Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis

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dc.contributor.authorJarvis, Joseph Nen_ZA
dc.contributor.authorMeintjes, Graemeen_ZA
dc.contributor.authorBicanic, Tihanaen_ZA
dc.contributor.authorBuffa, Vivianaen_ZA
dc.contributor.authorHogan, Louiseen_ZA
dc.contributor.authorMo, Stephanieen_ZA
dc.contributor.authorTomlinson, Gillianen_ZA
dc.contributor.authorKropf, Pascaleen_ZA
dc.contributor.authorNoursadeghi, Mahdaden_ZA
dc.contributor.authorHarrison, Thomas Sen_ZA
dc.date.accessioned2015-11-23T12:31:08Z
dc.date.available2015-11-23T12:31:08Z
dc.date.issued2015en_ZA
dc.description.abstractAuthor Summary Cryptococcal meningitis is a severe opportunistic infection, estimated to kill several hundred thousand HIV-infected individuals each year. One of the factors contributing to this high death toll is the inadequacy of antifungal treatments. As few novel antifungal drugs are being developed, several groups have started to investigate the potential of immune modulation, with treatments designed to change the patient's immune response to infection. However, our understanding of the immune response to cryptococcal infection in HIV-infected patients, and how these responses impact on clinical outcomes, is limited. In this study, we took advantage of the fact that we can sample cerebrospinal fluid (CSF) from the site of the infection in patients when they develop cryptococcal meningitis. We undertook a detailed analysis measuring levels of immune response parameters in the CSF of these patients, and demonstrated that there were several distinct components of the immune response. Variations in these responses were associated with both the rate at which patients cleared their infection during treatment, and with mortality. Our results provide a basis for the development of future immunomodulatory therapies, and may allow identification of patients most at risk of dying, enabling more intensive treatments to be given to those at highest risk.en_ZA
dc.identifier.apacitationJarvis, J. N., Meintjes, G., Bicanic, T., Buffa, V., Hogan, L., Mo, S., ... Harrison, T. S. (2015). Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis. <i>PLoS One</i>, http://hdl.handle.net/11427/15305en_ZA
dc.identifier.chicagocitationJarvis, Joseph N, Graeme Meintjes, Tihana Bicanic, Viviana Buffa, Louise Hogan, Stephanie Mo, Gillian Tomlinson, Pascale Kropf, Mahdad Noursadeghi, and Thomas S Harrison "Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/15305en_ZA
dc.identifier.citationJarvis, J. N., Meintjes, G., Bicanic, T., Buffa, V., Hogan, L., Mo, S., ... & Harrison, T. S. (2015). Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis. PLoS pathogens, 11(4), e1004754. doi:10.1371/journal.ppat.1004754en_ZA
dc.identifier.ris TY - Journal Article AU - Jarvis, Joseph N AU - Meintjes, Graeme AU - Bicanic, Tihana AU - Buffa, Viviana AU - Hogan, Louise AU - Mo, Stephanie AU - Tomlinson, Gillian AU - Kropf, Pascale AU - Noursadeghi, Mahdad AU - Harrison, Thomas S AB - Author Summary Cryptococcal meningitis is a severe opportunistic infection, estimated to kill several hundred thousand HIV-infected individuals each year. One of the factors contributing to this high death toll is the inadequacy of antifungal treatments. As few novel antifungal drugs are being developed, several groups have started to investigate the potential of immune modulation, with treatments designed to change the patient's immune response to infection. However, our understanding of the immune response to cryptococcal infection in HIV-infected patients, and how these responses impact on clinical outcomes, is limited. In this study, we took advantage of the fact that we can sample cerebrospinal fluid (CSF) from the site of the infection in patients when they develop cryptococcal meningitis. We undertook a detailed analysis measuring levels of immune response parameters in the CSF of these patients, and demonstrated that there were several distinct components of the immune response. Variations in these responses were associated with both the rate at which patients cleared their infection during treatment, and with mortality. Our results provide a basis for the development of future immunomodulatory therapies, and may allow identification of patients most at risk of dying, enabling more intensive treatments to be given to those at highest risk. DA - 2015 DB - OpenUCT DO - 10.1371/journal.ppat.1004754 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis TI - Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis UR - http://hdl.handle.net/11427/15305 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15305
dc.identifier.urihttp://dx.doi.org/10.1371/journal.ppat.1004754
dc.identifier.vancouvercitationJarvis JN, Meintjes G, Bicanic T, Buffa V, Hogan L, Mo S, et al. Cerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitis. PLoS One. 2015; http://hdl.handle.net/11427/15305.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2015 Jarvis et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plospathogensen_ZA
dc.subject.otherCytokinesen_ZA
dc.subject.otherCerebrospinal fluiden_ZA
dc.subject.otherChemokinesen_ZA
dc.subject.otherCryptococcusen_ZA
dc.subject.otherCell enumeration techniquesen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherLymphocytesen_ZA
dc.subject.otherMacrophagesen_ZA
dc.titleCerebrospinal Fluid Cytokine Profiles Predict Risk of Early Mortality and Immune Reconstitution Inflammatory Syndrome in HIV-Associated Cryptococcal Meningitisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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