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Cryptococcus
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Cryptococcus
1.
Epidemiology/Microbiology
·
Worldwide distribution, incidence 8 times higher
in cats than dogs.
·
2 species cause disease:
o
C. neoformans – primarily infects
immunocompromised people, viable for 2 years in environment (mostly pigeon
guano).
o
C. gatti – primarily associated with tropical
climates. Found in plant material and soil (proximity to areas with soil
disturbance is a risk factor in dogs/cats).
·
Transmission primarily through inhalation.
·
Nasal cavity likely primary site of infection in
dogs/cats (lungs in humans), may lead to mycotic rhinitis or be asymptomatic.
Once infection is established haematogenous spread to other sites, especially
CNS. Incubation period is 2-13 months. Other sites include eye (optic
neuritis/retinitis), skin, mandibular lymph nodes.
2.
Clinical
Findings
·
Cats – young adult (2-3 years) increased risk,
median age 6years.
·
Dogs – young adult (50% under 4y), median age
4y.
·
Cats
o
Often chronic causing listlessness and weight
loss.
o
URT – sneezing, MP nasal discharge, sometimes epistaxis
(unilateral or bilateral). Sometimes visible polyp in nostril, swelling over
bridge of nose.
o
LRT (uncommon) – tachypnoea/cough
o
Neuro – obtundation, temperament change, twitching,
seizures, circling, ataxia.
o
Ocular – retinitis, retinal detachment, less
commonly uveitis.
o
Cutaneous – solitary or multiple soft tissue
masses on bridge of nose. Multifocal, ulcerative skin lesions.
o
Other – lymph node enlargement, renal
involvement.
·
Dogs
o
Often develop severe disseminated disease.
o
Commonly affected organ systems – CNS
(multifocal), eyes, urinary system, nasal cavity
3.
Diagnostic
Investigations (incl sens/spec)
·
Routine bloods – non-specific change, often
neutrophilia (dogs).
·
CSF (if neuro signs) – elevated protein &
leukocytes (mixed cellular pleocytosis, occasionally eosinophilic).
·
Cytology/histo – nasal swabs/washing, FNA’s of
masses, BAL, pleural fluid, CSF, urine – readily identify organism.
·
Fungal culture
·
Serology – cryptococcal polysaccharide capsular
antigen on serum or CSF. 90 to 100% sensitivity, 97 to 100% specificity.
·
PCR also available.
4.
Treatment/prognosis
(incl MST & prognostic factors)
·
Surgery
o
Surgical excision of large aggregates of fungus
infected tissues may be beneficial and improve response to therapy.
·
Drug therapy – ideally based on sensitivity
testing
o
Amphotericin B – fungicidal and ?
proinflammatory so improving host immunity.
o
Flucytosine – used in combination with
amphotericin as rapid resistance develops if used alone. Good penetration into
CSF. Frequently causes cutaneous drug reaction after 10-14 days.
o
Fluconazole – most effective azole for crypto.
·
Specific management regimens:
o
Cats with mild to moderate disease and no CNS
involvement – Fluconazole until resolution of CS. Monitor antigen levels during
treatment. Typically this takes 2-12 months (median 4 months).
o
Cats with severe disease, CNS involvement or
failed to respond above – Combination of amphotericin B and flucytosine.
o
Dogs – Start with amphotericin B then move to an
azole.
·
Relapse reported as long as 10 years later so
suggest continue therapy until antigen titer is zero.
·
Prognosis:
o
Cats – Approximately 75% treated successfully,
30% relapse rate. CNS disease negative prognostic factor.
o
Dogs – 55% treated successfully in one study,
20-30% in another. Again CNS signs may be negative factor.
Recent Literature:
·
Terbinafine reported to be successful for
treatment of a dog with intestinal crypto, who had not responded to
amphotericin and fluconazole.
·
Report of a cat with coinfection with crypto and
mycobacterium avium.
·
Report of a cat infected with c. magnus