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Encephalitozoon Cuniculi
A talk given by Molly Varga from Ashleigh Veterinary Practice 26 June 2003


What is E-Cuniculi?
E-Cuniculi was theorised (recognised as a disease) in 1922.
E-Cuniculi is a parasite - a small protozoan that lives inside the body cells of its host.
It multiplies within the cells, eventually causing the cell to burst, which then enable it to spread to adjacent cells.
The multiplication of organism within the rabbit will cause the rabbit to develop granulomas. (balls of cells in it’s organ)
It is thought to travel through the body via white blood cells.
It heads for places in the body with high blood flow - ie brain, kidney etc. It can only be expelled if it is in the kidney. This is via urine.

E-Cuniculi and Humans
It can affect some humans too, more commonly people with compromised immune systems such as people suffering from aids, young children and the elderly. Human sufferers liken the symptoms to a severe hangover.

How is it transferred?
There are 4 ways E-Cuniculi can be passed:
1. Spores in the urine
2. Orally - an animal eats contaminated material (ie hay)
3. Parent to child - via the placenta or milk
4. Inhaled - the organism can become airborne

Mice are a major carrier of E-Cuniculi, be extra careful if keeping food/hay etc. in a garage or shed where mice may have access.

E-Cuniculi in the Environment
There is no definitive way to kill e-cuniculi spores in the environment but a strong disinfectant containing ammonia - Virkon, ARK Cleanse or 1/30 bleach solution is recommended.
Also extremes of heat or cold may kill spores.
Once school of thought is that the spores may last longer if the rabbit lives indoors as the environment is more favourable for the organism. A longer treatment time for Panacur is often recommended because of this.

Incubation and Time Scales
From infection there is a 30-day incubation period
The infected rabbit will shed spores for 90 days after this
After treatment, the rabbit will still shed spores for another 30 days
The total active infection time is approximately 5 months from start to finish.

Spore Pattern

30 days 90 days 30 days
Infected Shedding still spores present

It is not known if this pattern changes (increases/decreases) depending on the environment.
Areas Most Commonly Affected
The areas affected are the Brain, Kidneys, Liver and Eyes.

Brain:
NEUROLOGICAL
The signs your rabbit shows will depend on which structure between the brain and the spinal cord is affected.

Clinical Signs:
· Changes in Behaviour
· Seizures
· Depression
· Facial weakness
· Paralysis
· Weakness In one limb
· Weak or paralysed hind limbs
· Quadriplegia
· Head tilt
· Loss of appetite
Diagnosis by: Blood Tests, E-cuniculi titres, check teeth, check for middle ear infection
(Head tilt) and X-rays
BUT the organisms don’t always show up in X-rays a MIR scan is better but they are very expensive (MIR scans done in Yorkshire but cost £1000)

Kidney
(If the Kidneys are infected the bunny will shed spores in it’s urine.)
This is a long-term change - The rabbit will lose 66% of kidney function before you notice.
Clinical signs:
· Drinking excessively
· Loss of litter training (urinating)
· Reduced appetite
· Weakness
· Depression
The rabbit could have already had the illness for months/years before it becomes apparent,
At this time it will start to excrete spores.
Your vet would run Diagnostic tests - Blood Tests, Urine Tests & e-cuniculi Titres.

Eye
OCULAR
The foetus is infected at birth. This is not particularly common.
Clinical Signs:
· Inflammation of the eye, leading to blindness
The organisms multiply in the eye eventually rupturing it.
Treatment - Unfortunately the prognosis is poor and often the best treatment is to remove the eye.


Diagnosing E-Cuniculi
Titres

Current blood titres only look for the presence of E-Cuniculi antibodies within the rabbits’ bloodstream. This will not prove that the symptoms being shown by the rabbit are directly related to E-Cuniculi, only that the rabbit has been exposed to E-Cuniculi at some point in its life.

