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Encephalitozoonosis in rabbits


Encephalitozoon cuniculi is an obligatory intracellular microsporidian parasite that can infect a wide range of mammals, including rodents, rabbits, horses, carnivores and humans, in which the organism is known as an opportunistic pathogen of immunocompromised individuals. Nevertheless, the main host for E. cuniculi is the rabbit and infections usually have a sub-clinical course. However, severe disease is recognised in pet rabbits more frequently within the last years. As the central nervous system, the kidney and the eye are predilection organs for the organism, predominant histopathological alterations comprise granulomatous meningoencephalitis, chronical interstitial nephritis and phacoclastic uveitis. A definitive diagnosis of encephalitozoonosis in vivo is difficult, but it is important for specific treatment and the determination of possible zoonotic risks. This review article covers epidemiology, pathology, pathophysiology, immunology, clinical signs, differential diagnosis, diagnosis and treatment of encephalitozoonosis in rabbits.

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  1. Ashton N, Cook C, Clegg F (1976) Encephalitozoonosis (nosematosis) causing bilateral cataract in a rabbit. Br J Ophthal 60:618–631

  2. Baneux PJR, Pognan F (2003) In utero transmission of Encephalitozoon cuniculi strain type I in rabbits. Lab Anim 37:132–138

  3. Beauvais B, Sarfati C, Challier S, Derouin F (1994) In vitro model to asses effect of antimicrobial agents on Encephalitozoon cuniculi. Antimicrob Agent Chemother 38(10):2440–2448

  4. Biderre C, Pagès M, Méténier G, Canning EU, Vivarès CP (1995) Evidence for the smallest nuclear genome (2.9 Mb) in the microsporidium Encephalitozoon cuniculi. Mol. Biochem Parasitol 74(2):229–231

  5. Boot R, Hansen C, Nozari N, Thuis H (2000) Comparison of assays for antibodies to Encephalitozoon cuniculi in rabbits. Lab Anim 34(3):281–289

  6. Canning EU, Lom J (1986) The Microsporidia of vertebrates. Academic, London

  7. Chalupský J, Vávra J, Bedrník P (1979) Encephalitozoonosis in laboratory animals—a serological survey. Folia Parasitol (Praha) 26:1–8

  8. Chalupsky J, Vavra J, Gaudin J (1990) Mise en evidence serologique de la presence d‘ encephalitozoonose et de toxoplasmose chez le lapin de Gareene (Oryctolagus cuniculus) en France. Bull Soc Franc Parasitol 8:91–95

  9. Cox JC, Gallichio HA (1978) Serological and histological studies on adult rabbits with recent, naturally acquired encephalitozoonosis. Res Vet Sci 24:260–261

  10. Cox JC, Pye D (1975) Serodiagnosis of nosematosis by immunofluorescence using cell culture grown organisms. Lab Anim 9:297–304

  11. Cox JC, Ross J (1980) A serological survey of Encephalitozoon cuniculi infection in the wild rabbit in England and Scotland. Res Vet Sci 28:396

  12. Cox JC, Hamilton RC, Attwood HD (1979) An investigation of the route and progression of Encephalitozoon cuniculi infection in adult rabbits. J Protozool 26:260–265

  13. Cox JC, Pye D, Edmonds JW, Shepherd R (1980) An investigation of Encephalitozoon cuniculi in the wild rabbit Oryctolagus cuniculus in Victoria, Australia. J Hyg (Lond) 84(2):295–300

  14. Csokai J, Gruber A, Künzel F, Tichy A, Joachim A (2009a) Encephalitozoonosis in pet rabbits (Oryctolagus cuniculus): pathohistological findings in animals with latent infection versus clinical manifestation. Parasitol Res 104:629–635

  15. Csokai J, Joachim A, Gruber A, Tichy A, Pakozdy A, Künzel F (2009b) Diagnostic markers for encephalitozoonosis in pet rabbits. Vet Parasitol 163(1–2):18–26

  16. Deeb BJ, Carpenter JW (2004) Neurologic and musculoskeletal disease. In: Quesenberry KE, Carpenter JW (eds) Ferrets, Rabbits and Rodents: Clinical Medicine and Surgery, 2nd edn. Saunders, St. Louis, pp 203–210

  17. Deeb BJ, Di Giacomo RF (1994) Cerebral larva migrans caused by Baylascaris sp. in pet rabbits. J Am Vet Med Assoc 205:1744–1747

