Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries
Harrison, Thomas S
AffiliationCryptococcal Meningitis Group, Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, UK.
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JournalThe Lancet Infectious Diseases
AbstractCryptococcal 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.
- Flucytosine and cryptococcosis: time to urgently address the worldwide accessibility of a 50-year-old antifungal.
- Authors: Loyse A, Dromer F, Day J, Lortholary O, Harrison TS
- Issue date: 2013 Nov
- AMBIsome Therapy Induction OptimisatioN (AMBITION): High Dose AmBisome for Cryptococcal Meningitis Induction Therapy in sub-Saharan Africa: Study Protocol for a Phase 3 Randomised Controlled Non-Inferiority Trial.
- Authors: Lawrence DS, Youssouf N, Molloy SF, Alanio A, Alufandika M, Boulware DR, Boyer-Chammard T, Chen T, Dromer F, Hlupeni A, Hope W, Hosseinipour MC, Kanyama C, Lortholary O, Loyse A, Meya DB, Mosepele M, Muzoora C, Mwandumba HC, Ndhlovu CE, Niessen L, Schutz C, Stott KE, Wang D, Lalloo DG, Meintjes G, Jaffar S, Harrison TS, Jarvis JN
- Issue date: 2018 Nov 23
- Responding to the evidence for improved treatment for cryptococcal meningitis in resource-limited settings.
- Authors: Milani B, Ford N
- Issue date: 2012 Mar 14
- Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group.
- Authors: van der Horst CM, Saag MS, Cloud GA, Hamill RJ, Graybill JR, Sobel JD, Johnson PC, Tuazon CU, Kerkering T, Moskovitz BL, Powderly WG, Dismukes WE
- Issue date: 1997 Jul 3
- Antifungal Combinations for Treatment of Cryptococcal Meningitis in Africa.
- Authors: Molloy SF, Kanyama C, Heyderman RS, Loyse A, Kouanfack C, Chanda D, Mfinanga S, Temfack E, Lakhi S, Lesikari S, Chan AK, Stone N, Kalata N, Karunaharan N, Gaskell K, Peirse M, Ellis J, Chawinga C, Lontsi S, Ndong JG, Bright P, Lupiya D, Chen T, Bradley J, Adams J, van der Horst C, van Oosterhout JJ, Sini V, Mapoure YN, Mwaba P, Bicanic T, Lalloo DG, Wang D, Hosseinipour MC, Lortholary O, Jaffar S, Harrison TS, ACTA Trial Study Team.
- Issue date: 2018 Mar 15