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Small Mammal Medicine
Encephalitozoon cuniculi
Introduction
The most frequently seen infectious disease in rabbits is encephalitozoonosis. It is the
most common problem after dental disorders seen in rabbits at our practice. On the
basis of my experience, I will give you some practical tips and advice on how to deal
with suspected Encephalitozoon cuniculi infection.
Evert-Jan de Boer
Dierenkliniek
Wilhelminapark Utrecht
Dental website:
www.dierengebit.nl
[email protected]
Encephalitozoon cuniculi
An infected rabbit can excrete spores through urine and contaminate food, so that
another rabbit eating contaminated food will become infected (horizontal transmission). Infection spreads from the gastrointestinal tract through the bloodstream to
other organs. Predilection sites in rabbits are the brain, nervous system, and kidneys.
Clinical manifestations depend on the site of infection. Infected rabbits can be latently
infected or asymptomatic for many years. Although symptoms may be mild and persistent, they may also be so severe that the rabbit has to be euthanized within days or
weeks. The first symptoms can develop acutely and are often seen after a stressful incident (such as a vaccination or an operation). The number of spores increases, rupturing
the host cell, which causes an acute inflammatory response. The liberated spores invade
surrounding tissue and enter the bloodstream. Spores that reach the kidneys are shed
in urine, contaminating the environment. E. cuniculi spores can survive for weeks outside the host and remain infectious to other rabbits.
Another route of transmission is ‘in utero’ from an infected dam to her offspring (vertical
transmission). With this route of transmission, the lens of the eye of the embryo may
also become infected.
Clinical manifestation
The neurological signs of E. cuniculi infection of rabbits are seizures, head tilt, ataxia,
and loss of balance with circling behavior that develops into rolling behavior (rotational
movements around the body length axis). Mild signs include nystagmus, horizontal
swaying, and hemiparesis.
Abstracts | European Veterinary Conference Voorjaarsdagen 2013
The most common neurological sign is due to unilateral vestibular disease. The vestibular system is essential for equilibrium, balance, and hearing. Vestibular disease can be
subdivided into central vestibular disease, in which the vestibular nuclei in the brainstem or medulla are affected, and peripheral vestibular disease, in which receptors in
the inner ear and the vestibulocochlear nerve are affected.
Head tilt, nystagmus, circling, and vestibular strabismus may be caused by unilateral
peripheral vestibular disease due to E. cuniculi infection of the VIII cranial nerve (vestibulocochlear nerve) or bacterial otitis interna. The same symptoms accompanied by circling behavior that develops into rolling behavior are indicative of unilateral central vestibular disease. The prognosis of central vestibular disease is poor when rolling behavior
occurs. Another symptom of unilateral central vestibular disease is posterior paresis
(hemiparesis). Bilateral central vestibular disease is accompanied by horizontal swaying
of the head.
The differential diagnosis for vestibular disease caused by E. cuniculi includes bacterial
infection of the inner ear (animals might be deaf but it is difficult to test them for this),
central nervous system infection with bacteria, toxoplasmosis, or neoplasia.
Vestibular disease in humans
An interesting disease in humans is vestibular neuritis or neuronitis, which causes to
vertigo, dizziness and difficulties with balance, nystagmus, nausea, and vomiting. Clinical and histopathological evidence suggests that it is caused by an isolated lesion of the
vestibular nerve. Although the exact etiology remains obscure, it is thought to be
caused by a virus. Neuritis or inflammation of the vestibulocochlear nerve affects balance, but does not affect hearing, whereas labyrinthitis or inflammation of the labyrinth (inner ear) results in problems with balance and loss of hearing.
Posterior paralysis
Ataxia, paresis, or posterior paralysis can also been seen in rabbits infected with E.
cuniculi.
