Last reviewed: June 2020
Last updated: May  2018



History and exam

Key diagnostic factors

  • progressive headache
  • severe headache
  • meningismus
  • symptoms of hydrocephalus (impaired cognitive function, confusion, coordination and gait disturbances, and urinary incontinence)
  • behavioral or personality change
  • reduced visual acuity and papilledema

Other diagnostic factors

  • nausea or vomiting
  • fever
  • reduced conscious level
  • cranial nerve palsies
  • seizures
  • weight loss
  • mouth ulcers
  • focal neurologic signs
  • lymphadenopathy, hepatosplenomegaly
  • dyspnea
  • papular umbilicated skin lesions
  • retinal defects
  • nasal or palatal eschar

Risk factors

  • HIV infection
  • corticosteroid use
  • underlying chronic disease (e.g., malignancy, organ failure, autoimmune disease, organ transplant)
  • residing in or visiting northern Australia, Papua New Guinea, or Vancouver Island, Canada
  • exposure to disturbed soil, chicken guano, or bat caves
  • impaired cell-mediated immunity
  • Filipinos and African Americans
  • neutropenia or impaired phagocytic function
  • neurosurgery
  • infants and neonates
  • central vascular catheters
  • sinonasal disease
  • antibacterial usage
  • prior surgery
  • hyperalimentation
  • intravenous drug abuse

Diagnostic investigations

1st investigations to order

  • CT and/or MRI head scan
  • fungal blood cultures (3 sets)
  • serum cryptococcal antigen test
  • serum + urine Histoplasma antigen
  • immunodiffusion tests (IgM and IgG) and complement fixation test (IgG) for coccidioidomycosis
  • CSF opening pressure
  • CSF WBC and differential
  • CSF protein
  • CSF glucose
  • CSF India ink stain
  • CSF culture
  • CSF cryptococcal polysaccharide antigen test
  • CSF Histoplasma antigen
  • CSF Histoplasma antibodies
  • CSF coccidioidal IgG antibodies
  • CSF galactomannan antigen test
More 1st investigations to order

Investigations to consider

  • histopathology and culture of biopsies: meningeal, brain, extraneural sites of involvement
  • PCR
More investigations to consider

Emerging tests

  • 18F-FDG PET/CT
  • CSF (1-3)-beta-D-glucan
More emerging tests

Treatment algorithm


Consultant Neurologist

Clinical Lead of Neuroinflammation

Department of Neurology

Queen's Hospital




AC has received honoraria, speaker fees, and travel or international meeting sponsorship from Biogen, Genzyme, Merck, Novartis and Teva; he may receive travel and/or meeting sponsorship from Bial and Genzyme in 2018-2019. AC has attended or may attend the Advisory Board meetings for product development and/or marketing with Bial, Merck, Novartis, and Teva. AC declares that these posts and payments do not constitute any competing interest in relation to the topic of fungal meningitis.

Dr Abhijit Chaudhuri would like to gratefully acknowledge Dr Thomas S. Harrison and Dr Angela Loyse, previous contributors to this monograph. TSH and AL declare that they have no competing interests.

Peer reviewersVIEW ALL

Associate Professor of Medicine

University of Southern California

Keck School of Medicine

Los Angeles



RAL declares that he has no competing interests.

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