B609.2.w2)
• Rabbits with acute, severe diarrhoea may die despite treatment. Time elapsed to treatment and extent of infection are important factors in likelihood of survival. (B609.2.w2)
• Young rabbits that are under six months old and rabbits that are depressed and in shock also have a guarded prognosis despite treatment and even if there is only mild diarrhoea. (B609.2.w2)

COMPLICATIONS

• Death may occur due to enterotoxic shock or continued diarrhoea, dehydration and electrolyte imbalances. (B609.2.w2)

Pathology

Gross pathology 

• General
  • There may be faecal soiling of the perineum, rear legs and abdomen. (B614.8.w8)
  • Affected rabbits are often in good condition with sufficient body fat but there may be evidence of dehydration. (B614.8.w8)
• Gastrointestinal tract
  • The most characteristic findings are petechial and ecchymotic haemorrhages on the caecal serosal surface. This may also be evident on the proximal colon, appendix, and distal ileum. (B614.8.w8)
  • If there is bloat, the stomach and small intestines may be grossly dilated and thin walled. (B614.8.w8)
  • Caecum:
    • distended with gas;
    • may contains fluid to mucoid dark brown faeces;
    • mucosal haemorrhages with occasional ulcers or pseudomembranes;
    • thickened and oedematous submucosa (on a cut section).
    • (B614.8.w8)

Histopathology

• There may be diffuse necrosis of the stomach and intestinal mucosa. (B609.2.w2)
• Caecum: the most consistent changes are submucosal oedema and serosal haemorrhages. (B614.8.w8)
  • Submucosa and lamina propria: significant numbers of inflammatory cells, mainly neutrophils. However, in some cases inflammatory cells are rare. (B614.8.w8)
  • Mucosa: 
    • The affected epithelium is swollen, vacuolated and necrotic with focal erosions and ulcers. (B614.8.w8)
    • The ulcers are frequently overlain by an exudate layer that is composed of cell debris, inflammatory cells and proteinaceous fluid. (B614.8.w8)
    • In some cases, there may be evidence of epithelial cell proliferation in areas of intact mucosa, e.g. increased numbers of mitoses and lengthening of crypts. In other cases, mucosal attenuation is a prominent lesion. (B614.8.w8)

Human Health Considerations

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

• Oryctolagus cuniculus domesticus - Domestic European rabbit. (B609.2.w2, B614.8.w8s)

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

• Oryctolagus cuniculus domesticus - Domestic European rabbit

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

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

• --

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)

General Information on Environmental Factors/Events and Seasonality

• --

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

• --

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

• --

General Information on Investigation / Diagnosis

Investigation

Faecal flotation, zinc sulphate centrifugation and direct examination of faeces can be used to rule out gastrointestinal parasites. (B609.2.w2)

• Faecal Gram's stain
  • The Gram's stain is the preferred stain as it will allow the identification of concurrent overgrowth of Gram-negative bacteria. (B609.2.w2)
  • In patients with clinical disease there are usually large numbers of "large Gram-positive endospore-producing bacteria" in their faeces. (B609.2.w2)
    • Note: low numbers are a normal finding. (B609.2.w2)
  • It is necessary to differentiate Clostridium bacteria from the much larger, normal enteric yeast (Cyniclomyces guttulatus or Saccharomyces spp.). Saccharomyces are three to four times the size of Clostridia. (B609.2.w2)
• Faecal culture
  • Anaerobic faecal culture may be positive for Clostridia organisms but can occasionally be negative "due to the fastidious nature of the organism". (B609.2.w2)
• Imaging
  • Gas-filled intestinal tract is the commonest finding in this condition. (B609.2.w2)
  • Imaging is useful in ruling out other causes of diarrhoea, e.g. neoplasia, intussusception, foreign body. (B609.2.w2)

Presumptive diagnosis

• Identification of typical coiled gram-negative organisms in the caecal contents or the faeces. (B614.8.w8)

Definitive diagnosis

• Isolation of toxigenic microorganisms and the neutralisation of toxic contents of the caecum with specific antisera. (B614.8.w8)
  • Isolation of Clostridial spiroforme is facilitated by centrifuging the caecal contents for fifteen minutes at 20,000 g which will concentrate the bacteria at the interface of the pellet and the supernatant. "The surface of the pellet is washed and an aliquot is taken for gram staining. Another aliquot is plated on sheep blood agar and incubated anaerobically for 24-48 hr at 37°C". (B614.8.w8)
  • Clostridium spiroforme can be identified by its characteristic coiled appearance. (B614.8.w8)
  • The supernatent fluid can be analysed for the presence of toxin by various assays. (B614.8.w8)
  • "Identification of toxin depends on neutralization of the toxic effects of the supernatant by antiserum to iota toxin. Immunologic assays have also been proposed for detection of C. spiroforme toxin". (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)

In weaning-aged rabbits

• Intestinal Coccidiosis
• Colibacillosis
• Salmonellosis
• Tyzzer's Disease in Lagomorphs
• Viral enteritis, particularly Rotavirus Infection in Rabbits

(B609.2.w2)

In adult rabbits

• Colibacillosis
• Salmonellosis
• Intussusception in Lagomorphs
• Partial gastrointestinal tract obstruction
• Chronic disease
  • in some cases this may present as acute diarrhoea.
• Systemic illness
  • diarrhoea may result as a secondary event.