  18. De Groote M, Visvesvara G, Wilson M, Pieniazek N, Slemenda S, da Silva A, Leitch G, Bryan R, Reves R (1995) Polymerase chain reaction and culture confirmation of disseminated Encephalitozoon cuniculi in a patient with AIDS: Successful therapy with albendazole. J Infect Dis 171:1375–1378

  19. Deplazes P, Mathis A, Baumgartner R, Tanner I, Weber R (1996) Immunologic and molecular characteristics of Encephalitozoon-like microsporidia isolated from humans and rabbits indicate that Encephalitozoon cuniculi is a zoonotic parasite. Clin Infect Dis 22:557–559

  20. Didier PJ, Didier ES, Orenstein JM, Shadduck JA (1991) Fine structure of a new human microsporidian, Encephalitozoon hellem, in culture. J Protozool 38:502–507

  21. Didier E, Orenstein JM, Aldras A, Bertucci D, Rogers LB, Janney A (1995a) Comparison of three staining methods for detecting microsporidia in fluids. J Clin Microbiol 33:3138–3145

  22. Didier ES, Vossbrinck CR, Baker MD, Rogers LB, Bertucci DC, Shadduck JA (1995b) Identification and characterization of three Encephalitozoon cuniculi strains. Parasitology 111(Pt 4):411–421

  23. Dipineto L, Rinaldi L, Santaniello A, Sensale M, Cuomo A, Calabria M, Menna LF, Fioretti A (2008) Serological survey for antibodies to Encephalitozoon cuniculi in pet rabbits in Italy. Zoonoses Publ Health 55:173–175

  24. Dubey JP, Brown CA, Carpenter JL, Moore JJ (1992) Fatal toxoplasmosis in domestic rabbits in the USA. Vet Parasitol 44:305–309

  25. Ebrecht D, Müller E (2004) Zoonosen des Kaninchens. Tieraerztl Prax K 32:363–369

  26. Eröksüz Y, Eröksüz H, Özer H, Cevik A, Ünver Ö (1999) A survey of Encephalitozoon cuniculi infection in rabbit colonies in Elazig, Turkey: pathomorphologic and serologic (carbonimmunoassay test) studies. Isr J Vet Med 54:73–77

  27. Ewringmann A, Göbel T (1999) Untersuchungen zur Klinik und Therapie der Encephalitozoonose beim Heimtierkaninchen. Kleintierpraxis 44:357–372

  28. Feaga WP (1997) Wry neck in rabbits. JAVMA 210(4):480

  29. Fechle LM, Sigler RL (2002) Phacoemulsification for the management of Encephalitozoonon cuniculi-induced phacoclastic uveitis in a rabbit. Vet Ophthalmol 5:211–215

  30. Flatt RE, Jackson SJ (1970) Renal nosematosis in young rabbits. Path Vet 7:492–497

  31. Franssen FF, Lumeij JT, van Knapen F (1995) Susceptibility of Encephalitozoon cuniculi to several drugs in vitro. Antimicrob Agents Chemother 39(6):1265–1268

  32. Franzen C (2004) Microsporidia: how can they invade other cells? Trends Parasitol 20(6):275–279

  33. Furuoka H, Sato H, Kubo M, Owaki S, Kobayashi Y, Matsui T, Kamiya H (2003) Neuropathological observation of rabbits (Oryctolagus cuniculus) affected with raccoon roundworm (Baylisascaris procyonis) larva migrans in Japan. J Vet Med Sci 65(6):695–699

  34. Giordano C, Weigt A, Vercelli A, Rondena M, Grilli G, Giudice C (2005) Immunohistochemical identification of Encephalitozoon cuniculi in phacoclastic uveitis in four rabbits. Vet Ophthalmol 8:271–275

  35. Grahn B, Wolfer J, Keller Ch (1991) Diagnostic Ophtalmology. Can Vet J 32:372–373

  36. Grest P, Albicker P, Hoelzle L, Wild P, Pospischil A (2002) Herpes simplex encephalitis in a domestic rabbit (Oryctolagus cuniculus). J Comp Pathol 126(4):308–311

  37. Gruber A, Pakozdy A, Weissenböck H, Csokai J, Künzel F (2009) A retrospective study of neurological disease in 118 rabbits. J Comp Pathol 140(1):31–37

  38. Halánová M, Cisláková L, Valencákova A, Bálent P, Adam J, Trávnicek 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

