Encephalitozoon cuniculi

E.cuniculi is an obligate, intracellular, microsporidian parasite which infects many animals, including rabbits. It’s transmitted in utero and via the ingestion of infective spores shed in the urine, which enter the gut, then spread via the blood to the liver, lungs, heart, kidneys and brain. Disease is more likely in immunodeficient or young animals with immature immune systems, whilst animals with a healthy immune system may go on to develop a silent chronic infection. Rabbits with renal disease tend to have a worse prognosis than those with uveitis or neurological signs.

Posted: 12 August 2019

Encephalitozoon cuniculi


E.cuniculi – 3 presentations and clinical signs

Although most rabbits with E.cuniculi are asymptomatic, clinical disease is usually diagnosed when the central nervous system, eyes or kidneys are affected, either alone or in combination.

A. Neurological changes generally appear with vestibular and CNS signs such as;

  • Head tilt and torticollis – usually the head is held on one side in an odd way
  • Muscle spasms – the neck in particular can show a twisting appearance
  • Incoordination – many animals become wobbly and weak. They may even appear collapsed or paralysed
  • Nystagmus - horizontal nystagmus may indicate peripheral or central damage. Vertical nystagmus is always associated with CNS disease
  • Posterior paresis – the rabbit may find it difficult to stand, walk and jump. Proprioception may be delayed or absent
  • Circling, rolling and flipping
  • Head tremors
  • Seizures

B. Ocular disease – inflammation within the eye and cataracts are common. Ocular changes are generally only seen in young rabbits, when inflammatory cells infiltrate the lens. The lens capsule may eventually rupture causing uveitis, which appears as a white mass within the eye. Cataracts and uveitis can be either unilateral or bilateral.

C. Renal disease – the rabbit may drink more, urinate more and show evidence of weight loss. In cases where the kidneys are infected, the nephritis and renal disease may present with non-specific signs such as;

  • Anorexia – check if the rabbit is eating. Weigh the food and quantify the intake
  • Dehydration – check mucous membranes, skin tenting and body weight
  • Polyuria – an owner may comment on an increase in the frequency of litter tray changes
  • Polydipsia – it makes sense to measure the volume of water offered and consumed
  • Lethargy – changes in behaviour and interest are frequently altered
  • Incontinence – look for dribbling urine, wet fur around the back end or scalding of the skin

Making a diagnosis

As a clinician it can often be frustrating to diagnose E.cuniculi. The clinical signs are generally the clue, and you should always be more suspicious if the animal is stressed or immunocompromised. Clinical investigations would include;

  1. Haematology and biochemistry - patients with nephritis may develop changes consistent with chronic renal failure including azotaemia and anaemia.
  2. Serology – this is the most important diagnostic tool for diagnosis of E.cuniculi infection in the living animal. Both enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) are used. Some take home points of serology testing for E.cuniculi are;
    • A positive antibody titre does not necessarily indicate active or recent infection
    • The health status of the patient must be considered when assessing the serology results
    • A positive titre in a healthy animal only indicates exposure to the organism
    • Many seropositive rabbits are asymptomatic
    • Paired, rising titres should make you more suspicious of active E.cuniculi infection
    • Seronegative cases should be retested in 4 weeks in case the patient was recently infected and has not yet mounted an immune response
    • A rabbit will remain seropositive for life once infected
  3. PCR - no special medium is required for polymerase chain reaction (PCR) tests. A sample of urine, CSF or faeces can be submitted to specialist laboratories. Since E.cuniculi can be intermittently shed, a 3-day pooled sample should be taken. A positive result is conclusive of infection but not necessarily disease. Be aware that localised infections may produce negative results if a non-infected tissue is sampled.
  4. Radiology - skull radiographs can be offered to rule-out otitis media/interna.
  5. CT/MRI scan – for those clients who have sufficient funds, a computed tomography (CT) or magnetic resonance imaging (MRI) may be indicated to check for middle ear disease and CNS pathology

What treatment is available?

Treatment for E.cuniculi is not always successful but can result in improvement in some cases. Most treatment protocols include anti-protozoal drugs, anti-inflammatory agents, together with symptomatic treatment for vestibular disease.

  • Fenbendazole (20 mg/kg PO q24h x 28 days) – a small study by Suter et al has described the eradication of E.cuniculi organisms in rabbits treated with this dose.
  • Both corticosteroids and NSAID’s have been used, however the use of corticosteroids in rabbits with E.cuniculi is controversial.
  • Medical management of uveitis with topical dexamethasone has been used.
  • Phacoemulsification to remove the lens is the treatment of choice for phacoclastic uveitis.

As a general rule, rabbits that continue to eat voluntarily have a good chance of survival, but a poor response to treatment generally leads to euthanasia.

Transmission and prevention

E.cuniculi infection can be spread vertically or horizontally. Horizontal spread is by the ingestion of food which has been contaminated with infected urine. The source of infection may be contaminated enclosures or ingestion of food that has been contaminated with a companion’s urine. Vertical spread occurs in utero, when spores in an infected mother pass into the lens of a developing embryo.

The spores are also very resistant and can survive for several weeks in the environment. The key to minimizing the spread of the disease is to ensure everything is kept meticulously clean. It’s essential to always provide fresh water and food, and to keep the rabbit’s living area scrupulously clean. In your own clinical environment, there are some important ways to ensure that your practice doesn’t contribute to the spread of this parasite.

  • Be meticulous with cleaning – food bowls, water bowls, litter trays, cages and enclosures must be thoroughly cleaned between patients
  • Don’t allow sharing – resist the temptation to allow rabbits to occupy the same exercise run
  • Avoid areas that can’t be cleaned – outside garden runs in the clinic shouldn’t be used as they are impossible to clean
  • Be aware of urine leakage – rabbits housed in the typical hospital environment with one cage above another could potentially allow urine to dribble down to the lower cage