(B609.2.w2)

NB: Diarrhoea needs to be differentiated from the rabbit's normal production of caecotrophs (dark, soft faeces that tend to clump together and may be covered in mucus). Caecotrophs are produced in the caecum and are rich in nutrients. They are usually eliminated once daily (usually in the early morning hours) and tend not to be observed by the owner because the rabbit will ingest them straight from the anus. Occasionally, the rabbit is unable to eat the caecotrophs (e.g. due to neuromuscular / orthopaedic disorders or the application of an Elizabethan collar) and then this may be mistaken for diarrhoea by the owner. 

(B609.2.w2)

Specific Medical Treatment

APPROPRIATE LEVEL OF HEALTH CARE

• Adult rabbits with mild diarrhoea:
  • Most of these patients can be successfully treated as outpatients with subcutaneous or oral fluid therapy, dietary modification and metronidazole. (B609.2.w2)
• Rabbits with depression, lethargy, dehydration or shock:
  • Hospitalise even if diarrhoea is only mild or absent. (B609.2.w2)
• Rabbits with profuse diarrhoea:
  • Hospitalise because there is likely to be dehydration and electrolyte imbalance. (B609.2.w2)
• Rabbits that are under five months old:
  • Hospitalise regardless of the severity of diarrhoea. (B609.2.w2)

Antimicrobials

• "Antimicrobials have limited value in treating enterotoxaemia. Although C. spiroforme is sensitive to chloramphenicol, ampicillin, sulfaquinoxaline, and erythromycin, there is no evidence that these antibiotics are effective in treating individual cases or controlling outbreaks (Carman and Evans, 1984). This may be in part due to the rapid progression of the clinical disease. Imidazole derivatives, which have a good anaerobic spectrum, may be of value in controlling an outbreak". (B614.8.w8)
• Imidazole derivatives
  • Metronidazole, ipronidazole, and dimetridazole have been reported to decrease the number of deaths from this disease when added to the feed or drinking water. However, the efficacy of these agents is variable and influenced by the extent and stage of the outbreak. (B614.8.w8)
  • Metronidazole
    • 20 mg/kg orally or intravenously every twelve hours for three weeks. (B609.2.w2)

Ion-exchange resin 

• Cholestyramine (Questran, Bristol Laboratories)
  • This ion-exchange resin binds clostridial iota toxins. (B600.10.w10, B602.16.w16, B609.2.w2, B614.8.w8)
  • 2 g in 20 mL of water given by gavage every 24 hours from either one or three days after intravenous injection of 30 mg/kg clindamycin, until day 21 after administration of the antibiotic. This regime prevented mortality (while four of six rabbits not given the cholestyramine died) in rabbits with experimental clindamycin-induced enterotoxaemia. (B602.16.w16, B609.2.w2, B614.8.w8, J83.26.)

Analgesics

• Intestinal pain resulting from gas distension and ileus will impair mobility and decrease appetite and therefore can severely inhibit recovery. (B609.2.w2)
• Buprenorphine
  • 0.01 - 0.05 mg/kg by subcutaneous, intramuscular or intravenous injection  every eight to twelve hours. (B609.2.w2)
• Meloxicam
  • 0.2 mg/kg by subcutaneous or intramuscular injection every twenty four hours. (B609.2.w2)
  • Note: higher doses are now being recommended. See Meloxicam - Administration.

Contraindications

• Antibiotics that are often effective against Clostridia in other species , e.g. penicillins or clindamycin, are contraindicated in rabbits. Do not administer the following antibiotics orally in the rabbit:
  • amoxicillin
  • ampicillin
  • cephalosporins
  • clindamycin
  • erythromycin
  • lincomycin
  • penicillins

(B609.2.w2)

Patient monitoring

• Body temperature, appetite, faecal production and hydration should be monitored and it is also useful to perform serial faecal Gram's stains for a positive response to therapy.
• The response to therapy will support the diagnosis and repeat diagnostics are rarely necessary.

