Diseases / List of Parasitic Diseases / Disease description:

Hepatic Coccidiosis in Lagomorphs 

INFORMATION AVAILABLE

GENERAL INFORMATION

CLINICAL CHARACTERISTICS & PATHOLOGY

INVESTIGATION & DIAGNOSIS

TREATMENT & CONTROL

SUSCEPTIBILITY & TRANSMISSION

ENVIRONMENT & GEOGRAPHY

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General and References

Disease Summary

 
Lagomorphs
  • A protozoal hepatic infection caused by Eimeria stiedae, hepatic coccidiosis is a serious disease in rabbits. (B600.10.w10, B609.2.w2)

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Alternative Names (Synonyms)

  • Eimeria stiedae infection
  • Eimeria stiedai infection

See also: Intestinal Coccidiosis in Hedgehogs and Lagomorphs (with notes on Bears)

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Disease Type

Parasitic Infection

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Infectious/Non-Infectious Agent associated with the Disease

  • There is only one species of coccidia that infects the liver in rabbits, Eimeria stiedae. (B609.2.w2, J29.5.w1)
  • Eimeria parasitise epithelial cells. Each species of Eimeria found in rabbits is site and host specific; this species inhabits the epithelial cells of the bile duct. (B600.10.w10)
  • Oocysts are very resistant and will remain viable on vegetation, in soil and on fomites for long periods of time. (B600.10.w10)
  • Rabbits ingest the oocysts of this parasite from a contaminated environment. The oocysts are broken down by digestive enzymes in the duodenum releasing sporozoites. (B24, B600.10.w10, J29.5.w1)
  • Sporozoites penetrate the intestinal mucosa and travel to the liver either via the blood stream or within macrophages in the lymphatic system. (B24, B600.10.w10, J29.5.w1)
  • Replication occurs in the mesenteric lymph nodes and then the parasites travel via the hepatic portal circulation to the liver and then invade the bile duct epithelial cells. (B600.10.w10)
  • Oocysts pass through the bile ducts to the intestines. (J29.5.w1)
  • Oocysts are released into the bile duct. (B600.10.w10)
  • Oocysts: ovoid to ellipsoid, 36.9 x 19.9 m (range 28 - 40 x 16 - 25 m). The oocyst wall is smooth and yellowish-orange to salmon coloured; it has a distinct micropyle. (B24)
  • Oocysts become infective one to four days after they are shed in the faeces. (B609.2.w2) They can survive many years in the environment but are sensitive to dry conditions. (B600.10.w10)
    • Sporulation at room temperature takes three days, at 22 C it can be 58 hours. (B24)
    • Sporulation in 58 hours. (J40.7.w2)
  • Prepatent period:

Infective "Taxa"

Non-infective agents

--

Physical agents

-- Indirect / Secondary

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References

Disease Author

Nikki Fox BVSc MRCVS (V.w103)
Click image for main Reference Section

Referees

Richard Saunders BVSc BSc CertZooMed MRCVS (V.w121)

Major References / Reviews

Code and Title List

B24, B208.16.w18, B600.10.w10, B609.2.w2, B614.10.w10
J29.5.w1, J29.9.w1

Other References

Code and Title List

J3.162.w1, J11.27.w1, J32.22.w1, J32.32.w1, J42.124.w2, J82.1.w1, J501.40.w1, J524.60.w1, J528.12.w1

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Clinical Characteristics and Pathology

Detailed Clinical and Pathological Characteristics

General  

Clinical Characteristics

 
Lagomorphs There may be no clinical signs in mild infections. In heavy infections the clinical signs seen are due to blockage of the bile ducts and interference of hepatic function. (B614.10.w10)

The severity of clinical signs depends on infection severity and the individual's immune status. (B600.10.w10)

