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, it is more commonly seen in healthy hosts.
    • Association with anti-GM-CSF autoantibodies as a risk factor for C. gattii
    • It 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 the 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 the 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 HIV and non-HIV patients.
  • The 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).
    • It may disseminate to various other sites, including CNS (virtually any organ can be involved, but most common also include the bloodstream, skin, reticuloendothelial system, and prostate).