Encephalitozoon cuniculi in cats

Edited April 2019

These guidelines were authored by D.D. Addie et al.
 

Overview / Abstract

Encephalitozoon cuniculi is a common unicellular obligate intracellular microsporidial parasite of rabbits (Oryctolagus cuniculus), which is increasingly recognised as a pathogen of cats and other mammalian animal species.  The microsporidia were previously thought of as protozoa but are now classified as fungi.
 
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 infection is more common in stray or feral cats than in pet cats.  E. cuniculi infection should be considered as underlying cause of feline uveitis and cataract formation.  It is not significantly associated with either chronic kidney disease or meningoencephalitis.
 
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.
 
 

Introduction

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 susceptibility of cats to E. cuniculi infection was first reported in 1985, in an experimental infection of kittens infected with feline leukaemia virus (FeLV) (Pang and Shadduck, 1985).
 
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).
 
 

Epidemiology

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 also 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 infected than pet cats, although not statistically significantly so in the case of feral 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
 

CountryWhat detectedNumber of catsPrevalence %Reference
AustriaAntibodies1002.0Benz et al., 2011
Central EuropeSpores2553.5Kvac et al., 2017
IranSpores
Spores
40
26
0
0
Jamshidi et al., 2012
Askari et al., 2015
JapanAntibodies2956.1Tsukada et al., 2016
PolandSpores442.3Piekarska et al., 2017
Slovakia (Eastern)Antibodies7223.6Halánová et al., 2003
SpainSpores100Lores et al., 2002
UKAntibodies270Meredith et al., 2015
USA (Maryland)Antibodies2326.5Hsu et al., 2011

 
 

Transmission

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 from rabbits to cats or cats to cats occurs. 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.
 
 

Clinical signs

Ocular signs have been associated with E. cuniculi infection in cats.
 

Anterior uveitis and cataracts

Benz et al. (2011) reported a study investigating 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 antibodies (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) in cats does not seem to be associated with E. cuniculi infection; 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 also was not found to be caused by E. cuniculi.  None of 30 cats with non-suppurative and/or granulomatous meningoencephalitis in Austria examined by immunohistochemistry were positive for E. cuniculi antigen (Künzel et al., 2017).
 
 

Diagnosis

Serology

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, (Tsukada et al., 2016) indicating that healthy cats can be infected and that a positive result is not diagnostic for encephalitozoonosis.
 

PCR

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 and immunocytochemistry, respectively.  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 infection 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.
 
 

Treatment

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).
 
 

Prevention

There is no commercially available vaccine to prevent E. cuniculi infection in rabbits or cats. However, an experimental vaccine containing inactivated spores was shown to induce a long-lasting antibody response in rabbits (Sobottka et al., 2001).
 
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, although treatment does not prevent shedding of spores (Abu-Akkada and Oda, 2016).
 
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.

 
 

References

Abu-Akkada SS, Oda SS.  Prevention and treatment of Encephalitozoon cuniculi infection in immunosuppressed rabbits with fenbendazole. Iran J Vet Res. 2016 Spring;17(2):98-105.
 
Askari Z, Mirjalali H, Mohebali M, Zarei Z, Shojaei S, Rezaeian T, Rezaeian M (2015): Molecular Detection and Identification of Zoonotic Microsporidia Spore in Fecal Samples of Some Animals with Close-Contact to Human.  Iran J Parasitol 10(3), 381-388.
 
Benz P, Maass G, Csokai J, Fuchs-Baumgartinger A, Schwendenwein I, Tichy A, Nell B (2011): Detection of Encephalitozoon cuniculi in the feline cataractous lens.  Vet Ophthalmol 14 Suppl 1, 37-47.
 
Csokai J, Fuchs-Baumgartinger A, Maaß G et al (2010): Detection of Encephalitozoon cuniculi-infection (strain II) by PCR in a cat with anterior uveitis. Wien Tierärztl Monat – Vet Med Austria 97, 210–215.
 
Graczyk TK, Kacprzak M, Neczaj E, Tamang L, Graczyk H, Lucy FE, Girouard AS (2007): Human-virulent microsporidian spores in solid waste landfill leachate and sewage sludge, and effects of sanitization treatments on their inactivation. Parasitol Res 101(3), 569-575.
 
Halánová MCisláková LValencákova ABálent PAdam JTrávnicek M (2003): Serological screening of occurrence of antibodies to Encephalitozoon cuniculi in humans and animals in Eastern Slovakia. Ann Agric Environ Med 10(1), 117-120.
 
