Question
Cryptococcal meningitis – risk factors, pathogenesis and laboratory diagnosis
Answer
Cryptococcal meningitis
Risk factors: HIV/AIDS (particularly with CD4 count <100 cells/μL — the single most important risk factor globally, cryptococcal meningitis being a classical AIDS-defining opportunistic infection), other causes of immunosuppression (organ transplant recipients on immunosuppressive therapy, long-term corticosteroid use, haematological malignancy), and, less commonly, infection in apparently immunocompetent individuals (associated particularly with Cryptococcus gattii).
Pathogenesis: infection is acquired by inhalation of aerosolized Cryptococcus neoformans (or C. gattii) spores/desiccated yeast cells from the environment (classically associated with soil contaminated by pigeon droppings for C. neoformans, and eucalyptus trees for C. gattii). The organism first establishes a primary (often subclinical) pulmonary infection; in immunocompromised hosts, it fails to be contained and disseminates haematogenously, showing a marked tropism for the central nervous system — facilitated by the organism’s polysaccharide capsule, which is anti-phagocytic and immunomodulatory, allowing it to evade host immune clearance and cross the blood-brain barrier, producing a subacute-to-chronic meningitis/meningoencephalitis.
Laboratory diagnosis:
- CSF examination — typically shows raised opening pressure (often markedly elevated, an important prognostic/management factor), mildly elevated protein, low-to-normal glucose, and a lymphocytic pleocytosis (which may be minimal/absent in severely immunocompromised patients).
- India ink preparation of CSF — demonstrates the characteristic encapsulated budding yeast cells (a clear halo around the yeast against the black background), a classical rapid bedside test, though with only moderate sensitivity.
- Cryptococcal antigen (CrAg) testing — detection of capsular polysaccharide antigen in CSF or serum, by latex agglutination or lateral flow immunoassay (LFA); highly sensitive and specific, now the preferred rapid diagnostic test, and also used for screening asymptomatic HIV patients with low CD4 counts.
- Culture — CSF/blood culture on Sabouraud dextrose agar, definitive confirmation, though slower (several days).
- Histopathology (if tissue biopsy obtained) — mucicarmine or Alcian blue staining highlights the polysaccharide capsule.