Investigations into HIV-associated tuberculous meningitis

 

Show simple item record

dc.contributor.advisor Wilkinson, Robert J en_ZA
dc.contributor.advisor Meintjes, Graeme en_ZA
dc.contributor.advisor Wilkinson, Katalin en_ZA
dc.contributor.author Marais, Suzaan en_ZA
dc.date.accessioned 2014-11-07T09:16:54Z
dc.date.available 2014-11-07T09:16:54Z
dc.date.issued 2014 en_ZA
dc.identifier.citation Marais, S. 2014. Investigations into HIV-associated tuberculous meningitis. University of Cape Town. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/9304
dc.description Includes bibliographical references. en_ZA
dc.description.abstract [Background] Tuberculous meningitis (TBM) is a common form of tuberculosis in high TB incidence settings. However, the burden of disease and outcome in affected adults is unknown in Cape Town. The diagnosis of TBM is often challenging, particularly in HIV co-infected patients and no standardized clinical case definition exists. An emerging complication that contributes to poor outcome in HIV-associated TBM is neurological TB immune reconstitution inflammatory syndrome (TB-IRIS). [Methods] A consensus clinical TBM case definition was developed following a TBM meeting that I co-ordinated. I led two observational studies that determined the burden of HIV-associated TBM and neurological TB-IRIS at a district-level hospital in Cape Town. Patients with HIV-associated TBM were prospectively enrolled in a third cohort study to determine the clinical and immunological characteristics of paradoxical TBM-IRIS. [Results] TBM accounted for 57% of meningitis cases over a 6-months period; 88% of these patients were HIV-infected. At six months follow-up, mortality in HIV-associated TBM patients was 48%. Neurological TB-IRIS accounted for 21% of patients who presented with central nervous system (CNS) deterioration during the first year of antiretroviral therapy (ART) over a one-year period. TBM-IRIS developed in 47% of HIV-associated TBM patients and associated with extensive cerebrospinal fluid (CSF) inflammation both at TBM diagnosis and at TBM-IRIS presentation. Patients who did not develop TBM-IRIS, but who were culture-positive for Mycobacterium tuberculosis from CSF at TBM diagnosis, showed an immunological phenotype similar to TBM-IRIS patients; however neutrophils were increased in TBM-IRIS patients compared to culture-positive TBM-non-IRIS patients, both at TBM diagnosis and two weeks after ART initiation. [Conclusions] HIV-associated TBM is a common cause of meningitis with a poor outcome in Cape Town. TBM-IRIS is a frequent complication of ART in HIV-associated TBM patients. CSF Mycobacterium tuberculosis culture positivity drives an inflammatory response that manifests as TBM-IRIS in most, but not all TBM patients. Neutrophils associate closely with the CNS inflammation that characterizes TBM-IRIS. An intensified TB treatment regimen with increased CSF penetration early during TB treatment may lead to improved mycobacterial clearance from the CNS, which may result in improved outcome during TBM treatment and a reduced frequency of TBM-IRIS. We aim to test this hypothesis in future studies. en_ZA
dc.language.iso eng en_ZA
dc.title Investigations into HIV-associated tuberculous meningitis en_ZA
dc.type Thesis / Dissertation en_ZA
uct.type.publication Research en_ZA
uct.type.resource Thesis en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Department of Medicine en_ZA
dc.type.qualificationlevel Doctoral en_ZA
dc.type.qualificationname PhD en_ZA
uct.type.filetype Text
uct.type.filetype Image


Files in this item

This item appears in the following Collection(s)

Show simple item record