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Rabbits and Encephalitozoon cuniculi: what's new?

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01 August 2010, at 12:00am

This common parasite, microsporidium, is spread in urine and affects primarily the nervous system and kidneys (see Figure 1). Hind limb weakness and paralysis is a result of the inflammation surrounding the parasite causing destruction of the nervous tissue. 

Other signs commonly seen with this disease include a head tilt, seizuring, and loss of balance, tremors, renal failure and bladder weakness. Unfortunately, once the rabbit develops severe clinical signs this can lead to death. 

Encephalitozoon cuniculi primarily infects and causes significant disease in rabbits, but may also be found in other mammals including rodents, guinea pigs, foxes, cats, dogs, monkeys, goats, pigs, llamas and snakes (Shadduck and others, 1979; Pang and Shadduck, 1985; Illanes and others, 1993; Lobo and others, 2003). 

Three strains of E. cuniculi have been identified (Didier and others, 1995). 

  • Strain I = rabbit strain, also found in humans;
  • Strain II = rodent strain; and 
  • Strain III = dog strain, also found in humans. 

It is potentially zoonotic and has been associated with infections in immuno-compromised people. Infection has been diagnosed in rabbits in Europe, Africa, America and Australia. Good hygiene practices should reduce the risks of human infection from spores shed in the rabbit’s urine. 

Diagnostic investigation 

Diagnostic investigation of the disease should include a thorough history, clinical examination and a full neurological examination to enable the lesions to be localised, monitoring of progression and prognosis (see Figure 2). 

A urine sample may be collected for full urinalysis to rule out other causes of polyuria and a urine protein to creatinine ratio will help evaluate renal function (reference range 0.38, (Reusch, Murray, Papasouliotis and Redrobe, 2009). Blood samples may be taken for serum biochemistry to evaluate kidney function and rule out other disease, routine haematology to assess immune system and rule out other disease. 

Urine can be submitted for PCR detection of parasite shedding; as far as we know shedding only occurs in the one to three months following infection (Cox and others, 1979) (see Figure 3). 

A blood sample can be taken and submitted for serology for E. cuniculi antibodies. This will measure IgG antibodies that are produced by the rabbit if it has been exposed to the disease at some stage in its life. Serology for E. cuniculi antibodies is not useful in the short-term diagnosis, but raising titres can be suggestive of current infection. However, care must be taken with interpreting the results as 52% of healthy pet rabbits were found to be seropositive in the UK (Keeble & Shaw, 2006). 

More information indicating the stage of infection and immune response can be obtained by taking two blood samples one month apart. If the antibody levels to E. cuniculi are falling, this suggests that a recent history of infection or a possible flare-up of an existing E. cuniculi infection has occurred. 

Rising antibody levels between the two blood samples is more suggestive of a current active infection or a possible flare-up of the existing infection. However, if the antibody levels are the same at the first and second blood sample, it is difficult to conclude too much. The severity of the clinical signs does not appear to be related to how high antibody levels are in the blood (Kunstyr and others, 1986). 

Kidney and/or liver biopsy may be very useful in the diagnosis and management of the disease (Csokai, Gruber, Kunzel, Tichy and Joachim, 2009). Biopsies can be obtained by laproscopic surgery or laparotomy. 

Treatment and prognosis 

As we learn more about how this parasite affects the body, how the immune system can deal with it and in some cases fully recover, we will be able to interpret the clinical signs, results, give appropriate treatment, assess response to treatment and advise on prognosis based on scientific evidence. 

Several factors are likely to be involved in the development of clinical disease or recovery from infection including: the parasite species and strain, the route of infection, the age of the rabbit at the time of the infection and the rabbit’s immune status (Weber and others, 1994). 

Disease is more likely in immunodeficient rabbits, or young and newborn animals with immature immune systems (Didier and others, 2000). In rabbits with a healthy immune system, clinically silent chronic infection may develop. Concurrent infection, stress or immuno-suppression may then lead to the development of clinical disease. 

Rabbits with renal disease tend to have a worse prognosis than those with uveitus or neurological signs (Kuunzel et al., 2008). 

There is no specific treatment that will reverse the damage caused by the presence of the parasite. Medication [fenbendazole (Lapizole 20mg/kg PO q24h for 28 days)] can slow or halt the rate of multiplication of the E. cuniculi parasite with in the body (Suter, MüllerDoblies, Hatt and Deplazes, 2001). 

Rabbits with uveitus should be treated with topical steroid eye drops and where secondary glaucoma develops this should also be managed. Fenbendazole treatment should also be given. In most cases the eye can be saved with early and aggressive treatment; where this fails an enucleation may be indicated. 

Early use of steroids may help reduce the inflammation caused by the presence of the parasite and increase recovery rates from neurological signs, although some recover with time. Care needs to be taken with steroid use in rabbits as this causes severe immunospuression. 

