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

A Loyse, H Thangaraj, P Easterbrook… - The Lancet infectious …, 2013 - thelancet.com
A Loyse, H Thangaraj, P Easterbrook, N Ford, M Roy, T Chiller, N Govender, TS Harrison
The Lancet infectious diseases, 2013thelancet.com
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 …
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.
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