Description

• 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.

Epidemiology

• 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

• 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)

Prevalence

• 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.

Risk Factors

• Immunosuppression due to HIV (CD4 <100 cells/mm³)
• Immunosuppression from chronic steroid use or other medications (biologic agents)
• Organ transplant, malignancy, or sarcoidosis

General Prevention

• Early HAART in HIV-positive patients is the most important and cost-effective preventive strategy.
• Primary antifungal prophylaxis with fluconazole or itraconazole in patients with advanced HIV disease (CD4 <100 cells/mm³) decreases the incidence of cryptococcal disease; no overall mortality benefit yet demonstrated (4)[A]
• Fluconazole (200 mg/day) is effective as secondary antifungal prophylaxis after 10 weeks of induction and consolidation therapy. Itraconazole is inferior to fluconazole and should not be used to prevent relapse (4)[A].

Commonly Associated Conditions

HIV/AIDS