Encephalitozoon cuniculi in cats
Edited January 2020
These guidelines were authored and updated by D.D. Addie et al.
Overview / Abstract
Encephalitozoon (E.) cuniculi is a common unicellular obligate intracellular microsporidial infection of rabbits (Oryctolagus cuniculus), which is increasingly recognised as a pathogen of cats and other mammalian species.
Objectives: to review the literature on E. cuniculi in cats and provide recommendations for feline clinical conditions in which E. cuniculi should be considered as a possible differential diagnosis.
Conclusions: E. cuniculi should be considered in cases of feline uveitis and cataract formation. It is not significantly associated with either chronic kidney disease or meningoencephalitis. E. cuniculi infection is more common in stray or feral cats than in pet cats.
Serological tests for antibody detection in blood are easy to perform and can be useful for diagnosis, but their specificity is low as antibodies have been found in apparently healthy cats. PCR appears more sensitive than histopathology for diagnosis, and is more sensitive when performed on cataractous lenses compared to aqueous humour, although ease of sampling is an obvious limitation. Treatment is with fenbendazole for 3 weeks and phacoemulsification to remove microsporidia from cataractous lenses.
E. cuniculi is a potential zoonotic infection, posing a special risk to immunocompromised humans from infected rabbits. Spore shedding has been infrequently identified in cats, so care should be taken around infected cats.
Encephalitozoon cuniculi is a common obligate intracellular microsporidial parasite of rabbits (Oryctolagus cuniculus), which is increasingly recognised as a pathogen of cats and other mammals. The microsporidia were previously considered "primitive" protozoa however, molecular phylogenetic analysis has resulted in the insight that these organisms are not primitive but instead degenerate, and that Microsporidia are related to the Fungi, either as a basal branch of the Fungi or as a sister group (Han and Weiss, 2017).
In rabbits, E. cuniculi can infect all organs, but specifically causes chronic kidney and central nervous system disease (Wang et al., 2018) and cataract formation with lens capsule rupture and phacoclastic uveitis (Benz et al., 2011). Infected rabbits shed spores in urine and faeces (Wang et al., 2018).
The susceptibility of cats to E.cuniculi infection was first reported in 1985, in an experimental infection of FeLV-infected kittens (Pang and Shadduck, 1985).
Kvac et al. (2017) detected E. cuniculi spores in the faeces of one pet and eight stray cats from 255 cats sampled in central Europe, and Piekarska et al. (2017) found spores in the faeces of one of 44 Polish cats. No E. cuniculi spores were detected in the faeces of 40 and 26 cats in two studies in Iran, although E. bieneusi spores were found in the faeces of 3 /40, and 3/26 cats, respectively (Jamshidi et al., 2012; Askari et al., 2015). No E. cuniculi spores were found in the faeces of ten Spanish cats tested (Lores et al., 2002).
Halánová et al. (2003) found antibodies in 17/72 cats in Eastern Slovakia using an indirect immunofluorescence antibody (IFA) test. Specific anti-E. cuniculi antibodies were found in 26/456 (5.7%) human sera examined as shown by Halánová et al. (2003). The highest occurrence of anti-microsporidial antibodies was found in a group of 24 immunodeficiency patients: 37.5% (9/24) (Halánová et al., 2003).
Stray (Kvac et al., 2017) and feral (Tsukada et al., 2016) cats are more likely to be exposed or infected than pet cats.
A summary of prevalence data is shown in Table 1.
Table 1. Antibody / spores prevalence of E. cuniculi infection in the feline populations in various countries
|Country||What detected||Number of cats||Prevalence %||Reference|
|Austria||Antibodies||100||2.0||Benz et al., 2011|
|Central Europe||Spores||255||3.5||Kvac et al., 2017|
|Jamshidi et al., 2012
Askari et al., 2015
|Japan||Antibodies||295||6.1||Tsukada et al., 2016|
|Poland||Spores||44||2.3||Piekarska et al., 2017|
|Slovakia (Eastern)||Antibodies||72||23.6||Halánová et al., 2003|
|Spain||Spores||10||0||Lores et al., 2002|
|UK||Antibodies||27||0||Meredith et al., 2015|
|USA (Maryland)||Antibodies||232||6.5||Hsu et al., 2011|
Cats, like humans, are most likely to become infected by ingestion of water or food contaminated with infective spores (Wang et al., 2018). Oral and nasal transmission has been described in rabbits (Harcourt-Brown and Holloway, 2003) but it is unknown if direct transmission occurs in cats. Two uninfected cats that had been in direct contact with infected ones tested negative for blood antibodies in one study (Benz et al., 2011). In utero infection occurs in rabbits, but it is unknown if transmission by this route occurs in the cat (Benz et al., 2011). Rebel-Bauder et al. (2011) reported a case of generalised encephalitozoonosis in a kitten with cerebellar hypoplasia, which could have been related to in utero infection.
Ocular signs have been associated with E. cuniculi infection in cats.
