Managing E. cuniculi in Rabbits: From Diagnosis to Supportive Care

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Anne Staudenmaier, VMD, DABVP (Avian Practice)
angell.org/avianandexotic
avianandexotic@angell.org
617-989-1561
April 2025

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Encephalitozoon cuniculi is a spore-forming, single-celled parasite, most closely related to fungi. In the United States, an estimated 25% to 80% of the rabbit population is seropositive, and antibodies have been found in dogs, cats, birds, non-human primates, and humans. The parasite has a predilection for the central nervous system, kidneys, and ocular tissue, but it can also be found in the liver, lungs, and heart. The parasite can infect non-human primates and immunocompromised humans, causing disease in them and rabbits.

The parasite replicates within mammalian cells until the cells rupture, and the infective spore is shed into the environment mainly through urine but also in feces and respiratory secretions. Rabbits can shed the parasite for one to three months after initial infection, then intermittently throughout life. Vertical transmission has also been reported. E. cuniculi can survive up to four weeks on dry surfaces, though both 0.1% bleach (10 minutes contact time) and 70% ethanol (30-second contact time) kill it effectively.

Clinical Signs

Clinical signs of E. cuniculi are varied and depend on which body system(s) the parasite affects. There are four major manifestations that we will discuss below:

Neurologic

The neurological form of E. cuniculi is likely the most “classical” presentation of the disease. Clinical signs often include ataxia, torticollis, head tilt, and circling. Hind limb paresis and stroke-like events have also been reported. An inability to stand or lack of appetite has been linked with a worse prognosis, but a down rabbit can still recover. So, while it is important to relay the prognosis to owners, it is still reasonable to try treating these cases. Some neurological defects can be permanent, but many rabbits recover well or learn to compensate for these deficits.

Renal

1. cuniculi can cause both acute and chronic kidney injury. Many rabbits with this manifestation present UTI-like signs, including declining litter box habits, urine scald, and urinary incontinence. Bladder atony can also be seen, but this is usually secondary to spinal cord disease rather than primary kidney infection.

Even severe azotemia can respond very well to treatment in cases of AKI, so don’t necessarily recommend euthanasia based on initial values. What is a more important indicator is changes in values in response to treatment. Improvement or resolution during and after treatment generally carries a good prognosis.

GI

1. cuniculi is commonly overlooked as a potential cause of rabbit gastrointestinal syndrome (GI stasis). The parasite has been shown to affect both stomach and intestinal motility secondary to spinal cord disease and neuropathy associated with GI innervation. Any rabbit with recurrent GI stasis should be tested for E. cuniculi to rule it out as a contributing factor.

Ocular

The globe is another common site of E. cuniculi infection. The parasite invades ocular tissue and can cause both uveitis and intraocular/lens masses, often white or yellow. E. cuniculi cataracts, caused by an influx of white blood cells into the lens, often look “chunkier” than typical cataracts and are usually unilateral. However, Bilateral cases can occur and appear at different times, rather than concurrently. Once a cataract develops, changes cannot be reversed, but vision loss is usually tolerated well in rabbits.

Diagnosis

Figure 1. Typical torticollis/neurological presentation of a rabbit with E. cuniculi.

Several diagnostic tests exist for E. cuniculi. The University of Miami’s serology panel is the gold standard and has a high detection rate¹. The panel includes IgG and IgM titers and CRP (C-reactive protein) levels.

IgM is produced in early infection, and for E. cuniculi, is detectable for 4-7 days. Elevations are frequently seen in initial infections, but not necessarily in subsequent flare-ups after seroconversion occurs, meaning that a normal IgM titer does not mean that a rabbit is E. cuniculi negative. The body begins to produce IgG antibodies after seven to 14 days from the initial infection and can continue to produce IgG antibodies for months to years. This is the most commonly elevated value seen in positive cases. CRP is an acute-phase protein in rabbits and can be a good indicator of an active flare-up. However, CRP can be elevated due to any acute inflammatory event, and elevated CRP values are seen in almost every GI stasis case.

PCR testing for urine, CSF, and lens material also exists. Urine and CSF PCR are unreliable with high rates of false negatives due to intermittent shedding of the parasite in these fluids. Lens PCR is reliable in ocular cases, but is not a common tissue submitted in clinical practice.

Treatment

While a small number of rabbits are thought to clear the infection, the majority are considered to remain chronically infected. Treatment is focused on controlling active infection/flare-ups until the immune system can wall it off. Chronic, uninterrupted treatment is generally not recommended, as it increases both the risk of resistance and the risk of bone marrow suppression in rabbits.

The benzimidazoles are the cornerstone of treatment for active flare-ups of E. cuniculi. Their mechanism of action against the parasite is still not entirely understood, but theorized to involve potential inhibition of beta tubulins, a key component of the eukaryotic cytoskeleton. There is a higher risk of side effects due to the mechanism, and rabbits seem to be more sensitive to side effects than other species. Reversible bone marrow suppression is the most common side effect of treatment with benzimidazoles, and a CBC should be checked before and then every two weeks during treatment. If heteropenia or leukopenia is found, treatment should be discontinued. While rare, hepatotoxicity and GI upset are also potential side effects.

Fenbendazole, oxibendazole, albendazole, and thiabendazole have all been used to treat E. cuniculi in rabbits, and there is still debate over which to use. Research shows that albendazole and fenbendazole reduce E. cuniculi loads, while less research supports the use of oxibendazole and thiabendazole. Fenbendazole, though, has been shown to have higher rates of bone marrow suppression and teratogenicity². It is important to choose a benzimidazole with which the clinician feels comfortable and understands the risks and benefits.

In addition to treating the E. cuniculi, the clinician should offer supportive care for signs and secondary issues, like GI stasis. Meloxicam helps decrease inflammation from both the disease itself and inflammation secondary to the die-off of organisms. It should not be given in cases of acute or chronic kidney injury. Meclizine is an antihistamine used to treat vertigo in humans, and anecdotal evidence suggests that it can help in vestibular cases of the disease. Cerenia or metoclopramide can be helpful in their anti-nausea effects. Subcutaneous fluids, pain management, and nutritional support should be remembered in GI stasis cases, and padding/bumpers with wickaway material for bedding can help support down rabbits with severe torticollis.

Figure 2. Positive (top) versus Negative (bottom) E. cuniculi titers. Note the elevated CRP levels in the negative case.

References

1. Cray, M.P. Liebl, K. Arheart, R. Peschke, F. Kunzel, and A. Joachim. Comparison of enzyme-linked immunosorbent assay and immunofluorescence test for determination of anti-Encephalitozoon cuniculiantibodies in sera from rabbits with different clinical and histopathological presentations. Journal of Exotic Pet Medicine 32:39-42, 2020.
2. A. Dobosi, L. Bel, A.I. Pastiu, and D. L. Pusta. A Review of Encephalitozoon cuniculi in Domestic Rabbits (Oryctolagus cuniculus)—Biology, Clinical Signs, Diagnostic Techniques, Treatment, and Prevention. Pathogens. 11(12), 2022.Online.