title: Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy.
abstract: HIV-associated cryptococcal meningitis is by far the most common cause of adult meningitis in many areas of the world that have high HIV seroprevalence. In most areas in Sub-Saharan Africa, the incidence of cryptococcal meningitis is not decreasing despite availability of antiretroviral therapy, because of issues of adherence and retention in HIV care. In addition, cryptococcal meningitis in HIV-seronegative individuals is a substantial problem: the risk of cryptococcal infection is increased in transplant recipients and other individuals with defects in cell-mediated immunity, and cryptococcosis is also reported in the apparently immunocompetent. Despite therapy, mortality rates in these groups are high. Over the past 5 years, advances have been made in rapid point-of-care diagnosis and early detection of cryptococcal antigen in the blood. These advances have enabled development of screening and pre-emptive treatment strategies aimed at preventing the development of clinical infection in patients with late-stage HIV infection. Progress in optimizing antifungal combinations has been aided by evaluation of the clearance rate of infection by using serial quantitative cultures of cerebrospinal fluid (CSF). Measurement and management of raised CSF pressure, a common complication, is a vital component of care. In addition, we now better understand protective immune responses in HIV-associated cases, immunogenetic predisposition to infection, and the role of immune-mediated pathology in patients with non-HIV associated infection and in the context of HIV-associated immune reconstitution reactions.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Williamson
authors.affiliation: Botswana-University of Pennsylvania Partnership, P.O. Box AC157AC, Gaborone, Botswana.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Jarvis
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Panackal
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College School of Public Health, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Fisher
authors.affiliation: Institute of Infection and Immunity, St Georges University of London, Cranmer Terrace, London, SW17 ORE, UK.
authors.forename: Síle F
authors.initials: SF
authors.lastname: Molloy
authors.affiliation: Institute of Infection and Immunity, St Georges University of London, Cranmer Terrace, London, SW17 ORE, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Loyse
authors.affiliation: Institute of Infection and Immunity, St Georges University of London, Cranmer Terrace, London, SW17 ORE, UK.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
mesh_terms: D006801:Humans; D016919:Meningitis, Cryptococcal