(B609.2.w2)

• Treatment and Care

General Nursing and Surgical Techniques

APPROPRIATE LEVEL OF HEALTH CARE

• Adult rabbits with mild diarrhoea:
  • Most of these patients can be successfully treated as outpatients with subcutaneous or oral fluid therapy, dietary modification and metronidazole. (B609.2.w2)
• Rabbits with depression, lethargy, dehydration or shock:
  • Hospitalise even if diarrhoea is only mild or absent. (B609.2.w2)
• Rabbits with profuse diarrhoea:
  • Hospitalise because there is likely to be dehydration and electrolyte imbalance. (B609.2.w2)
• Rabbits that are under five months old:
  • Hospitalise regardless of the severity of diarrhoea. (B609.2.w2)

Fluid therapy 

Fluid therapy and correction of any electrolyte imbalances are an important part of treatment. (B602.16.w16, B609.2.w2)

• Crystalloid fluid therapy:
  • Subcutaneously or orally if the rabbit is not dehydrated, intravenously or intraosseously in dehydrated individuals. (B600.10.w10, B602.16.w16, B609.2.w2)
  • The aim is to return the patient to a proper hydration status over twelve to twenty four hours and then replace any ongoing losses. (B609.2.w2)
  • Aggressive shock fluid therapy is necessary if severe volume depletion has occurred with acute diarrhoea. (B609.2.w2)
  • Fluid choice should take into account the electrolyte and hydration status. (B609.2.w2)
  • Lactated Ringer's solution (Hartmann's) solution is appropriate. (B600.10.w10)
  • See: Treatment and Care - Fluid Therapy

Diet

• It is vital that the rabbit continues to eat during and after the treatment period because otherwise continued anorexia will lead to an exacerbation of gastrointestinal motility disorders leading to further derangement of microflora and overgrowth of the intestinal bacterial pathogens. See: 
  • Treatment and Care - Supportive Care and Nursing
  • Food and Feeding for Mammals - Convalescent Diets / Nutritional Support
• To encourage oral fluid intake, offer fresh water, wet leafy vegetables or flavour water with vegetable juice.
• Syringe feeding
  • See: Oral Medication and Syringe Feeding of Rabbits (Techniques) - necessary if the rabbit is refusing to eat. 
  • Details of syringe feeding formulae for rabbits are given in Food and Feeding for Mammals - Convalescent Diets / Nutritional Support
• Nasogastric intubation - this is indicated if the rabbit refuses sufficient volumes of food.
  • See: Nasogastric Tube Placement in Rabbits
• Avoid high carbohydrate or high fat nutritional supplements.
• Long term permanent dietary modification:
  • The bulk of the diet should be made up of high quality fresh hay (timothy or grass preferred; the commercially available hay cubes are often not sufficient) plus a selection of washed, fresh leafy greens. Pellets should be limited to one quarter of a cup per 5 lb. (2.27 kg) body weight if at all. Foods that are high in simple carbohydrates should be strictly cut out of the diet or limited to the occasional treat. 

(B609.2.w2)

• Treatment and Care

Preventative Measures

--

Diet

• Feed a diet that is composed of good-quality grass hay, fresh leafy greens along with only a minimal amount of pellets. (B602.16.w16, B609.2.w2)
• If feeding concentrate food, use a high quality diet with at least 18-20% fibre. (B602.16.w16, B614.8.w8)
  • Give a maximum of a third of a cup per 2.3 kg (5 lb) bodyweight. (B602.16.w16)
• Avoid sudden changes in food. If a change in diet is necessary then gradually introduce the new food over seven days. (B602.16.w16, B614.8.w8)
• Young rabbits should have feed available at two to three weeks of age and they should not be early or forced weaned. (B602.16.w16, B614.8.w8)

Copper sulphate

• Copper sulphate has been reported to decrease the mortality in this disease in rabbit colonies when it is added to the diet at 400 ppm. This is possibly due to inhibition of the toxin production by Clostridium spiroforme. (B614.8.w8)
  • "levels over 250 ppm have been shown to inhibit toxin production in vitro". (B614.8.w8)

Probiotics

• Probiotics appear to reduce the mortality from enterotoxaemia when used in weanlings. They can be added to the food or water. (B614.8.w8)

Antimicrobials

• In general, antibiotics should be used conservatively in rabbits because they can precipitate enteric disease in some animals particularly when Penicillin G or one of its derivatives (amoxicillin, Ampicillin), Clindamycin, erythromycin or lincomycin is administered orally. (B614.8.w8)  

• Preventative Medicine for Mammals

Environmental and Population Control Measures

Lagomorphs

• Infection in rabbits of weaning age is often associated with environmental contamination. However, disinfection is difficult. (B609.2.w2)
• Minimise stress. (B614.8.w8)

• Environmental and Population Management