  • With mild disease, ill thrift and reduced weight gain; with severe disease, anorexia, diarrhoea, abdominal distension, jaundice and death. (J29.9.w1)
  • Anorexia (B24, B609.2.w2, B614.10.w10, J29.5.w1, J29.9.w1)
  • Debilitation (B614.10.w10)
  • Depression/dullness (B609.2.w2, J501.40.w1)
  • Weight loss (B600.10.w10, J29.5.w1)
  • Abdominal enlargement due to ascites and hepatomegaly. (B24, B600.10.w10, B609.2.w2, B614.10.w10)
  • Diarrhoea (B24, B600.10.w10, B609.2.w2, J29.9.w1)
    • Particularly in the terminal stage of disease. (B614.10.w10)
  • Constipation (B614.10.w10)
  • Jaundice (B600.10.w10, J501.40.w1, J29.9.w1)
    • In severe or advanced disease. (B614.10.w10, J29.9.w1)
  • Hepatomegaly (B600.10.w10, B614.10.w10, J29.5.w1, J29.9.w1)
    • The enlarged liver may make up to 20 % of the total body weight of the rabbit (should be 3.7 % in normal rabbits). (B614.10.w10)
  • Cranial abdominal pain (B609.2.w2)
  • Progressive emaciation. (B24)
  • Acute death (B609.2.w2, J501.40.w1)
    • Death is rare apart from in very heavy infections of young rabbits. (B614.10.w10)
  • Affected newly acquired young pet rabbits: "are often thin, pot-bellied and thin for their age". (B600.10.w10)
  • Vitamin E deficiency has been reported in experimental hepatic coccidiosis and was thought to be due to malabsorption, impaired storage, and destruction or increased use of this vitamin due to hepatobiliary dysfunction. (B529.15.w15, B614.10.w10)

Clinical pathology:

Incubation

--
Lagomorphs
  • Prepatent period: fifteen to sixteen days and then oocysts can be found in faeces for at least ten to fourteen days after this. (B600.10.w10)
  • In experimental infection of Sylvilagus audubonii - Desert cottontail , the prepatent period was 18 days. (J11.27.w1)

Mortality / Morbidity

  • Variable. The severity of clinical signs depends on infection severity and the individual's immune status. (B600.10.w10)
  • Coccidiosis is only seen occasionally in adult rabbits but can cause moderate to severe clinical disease in young, recently weaned rabbits. . (B609.2.w2)
Lagomorphs
EXPECTED COURSE AND PROGNOSIS
  • If the rabbit is eating well and is active then the prognosis is usually good with treatment. (B600.10.w10)
  • Often by the time young newly acquired pet rabbits are presented for treatment they are usually recovering from infection. (B600.10.w10)
  • In rabbits that have a heavy infestation and signs of hepatic failure, the prognosis is guarded to poor. (B609.2.w2)

