HIV/AIDS

Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries

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Authors:
Angela Loyse MRes, Harry Thangaraj MBBS, Prof Philippa Easterbrook MD, Nathan Ford PhD, Monika Roy MD, Tom Chiller MD, Nelesh Govender MBBC, Prof Thomas S Harrison FRCP, Tihana Bicanic BM BCh

Publication details

Editors: The Lancet Infectious Diseases
Publication date: 2 June 2013
Languages: English

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Abstract

Summary

Cryptococcal meningitis is the leading cause of adult meningitis in sub-Saharan Africa, and contributes up to 20% of AIDS-related mortality in low-income and middle-income countries every year. Antifungal treatment for cryptococcal meningitis relies on three old, off-patent antifungal drugs: amphotericin B deoxycholate, flucytosine, and fluconazole. Widely accepted treatment guidelines recommend amphotericin B and flucytosine as first-line induction treatment for cryptococcal meningitis. However, flucytosine is unavailable in Africa and most of Asia, and safe amphotericin B administration requires patient hospitalisation and careful laboratory monitoring to identify and treat common side-effects.

Therefore, fluconazole monotherapy is widely used in low-income and middle-income countries for induction therapy, but treatment is associated with significantly increased rates of mortality. We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical effectiveness and access issues specific to low-income and middle-income countries. Each drug poses unique access challenges: amphotericin B through cost, toxic effects, and insufficiently coordinated distribution; flucytosine through cost and scarcity of registration; and fluconazole through challenges in maintenance of local stocks—eg, sustainability of donations or insufficient generic supplies. We advocate ten steps that need to be taken to improve access to safe and effective antifungal therapy for cryptococcal meningitis.