Cryptococcal Meningitis

Shmuel Shoham, M.D.
Cryptococcal Meningitis is a topic covered in the Johns Hopkins ABX Guide.

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PATHOGENS

  • Two main species complexes of Cryptococcus are important for human disease.
    • Cryptococcus neoformans
      • This is the predominant pathogen (~80% of human cryptococcosis cases) and is the most common cause of non-viral meningitis in people.
      • Worldwide distribution. Particularly prevalent in soil contaminated by guano.
      • Nomenclature is in flux with some arguing for two species (C. neoformans and C. deneoformans) while others arguing for a more comprehensive term C. neoformans complex.
    • Cryptococcus gattii:
      • Responsible for approximately 20% of human cases of cryptococcosis.
      • Understanding of distribution is evolving, but predominantly seen in tropical and subtropical climates (e.g., Australia, Oceania and parts of Africa, Asia, Europe and the Americas).
      • In North America, it has been associated with outbreaks in the Pacific Northwest (Vancouver Island, Washington, Oregon).
      • Nomenclature in flux with some arguing for 5 species (C. gattii, C deuterogattii, C. bacillisporus, C. tetragattii and C. decagattii) while others for a comprehensive C. gattii complex.
      • Unlike C. neoformans, is more commonly seen in healthy hosts.
      • Has reduced sensitivity to fluconazole and appears to be more virulent.
  • Pathogenesis:
    • Acquisition of organism:
      • The most common form of exposure is via inhalation of the fungal spore into airways.
      • Other forms of exposure are direct inoculation into the skin or transmission via organ transplant.
    • Cryptococcus has multiple virulence factors.
      • Foremost amongst those is the polysaccharide capsule that impairs immune response to the fungus and contributes to CNS disuse manifestations.
    • An effective immune response is critical to protection from infection, but an over-exuberant response is also responsible for neurological symptoms in both HIV and non-HIV patients.
    • Fate of infection:
      • Controlled via immune response and cleared--or remains in a chronic latent form (with the possibility of future reactivation).
      • Localized to the site of exposure (e.g., lung or skin).
      • May disseminate to various other sites including CNS (virtually any organ can be involved but most common also include bloodstream, skin, reticuloendothelial system, prostate).

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PATHOGENS

  • Two main species complexes of Cryptococcus are important for human disease.
    • Cryptococcus neoformans
      • This is the predominant pathogen (~80% of human cryptococcosis cases) and is the most common cause of non-viral meningitis in people.
      • Worldwide distribution. Particularly prevalent in soil contaminated by guano.
      • Nomenclature is in flux with some arguing for two species (C. neoformans and C. deneoformans) while others arguing for a more comprehensive term C. neoformans complex.
    • Cryptococcus gattii:
      • Responsible for approximately 20% of human cases of cryptococcosis.
      • Understanding of distribution is evolving, but predominantly seen in tropical and subtropical climates (e.g., Australia, Oceania and parts of Africa, Asia, Europe and the Americas).
      • In North America, it has been associated with outbreaks in the Pacific Northwest (Vancouver Island, Washington, Oregon).
      • Nomenclature in flux with some arguing for 5 species (C. gattii, C deuterogattii, C. bacillisporus, C. tetragattii and C. decagattii) while others for a comprehensive C. gattii complex.
      • Unlike C. neoformans, is more commonly seen in healthy hosts.
      • Has reduced sensitivity to fluconazole and appears to be more virulent.
  • Pathogenesis:
    • Acquisition of organism:
      • The most common form of exposure is via inhalation of the fungal spore into airways.
      • Other forms of exposure are direct inoculation into the skin or transmission via organ transplant.
    • Cryptococcus has multiple virulence factors.
      • Foremost amongst those is the polysaccharide capsule that impairs immune response to the fungus and contributes to CNS disuse manifestations.
    • An effective immune response is critical to protection from infection, but an over-exuberant response is also responsible for neurological symptoms in both HIV and non-HIV patients.
    • Fate of infection:
      • Controlled via immune response and cleared--or remains in a chronic latent form (with the possibility of future reactivation).
      • Localized to the site of exposure (e.g., lung or skin).
      • May disseminate to various other sites including CNS (virtually any organ can be involved but most common also include bloodstream, skin, reticuloendothelial system, prostate).

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Last updated: November 8, 2019