title: Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries.
abstract: 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.
authors.affiliation: Cryptococcal Meningitis Group, Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, UK. Electronic address: angelaloyse@hotmail.com.
authors.forename: Angela
authors.initials: A
authors.lastname: Loyse
authors.affiliation: Access to Pharmaceuticals Project, Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, UK.
authors.forename: Harry
authors.initials: H
authors.lastname: Thangaraj
authors.affiliation: HIV Department, World Health Organisation, Geneva, Switzerland.
authors.forename: Philippa
authors.initials: P
authors.lastname: Easterbrook
authors.affiliation: Médecins Sans Frontières and Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Monika
authors.initials: M
authors.lastname: Roy
authors.affiliation: Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Chiller
authors.affiliation: National Institute for Communicable Diseases, a Division of the National Health Laboratory Service (NHLS), University of the Witwatersrand, Johannesburg, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Nelesh
authors.initials: N
authors.lastname: Govender
authors.affiliation: Cryptococcal Meningitis Group, Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, UK.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
authors.affiliation: Cryptococcal Meningitis Group, Research Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, UK.
authors.forename: Tihana
authors.initials: T
authors.lastname: Bicanic
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000453:epidemiology; D017954:Africa South of the Sahara / Q000453:epidemiology; D000935:Antifungal Agents / Q000627:therapeutic use*; D003906:Developing Countries; D006297:Health Services Accessibility / Q000639:trends*; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000453:epidemiology*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents