New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis

Curr Neurol Neurosci Rep. 2019 Oct 31;19(10):81. doi: 10.1007/s11910-019-0993-0.

Abstract

Purpose of review: Defective cell-mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM.

Recent findings: Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200 mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4-6 weeks to prevent immune reconstitution inflammatory syndrome, common in CM. CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.

Keywords: Cryptococcal antigen; Cryptococcus; Induction therapy; Intracranial pressure; Lateral flow assay.

Publication types

  • Review

MeSH terms

  • Amphotericin B / therapeutic use*
  • Antifungal Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / methods
  • Cryptococcus / physiology*
  • Drug Therapy, Combination
  • Fluconazole / therapeutic use*
  • Flucytosine / therapeutic use*
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • Humans
  • Immunologic Deficiency Syndromes / diagnosis
  • Intracranial Hypertension / surgery
  • Meningitis, Cryptococcal* / diagnosis
  • Meningitis, Cryptococcal* / drug therapy
  • Meningitis, Cryptococcal* / prevention & control
  • Risk Factors

Substances

  • Antifungal Agents
  • Amphotericin B
  • Fluconazole
  • Flucytosine

Supplementary concepts

  • Immune Deficiency Disease