Cryptococcal meningitis in advanced HIV — DTM&H MCQ

Correct answer: C — Amphotericin-based induction with flucytosine and therapeutic lumbar punctures

The correct answer is C, amphotericin-based induction with flucytosine and therapeutic lumbar punctures. This patient has HIV-associated cryptococcal meningitis (advanced immunosuppression with CD4 24 cells/microlitre, positive cryptococcal antigen, and a clinical picture of meningo-encephalitis) with markedly raised CSF opening pressure (34 cm H2O, normal <20 cm). WHO guidance for advanced HIV disease recommends induction with amphotericin B (liposomal single high-dose or conventional) plus flucytosine as first-line therapy, since this combination gives the fastest fungal clearance and best survival compared with fluconazole-based regimens. Raised intracranial pressure is a major driver of early mortality and morbidity (blindness, coma), so repeated therapeutic lumbar punctures to reduce opening pressure are an essential adjunct alongside antifungal induction. Why the other options are wrong: E. High-dose ceftriaxone alone: this treats bacterial meningitis, not fungal disease; ceftriaxone has no activity against Cryptococcus and would leave the causative organism untreated while intracranial pressure continues to rise. D. Cotrimoxazole prophylaxis without antifungal therapy: cotrimoxazole prevents Pneumocystis and toxoplasmosis, not cryptococcosis; withholding definitive antifungal induction in confirmed cryptococcal meningitis is uniformly fatal without treatment. A. Isoniazid preventive therapy: this targets latent tuberculosis, is irrelevant to an acute cryptococcal meningitis presentation, and does not address the immediate life-threatening infection or raised intracranial pressure. B. Immediate dolutegravir-based ART as the first step: starting ART immediately in untreated cryptococcal meningitis risks precipitating cryptococcal immune reconstitution inflammatory syndrome (IRIS); ART should be deferred until the antifungal induction phase is established, typically around 4 to 6 weeks later. Key point: In HIV-associated cryptococcal meningitis, amphotericin-flucytosine induction combined with aggressive management of raised CSF pressure via therapeutic lumbar puncture takes priority, with ART deferred to avoid IRIS.

Reference: WHO Guidelines on the Management of Advanced HIV Disease and Cryptococcal Disease, 2022 (NCBI Bookshelf NBK620076), section on cryptococcal disease management and therapeutic lumbar puncture: https://www.ncbi.nlm.nih.gov/books/NBK620076/