Medilab (Cheshire, UK) - have (very*) recently developed tests that are quantitive. This means the amount of antibody in the bloodstream can be determined. how much of the antibodies are being produced by the rabbit.
It is now recommended that the rabbit is tested twice.
One test should be carried out when symptoms are first shown and then again at the end of the course of treatment (approx 30 days later.)
If the rabbit has a lower titre at the first test and but higher at the second test, this would indicate that the rabbit’s immune system is fighting it because it is producing more antibodies.
If the titre is lower at the second test than the first, this can indicate that the E-Cuniculi has been fought but the rabbits’ immune systems is still providing protection

*June 2003 (This form of testing can only be used to test new cases, as old cases wouldn’t have levels of antibody readings to compare)

America and E-Cuniculi

“I would be reluctant to use an unproven medication at a dose picked out of a hat for a disease we don’t know exists”
Karen Rosenthal (U.S. rabbit savvy vet)

A study done in America showed that 80% of rabbits had positive E-cuniculi titres.
It is not felt that there is enough evidence to justify treating a rabbit because tests simply show it has been exposed to e-cuniculi at some point in it’s life. This was the theory prior to quantitive testing.

Treatments
· No medication: studies have shown that rabbits still recover in the same time if they
receive no medication.
· Support Care : treat individual symptoms. i.e. Head Tilt

The UK is more convinced and will treat E-Cuniculi.


Possible Treatments of E-Cuniculi

Steroids not used by Ashleigh vets as they can affect a rabbit’s immune system leaving it open to other infections.
ie a bunny treated with steroids may develop Pasteurella, which was previously held at bay by the rabbit’s immune system.


Wormers These are used to treat the E-Cuniculi itself, not any symptoms.
Oxibendazole not safe, has serious side effects, difficult to get hold of in the UK
Albendazole not available any more
Fenbedazole (Panacur) Clears infection, and can also be used to treat any other rabbits living with the E-Cuniculi positive rabbit

OverView of E-Cuniculi
(Problems/ Dilemmas)

There is still a lot of research that needs to be done as E-Cuniculi is still very much an unknown quantity.

There is no actual proof that E-Cuniculi causes disease.

E-Cuniculi is often blamed for symptoms that are actually caused by middle ear disease or teeth problems.
It can contribute to symptoms but is not always the sole cause

E-cuniculi cells have not been found in neurological cases - i.e. post mortems of brain have revealed no E-Cuniculi spores.

The info that we have on E-cuniculi is from studies done on farmed rabbits whose life expectancy was only 2 years we need new updated studies as pet rabbits are living longer lives.

We don’t know if the rabbits response is the best way to fight it - increasing it’s antibodies to fight the organisms - we may be doing harm by administering the drugs (hence the American view)

The fact that rabbit’s live indoors could now be a contributing factor to the spread of E-Cuniculi, as rabbits normally live outdoors the cold temperature may have previously killed the spores.

E-Cuniculi is incurable but once treated the rabbit should stop shedding spores, in these circumstances it wouldn’t be fair to keep a rabbit without a partner however if the rabbit’s immune system becomes compromised in the future the spores may again be shed.

Studies need to be done on whether E-cuniculi can be passed onto humans via the rabbit or what the risks are i.e. if pregnant.

The rabbit will only show clinical signs of E-Cuniculi 30 days after it has been infected.

Only 12% of infected rabbits show clinical signs of E-Cuniculi after being infected.

The vast majority of rabbits never suffer any ill effects from it.

This could depend on how strong the rabbit’s genetics and immune system is at the time of infection.
It is only when the rabbit’s immune system is failing to cope with e-cuniculi that it’s symptoms become apparent to us.

Current titres only evaluate part of the immune system.

There is a possibility that the damage done to the rabbits organs may be due to the rabbits immune system’s response to a non-threatening pathogen

THE FUTURE

The future treatment of E-Cuniculi will concentrate on trying to stop the organism from multiplying and spreading.

A possible drug for future use is called PROGRAM, it is a drug currently used as a flea treatment on cats and dogs.
The outer coating of the E-Cuniculi spore is made of “kitin” which is the same substance as the shell of a flea. Program works in such a way that it attacks kitin.
Although Program is licensed for rabbits this treatment has not been tried as it would involve the rabbit taking the drug orally. Further tests and studies are required.

The drug Thalidomide proved very effective in killing the E-Cuniculi organism in humans but so far no trials have been carried out on rabbits.

E-Cuniculi relies on “trebazole” to reproduce. Investigations are currently underway on a drug which prevents the production of trebazole. This drug will not be available for some time.