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