An HIV patient (CD4 = 60 cells/µL) presents with headache, photophobia, and positive India ink preparation of CSF showing encapsulated budding yeast with a wide clear halo. CSF cryptococcal antigen (CrAg) titre is 1:2048. What is the significance of the capsule, and which antifungal treatment phase applies?

• A Capsule acts as adhesin; induction phase with fluconazole 400 mg/day for 8 weeks is recommended
• B Capsule is detected by India ink as a positive staining structure (blue against black background); amphotericin B monotherapy for 4 weeks is preferred
• C Capsule is the primary virulence factor inhibiting phagocytosis and complement deposition; induction phase uses liposomal amphotericin B + flucytosine for 2 weeks (WHO 2022 preferred), followed by consolidation with fluconazole ✓
• D High CrAg titre indicates antifungal resistance; send for MIC testing before initiating therapy

Explanation

The polysaccharide capsule of Cryptococcus neoformans is its primary virulence factor. It prevents neutrophil phagocytosis, inhibits complement opsonisation, suppresses T-cell proliferation, and induces IL-10 promoting immune tolerance. India ink demonstrates the capsule as a clear halo (negative staining — the ink particles are excluded by the capsule, leaving it clear against the black background). WHO 2022 guidelines recommend induction with liposomal amphotericin B (3–4 mg/kg/day) + flucytosine (25 mg/kg QID) for 14 days, then consolidation with fluconazole 400 mg/day for 8 weeks, then maintenance with fluconazole 200 mg/day until CD4 >200 for >6 months on ART. Fluconazole monotherapy induction is inferior.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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Written and medically reviewed by the StethoPrep medical team.