  39. Harcourt-Brown F (2002) Textbook of rabbit medicine. Butterworth-Heinemann, Oxford

  40. Harcourt-Brown FM (2004) Encephalitozoon cuniculi infection in rabbits. Semin Avian Exot Pet Med 13:86–93

  41. Harcourt-Brown FM, Holloway HKR (2003) Encephalitozoon cuniculi in pet rabbits. Vet Rec 152:427–431

  42. Horváth M, Svicky E, Sevcikova Z (1998) Pathomorphological response to Encephalitozoon cuniculi infection in cyclophosphamide-treated rabbits. Acta Vet (Brno) 67:37–42

  43. Igarashi M, Oohashi E, Dautu G, Ueno A, Kariya T, Furuya K (2008) High seroprevalence of Encephalitozoon cuniculi in pet rabbits in Japan. J Vet Med Sci 70(12):1301–1304

  44. Jass A, Matiasek K, Hartmann K, Küchenhoff H, Fischer A (2006) Evaluierung von Liquoruntersuchung und PCR zur Diagnose der Enzephalitozoonose beim Kaninchen. Prakt Tierarzt 87:518–524

  45. Jass A, Matiasek K, Henke J, Küchenhoff H, Hartmann K, Fischer A (2008) Analysis of cerebrospinal fluid in healthy rabbits and rabbits with clinically suspected encephalitozoonosis. Vet Rec 162(19):618–622

  46. Jordan CN, Zajac AM, Lindsay DS (2006) Encephalitozoon cuniculi infection in rabbits. Compend Contin Educ Vet 28:108–116

  47. Karp BE (1999) Rabies in two privately owned domestic rabbits. J Am Vet Med Assoc 215:1824–1827

  48. Katinka MD, Duprat S, Cornillot E, Méténier G, Thomarat F, Prensier G, Barbe V, Peyretaillade E, Brottier P, Wincker P, Delbac F, El Alaoui H, Peyret P, Saurin W, Gouy M, Weissenbach J, Vivarès CP (2001) Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414(6862):450–453

  49. Katzwinkel-Wladarsch S, Lieb M, Heise W, Löscher T, Rinder H (1996) Direct amplification and species determination of microsporidian DNA from stool specimens. Trop Med Int Health 1:373–378

  50. Katzwinkel-Wladarsch S, Deplazes P, Weber R, Löscher T, Rinder H (1997) Comparison of polymerase chain reaction with light microscopy for detection of microsporidia in clinical specimens. Eur J Clin Microbiol Infect Dis 16:7–10

  51. Keeble EJ, Shaw DJ (2006) Seroprevalence of antibodies to Encephalitozoon cuniculi in domestic rabbits in the United Kingdom. Vet Rec 158:539–544

  52. Khan IA, Moretto M (1999) Role of gamma interferon in cellular immune response against murine Encephalitozoon cuniculi infection. Infect Immun 67(4):1887–1893

  53. Khan IA, Schwartzman JD, Kasper LH, Moretto M (1999) CD8+ CTLs are essential for protective immunity against Encephalitozoon cuniculi infection. J Immunol 162(10):6086–6091

  54. Khan IA, Moretto M, Weiss LM (2001) Immune response to Encephalitozoon cuniculi infection. Microbes Infect 3(5):401–405

  55. Kock NP, Petersen H, Fenner T, Sobottka I, Schmetz C, Deplazes P, Pieniazek NJ, Albrecht H, Schottelius J (1997) Species-specific identification of microsporidia in stool and intestinal biopsy specimens by the polymerase chain reaction. Eur J Clin Microbiol Infect Dis 16:369–376

  56. Koudela B, Vítovec J, Kucerová Z, Ditrich O, Trávnícek J (1993) The severe combined immunodeficient mouse as a model for Encephalitozoon cuniculi microsporidiosis. Folia Parasitol. (Praha) 40(4):279–286

  57. Kunstýř I, Naumann S (1985) Head tilt in rabbits caused by pasteurellosis and encephalitozoonosis. Lab Anim 19:208–213

  58. Künzel F, Gruber A, Tichy A, Edelhofer R, Nell B, Hassan J, Leschnik M, Thalhammer JG, Joachim A (2008) Clinical symptoms and diagnosis of encephalitozoonosis in pet rabbits. Vet Parasitol 151:115–124

