Cryptococcus

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