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{{OpenPagesTop}}
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{{Taxobox
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|name              = ''Encephalitozoon cuniculi
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|kingdom            = Fungi
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|phylum            = Microspora
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|class              = Microsporida
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|sub-class          =
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|order              = Microsporidia
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|super-family      =
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|family            =
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|sub-family        =
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|genus              = ''Encephalitozoon
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|species            = ''E. cuniculi
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}}
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Causes '''''Encephalitozoonosis'''''
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==Taxonomy==
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==Introduction==
*Phylum Microspora; no mitochondria polar tube polar cap
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''E. cuniculi'' is a '''microsporidian protozoan''' parasite infecting a wide range of hosts. At least three strains have been identified on the basis of host specificity and other criteria.
*Class Microsporida
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*Order Microsporidia
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*May be more related to fungi than to protozoa (Wasson and Peper 2000)
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*Obligate intracellular protozoan parasite
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*52% normal healthy domestic pet rabbits arte infected (Keeble and Shaw 2006)
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*Ubiquitous in other species too
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==The life cycle==
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It has recently been found to be more related to fungi than to protozoa.
The life cycle of this coccidian is 3 – 4 weeks in total:
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*Inhaled, ingested or transplacental – rabbits of 4 – 6 weeks appear most vulnerable
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*In utero infections => invasion of foetal lens  => => => => => => multiplication and euption of spores later in the rabbit’s life => cataracts, lens rupture and phacoclastic [[Uveitis – Rabbit|uveitis]]
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*Invasion of the mucosa per polar tube
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*Spiroplasm extruded and multiplication occurs in vacuole
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*Distribution by reticulo-endothelial cells => invasion of organs with high blood flow
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*Invasion of target organs
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*Intracellular multiplication, cell rupture (=> inflammation) and invasion of neighbouring cells or passage to circulation in 3-4 weeks
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*Shedding in urine 35 days after initial infection.
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==Presentations of ''Encephalitozoon cuniculi'' in pet rabbits==
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Usually, no clinical signs are seen and '''approximately 50% of healthy domestic pet rabbits are thought to be infected'''.
*Granulomatous nephritis or interstitial infiltration of lymphocytes and plasma cells
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**Usually asymptomatic
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**Possibly haematuria
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**Incontinence could be neurological in origin
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**Treat with benzimidazoles and antibiotics
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*Pyogranulomatous phacoclastic [[Uveitis – Rabbit|uveitis]]
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**See treatment under [[Iridal Abscesses – Rabbit|iridal abscesses]]
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**Use topical ophthalmic preparations, parenteral oxytetracycline and a benzimidazole
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*Neurological manifestation of ''E. cuniculi'' infection: granulomatous encephalitis
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**Sometimes perivascular infiltration with lymphocytes and plasma
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**All areas of the brain
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**[[Head Tilt – Rabbit|Torticollis]]
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**Treatment
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***Initial short-acting corticosteroids, parenteral oxytetracycline and benzimidazoles awaiting lab results
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***Vestibular agents
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==Transmission of ''Encephalitozoon cuniculi''==
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==Life Cycle==
*Shedding in urine
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The life cycle of this coccidian takes 3 – 4 weeks in total to complete:
*Oral and tracheal access
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*Neonates can be infected but can also receive immunity from dam.
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*Ecto- and endo-parasites? May aid in transmission
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*Provision of recently cut short grass gathered from the wild
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==Pathology==
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The spore extrudes its polar tube and infects the host cell. It injects the infective spiroplasm into the cell where it undergoes extensive multiplication, which occurs inside a vacuole. Once the spores increase in number and obliterate the host cell cytoplasm, the cell membrane is disrupted and spores are released and free to infect new cells. Reticulo-endothelial cells are responsible for distributing the organism in the body, and organs with a high blood flow are commonly affected.
*Principal target organs are kidney, brain, spinal cord
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*Other target organs include liver and heart
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*Rupture of host cell => invasion of neighbouring cells => chronic, granulomatous inflammation.
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*In utero infections => invasion of foetal lens  => => => => => => multiplication and eruption of spores later in the rabbit’s life => cataracts, lens rupture and phacoclastic [[Uveitis – Rabbit|uveitis]]
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==Survival of ''Encephalitozoon cuniculi'' in the environment==
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Shedding in the urine occurs 35 days after initial infection.
*Survives in extreme cold or heat
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*At average temperature and in dry conditions it survives 4 weeks
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==Transmission==
*Easily killed by routine disinfection
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Transmission is usually via inhalation or '''ingestion of spores''' from contaminated tissues, food items or infected urine. Rabbits aged 4-6 weeks appear most vulnerable to infection.
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Neonates can be infected '''trans-placentally''' but can also receive immunity from the dam.
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==Clinical Signs==
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Infection is '''usually asymptomatic''', but clinical signs may include:
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'''Neurological signs''': incontinence, [[Head Tilt – Rabbit|head tilt]], obtundation, paralysis, seizures
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'''Polyuria, polydipsia''' if the kidneys have been infiltrated
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With in utero infections, there is invasion of the foetal lens and development of '''phacoclastic [[Uveitis – Rabbit|uveitis]], cataracts and lens rupture'''.
    