Pathology

--
Lagomorphs

Gross Pathology

  • Abdominal cavity: there may be ascites. (B614.10.w10, J501.40.w1)
  • Hepatic:
    • Enlarged and fibrotic. (B600.10.w10, B614.10.w10)
      • The liver may be difficult to cut due to the fibrous capsule that surrounds some of the lesions. (B529.15.w15, B614.10.w10)
      • The liver can be as much as five to 10 times normal size. (B24)
    • Liver pale. (B24)
    • Pale yellow or yellow-grey cords, foci or nodules. (B600.10.w10, B529.15.w15)
      • These lesions are the affected bile ducts that are dilated and contain a yellow exudate. (B614.10.w10)
      • Yellow-green miliary abscesses. (J501.40.w1)
      • Lesions may reach 2 cm diameter and are often cord-like and tortuous, elevated above the capsular surface. (B529.15.w15)
      • The yellow lesions contain pus-like material. (B24)
    • Impression smears: may show various stages of the parasite. (B600.10.w10)
  • Note: Remnant pathology of the disease can be evident for life and may be discovered incidentally at post mortem examination many years later. (B600.10.w10)
    • Gall bladder and bile ducts:
      • There may be thickening and distension of the gall bladder and bile ducts. (B529.15.w15, B600.10.w10, J501.40.w1)
      • The gall bladder may be enlarged and packed with oocysts; these can be observed in wet smears. (B600.10.w10)
  • Mesenteric lymph nodes:
    • Impression smears: may show various stages of the parasite. (B600.10.w10)
  • In experimentally infected Sylvilagus floridanus - Eastern Cottontail (infected with 13,000 - 1,000,000 oocysts), no liver enlargement was seen. Macroscopic yellowish lesions were visible in 7/10 rabbits and were barely visible in the other three. (J40.7.w2)
Histopathology:
  • Hepatic:
    • Bile ducts: hyperplasia and inflammation; large numbers of ellipsoid oocysts in the walls and lumen of the bile ducts. (J501.40.w1)
      • Destruction and regeneration of the epithelium of the bile duct that results in significant papillomatous hyperplasia, reduplication of bile ducts, and also cystic enlargement of the bile ducts. There is usually accompanying infiltration of plasma cells, lymphocytes, and occasional epitheloid cells. (B614.10.w10)
      • "Dramatic papilliferous hyperplasia, with numerous developing and mature schizonts, gametocytes, and oocysts within epithelial cells." (B529.15.w15)
      • Enlarged bile ducts may contain purulent material. (J501.40.w1)
    • Some enlarged bile ducts end up rupturing and releasing their contents. This initiates a severe granulomatous response. (B614.10.w10)
    • Fibrosis is often a prominent feature of the lesions. (B614.10.w10)
    • The exudate is primarily made up of oocysts; there may also be some inflammatory cells. The oocysts may obstruct the biliary outflow resulting in a distended bile duct. Ischaemic necrosis can occur in the surrounding liver parenchyma due to compression of adjacent blood vessels by the bile duct enlargement; however, the hepatic cells themselves are not actually parasitised. (B614.10.w10)
    • The bile ducts are enlarged with the epithelium proliferated and thrown into numerous folds; the epithelium is filled with developmental stages of Eimeria steidai and there is huge infiltration of lymphocytes, plasma cells and eosinophils, with smaller numbers of neutrophils. In the ducts are desquamated epithelial cells together with gametogenous stages of the parasite and oocysts. (B24)
    • In rabbits which have survived such infection, fibrous tissue replaces much of the normal liver tissue. (B24)

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Human Health Considerations

None: the Eimeria sp. involved in hepatic disease in rabbits is host-specific. (B609.2.w2, B529.15.w15)

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Susceptibility / Transmission

General information on Susceptibility / Transmission

Transmission
  • Note: coccidial ooccysts are very resistant and can survive in the environment for several years. (B46)
Lagomorphs The severity of disease depends on:
  • The animal's immune status (including environmental stressors and age). (B600.10.w10, B609.2.w2)
  • The number of oocysts that are ingested. (B600.10.w10, B609.2.w2)
SUSCEPTIBILITY 
  • Age
    • Can occur in any age of rabbit. (B609.2.w2)
    • Weanling rabbits are most susceptible and therefore most commonly affected. (B600.10.w10)
  • Immunity
    • Natural lifelong immunity develops in the rabbit against each Eimeria species following exposure. The immunity is specific against a particular species of Eimeria so there is no cross protection against another Eimeria species that the rabbit may subsequently be exposed to. (B600.10.w10, B609.2.w2)
  • Predisposing factors:
    • Intensive, damp, dirty conditions. (B600.10.w10)
TRANSMISSION
  • Rabbits are infected by ingesting sporulated oocysts in food that has become contaminated by faeces. (B600.10.w10)
  • Infected rabbits contaminate the environment with oocysts of Eimeria spp. (B609.2.w2)
  • The environment can become heavily contaminated in intensive conditions. (B600.10.w10)
  • Oocysts need at least two days outside of the host for sporulation to occur and thus infectivity to develop, therefore recently passed faeces do not contain infective oocysts. (B600.10.w10)
  • Wild rabbits can be a potential source of infection to domestic rabbits that are allowed access to grass. Long grass that is hand picked is less likely to be contaminated with oocysts then short grass that is grazed by numerous wild rabbits. (B600.10.w10)
  • Oocysts are very resistant and will remain viable on vegetation, in soil and on fomites for long periods of time. (B600.10.w10)

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

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:

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

--

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

  • Eimeria stiedae is found worldwide. (B529.15.w15, B614.10.w10)

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

  • --

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General Investigation / Diagnosis