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Polyuria and polydipsia or urine scalding
The kidneys are organs with a high blood flow and are readily infected with E. cuniculi
spores. If there are signs of a kidney problem, there may be a bacterial infection
(pyelonephritis) or a granulomatous infection with E. cuniculi. Sometimes affected rabbits with encephalitozoonosis drink all day, with polyuria and polydipsia, but chronic
renal failure cannot be diagnosed on the basis of blood chemistry or urine abnormalities (bacterial culture, protein-creatinine ratio). The specific gravity of urine is lower in
affected rabbits with encephalitozoonosis than it is in rabbits with renal insufficiency
based on my experience.
Sometimes potty-trained rabbits become incontinent. If there is bladder atony and
incomplete emptying, leaking urine can cause urine scalding. Urine scalding can also
been caused by obesity, urinary tract infection, bladder stones, or sludge.
Signs of ocular disease
Signs of ocular disease caused by E. cuniculi include cataracts, lens rupture, and phacoclastic uveitis. Cataracts may become manifest suddenly after a stressful event. If a rabbit is infected in the uterus, E. cuniculi can invade the lens (vertical transmission), where
it will be present as a subclinical asymptomatic infection until the latent infection is activated by a stressful event, leading to cataract development. The anterior capsule of the
lens may rupture, leading to uveitis of the anterior chamber.
Weight loss without a clear cause
If a rabbit is losing weight but there are no abnormalities on clinical examination, dental
investigation, blood chemistry, ultrasound, or x-ray, then E. cuniculi may be the cause.
Polyuria and polydipsia of unknown cause are often seen in combination with weight
loss, and I will present some examples of this.
Diagnosis
It is difficult to establish a diagnosis of encephalitozoonosis in living rabbits, as there are
no specific blood tests to show that symptoms are caused by E. cuniculi. In 2006, we
started a study of pet rabbits in the Netherlands. Overall, 50–60% of healthy rabbits and
70–80% of rabbits with clinical symptoms were positive for antibodies (IgG) against E.
Abstracts | European Veterinary Conference Voorjaarsdagen 2013
cuniculi, but the antibody titer was not correlated with the severity of clinical symptoms.
The E. cuniculi antibody (IgM/IgG) or antigen test can be used as an adjunct test but not
as a diagnostic test for encephalitozoonosis. Rabbits can be infected with E. cuniculi
regardless of whether IgM/IgG antibody titers are positive or not. Serum titers may also
be positive in healthy rabbits without clinical symptoms. We did not detect an increase
in antibody titers in clinically affected rabbits with neurological signs after 3–4 and 7–8
weeks, but this may have been because the rabbits were treated with fenbendazole.
False-negative results may be seen in immunodeficent or latently infected rabbits when
the infection flares up without the spores previously being detected by the immune
system. Some studies have reported negative antibody titers even though the diagnosis
encephalitozoonosis was confirmed by PCR and histopathology. Moreover, postmortem
examination may prove negative for E. cuniculi spores even though the animal showed
clinical symptoms and the disease was suspected on the basis of granulomatous infections.
Keep it practical
Infection of living animals with E. cuniculi is usually diagnosed on the basis of a combination of clinical signs and exclusion of other probable causes. Veterinarians should
always bear in mind that a diagnosis other than encephalitozoonosis is possible.
Therapy
The aim of the treatment is to reduce the clinical symptoms and to stabilize the rabbit.
Most symptoms are caused by an inflammatory infection and edema in the neural tissue, which affects neurotransmission. Treatment should be started as soon as possible
and not delayed until laboratory results come through, because serum antibody titers
against E. cuniculi may not prove diagnostic.
Conclusion
Encephalitozoonosis is a major under-diagnosed disease because it cannot be diagnosed in the living animal. Without a reliable blood test, E. cuniculi infection can only be
diagnosed by ruling out other possible causes.
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References
References will be cited during the presentation. Reference list can be obtained from the author in response
to an email request.
Abstracts | European Veterinary Conference Voorjaarsdagen 2013
www.voorjaarsdagen.eu