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CRYPTOCOCCAL INFECTIONS IN PATIENTS WITH AIDS. Stephen J. Gluckman, M.D. Botswana-UPENN Partnership. Microbiology. Encapsulated yeast 4 serotypes A ( C. neoformans v grubii ) B and C ( C. gatti ) D ( C. neoformans v neoformans ) All types can cause human disease Life cycle

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cryptococcal infections in patients with aids

CRYPTOCOCCAL INFECTIONS IN PATIENTS WITH AIDS

Stephen J. Gluckman, M.D.

Botswana-UPENN Partnership

microbiology
Microbiology
  • Encapsulated yeast
  • 4 serotypes
    • A (C. neoformans v grubii)
    • B and C ( C. gatti)
    • D (C. neoformans v neoformans)
  • All types can cause human disease
  • Life cycle
    • Asexual: yeast that reproduce by budding
      • Human infections
    • Sexual: only seen in the laboratory
ecology and epidemiology
Ecology and Epidemiology
  • World wide
    • C. neoformans associated with bird droppings
    • C. gatti not associated with birds, associated with eucalyptus trees
  • Generally an infection of immunocompromised but can cause clinical disease in healthy persons
    • Decreased Cell-mediated immunity
      • AIDS – CD 4 usually < 100
      • Prolonged corticosteroids
      • Organ transplant
ecology and epidemiology4
Ecology and Epidemiology
  • 15-30% of AIDS patients in Sub-Saharan Africa*
  • Much less common in children
  • No person to person transmission

*Powderly, WG Clin Infect Dis 1993

clinical presentations
Clinical Presentations
  • Pulmonary
    • Asymptomatic nodule
    • Symptomatic: not distinguishable from other causes
      • History, PE, routine laboratory testing does not produce features peculiarly suggestive of cryptococcal infection
    • Diagnosis
      • Staining of biopsy specimen
      • Culture of sputum and/or blood
      • Serum cryptococcal antigen (CRAG)
    • All patients with pulmonary disease need a CSF examination to r/o sub clinical meningitis
clinical presentations7
Clinical Presentations
  • Cutaneous
    • Disseminated disease
    • Looks similar to molluscum contageosum
    • Diagnosis:
      • Unroofing a lesion and making a smear and culture
      • Serum CRAG
    • All patients with cutaneous disease need a CSF examination to r/o sub clinical meningitis
clinical presentations10
Clinical Presentations
  • Cryptococcal Meningitis
    • Typical
      • Subacute onset of fever and headache
      • Photophobia and/or meningeal signs in only 25%
    • Less typical
      • Seizures
      • Confusion
      • Progressive dementia
      • Visual or hearing impairment
      • FUO
    • Diagnosis
      • CSF
      • Serum CRAG: > 99% sensitive in AIDS patients
cryptococcal meningitis
Cryptococcal Meningitis
  • In 2003 there were 193 (+) CSF cultures for cryptococcus from PMH *
    • Leucocytes
      • No leucocytes in 31%
      • Only 1-10 leucocytes in 23%
      • 7% had > 250 leucocytes
        • 30% of these had predominately PMN’s
    • 95% (+) India Ink
    • 1% (-) cryptococcal antigen
      • Literature
        • Sensitivity: 93-100%
        • Specificity: 93-98 %

*Bisson et al

prognosis for cryptococcal meningitis
Prognosis for Cryptococcal Meningitis
  • Prior to 1950 it was uniformly fatal
  • Amphotericin B introduced and mortality fell to the 30-40% range
  • In 1970’s 5-FC was released
    • Not for monotherapy
    • Decreased relapse rate when used with Amphotericin B
  • Mortality with current regimens: 10%
  • Predictors of death
    • Altered mental status
    • CSF CRAG > 1024
    • CSF cell count < 20
  • Changes in serum CRAG titer do not correlate with clinical outcome. So no need to follow
summary of diagnostic options
Summary of Diagnostic Options
  • Culture
    • White mucoid colonies within 48hours
    • Blood cultures often (+) in immunosuppressed patients
      • 2/3rds with meningitis
  • Tissue
    • Silver or mucicarmine stain
  • India Ink for CSF
  • Cryptococcal antigen
    • Serum and CSF are 99% sensitive in AIDS patients
    • Serum is less sensitive in normal hosts
cryptococcal meningitis treatment
Cryptococcal MeningitisTreatment
  • Antifungal agents
    • Induction
    • Consolidation
    • Maintenance
  • Pressure management
treatment modified idsa guidelines
Treatment**Modified IDSA Guidelines
  • Immunosuppressed (pulmonary, cutaneous, or meningitis)
    • Induction
      • Amphotericin B 0.7-1 mg/kg/day plus 5-flucytosine 100mg/kg/day x 2 weeks then
    • Consolidation
      • Fluconazole 400 mg/day x 6-10 weeks then
    • Suppression
      • Fluconazole 200 mg/day x ?
cryptococcal meningitis treatment one more thing
Cryptococcal MeningitisTreatmentOne More Thing
  • Anti-fungal: induction, consolidation, maintenance
  • Pressure management
    • Elevated pressure
      • 75% > 200
      • 25% > 350
    • Repeated lumbar punctures
      • Increased pressure: daily until normal x several days
      • Normal pressure: recheck at 2 weeks prior to switching to fluconazole
    • Lumbar drain
    • VP shunt: if still elevated at 1 month
    • No role for
      • acetazolamide, mannitol
    • Steroids: ?
treatment
Treatment
  • Other options
    • Fluconazole induction
      • Increased mortality
      • Not IDSA first choice
    • 5 FC monotherapy
      • Not an option because of resistance
    • 5-FC plus Fluconazole
      • Increased long term toxicity but an option
    • Caspofungin
      • No efficacy
    • Voriconazole
      • Good in vitro activity but little clinical experience
summary
Summary
  • Cryptococcal infections are common in patients with AIDS
  • In patients with AIDS cryptococcal infections are seen in patients with the lowest CD 4 (+) cell counts
  • Prolonged therapy and secondary prophylaxis is necessary
  • For meningitis both anti-fungal therapy and aggressive pressure management are required