revised, August 2011.  

The information provided here is intended for educational purposes only and is not intended to substitute for a

veterinary consultation. Please, Please consult a professional practitioner

prior to the administration of the drugs listed in this article.

Various studies suggest that up to 80% of the healthy rabbit population carries the protozoa Encephalitozoon cuniculi in its body, without ever showing clinical symptoms of the disease and without development of the disease. There is limited knowledge about the biology and life cycle of E. cuniculi, and the mode of transmission is not yet fully understood. The primary method of transmission appears to be vertical, from mother to her litter, as opposed to the horizontal transmission via infected droppings and urine. It is possible that a rabbit may become infected later in life from an infected companion or from contaminated dirt. However, there are numerous examples where a rabbit with E. cuniculi has cohabited with a rabbit without E. cuniculi, without infecting the latter. The presence of Microsporidae parasites in mammals can lead to micronutrient/vitamin deficiencies, which may result in anemia. Unfortunately, there is a lack of specific information regarding E. cuniculi.

The protozoan parasite attacks the nervous system and major organs, causing a variety of clinical signs. These include torticollis (commonly called head tilt or wry neck), liver failure, kidney failure and calcification, incontinence, phacoclastic uveitis, cataracts, fore- or hindquarter paresis (one, or both sides), nystagmus (eye twitching), and/or other neurological symptoms. The rabbit is likely to succumb due to meningoencephalitis.

The various treatment options are aimed at eradicating the E. cuniculi protozoa, but they are ineffective against the spores. The death of protozoa will result in the surrounding tissues becoming inflamed. To reduce the inflammatory reaction, corticosteroids can be administered for three days in conjunction with fenbendazole. As the use of corticosteroids is controversial and should be avoided in rabbits, they can be replaced by NSAIDs (nonsteroidal anti-inflammatories), e.g., meloxicam (Metacam).

Commonly given treatment: Benzimidazoles

E. cuniculi is now routinely treated with benzimidazoles. While these drugs have successfully treated many rabbits, they may cause mild to moderate elevation of liver enzymes. Therefore, it is recommended that a blood test and biochemical parameter analysis be performed 14 days after treatment initiation.

The action of benzimidazoles is slow, and depends rather on their presence in the gastro-intestinal tract and the blood than on the concentration present. Benzimidazoles bind to the tubulin of the parasite, thereby blocking it. The formation of this dimeric tubulin protein results in the assembly of microtubules, which play important functional and structural roles in the parasites (transport of nutritive molecules, cell division). Benzimidazoles also block a certain parasite metabolism, such as the transport and uptake of glucose, without affecting the host (rabbit, cat, dog). The properties of the various benzimidazoles used to treat E. cuniculi vary.:

Albendazole is broken down in the liver into more hydrophilic products, which decreases its capacity to pass through the brain-blood barrier. However, the efficacy of the breakdown products against E. cuniculi remains to be elucidated. The use of albendazole, a drug not licensed for use in rabbits, has led to the sudden death of healthy rabbits or the appearance of bone marrow failure, although this has not been clinically tested.
In general, it was determined that albendazole was less effective than oxibendazole.

Oxibendazole is a rather lipophilic molecule that is not degraded in the body. Oxibendazole offers several advantages over albendazole, including its ability to cross the blood-brain barrier into the brain or central nervous system (CNS), its non-teratogenic properties in rabbits, and its resistance to degradation in the liver, unlike with albendazole. Research is needed to determine the extent to which oxibendazole is effective against E. cuniculi and the long-term side effects of this compound.

Fenbendazole was studied for its preventive and curing properties in rabbits affected by E. cuniculi and the results have been reported in a scientific journal (Veterinary Record, 2001, pp.478-480). This was a significant breakthrough, as it was the first treatment believed to cure the condition, rather than merely control it, and it was supported by scientific data. In addition, it was demonstrated that fenbendazole is capable of crossing the blood-brain barrier in mice when administered as a standalone treatment. In rare cases, long-term intake of fenbendazole has been associated with the onset of bone marrow failure, digestive problems, and anorexia. However, these findings have not been clinically investigated. After consultation with veterinarians who have treated a significant number of rabbits with fenbendazole, it was noted that no cases of bone marrow failure were observed in the treated rabbits given the correct doses over a 28-day period.

REMARK:

Fenbendazole remains currently the drug of choice for the treatment of E. cuniculi.

Laboratory rabbits have shown a high titer one year after being treated with fenbendazole, and upon autopsy, the presence of the parasite was observed in their brain. However, these rabbits were clinically asymptomatic.

However, there has been a notable increase in cases of rabbits treated with benzimidazoles relapsing during or after treatment. Recently, several caretakers who have been treating rabbits long-term with oxibendazole have reported that the treatment is gradually losing its effectiveness, as if the parasite is developing a resistance to it. It is possible for two different parasites to infect the rabbit, such as E. cuniculi and toxoplasmosis

Use of pyrimethamine ?

In "desperate cases," some alternative drugs are used, based on scientific literature or a veterinarian's experience, for rabbits facing euthanasia. The compounds that have been tested include lufenuron, pyrimethamine (used to treat toxoplasmosis in rabbits), and ponazuril combined with fenbendazole (5 days and 28 days, respectively). The results have shown varying degrees of success.

A treatment protocol for E. cuniculi was developed based on treatment against Sarcocystis sp. or Toxoplasma sp. in horses and cats, respectively, using the anti-protozoal drug pyrimethamine (Daraprim), associated with trimethoprim-sulfa coupled with non-steroidal anti-inflammatory. The treatment is administered over a period of one month in horses and two weeks in cats. It appears that the adverse effects are uncommon.

Although a previous study showed that pyrimethamine was ineffective against E. cuniculi at the studied concentrations of 5 and 20 mg/ml, the 50 mg/ml showed a 35% growth inhibition. Recent preliminary in-vivo tests have, however, shown that the growth of E. cuniculi spores was stopped in presence of therapeutic concentration of pyrimethamine (1 mg/kg).

In rabbits, pyrimethamine has been used to treat toxoplasmosis, Pneumocystis carinii, hepatic coccidial infection, etc. Studies have demonstrated the safety of pyrimethamine when administered at the appropriate dosage in rabbits. The anti-protozoal drug will directly attack the parasite, where it will both block the metabolism of folic acid in the parasite and increase the activity of trimethoprim-sulfa against the parasite.

This treatment is based on a protocol that has been successfully utilized in cats to address toxoplasmosis.