- Major invasive fungal infection, caused by encapsulated yeasts
- There are >30 different species of Cryptococcus. Two species cause nearly all cryptococcal disease in humans—Cryptococcus neoformans and Cryptococcus gattii. C. neoformans is the principal human pathogen:
- C. neoformans infection is more common in immunocompromised persons.
- Two varieties: C. neoformans var. grubii, C. neoformans var. neoformans
- C. gattii causes disease in otherwise healthy persons (1).
- Cryptococcus is found in the droppings of wild birds, often pigeons. Dust from the droppings (soil or vegetation) can infect humans (or pets) by inhalation.
- Infected humans and animals are not infectious.
- Primary route of infection is inhalation of spores, followed by hematogenous spread.
- Predisposition for nervous system and skin
- Can remain latent in the lungs for varying periods
- Cryptococcal meningitis is a common AIDS-defining infection in HIV-seropositive persons.
- Predominant group: immunosuppressed adults, with CD4 cell counts below 100 cells/μL
- Predominant gender: male > female (reflecting HIV prevalence)
- Major disease burden in sub-Saharan Africa followed by South and Southeast Asia, Oceania, Western and Central Europe. North Africa, Middle East, and North America have the fewest cases (1,2).
- Incidence decreasing in developed nations due to highly active antiretroviral therapy (HAART) for HIV:
- 1 million new cases worldwide each year
- 600,000 deaths worldwide each year mostly in sub-Saharan Africa (500,000)
- 2–7% of opportunistic infections in AIDS patients in the United States with fatality rate of 12%
- 0.5–1% incidence among HIV-infected children in United States
- 0.4 to 1.3 cases per 100,000 in general population (1,3)
- U.S. AIDS patients: 3%
- AIDS patients in developing world: up to 38%
- U.S. organ transplantation recipients: 3%
- Common in renal transplant patients
- Can be seen in extrathoracic sarcoidosis
Etiology and Pathophysiology
- Cryptococcus is found in pigeon droppings; transmission likely through exposure to contaminated soil or vegetation rather than direct exposure
- Virulence factors: polysaccharide capsule and capacity for biofilm formation. Unencapsulated forms are readily phagocytosed. Polysaccharide capsule resists phagocytosis and inhibits leukocyte migration to areas of fungal replication.
- Immunosuppression due to HIV (CD4 <100 cells/mm3)
- Immunosuppression from chronic steroid use or other medications (biologic agents)
- Organ transplant, malignancy, or sarcoidosis
- Early HAART in HIV-positive patients is the most important and cost-effective preventive strategy.
Commonly Associated Conditions
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