General Information on Investigation / Diagnosis

--
Lagomorphs
Physical Examination
CBC, BIOCHEMISTRY AND URINALYSIS
  • Increased liver enzymes (even mild increases may be significant). (B609.2.w2)
    • Raised ALT and alkaline phosphatase. (J29.9.w1)
    • AST, ALT, GGT, and alkaline phosphatase all may be raised. (B600.10.w10)
  • Increased bilirubin. (B609.2.w2)
    • In young rabbits this is virtually pathognomonic for hepatic coccidiosis, particularly if liver enzymes are raised also. (B600.10.w10)
  • Hypoalbuminaemia. This is seen with advanced liver disease, of whatever type. (B600.6.w6)
  • See: Clinical Pathology of Lagomorphs
IMAGING (Radiography) 
FAECAL CYTOLOGY
NECROPSY
  • Necropsy findings - enlarged liver with yellowish-white abscess-like nodules; often also a distended, enlarged gall bladder. (J29.9.w1)
  • Identify organisms during the post mortem examination.
    • Wet smears of bile may reveal oocysts. (B600.10.w10, J29.9.w1)
    • Impression smears taken from the cut surface of the liver or mesenteric lymph nodes may demonstrate several of the different schizont stages. (B600.10.w10)
    • Oocysts present on histological examination of the liver. (J29.9.w1)
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Similar Diseases (Differential Diagnosis)

--
Lagomorphs

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Treatment and Control

Specific Medical Treatment

 
Lagomorphs Note: Treatment of established disease in rabbit colonies using medication in the feed can be difficult because rabbits that are inappetant will not receive treatment. (B600.10.w10)
  • The aim of drug treatment is to control the infection while the rabbit develops immunity. (J29.9.w1)
  • Sulphonamides, e.g. sulphamerazine or sulphaquinoxaline, in drinking water at 0.02 - 0.2% or in feed at 0.03 - 1.0%. (B529.15.w15)
  • Sulphadimidene
    • 100 - 233 mg/L via the drinking water, for the treatment of rabbit colonies. (B600.10.w10)
  • Sulfadimethoxine
    • 50 mg/kg by oral administration for the first dose and then 25 mg/kg every 24 hours for ten to 14 (J29.5.w1) or 20 days. (B609.2.w2)
    • 15 mg/kg orally every 12 hours for ten days. (J29.9.w1)
  • Toltrazuril
    • 25 ppm in the drinking water for the treatment of rabbit colonies. (B600.10.w10, J32.22.w1)
    • Highly effective for reducing oocyst output. Two days of treatment repeated after five days is effective in reducing clinical signs and output of oocysts while allowing immunity to develop. (B600.10.w10, J32.22.w1)
    • 25 ppm in drinking water is equivalent to 2.5 mg/kg (assuming a water intake of 100 mL/kg/day); given orally by syringe as a single dose of 2.5 mg/kg it is effective in significantly reducing faecal oocyst counts. (P602.2009.w1)
  • Diclazuril
    • 4 mg/kg subcutaneously produced a significant reduction in shedding of oocysts and a significant reduction in the burden of oocysts in the liver. (J3.162.w1)
  • Trimethoprim/sulfamethoxazole
    • 30 mg/kg orally every twelve hours for 10 days. (B609.2.w2, J29.9.w1)
    • 40 mg/kg orally every twelve hours for seven days. (B600.10.w10)
      • "Co-trimoxazole" human formulation is available as a paediatric syrup. (B600.10.w10)
  • Monensin. (B529.15.w15)
  • Salinomycin. (B529.15.w15)
  • Note: Coccidiostats will only slow multiplication of the organisms (not kill the coccidia) until the host immunity develops. Adult rabbits with subclinical infections should develop natural immunity and therefore may not need medication. (B609.2.w2)
ALTERNATIVE DRUGS AGAINST COCCIDIA
  • Amprolium 9.6% in drinking water (0.5 ml per 500 ml). Note: this product is not consistently effective because the water consumption of the rabbits is variable. (B609.2.w2)
FOLLOW UP
  • Repeat the faecal examination for oocysts one to two weeks after treatment. (B609.2.w2)
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General Nursing and Surgical Techniques

 
Lagomorphs
APPROPRIATE LEVEL OF HEALTH CARE
  • Rabbits with mild disease can usually be treated as outpatients. 
  • Rabbits with moderate to severe disease will often require hospitalisation for parenteral medication and fluid therapy.

