Question
Cryptococcus neoformans
Answer
Cryptococcus neoformans is a systemic fungal pathogen — an encapsulated yeast, widely found in soil, particularly soil contaminated with pigeon droppings, causing cryptococcosis.
Morphology: a round to oval yeast (4–10 μm), reproducing by narrow-based budding, distinguished by a thick polysaccharide capsule — its most important virulence factor, antiphagocytic and central to immune evasion.
Transmission: inhalation of aerosolized yeast cells/basidiospores; primary pulmonary infection is often asymptomatic in immunocompetent hosts, but can disseminate haematogenously in the immunocompromised, with a striking predilection for the central nervous system.
Clinical significance: an important AIDS-defining opportunistic infection, causing cryptococcal meningitis/meningoencephalitis, a major cause of morbidity/mortality in advanced HIV disease (typically CD4 <100 cells/μL); presents with subacute headache, fever, and altered mental status, often with a relatively indolent course reflecting blunted host inflammatory response in severe immunosuppression.
Laboratory diagnosis:
- India ink preparation of CSF — demonstrates the encapsulated yeast as a clear halo against the dark background; rapid classic bedside test, moderately sensitive.
- Cryptococcal antigen (CrAg) test — latex agglutination or lateral flow immunoassay on CSF/serum, detecting capsular polysaccharide antigen; highly sensitive/specific, now the preferred rapid test.
- Culture — on Sabouraud dextrose agar, confirms diagnosis and allows susceptibility testing.
- Histopathology — mucicarmine stain highlights the polysaccharide capsule.
- CSF typically shows lymphocytic pleocytosis with often markedly raised opening pressure — an important prognostic/management factor, treated with therapeutic CSF drainage.
Treatment: induction therapy with amphotericin B plus flucytosine, followed by consolidation/maintenance fluconazole; management of raised intracranial pressure is an important adjunct.