Anterior uveitis and cataracts
Benz et al. (2011) reported a study of 19 eyes from 11 European shorthair cats (median age 3.5 years) in Austria. Nine of these cats had bilateral cataracts, with 12/19 eyes having focal anterior cortical cataracts and 7/19 eyes having mature cataracts. In 14/19 eyes anterior uveitis was present. All cats had antibody titres in the blood (titre 1:80–1:10,000) for E. cuniculi (Benz et al., 2011). E. cuniculi DNA was detected by PCR and sequencing in 18/19 lenses and in 10/19 aqueous samples (Csokai et al., 2010; Benz et al., 2011).
E. cuniculi was not associated with
Chronic kidney disease (CKD): 4/36 cats with CKD tested positive for E. cuniculi antibodies in blood and this prevalence was not significantly different (P>0.05) from cats without CKD (Hsu et al., 2011).
Meningoencephalitis (ME): Künzel et al. (2017) concluded that E. cuniculi was unlikely to be directly associated with (non-suppurative and/or granulomatous) ME in cats in Austria: none of 30 affected cats examined by immunohistochemistry was positive.
To detect antibodies in blood by means of western blot or immunofluorescent antibody test (IFAT) remains the major diagnostic tool used in living animals. As the IFAT is quick and easy to perform, it is recommended for routine use in the diagnosis of feline encephalitozoonosis (Künzel et al., 2014). However, antibodies have been detected in cats who appeared to be clinically healthy, which has to be borne in mind when interpreting positive results: a positive result supports a diagnosis of encephalitozoonosis, but is not diagnostic.
Encephalitozoon cuniculi DNA was detected by PCR and sequencing in 18/19 lenses (liquefied lens material) and in 10/19 aqueous humour samples from 11 cats with cataracts caused by E. cuniculi (Benz et al., 2011).
Histopathology / cytology
Histopathology and cytology are aided by immunohistochemistry. Five tentative positive results were detected by cytologic examination of material removed from cataractous lenses (Benz et al., 2011). Spores were detected in 15 of 19 samples of cataractous lens material with immunohistochemical staining (Benz et al., 2011). To diagnose E. cuniculi in rabbits, Leipig et al. (2013) recommended that confirmation of pathogenic E. cuniculi infection should include standard histology of the predilection sites in combination with a specific aetiological assay, preferably real-time PCR. Presumably the same is true for diagnosis in cats.
Fenbendazole is used to treat E. cuniculi infection in cats at a dose of 20 mg/kg q 24 h for three weeks (Benz et al., 2011). Cataracts can be successfully treated by phacoemulsification alongside medical treatment for E. cuniculi and symptomatic treatment for uveitis (for example ointment or drops containing dexamethasone), as shown by Benz et al. (2011).
There is no commercially available vaccine to prevent E. cuniculi infection in rabbits or cats. It is of note, however, that an experimental vaccine containing inactivated spores was shown to induce a long-lasting antibody response in rabbits (Sobottka et al., 2001). However, it is unknown whether antibodies are protective in this infection.
Where cats and rabbits are kept together, the main method of prevention of infection is the maintenance of excellent hygiene. Heat or steam cleaning will be the most effective methods for eliminating E. cuniculi spores. Suspect infected rabbits should be tested and treated.
The safest option for both cats and humans who eat rabbit meat is for it to use E. cuniculi-free sources. Where rabbit meat is prepared for feline or human consumption it should be well cooked; microsporidia spores in fish were shown to be inactivated by heating to 60°C for 10 min or by microwaving at 750 W, for 20s (Leiro et al., 2012); similar treatment is likely to be effective for rabbit meat. However, Graczyk et al. (2007) found microwaving to be ineffective against the spores of E. bieneusi and E. intestinalis in sewage sludge, so more work in this field is needed to determine appropriate conditions to inactivate E. cuniculi spores. Microsporidia spores in fish were also inactivated by freezing at -20°C for more than 48 hours (Leiro et al., 2012).
Any area used to prepare rabbit meat should be cleaned with chlorine (household bleach), ensuring a contact time of at least 16 minutes (Wolk et al., 2000), followed by rinsing with boiling water or steam. Exposure to 70% ethanol for 15 min inactivated fish microsporidia spores (Leiro et al., 2012) and so is likely to be effective for cleaning hands and utensils following the preparation of rabbit meat (although wearing disposable gloves would be more practical in the case of hands).
ABCD recommends that immunosuppressed cats should not have any contact with infected rabbits or their urine and faeces. Since E. cuniculi is a zoonotic infection, veterinary surgeons and nurses should wear gloves when dealing with infected cats or rabbits. Calcium oxide (quicklime, burnt lime) was 100% effective in inactivating microsporidia spores in landfill leachate and sewage sludge (Graczyk et al., 2007), so could be used to dispose of infected cadavers.
ABCD Europe gratefully acknowledges the support of Boehringer Ingelheim (the founding sponsor of the ABCD) and Virbac.
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