Medicine & USMLE

Cryptococcus neoformans

  1. Histoplasma
  2. Blastomyces
  3. Coccidioides
  4. Paracoccidioides
  5. Tinea (Dermatophytes)
  6. Malassezia
  7. Candida albicans
  8. Aspergillus fumigatus
  9. Cryptococcus neoformans
  10. Mucor and Rhizopus
  11. Pneumocystis jirovecii
  12. Sporothrix schenckii


Cryptococcus neoformans is a fungus that can cause opportunistic infections in immunocompromised people. It exists as an oval-shaped yeast with a thick polysaccharide capsule. This capsule can be visualized as having a ‘halo’ like appearance under the India ink stain, and the capsule will also stain bright red with mucicarmine. Transmission normally occurs by way of inhaling spores that are present in our natural environment.  As an opportunistic pathogen, this fungi primarily affects immunocompromised patients, and cryptococcal infections of the brain are actually an AIDS defining illness when seen in patients with HIV. In immunocompromised individuals, fungal spores can spread past the lungs to reach the central nervous system, where they can cause meningoencephalitis. This can be recognized by the appearance of soap bubble lesions on MRI scans, as well as the detection of polysaccharide capsule antigens on latex agglutination tests of cerebrospinal fluid. Finally, patients with cryptococcal meningoencephalitis are treated by a short course of combined amphotericin B and flucytosine, followed by a maintenance regimen of fluconazole.

Key Points

  • Cryptococcus neoformans
    • Characteristics
      • Narrow oval budding yeast
        • Not dimorphic; no mold form
        • Does not form hyphae or pseudohyphae
      • Thick polysaccharide capsule
        • Highlighted with
          • India ink stain (clear halo)
          • mucicarmine (red inner capsule)
      • Makes melanin
    • Transmission
      • Opportunistic
        • Infects immunocompromised individuals (esp. HIV/AIDS)
      • Found in soil via bird (pigeon) droppings
      • Yeast is inhaled into lungs
        • Hematogenous dissemination to meninges
    • Presentation: Cryptococcosis
      • Meningoencephalitis
        • “Soap bubble” lesion in brain
        • Present with fevers, relentless headaches, and generalized malaise
    • Diagnosis
      • CSF with wide halos on India ink stain
      • Latex agglutination test
        • Detects polysaccharide capsular antigen in CSF
        • Sensitive and specific; but has been largely replaced with lateral flow assays which are faster with same diagnostic accuracy
    • Treatment
      • Amphotericin B and  flucytosine, followed by fluconazole