  59. Leland MM, Hubbard GV, Dubey JP (1992) Clinical toxoplasmosis in domestic rabbits. Lab Anim Sci 42:318–319

  60. Lev L (1982) Untersuchungen von experimentellen und spontanen Encephalitozoon cuniculi-Infektionen bei Kaninchen mit 3 serologischen Methoden. Dissertation, Veterinary University of Hannover

  61. Levkut M, Lesnik F, Balent P, Levkutová M, Kolodzieyski L, Horváth M (1998) An unusal manifestation of encephalitozoonosis in chinchilla rabbits. Can Vet J 39(9):576–577

  62. Lyngset A (1980) A survey of serum antibodies to Encephalitozoon cuniculi in breeding rabbits and their young. Lab Anim Sci 30:558–561

  63. Mathis A (2000) Microsporidia: emerging advances in understanding the basic biology of these unique organisms. Int J Parasitol 30:795–804

  64. Mathis A, Weber R, Deplazes P (2005) Zoonotic potential of the microsporidia. Clin Microbiol Rev 18:423–445

  65. Méteniér G, Vivarès CP (2001) Molecular characteristics and physiology of microsporidia. Microbes Inf 3:407–415

  66. Metzler A, Ehrensperger F, Wyler R (1978) Natural borna virus infection in rabbits. Zentralbl Veterinarmed B 25(2):161–164

  67. Meyer-Breckwoldt A (1996) Epidemiologische und klinische Untersuchungen zur Encephalitozoonose beim Zwergkaninchen. Dissertation, Veterinary University, Hannover

  68. Müller C (1998) Untersuchungen zur Diagnostik, Biologie und Verbreitung von Microsporidien bei Kaninchen und anderen Tierarten. Dissertation, University of Zürich

  69. Müller K, Fuchs W, Heblinski W, Teifke W, Brunnberg L, Gruber AD, Klopfleisch R (2009) Encephalitis in a rabbit caused by human Herpes virus-1. JAVMA 235(1):66–69

  70. Murray KA, Hobbs BA, Griffith JW (1985) Acute meningoencephalomyelitis in a rabbit infected with Pasteurella multocida. Lab Anim Sci 35(2):169–171

  71. Nast R, Middleton DM, Wheler CL (1996) Generalized encephalitozoonosis in a Jersey wooly rabbit. Can Vet J 37:303–305

  72. Neuschl J, Čonkova E, Krokavec P, Čelarova E, Halanova M, Hipikova V, Balent P, Šutiak V (1999) The development of encephalitozoonosis in rabbits after infection by Encephalitozoon cuniculi and treatment with albendazole. Acta Vet (Beograd) 49(4):327–334

  73. Neuwirt E (1988) Ein Beitrag zur Diagnose der Encephalitozoonose (Nosematose) beim Kaninchen; Vergleich zwischen direkten und indirekten Nachweismethoden. Dissertation, University of Munich

  74. Okewole EA (2008) Seroprevalence of antibodies to Encephalitozoon cuniculi in domestic rabbits in Nigeria. Onderstepoort J Vet Res 75(1):33–38

  75. Pakes SP, Gerrity LW (1994) Protozoal Diseases. In: Manning PJ, Ringler DH, Newcomer CE (eds) The biology of the laboratory rabbit, 2nd edn. Academic, London, pp 205–224

  76. Petri M (1969) Studies on Nosema cuniculi found in transplantable ascites tumors with a survey of microsporidiosis in mammals. Acta Pathol Microbiol Scand 204(Suppl):1–91

  77. Rönnebäumer K, Gross U, Bohne W (2008) The nascent parasitophorous vacuole membrane of Encephalitozoon cuniculi is formed by host cell lipids and contains pores which allow nutrient uptake. Eukaryot Cell 7(6):1001–1008

  78. Santaniello A, Dipineto L, Rinaldi L, Menna LF, Cringoli G, Fioretti A (2009) Serological survey of Encephalitozoon cuniculi in farm rabbits in Italy. Res Vet Sci 87(1):67–69

  79. Scharmann W, Reblin L, Griem W (1986) Untersuchungen über die Infektion von Kaninchen durch Encephalitozoon cuniculi. Berl Münch Tierärztl Wschr 99:20–24

  80. Schmidt EC, Shadduck JA (1983) Murine encephalitozoonosis model for studying the host-parasite relationship of a chronic infection. Infect Immun 40(3):936–942

