ISSN 2398-2969      



Synonym(s): E. cuniculi, Nosema cuniculi


  • CauseEncephalitozoon cuniculi Encephalitozoon cuniculi is a microsporidian obligate intracellular protozoan parasite that is shed as spores mainly in the urine of infected rabbits.
  • The significance of clinical disease caused by E. cuniculi (encephalitozoonosis) in pet rabbits is unknown due to widespread seroprevalence, extreme difficulty for a definitive diagnosis, difference between research and clinical reports, and little correlation between infection and many parameters of disease. In addition, much of the previously reported information deals with suspected cases without a proper definitive diagnosis. caa definitive diagnosis was not reached and affected animals could have been suffering from other disease(s).
  • Signs: neurological problems (head tilt is the most noticeable symptom) and ophthalmological problems (mainly unilateral phacoclastic uveitis with subsequent cataracts) are most commonly and consistently reported clinical signs. Urinary signs are also possible, but less important and frequent than neurological or ocular.
  • Diagnosis: ELISA, serum protein electrophoresis, PCR, biopsy, histopathology.
  • Treatment: fenbendazole.
  • Prognosis: prognosis is unknown due to the difficulty of properly diagnosing the disease. This means that many of the prognoses described may have not corresponded to actual cases of clinical encephalitozoonoses. Prognoses reported are very variable.

Print off the owner factsheets on Encephalitozoon cuniculi and Samples - how they help your vet to give to your clients.

  • Encephalitozoonosis is a complex disease that it is still far from being understood in pet rabbits.
  • The root of this uncertainty is multifactorial:
    • Many animals are seropositive without showing clinical signs.
    • Seropositive animals may demonstrate typical histopathological changes without showing clinical signs.
    • Histological lesions compatible with encephalitozoonosis have been found in seronegative rabbits.
    • The organism cannot always be demonstrated within these typical histopathological changes.
    • The organism has not fulfilled Koch’s postulates.
    • Seropositivity does not correlate well (or does not correlate at all) with clinical signs, life expectancy or urine:creatinine ratio.
    • Among seropositive animals, antibody titers are not correlated with spores in the brain, severity of symptoms or prognosis.
    • Overall, a seropositive animal with compatible clinical signs may not have the disease.
  • While many texts mention that it is a significant disease of domestic rabbits, up to now there is not enough evidence to suggest such statement. As many reported cases were actually suspected cases without a definitive diagnosis, care should be taken when drawing conclusions from these studies.
  • Arriving at a clinical diagnosis is not straightforward due to involvement of histopathology in the definitive diagnosis, inconsistent relationship between histological lesions and clinical signs, and inconsistent and unknown relationship between seropositivity and both clinical disease and histological lesions. In addition, the disease typically relates with neurological disease, and obtaining a biopsy from the central nervous system is extremely challenging.
  • Veterinarians need to understand the gaps of knowledge that are currently missing regarding clinical encephalitozoonosis in pet rabbits, together with the fact that newer/future research might bring light to the issue and might demonstrate that some classical beliefs are not accurate. In addition, conflicting results among studies mean that there are many gray areas prone to subjectivity and different interpretations.
  • Typically, the disease has been associated with neurological, ocular and renal disease. However, the significance of renal problems is debatable.
  • Encephalitozoon cuniculi has been found in rabbits, sheep, goats, pigs, dogs, cats, wildlife and people; it is therefore a zoonosis that has been most commonly reported in immune suppressed people.
  • Seroprevalence in the pet rabbit population is usually 25-85% depending on the area sampled and the technique used to detect antibodies. However, seroprevalence is low in wild rabbits and hares.
  • Young animals show lower seroprevalences than adult ones.

Presenting signs

  • Spores are released mainly in brain, kidney and eye, causing a granulomatous inflammation; therefore, the clinical signs described for this disease have been typically neurological, renal and ocular.
  • When Encephalitozoon affects the brain, a non-suppurative meningoencephalitis may be developed, causing a variety of neurological clinical signs, including changes in behavior, mental dullness, head tilt Head tilt (the most typical or easily detected clinical sign ), nystagmus, tremors, convulsions, blindness, rear limb paralysis/paresis or abnormal gait:
    • Severity of neurological signs do not correlate with severity of lesions in CNS. The fact that owners and veterinarians are more likely to identify head tilt does not mean that head tilt is the main neurological sign in rabbits. Other signs may be more compatible with histological lesions, eg changes of mentation, but may be more difficult to detect by owners.
    • Peripheral vestibular disease does not occur in cases of encephalitozoonosis.
  • In the eye, the disease causes a phacoclastic uveitis, that eventually causes lens rupture and cataracts. Unilateral phacoclastic uveitis is more significantly correlated with encephalitozoonosis than neurological disease.
  • When the parasite affects the kidney, urinary incontinence Urinary incontinence or kidney failure Kidney: renal failure may be seen:
    • However, it is unknown the incidence of significant renal dysfunction in cases of encephalitozoonosis.
    • Rabbits showing just renal dysfunction may be unlikely to be suffering from clinical encephalitozoonosis.
    • It is likely that renal problems (generally not severe) are only noted once severe neurological or ocular disease has been detected.
  • Involvement of liver, lungs and heart can also occur.
  • Overall, when considering clinical signs, one should take into consideration that part of these clinical signs have been described in animals without a definitive diagnosis of encephalitozoonosis.
  • In addition, as infection with E. cuniculi suppresses both humoral and cell-mediated immunity, seropositive animals are more likely to become unwell from any cause.

