Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis

The Journal of Infectious Diseases, 09/09/2013

The authors investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype. Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis.

Methods

  • In total, 134 human immunodeficiency virus (HIV)–infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines; 108 had complete data.
  • Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.

Results

  • Cryptococcal strains producing larger ex vivo capsules in the baseline (pretreatment) CSF correlated with higher ICP (P = .02), slower rate of fungal clearance (P = .02), and paucity of CSF inflammation, including decreased CSF white blood cell (WBC) count (P < .001), interleukin (IL)–4 (P = .02), IL–6 (P = .01), IL–7 (P = .04), IL–8 (P = .03), and interferon γ (P = .03).
  • CSF capsule shedding did not correlate with ICP.
  • On multivariable analysis, capsule size remained independently associated with ICP.
  • Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro.

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