Outcomes of central nervous system cryptococcosis vary with host immune function: results from a multi-center, prospective study

J Infect. 2010 Nov;61(5):419-26. doi: 10.1016/j.jinf.2010.08.004. Epub 2010 Aug 21.

Abstract

Background: Central nervous system (CNS) cryptococcosis is most commonly encountered among HIV-infected and other immunosuppressed hosts but is less well-characterized among non-immunosuppressed patients.

Methods: We conducted a three year, prospective, observational study to compare the clinical manifestations and outcome of CNS cryptococcosis in three patient populations: HIV-infected patients (n = 54), HIV-negative immunosuppressed patients (n = 21), and non-immunosuppressed patients (n = 11).

Results: Time from initial symptoms to presentation did not differ between the groups. HIV-infected patients were significantly more likely to present with fevers (p < 0.0001), but were less likely to have abnormal mental status, CNS mass lesions and pulmonary involvement (p = 0.001, 0.01 and 0.03, respectively). The clinical manifestations among HIV-negative immunosuppressed patients were generally intermediate to the other groups. Overall, acuity of illness was worse among non-immunosuppressed patients, as measured by APACHE II scores (p = 0.02). Intracranial pressure was higher in HIV-infected and non-immunosuppressed patients than immunosuppressed patients (p = 0.008 and 0.01, respectively). Repeated lumbar punctures were more common among HIV-infected patients (p = 0.01). There was a trend toward more frequent placement of permanent CNS shunts among non-HIV patients (p = 0.05). The mortality rate was greatest for non-immunosuppressed patients (p = 0.04).

Conclusion: CNS cryptococcosis in non-immunosuppressed patients was associated with poorer prognosis. Our findings suggest that host immune responses may contribute to pathogenesis of CNS cryptococcosis, with more intact immune function associated with increased CNS-related morbidity and overall mortality.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • APACHE
  • Adult
  • Antifungal Agents / therapeutic use
  • Australia / epidemiology
  • CD4 Lymphocyte Count
  • Central Nervous System Fungal Infections / complications
  • Central Nervous System Fungal Infections / immunology*
  • Central Nervous System Fungal Infections / mortality
  • Central Nervous System Fungal Infections / physiopathology*
  • Central Nervous System Fungal Infections / therapy
  • Cerebrospinal Fluid Shunts
  • Cryptococcosis / complications
  • Cryptococcosis / immunology*
  • Cryptococcosis / mortality
  • Cryptococcosis / physiopathology*
  • Cryptococcosis / therapy
  • Cryptococcus / isolation & purification
  • HIV Infections / complications
  • Humans
  • Immunocompetence*
  • Immunocompromised Host*
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • Taiwan / epidemiology
  • Treatment Outcome
  • United States / epidemiology

Substances

  • Antifungal Agents