Acute presentation

  • Head tilt Head tilt, collapse, paralysis, hindlimb paresis Paresis / paralysis: limb .
  • The presentation of head tilt (either acute or more chronic) does not seem to be different from the that in cases of internal otitis Otitis media/interna .
  • Acute presentation of some signs such as head tilt may be accompanied with previous gradual development of brain lesions and less evident neurological problems, eg mental dullness. These problems are not usually detected by the owner.

Geographic incidence

  • Not enough information to suggest a clear difference in seroprevalence depending on the country or region.

Age predisposition

  • Young rabbits more often affected.

Gender predisposition

  • None detected.

Breed predisposition

  • It seems that head tilt is more likely to be caused by encephalitozoonosis in dwarf breeds Netherland Dwarf; while the same presentation is more likely to be caused by internal otitis in lop-eared breeds English Lop.

Public health considerations

  • E. cuniculi is a zoonosis.
  • Disease in people has been more commonly associated with immune suppression.


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Further Reading


Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Latney L V, Bradley C W & Wyre N R (2014) Encephalitozoon cuniculi in pet rabbits: diagnosis and optimal management. Vet Med Res Report 5, 169-180 PubMed.
  • Varga M (2014) Questions around Encephalitozoon cuniculi in rabbits. Vet Rec 174 (14), 347-348 PubMed.
  • Graham J E, Garner M M & Reavill D R (2014) Benzimidazole toxicosis in rabbits: 13 cases (2003 to 2011). J Exotic Pet Med 23 (2), 188-195 SciDirect.
  • Hein J, Flock U, Sauter-Louis C et al (2014) Encephalitozoon cuniculi in rabbits in Germany: prevalence and sensitivity of antibody testing. Vet Rec 174 (14), 350 PubMed.
  • Richardson V (2012) Urogenital diseases in rabbits. In Pract 34 (10), 554-563 VetMedResource.
  • Sieg J, Hein J, Jass A et al (2012) Clinical evaluation of therapeutic success in rabbit with suspected encephalitozoonosis. Vet Parasitol 187 (1-2), 328-332 PubMed.
  • Wright I (2011) Encephalitozoon cuniculi: Infecting the rabbit next door. UK Vet: Companion Animal 16, 49-50 VetMedResource
  • Keeble E (2011) Companion animal practice: Encephalitozoonosis in rabbits - what we do and don't know. In Pract 33 (9), 428-435 VetMedResource.
  • Csokai J, Gruber A, Künzel F et al (2009) Encephalitozoonosis in pet rabbits (Oryctolagus cuniculus): pathohistological findings in animals with latent infection versus clinical manifestation. Parasitol Res 104 (3), 629-635 PubMed.
  • Reusch B, Murray J K, Papasouliotis K et al (2009) Urinary protein:creatinine ratio in rabbits in relation to their serological status to Encephalitozoon cuniculi. Vet Rec 164 (10), 293-295 PubMed.
  • Jass A, Matiasek K, Henke J et al (2008) Analysis of cerebrospinal fluid in healthy rabbits and rabbits with clinically suspected encephalitozoonosis. Vet Rec 162 (19), 618-622 PubMed.
  • Keeble E (2006) Common neurological and musculoskeletal problems in rabbits. In Pract 28 (4), 212-218 VetMedResource.
  • Harcourt-Brown F M & Holloway H K (2003) Encephalitozoon cuniculi in pet rabbits. Vet Rec 152 (14), 427-431 PubMed.
  • Suter C, Müller-Doblies U U, Hatt J M et al (2001) Prevention and treatment of Encephalitozoon cuniculi infection in rabbits with fenbendazole. Vet Rec 148 (15), 478-480 PubMed.
  • Boot R, Hansen A K, Hansen C K et al (2000) Comparison of assays for antibodies to Encephalitozoon cuniculi in rabbits. Lab Anim 34 (3), 281-289 PubMed.
  • Feaga W P (1997) Wry neck in rabbits. JAVMA 210 (4), 480 PubMed.
  • Levkut M, Horváth M, Bálent P et al (1997) Catecholamines and encephalitozoonosis in rabbits. Vet Parasitol 73 (1-2), 173-176 PubMed.
  • Stiles J, Didier E, Ritchie B et al (1997) Encephalitozoon cuniculi in the lens of a rabbit with phacoclastic uveitis - confirmation and treatment. Vet Comp Ophthalmol (4), 233-238 VetMedResource.
  • Thomas C, Finn M, Twigg L et al (1997) Microsporidia (Encephalitozoon cuniculi) in wild rabbits in Australia. Austr Vet J 75 (11), 808-810 PubMed.
  • Nast R, Middleton D M & Wheler C L (1996) Generalized encephalitozoonosis in a Jersey wooly rabbit. Can Vet J 37 (5), 303-305 PubMed.
  • Hillyer E V (1994) Pet rabbits. Vet Clin North Am Small Anim Pract 24 (1), 25-65 PubMed.
  • Wesonga H O & Munda M (1992) Rabbit encephalitozoonosis in Kenya. Lab Anim 26 (3), 219-221 PubMed.
  • Greenstein G, Drozdowicz C K, Garcia F G et al (1991) The incidence of Encephalitozoon cuniculi in a commercial barrier-maintained rabbit breeding colony. Lab Anim 25 (4), 287-290 PubMed.
  • Kunstyr I & Naumann S (1985) Head tilt in rabbits caused by pasteurellosis and encephalitozoonosis. Lab Anim 19 (3), 208-213 PubMed.
  • Cox J C & Ross J (1980) A serological survey of Encephalitozoon cuniculi infection in the wild rabbit in England and Scotland. Res Vet Sci 28 (3), 396 PubMed.
  • Gannon J (1980) A survey of Encephalitozoon cuniculi in laboratory animal colonies in the United Kingdom. Lab Anim 14 (2), 91-94 PubMed.
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