It seems, lately, that if anyone knows anything about rabbit diseases, the first thing after dental disease seems to be Encephalitozoon cuniculi and the need for routine treatment with fenbendazole. This, hopefully, thought-provoking lecture seeks to examine what evidence we have for that idea and where current investigations are heading.

Encephalitozoon cuniculi is an infection of the central nervous system, eyes and kidneys of rabbits and is a cause of central nervous system lesions, lens rupture and uveitis, and renal failure in rabbits. The rabbit is infected by ingestion of spores. General clinical symptoms of the disease are characterised by head tilt, circling, falling over, hindlimb paresis, urinary incontinence and renal failure. Various rates of infection of UK pet rabbits have been supposedly based upon serological testing; 27% of pet rabbits were found to be seropositive for E. cuniculi in a 2009 study in southwest England, which is much lower than the seroprevalence of 52% from 2003 in Scotland, although similar to the 23% of clinically healthy rabbits sampled at a veterinary practice in North Yorkshire in 2003.

Since the publication of the earlier papers on prevalence of serological positives in UK pet rabbits, there has been a vast increase in rabbits being tested and treated for disease in clinical practice. There is little scientific evidence that a serological positive test equates to clinical disease, specifically the 'head tilt' rabbit commonly seen in practice, nor is there more than one published paper describing treatment of this condition. An understanding of the disease, that it is primarily a renal parasite, would lead one to conclude that a serologically positive rabbit would have renal compromise, eventually. Whether or not the parasite migrates to the central nervous system (CNS) is perhaps 'random' but seems to occur consistently in experimentally infected rabbits. Nevertheless, a study investigating whether renal function was clinically impaired in serologically positive rabbits did not find a correlation between serological status and urine protein:creatinine ratios. This begs the question as to whether many of these serological positives are clinically silent or even whether the test currently being used is useful.

Anecdotally, serological titres are reported to decline, and shedding of organisms cease, following treatment. However, this has not been fully investigated. As to whether serological status indicates infection or mere exposure to the disease; there is little research to offer an answer. A polymerase chain reaction (PCR), available in the UK, should detect active shedding of the organism and given the nature of the paradise, positives detected in the urine should indicate active infection. The organism is not shed in the faeces and PCR tests are notoriously unreliable on faeces so sampling of the droppings should be undertaken with caution, or avoided in the author's opinion.

There are two oral fenbendazole products currently marketed in the UK for use in the rabbit for E. cuniculi treatment/prevention. Regimes on the datasheet state courses of for 9 days as prophylactic use and 28 days for treatment. Data on the use of fenbendazole, for both treatment and prophylaxis, are scarce in the literature, with anecdotal usage protocols existing, suggesting short courses repeated frequently to control infection in multi-rabbit households or longer one-off courses of up to 42 days being advocated by some sources. The doses used (20 mg/kg) are also based largely on just one published paper which experimentally infected rabbits and started treatment within days and for 28 days. This is unlikely to be the same timeframe of infection to treatment in clinically infected pet rabbits.

In the absence of a number of studies on this topic, it is clear that there is some uncertainty as to required duration, dose and frequency of fenbendazole for treating E. cuniculi. Treating large numbers of rabbits, in rescue or breeding centres, or those rabbits who do not readily take oral medications, for long courses (e.g., 28 days) can prove challenging.

Whilst there are well documented reports of benzimidazole toxicity in avian species and tortoises, and anecdotal concerns have been raised regarding its use in rabbits, there are no confirmed cases of toxicity problems in rabbits in the literature at the time of writing. Signs of toxicity in birds are related to the damage to the rapidly dividing cells of the small intestine, renal tubules and bone marrow leading to acute, even fatal, diarrhoea and dehydration or death from secondary disease due to the profound immunosuppression resulting from toxicity.

References

1.  Harcourt-Brown FM, Holloway HK. Encephalitozoon cuniculi in pet rabbits. Veterinary Record 2003;152(14):427–431.

2.  Howard LL, Papendick R, et al. Fenbendazole and albendazole toxicity in pigeons and doves. Journal of Avian Medicine and Surgery 2002;16(3):203–210.

3.  Jass A, Matiasek K, et al. Analysis of cerebrospinal fluid in healthy rabbits and rabbits with clinically suspected encephalitozoonosis. Veterinary Record 2008;162(19):618–622.

4.  Keeble EJ, Shaw DJ. Seroprevalence of antibodies to Encephalitozoon cuniculi in domestic rabbits in the United Kingdom. Veterinary Record 2006;158:539–544.

5.  Reusch B, Murray JK, et al. Urinary protein:creatinine ratio in rabbits in relation to their serological status to Encephalitozoon cuniculi. Veterinary Record 2009;64:293–295.