==Diagnosis==
 
==Diagnosis==
*Urine microscopy (35 days after initial infection)
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'''Urine microscopy''' can be performed 35 days after initial infection.
*Serology antibodies develop soon after infection but clinical signs take much longer (several weeks)
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*Antibodies demonstrated 2 weeks before organisms can be demonstrated intracellularly and 4 weeks before histopathological changes are demonstrated in kidney or organisms demonstrated in urine (Harcourt Brown 2002)
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'''Serology''': antibodies develop soon after infection but clinical signs take much longer (several weeks). Antibodies can be demonstrated 2 weeks before organisms are found intracellularly and 4 weeks before histopathological changes are demonstrated in the kidney.
*PCR
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*CSF analysis
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'''[[PCR]]'''
**Procedure:  
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***Propofol and intubation
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'''CSF analysis''': will show lymphomonocytic pleocytosis, increased protein, but these are non-specific findings.
***Head flexed 90º to spine
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***38mm 22G spinal needle in cisterna magna
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On '''post-mortem examination''': principal target organs are the kidney, brain and spinal cord, but other targets may include the liver and heart. Lesions are often confined to the kidney and appear as focal, irregular, compressed areas, pale grey or white in colour.
***700-1000μl sample.
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***Vestibular signs are accentuated for up to 8hrs post sampling.
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**Findings
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***Lymphomonocytic pleocytosis 15 cells/μl (n=1.5 /μl)
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***Increased protein 0.79g/μl (n= 0.24g/μl)
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***Unfortunately other viral, protozoan or immune-mediated encephalitis may induce similar lymphomonocytic pleocytosis
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==Interpretation of Encephalitozoon antibody tests (Keeble 2007)==
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'''Histopathology''' will reveal granulomatous lesions in the target organs, with periportal lymphocytic infiltration. Organisms can usually be readily demonstrated in the organs. In the kidneys, there is granulomatous nephritis or interstitial infiltration of lymphocytes and plasma cells.
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==Interpretation of ''Encephalitozoon'' serology==
 
===Single positive result in healthy rabbit===
 
===Single positive result in healthy rabbit===
*Recent infection prior to development of clinical signs
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This may represent:
*Chronically infected with no clinical signs
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:Recent infection prior to development of clinical signs
*Previously infected and recovered
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:Chronically infected with no clinical signs
*Antibody levels can persist for many years in symptomless animals
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:Previously infected and recovered as antibody levels can persist for many years in symptomless animals
    
===Single positive result in  rabbit with clinical signs of encephalitozoonosis===
 
===Single positive result in  rabbit with clinical signs of encephalitozoonosis===
*Could be active Encephalitozoon cuniculi infection (or other infection causing signs)
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:This could be an active ''Encephalitozoon cuniculi'' infection (or another infection causing the same clinical signs).
    
===Single negative result in healthy rabbit===
 
===Single negative result in healthy rabbit===
*Could be free from infection
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:This may signify that the rabbit is free from infection  
*Could be infected less than 2 weeks ago
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:Or it may have been infected less than 2 weeks ago.
*Retest in four weeks
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The rabbit should be retested in four weeks.
    
===Single negative result in  rabbit with clinical signs of encephalitozoonosis===
 
===Single negative result in  rabbit with clinical signs of encephalitozoonosis===
*Rules out ''Encephalitozoon cuniculi'' infection as the cause of clinical signs
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:This rules out ''Encephalitozoon cuniculi'' infection as the cause of the clinical signs.
*Advise further tests
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**renal biopsy
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Further tests may be advisable, including CSF analysis, MRI scans or a renal biopsy
**CSF analysis
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**mononulear pleocytosis and elevated protein
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==Treatment==
**MRI/CT scans
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Usual treatment is '''fenbendazole daily for 4 weeks'''.
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'''Albendazole''' has also been used for up to 10 days.
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'''Oxytetracycline''' kills the parasite but care must be taken with causing [[Antibiotic-Associated Dysbacteriosis|antibiotic-induced diarrhoea]].
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'''Corticosteroids''' may be helpful in suppressing the inflammatory response and resolving clinical signs.
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It is important to never guarantee a cure, as clinical signs may abate with treatment but may recur once it is stopped.
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To establish a '''disease-free colony''', screening and culling on positive cases can be performed, testing fortnightly for two months.
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''E. cuniculi'' is a '''potential zoonosis''' and immunosuppressed individuals should not come into contact with an infected rabbit.
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{{Learning
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|flashcards = [[Rabbit Medicine and Surgery Q&A 11]]
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|full text = [http://www.cabi.org/cabdirect/FullTextPDF/2010/20103220029.pdf ''' Encephalitozoon cuniculi-associated phacoclastic uveitis in the rabbit: a review.''' Donnelly, T. M.; Veterinary Learning Systems, Yardley, USA, Journal of Exotic Mammal Medicine and Surgery, 2003, 1, 1, pp 1-3, 18 ref]
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}}
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==References==
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Sayers, I. (2011) '''Rabbit Medicine, E. cuniculi''' ''RVC Small mammal elective student notes''
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Baker, D. (2003) '''Natural pathogens of laboratory animals''' ''ASM Press''
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Percy, D. (2007) '''Pathology of laboratory rodents and rabbits''' ''John Wiley and Sons''
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{{review}}
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===To establish an Encephalitozoon-free colony===
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{{OpenPages}}
*Test fortnightly for two months or until all animals are negative for a month, whichever is longer
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*Sacrifice any positive cases
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===Treatment===
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[[Category:Rabbit Parasites]]
*Albendazole q 24 hrs - ?teratogenic (Pollock 2006)
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[[Category:Expert Review - Exotics]]
*Fenbendazole q 24 hrs
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[[Category:Zoonoses]]
*Oxytetracycline SC q 72hrs.
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[[Category:Rabbit Neurology]]
*Three possible therapies – my cocktail is albendazole and oxytetracycline as shown above.
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*Vestibular-calming agents
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*Environmental disinfection
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*Corticosteroids
 
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