Encephalitozoon cuniculi

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 10 mg/kg q 24 hrs - ?teratogenic (Pollock 2006)
• Fenbendazole 20 mg/kg q 24 hrs
• Oxytetracycline 30 mg/kg SC q 72hrs.
• Three possible therapies – my cocktail is albendazole and oxytetracycline as shown above.
• Vestibular-calming agents
• Environmental disinfection
• Corticosteroids