(B609.2.w2)

FLUID THERAPY 

Fluid therapy and correction of any electrolyte imbalances are an important part of treatment in most cases. (B609.2.w2)

  • Crystalloid fluid therapy:
    • Give subcutaneously, orally or intravenously as required. (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)
DIET
  • Note: hepatic coccidiosis interferes with vitamin metabolism, so a well balanced diet is required. (B600.10.w10)
  • 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. 
  • Offer the rabbit good quality grass hay and a decent selection of fresh greens. Note: in some rabbits, the addition of leafy greens can result in an exacerbation of the diarrhoea so for these animals only good quality hay should be offered. (B609.2.w2) See: 
  • To encourage oral fluid intake, offer fresh water, wet leafy vegetables or flavour the water with vegetable juice.
  • Syringe feeding is necessary if the rabbit is refusing to eat. 
  • Nasogastric intubation is indicated if the rabbit refuses sufficient volumes of food. 
  • Contraindications:
    • Avoid high carbohydrate or high fat nutritional supplements. (B609.2.w2)

(B609.2.w2)

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Preventative Measures

Vaccination --
Lagomorphs --
Prophylactic Treatment

--

Lagomorphs
  • Rabbit colonies are often fed on commercial pellets that contain a coccidiostat. This prevents clinical disease but allows mild infection and an immunological response, resulting in immunity. (B600.10.w10)
  • Sulfadimethoxine
    • 15 mg/kg orally every 12 hours for ten days. (J29.9.w1)
  • Toltrazuril
    • 25 ppm in the drinking water for the treatment of rabbit colonies. (B600.10.w10)
      • Highly effective for reducing oocyst output. Two days of treatment repeated after five days is effective to reduce clinical signs while allowing immunity to develop. (B600.10.w10)
    • 10 - 15 ppm in drinking water was highly effective in preventing clinical signs and macroscopic lesions, and reducing output of oocysts. (J32.22.w1)
  • Diclazuril
    • 1.0 - 4.0 mg/kg subcutaneously five days before experimental inoculation produced a significant reduction (P <0.05) in shedding of oocysts and a siginificant (P <0.05) reduction in the burden of oocysts in the liver. This, rather than a pharmacological agent which completely prevents infection, may assist in development of immunity. (J3.162.w1)
    • Diclazuril can be added to feed. (J3.162.w1)
    • Diclazuril at 1 ppm in feed effectively reduced oocyst output, allowed maintenance of normal weight gain and food efficiency and prevented development of liver lesions. (J32.32.w1)
  • Trimethoprim/sulfamethoxazole
    • 30 mg/kg orally every twelve hours for 10 days. (B609.2.w2, J29.9.w1)
  • Robenidine, at 66 ppm in the food, prevented infection following experimental inoculation. (J3.162.w1)
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Environmental and Population Control Measures

General Environment Changes, Cleaning and Disinfection --

Lagomorphs

  • Good hygiene. Sanitation is critical for the control of coccidiosis, especially within multirabbit homes or rabbit colonies. 
    • Hutches, cages or pens should be cleaned out regularly, preferably daily. (B24)
    • Cages, food bowls and water bottles need to be routinely disinfected preferably with a suitable detergent and hot water. (B609.2.w2, B614.10.w10, J501.40.w1)
    • Food should not be given on the floor. Food and water bowls/troughs should be in positions where they are unlikely to become contaminated by droppings. (B24, J29.9.w1)
    • 10% ammonia chloride is lethal to coccidial oocysts. (B614.10.w10)
  • Rabbits need to be prevented from having contact with food or water that is contaminated with infective faeces. (B614.10.w10)
  • Removal of faeces, thorough cleaning of cages, control of mechanical vectors such as flies. (B529.15.w15)
  • Flies and vermin should be controlled in rabbitries because they may act as mechanical vectors. (B614.10.w10)
Population Control Measures --
Lagomorphs --
Isolation, Quarantine and Screening --
Lagomorphs
  • Rabbits should be screened for the presence of oocysts in faeces; those that are shedding should be separated from young rabbits. (B609.2.w2)
  • Remove kits from infected dams as soon as possible. (B529.15.w15)
  • Strict barrier procedures are required to ensure rabbits are free of this coccidian. (B529.15.w15)
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