Supportive care should be provided for all rabbits with urine scalding due to renal or neurological disease (see Figure 4). Supportive nutrition may also be required. Benazepril hydrochloride, an ACE inhibitor, has also been shown, in a preliminary study, to decrease proteinuria and reduce azotaemia, indicating improved renal function in rabbits. Further work is being carried out into ensuring safe dosages, currently a dose of <0.1mg/kg orally once daily is recommended, as evidence suggests rabbits may be highly sensitive to the hypotensive effects of benazepril (Girling, 2003). The author has found this dose to be very effective at reducing the proteinuria. 

Regular monitoring of blood pressure, serum creatinine, urea and electrolytes is strongly recommended with ACE inhibitor treatment in rabbits. In some cases glomerular filtration rate is dependent on hypertension and treatment with ACE inhibitors can be associated with an increase in azotaemia; this and hypotension, or hyperkalaemia, are all indications to stop or reduce ACE inhibitor treatment in rabbits. 

Prevention 

Prevent transmission by reducing environmental contamination. The parasite can be easily removed with thorough disinfection. 

The following common disinfectants have been found to be very effective: bleach requires more than seven minutes contact time to be lethal to E. cuniculi whereas a dilution of 1-10% bleach requires only 30 seconds to render the parasite non-infectious; the routine use of 70% ethanol following the cleaning up of rabbit urine in the veterinary surgery, rescue centres, pet shops and rabbit shows will help reduce cross-contamination as it only requires 30 seconds to render the parasite non-infectious (Waller, 1979). 

  • Reduce mixing of rabbits in pet shops, rescue homes and breeding establishments.
  • Prophylactic treatment with fenbendazole (Lapizole) is currently recommended. 

References 

Csokai, J., Gruber, A., Kunzel, F., Tichy, A. and Joachim, A. (2009) Encephalitozoonosis in pet rabbits (Oryctolagus cuniculus): Pathohistological findings in animals with latent infection versus clinical manifestation. Parasitology Research 104 (3): 629-635. 

Didier, E. S., Vossbrinck, C. R., Baker, M. D., Rogers, L. B., Bertucci, D. C. and Shadduck, J. A. (1995) Identification and characterisation of three Encephalitozoon cuniculi strains. Parasitology 111: 411-21. 

Girling, S. J. (2003) Preliminary study into the possible use of benazepril on the management of renal disease in rabbits. Paper presented at the British Veterinary Zoological Society Proceedings: Infectious diseases of exotics, Edinburgh Zoo. Illanes, O. G, Tiffani-Castiglioni, E., Edwards, J. F. and Shadduck, J. A. (1993) Spontaneous encephalitozoonosis in an experimental group of guinea pigs. Journal of Veterinary Diagnostic Investigation 5: 649651. 

Keeble, E. J. and Shaw, D. J. (2006) Seroprevalence of antibodies to Encephalitozoon cuniculi in domestic rabbits in the United Kingdom. Veterinary Record 158: 539-544. 

Kunstyr, I., Lev, L. and Naumann, S. (1986) Humoral antibody response of rabbits to experimental infection with Encephalitozoon cuniculi. Veterinary Parasitology 21: 223-232. 

Kuunzel, F., Gruber, A., Tichy, A., Edelhofer, R., Nell, B., Hassan, J., Leschnik, M., Thalhammer, J. G. and Joachim, A. (2008) Clinical symptoms and diagnosis of encephalitozoonosis in pet rabbits. Veterinary Parasitology 151 (2-4): 115-124. 

Lobo, M., Teles, A., Barao Da Cunha, M., Henriques, J., Mafalda Lourenco, A., Antunes, F. and Matos, O. (2003) Microsporidia detection in stools from pets and animals from the zoo in Portugal: A preliminary study. Journal of Eukaryotic Microbiology, 581-582 

Pang, V. F. and Shadduck, J. A. (1985) Susceptibility of cats, sheep and swine to a rabbit isolate of Encephalitozoon cuniculi. American Journal of Veterinary Research 46:
1,071-1,077. 

Reusch, B., Murray, J.  K., Papasouliotis, K. and Redrobe, S. P. (2009) Urinary protein:creatinine ratio in rabbits in relation to their serological status to Encephalitozoon cuniculi. Veterinary Record 164 (10): 293-295. 

Shadduck, J. A., Watson, W. T., Pakes, S. P. and Cali, A. (1979) Animal infectivity of Encephalitozoon cuniculi.J. Parasitol. 65: 123129. 

Suter, C., Müller-Doblies, U. U., Hatt, J.M. and Deplazes, P. (2001) Prevention and treatment of Encephalitozoon cunicui infection in rabbits with fenbendazole. Veterinary Record 148: 478480. 

Waller, T. (1979) Sensitivity of Encephalitozoon cuniculi to various temperatures, disinfectants and drugs. Laboratory Animal Science 13: 227-230.