Difference between revisions of "Encephalitozoon cuniculi"

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

Revision as of 01:17, 11 August 2010



Taxonomy

  • Phylum Microspora; no mitochondria polar tube polar cap
  • Class Microsporida
  • Order Microsporidia
  • May be more related to fungi than to protozoa (Wasson and Peper 2000)
  • Obligate intracellular protozoan parasite
  • 52% normal healthy domestic pet rabbits arte infected (Keeble and Shaw 2006)
  • Ubiquitous in other species too

The life cycle

The life cycle of this coccidian is 3 – 4 weeks in total:

  • Inhaled, ingested or transplacental – rabbits of 4 – 6 weeks appear most vulnerable
  • In utero infections => invasion of foetal lens => => => => => => multiplication and euption of spores later in the rabbit’s life => cataracts, lens rupture and phacoclastic uveitis
  • Invasion of the mucosa per polar tube
  • Spiroplasm extruded and multiplication occurs in vacuole
  • Distribution by reticulo-endothelial cells => invasion of organs with high blood flow
  • Invasion of target organs
  • Intracellular multiplication, cell rupture (=> inflammation) and invasion of neighbouring cells or passage to circulation in 3-4 weeks
  • Shedding in urine 35 days after initial infection.

Presentations of Encephalitozoon cuniculi in pet rabbits

  • Granulomatous nephritis or interstitial infiltration of lymphocytes and plasma cells
    • Usually asymptomatic
    • Possibly haematuria
    • Incontinence could be neurological in origin
    • Treat with benzimidazoles and antibiotics
  • Pyogranulomatous phacoclastic uveitis
    • See treatment under iridal abscesses
    • Use topical ophthalmic preparations, parenteral oxytetracycline and a benzimidazole
  • Neurological manifestation of E. cuniculi infection: granulomatous encephalitis
    • Sometimes perivascular infiltration with lymphocytes and plasma
    • All areas of the brain
    • Torticollis
    • Treatment
      • Initial short-acting corticosteroids, parenteral oxytetracycline and benzimidazoles awaiting lab results
      • Vestibular agents

Transmission of Encephalitozoon cuniculi

  • Shedding in urine
  • Oral and tracheal access
  • Neonates can be infected but can also receive immunity from dam.
  • Ecto- and endo-parasites? May aid in transmission
  • Provision of recently cut short grass gathered from the wild

Pathology

  • Principal target organs are kidney, brain, spinal cord
  • Other target organs include liver and heart
  • Rupture of host cell => invasion of neighbouring cells => chronic, granulomatous inflammation.
  • In utero infections => invasion of foetal lens => => => => => => multiplication and eruption of spores later in the rabbit’s life => cataracts, lens rupture and phacoclastic uveitis

Survival of Encephalitozoon cuniculi in the environment

  • Survives in extreme cold or heat
  • At average temperature and in dry conditions it survives 4 weeks
  • Easily killed by routine disinfection

Diagnosis

  • Urine microscopy (35 days after initial infection)
  • Serology – antibodies develop soon after infection but clinical signs take much longer (several weeks)
  • 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)
  • PCR
  • CSF analysis
    • Procedure:
      • Propofol and intubation
      • Head flexed 90º to spine
      • 38mm 22G spinal needle in cisterna magna
      • 700-1000μl sample.
      • Vestibular signs are accentuated for up to 8hrs post sampling.
    • Findings
      • Lymphomonocytic pleocytosis 15 cells/μl (n=1.5 /μl)
      • Increased protein 0.79g/μl (n= 0.24g/μl)
      • Unfortunately other viral, protozoan or immune-mediated encephalitis may induce similar lymphomonocytic pleocytosis

Interpretation of Encephalitozoon antibody tests (Keeble 2007)

Single positive result in healthy rabbit

  • Recent infection prior to development of clinical signs
  • Chronically infected with no clinical signs
  • Previously infected and recovered
  • Antibody levels can persist for many years in symptomless animals

Single positive result in rabbit with clinical signs of encephalitozoonosis

  • Could be active Encephalitozoon cuniculi infection (or other infection causing signs)

Single negative result in healthy rabbit

  • Could be free from infection
  • Could be infected less than 2 weeks ago
  • Retest in four weeks

Single negative result in rabbit with clinical signs of encephalitozoonosis

  • Rules out Encephalitozoon cuniculi infection as the cause of clinical signs
  • Advise further tests
    • renal biopsy
    • CSF analysis
    • mononulear pleocytosis and elevated protein
    • MRI/CT scans

To establish an Encephalitozoon-free colony

  • Test fortnightly for two months or until all animals are negative for a month, whichever is longer
  • Sacrifice any positive cases

Treatment

  • Albendazole q 24 hrs - ?teratogenic (Pollock 2006)
  • Fenbendazole q 24 hrs
  • Oxytetracycline SC q 72hrs.
  • Three possible therapies – my cocktail is albendazole and oxytetracycline as shown above.
  • Vestibular-calming agents
  • Environmental disinfection
  • Corticosteroids

References