by Brendan Noonan, DVM, DABVP (Avian practice)
Encephalitozoon cuniculi (E. cuniculi) is a microsporidium organism that is well recognized as a cause of disease in pet rabbits and is internationally prevalent. Since first being identified in 1922 as the causative agent in a rabbit with paralysis it went on to be acknowledged as endemic in the laboratory setting1. Decades later, seroprevalence would show significant presence in farms, breeding facilities, and permeating the global pet trade. Given the zoonotic potential of this opportunistic organism, primarily to those who are immunocompromised; disease prevelance, transmission, and control remain important topics of interest. Considering the wide range of neurologic, renal and ocular presentations in combination with a limited number of controlled studies directing effective treatment options for these patients, this disease can be frustrating for even the most experienced rabbit clinician. Varied response to treatment and often intense nursing requirements by owners can result in euthanasia for many rabbits, but resolution of even the most severe torticollis can occur.
E. cuniculi is an obligate intracellular parasite which was long considered a protozoon, but later classified as fungi due to the recognition of fungal proteins related to zygomycetes2. There are three recognized strains of E. cuniculi with genotype 1 being the causative agent in rabbits. The organism has a direct life cycle which can be spread through horizontal and vertical transmission. The horizontal transmission is primarily accomplished via intestinal absorption after ingestion of urine contaminated feed. Transmission through the respiratory epithelium is also possible if aerosolized spores are encountered. Experimental infection has been successful via transmucosal, intrathecal, intravenous, and rectal inoculation3. The primary method of entering host cells is by extruding the spore’s polar filament and injecting the sporoplasm. Once in the host cell, the proliferative form divides by merogeny and creates infective spores which are disseminated to new cells after host cell lysis3. The spores have a tissue predilection for brain, kidney, lens, lung, and myocardium4.
The most commonly reported clinical sign associated with E. cuniculi are associated with the central nervous system. Neurologic signs include torticollis, seizures, ataxia, and paresis. Differential diagnoses to consider include causes of meningioencehpalomyelitis (bacterial, viral, parasitic), bacterial otitis, neoplasia, inflammatory and traumatic lesions. Less common differentials could include Toxoplasma gondii, rabies, Baylisascaris procyonis, lead toxicity, cerebral infarcts or idiopathic vestibular disease. Ocular lesions are most often seen after vertical transmission resulting in unilateral phacoclastic uveitis. Cataracts and granuloma formation have also been reported. Renal signs can include azotemia, urine scald, polyuria/polydipsia or change in litter box habits3.
Antemortem diagnosis of E. cuniculi can be difficult due to the variation in presentation and host response to the disease. It is a well-equipped intracellular parasite able to evade host destruction; however, cell-mediated immunity has been experimentally shown to be the main host defense. Any immune competent animal will develop a humoral response after exposure to the parasite, but antibodies developed do not provide protection from reinfection5. Experimental variation in IgG titers have made the sole use of this antibody as a diagnostic tool difficult to interpret. Two negative IgG titers 3 weeks apart in an immune competent animal indicate non-exposure. However, a single positive titer in a clinically normal animal does not help differentiate acute from latent infections. IgM has a more predictive trend making identification of an acute infection more likely. Experimentally the IgM titers will be elevated from 0-35 days post exposure but can remain elevated for 18 weeks. Spores may be shed in the urine during this time and isolation from naive animals is indicated6. Evaluation of titers in combination with CRP, a major acute phase protein, can also be supportive of a diagnosis. Serology testing available other than ELISA includes immunofluorescence assay (IFA) and carbon immunoassay (CIA). Polymerase chain reaction assays (PCR) are available for identifying infective spores in urine, cerebrospinal fluid, lens material and target tissues. PCR appears to be most sensitive and specific for recovered phacoclastic uveitis material given the high numbers of spores concentrated in the lens4,7.
Treatment protocols for E. cuniculi are not only directed to reduce the spore propagation and spread, but also the inflammatory signs associated with host cell rupture. With a limited number of studies to date testing efficacy of treatment, there is still no universal agreement on the best protocol. Fenbendazole administration has been shown to prevent experimental infection with E. cuniculi. Animals remained seronegative at 21 days and no spores were recovered from brain tissue postmortem8. Other benzimidazole medications such as albendazole and oxibendazole have been used in treatment, but intra-treatment CBCs should be obtained to monitor for bone marrow suppression. Steroid therapy has been suggested to decrease the severe inflammatory reaction, but may be contraindicated due to the known immunosuppressive effects9. The use of NSAIDs instead of steroids to control inflammation is recommended as long as the patient’s renal function is first evaluated. During the initial phase of treatment for the acute torticollis patient sedation with midazolam may be indicated to prevent injury secondary to repeated rolling. Heavily padding the enclosure may also be indicated. Corneal injury may be seen, especially in the down facing eye, and should be treated accordingly. Duration and degree of supportive care varies from patient to patient, but should focus on preventing the development of gastrointestinal stasis.
E. cuniculi is environmentally resistant, but susceptible to many routine disinfectants. In order to control spread of disease cleaning with 0.1% bleach (10 minute contact time) or 70% ethanol (30 second contact time) have both been proven effective. Other sanitizers such as sodium hydroxide and hydrogen peroxide are effective, but require a much longer contact time (30 minutes)10.
Seroprevalence of E. cuniculi has a global reach in pet rabbits and is a potential zoonotic disease for immunosuppressed individuals. It has the ability to create lifelong debilitation in rabbits that survive infection or create latent carriers in subclinical hosts. Given the varied success of antemortem diagnosis and few controlled studies demonstrating effective treatment strategies this disease presents a challenge for veterinarians and owners alike.
For more information about E. cuniculi in rabbits or about Angell’s Avian and Exotic service, please call 617 989-1561 or e-mail email@example.com.
- Wright JH, Craighead EM. Infectious motor paralysis in young rabbits. J Exp Med. 1922; 36 (1): 113-128.
- Bohne W, Bottcher K, Gross U. The parasitophorous vacuole of Encephalitozoon cuniculi: biogenesis and characteristics of the host cell-pathogen interface. Int J Med Microbiol. 2011; 301(5): 395-399.
- Latney LT, Bradley CW, Wyre NR. Encephalitozoon cuniculi in pet rabbits: diagnosis and optimal management. Vet Med: Research & Reports. 2014(5): 169-180.
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- Cray C, Arcia G, Schneider R, Kelleher SA, Arheart KL. Evaluation of the usefulness of an ELISA and protein electrophoresis in the diagnosis of Encephalitozoon cuniculi infection in rabbits. Am J Vet Res. 2009; 70 (4): 478-482.
- Fisher PG, Carpenter JW. Neurological and Musculoskeletal Diseases. In Quesenberry K, Carpenter J (eds): Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery, 3rd ed. St. Louis: Elsevier, 2012, P 245-250.