  81. Shadduck JA (1980) Effect of fumagillin on in vitro multiplication of Encephalitozoon cuniculi. J Protozool 27(2):202–208

  82. Shadduck JA, Pakes SP (1971) Encephalitozoonosis (nosematosis) and toxoplasmosis. Am J Pathol 64(3):657–673

  83. Shadduck JA, Watson WT, Pakes SP, Cali A (1979) Animal infectivity of Encephalitozoon cuniculi. J Parasitol 65:123–129

  84. Snyder SB, Fox JG, Soave OA (1973) Sub-clinical otitis media associated with Pasteurella multocida infections in New Zealand White rabbits (Oryctolagus cuniculus). Lab Anim Sci 23(2):270–272

  85. Stiles J, Didier E, Ritchie B, Greenacre C, Willis M, Martin C (1997) Encephalitozoon cuniculi in the lens of a rabbit with phacoclastic uveitis: confirmation and treatment. Vet Comp Ophthalmol 7:233–238

  86. Suter C, Müller-Doblies UU, Hatt JM, Deplazes P (2001) Prevention and treatment of Encephalitozoon cuniculi infection in rabbits with fenbendazole. Vet Rec 148:478–480

  87. Thomas WB (2000) Vestibular dysfunction. Vet Clin N Am: Small Anim Pract 30:227–249

  88. Thomas C, Finn M, Twigg L, Deplazes P, Thompson RC (1997) Microsporidia (Encephalitozoon cuniculi) in wild rabbits in Australia. Aust Vet J 75(11):808–810

  89. Von Kücken U, Ludwig HJ, Lange S, Günther H, Dix B, Lange M, Müller D (1987) Eine generalisierte Erkrankung des Kaninchens durch Encephalitozoon cuniculi. Mh Vet Med 42:781–784

  90. Waller T (1977) The India ink immunoreaction: a method for the rapid diagnosis of encephalitozoonosis. Lab Anim 11:93–97

  91. Waller T (1979) Sensitivity of Encephalitozoon cuniculi to various temperatures, disinfectants and drugs. Lab Anim 13:227–230

  92. Waller T, Morein B, Fabiansson E (1978) Humoral immune response to infection with Encephalitozoon cuniculi in rabbits. Lab Anim 12:145–148

  93. Wasson K, Peper RL (2000) Mammalian microsporidiosis. Vet Pathol 37:113–128

  94. Weber R, Mathis A, Deplazes P (1996) Intestinal and systemic infections due to microsporidia. Internist 37:912–918

  95. Weber R, Schwartz DA, Deplazes P (1999) Laboratory Diagnosis of Microsporidiosis. In: Wittner M, Weiss LM (eds) The Microsporidia and Microsporidiosis. American Society for Microbiology, Washington, D.C., pp 315–362

  96. Weissenböck H, Hainfellner JA, Berger J, Kasper I, Budka H (1997) Naturally occurring herpes simplex encephalitis in a domestic rabbit (Oryctolagus cuniculus). Vet Pathol 34(1):44–47

  97. Wicher V, Baughn RE, Fuentealba C, Shadduck JA, Abbruscato F, Wicher K (1991) Enteric infection with an obligate intracellular parasite, Encephalitozoon cuniculi, in an experimental model. Infect Immun 59:2225–2231

  98. Williams DL (1999) Laboratory Animal Ophthalmology. In: Gelatt KN (ed) Veterinary Ophthalmology, 3rd edn. Lippincott Williams and Wilkins, Philadelphia, pp 1209–1236

  99. Wilson JM (1979) Encephalitozoon cuniculi in wild European rabbits and a fox. Res Vet Sci 26:114

  100. Wolfer J, Grahn B, Wilcock B, Percy D (1993) Phacoclastic uveitis in the rabbit. Prog Vet Comp Ophthalmol 3:92–97

  101. Wright JH, Craighead EM (1922) Infectious motor paralysis in young rabbits. J Exp Med 36:135–140

  102. Xu Y, Weiss LM (2005) The microsporidian polar tube: a highly specialised invasion organelle. Int J Parasitol 35:941–953

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Correspondence to Frank Künzel.

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Künzel, F., Joachim, A. Encephalitozoonosis in rabbits. Parasitol Res 106, 299–309 (2010).

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  • Nest Polymerase Chain Reaction
  • Albendazole
  • Bovine Leukaemia Virus
  • Head Tilt
  • Otitis Externa