Response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries

by Loyse A, Bury J, Cohn J, Ford N, Chiller T, Ribeiro I, Koulla-Shiro S, Mghamba J, Ramadhani A, Nyirenda R, Aliyu SH, Wilson D, Le T, Oladele R, Lesikari S, Muzoora C, Kalata N, Temfack E, Mapoure Y, Sini V, Chanda D, Shimwela M, Lakhi S, Ngoma J, Gondwe-Chunda L, Perfect C, Shroufi A, Andrieux-Meyer I, Chan A, Schutz C, Hosseinipour M, Van der Horst C, Klausner JD, Boulware DR, Heyderman R, Lalloo D, Day J, Jarvis JN, Rodrigues M, Jaffar S, Denning D, Migone C, Doherty M, Lortholary O, Dromer F, Stack M, Molloy S, Bicanic T, van Oosterhout J, Mwaba P, Kanyama C, Kouanfack C, Govender N, Mfinanga S, Harrison TS. The Lancet Infectious Diseases 2018. doi: https://doi.org/10.1016/S1473-3099(18)30493-6

Summary: HIV-related cryptococcal meningitis is the most common cause of meningitis in many low and middle-income countries (LMICs). Effective treatments in resource-limited settings consist of flucytosine with either fluconazole or amphotericin B (in standard or liposomal formulation). Despite being an old, off-patent, and easy to manufacture medicine, flucytosine is unavailable in LMICs and unregistered in any African country. The authors present the latest burden of disease and clinical trial data that underline the need for urgent action to ensure access to flucytosine and amphotericin B in LMICs, and highlight the publication of new WHO guidelines about HIV-related cryptococcal disease. They also review the safety profile of flucytosine for this indication, outline the barriers to access to standard formulations of flucytosine and standard and liposomal formulations of amphotericin B, and highlight the need for better adapted modified release formulations of flucytosine.

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