Harcourt-Brown FM, Holloway HKR (2003): Encephalitozoon cuniculi in pet rabbits. Vet Rec 152, 427–431.
 
Hsu V, Grant DC, Zajac AM, Witonsky SG, Lindsay DS (2011): Prevalence of IgG antibodies to Encephalitozoon cuniculi and Toxoplasma gondii in cats with and without chronic kidney disease from Virginia. Vet Parasitol 176(1), 23-26.
 
Jamshidi ShTabrizi ASBahrami MMomtaz H (2012): Microsporidia in household dogs and cats in Iran; a zoonotic concern. Vet Parasitol 185(2-4), 121-123.
 
Künzel FPeschke RTichy AJoachim A (2014): Comparison of an indirect fluorescent antibody test with Western blot for the detection of serum antibodies against Encephalitozoon cuniculi in cats. Parasitol Res 113(12), 4457-4462.
 
Künzel F, Rebel-Bauder B, Kassl C, Leschnik M, Url A (2017): Meningoencephalitis in cats in Austria: a study of infectious causes, including Encephalitozoon cuniculi. J Feline Med Surg 19(2), 171-176.
 
Kvac M, Hofmannova L, Ortega Y, Holubova N, Horcickova M, Kicia M, Hlaskova L, Kvetonova D, Sak B, McEvoy J (2017):  Stray cats are more frequently infected with zoonotic protists than pet cats. Folia Parasitol (Praha) 6, 64.
 
Leipig M,  Matiasek K, Rinder H, Janik D, Emrich D, Baiker K, Hermanns W (2013): Value of histopathology, immunohistochemistry, and real-time polymerase chain reaction in the confirmatory diagnosis of Encephalitozoon cuniculi infection in rabbits. J Vet Diagn Invest 25(1), 16–26.
 
Leiro JM, Piazzon C, Domínguez B, Mallo N, Lamas J (2012): Evaluation of some physical and chemical treatments for inactivating microsporidian spores isolated from fish. Int J Food Microbiol 156(2), 152-160.
 
Lores Bdel Aguila CArias C (2002): Enterocytozoon bieneusi (microsporidia) in faecal samples from domestic animals from Galicia, Spain. Mem Inst Oswaldo Cruz 97(7), 941-945.
 
Meredith ALCleaveland SCBrown JMahajan AShaw DJ (2015): Seroprevalence of Encephalitozoon cuniculi in wild rodents, foxes and domestic cats in three sites in the United Kingdom. Transbound Emerg Dis 62(2), 148-156.
 
Pang VFShadduck JA (1985): Susceptibility of cats, sheep, and swine to a rabbit isolate of Encephalitozoon cuniculi. Am J Vet Res 46(5), 1071-1077.
 
Piekarska J, Kicia M, Wesołowska M, Kopacz Ż, Gorczykowski M, Szczepankiewicz B, Kváč M, Sak B (2017): Zoonotic microsporidia in dogs and cats in Poland. Vet Parasitol 246, 108-111.
 
Rebel-Bauder BLeschnik MMaderner AUrl A (2011): Generalized encephalitozoonosis in a young kitten with cerebellar hypoplasia. J Comp Pathol 145(2-3), 126-131.
 
Sobottka I, Iglauer F, Schüler T, Schmetz C, Visvesvara GS, Albrecht H, Schwartz DA, Pieniazek NJ, Bartscht K, Laufs R, Schottelius J (2001): Acute and long-term humoral immunity following active immunization of rabbits with inactivated spores of various Encephalitozoon species. Parasitol Res 87(1), 1-6.
 
Tsukada R, Osaka Y, Takano T, Sasaki M, Inose M, Ikadai H (2016): Serological survey of Encephalitozoon cuniculi infection in cats in Japan.  J Vet Med Sci 78(10), 1615-1617.
 
Wang S, Yao Z, Li L, Pan Y, Li P, Nan X, Xie Q, Zhang Z (2018): Seroprevalence of Toxoplasma gondii and Encephalitozoon cuniculi among domestic rabbits in central China.  Parasite 25, 9.
 
Wolk DM, Johnson CH, Rice EW, Marshall MM, Grahn KF, Plummer CB, Sterling CR (2000): A spore counting method and cell culture model for chlorine disinfection studies of Encephalitozoon syn. Septata intestinalis. Appl Environ Microbiol 66(4), 1266-1273.

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