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Investigations into HIV-associated tuberculous meningitis
Includes bibliographical references.
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| Main Author: | |
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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Department of Medicine
2014
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| _version_ | 1867614428224028672 |
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| access_status_str | Open Access |
| author | Marais, Suzaan |
| author2 | Wilkinson, Robert J |
| author_browse | Marais, Suzaan Wilkinson, Robert J |
| author_facet | Wilkinson, Robert J Marais, Suzaan |
| author_sort | Marais, Suzaan |
| collection | Thesis |
| description | Includes bibliographical references. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/9304 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:51:53.147Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2014 |
| publishDateRange | 2014 |
| publishDateSort | 2014 |
| publisher | Department of Medicine |
| publisherStr | Department of Medicine |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/9304 Investigations into HIV-associated tuberculous meningitis Marais, Suzaan Wilkinson, Robert J Meintjes, Graeme Wilkinson, Katalin Includes bibliographical references. [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. 2014-11-07T09:16:54Z 2014-11-07T09:16:54Z 2014 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/9304 eng application/pdf Department of Medicine Faculty of Health Sciences University of Cape Town |
| spellingShingle | Marais, Suzaan Investigations into HIV-associated tuberculous meningitis |
| thesis_degree_str | Doctoral |
| title | Investigations into HIV-associated tuberculous meningitis |
| title_full | Investigations into HIV-associated tuberculous meningitis |
| title_fullStr | Investigations into HIV-associated tuberculous meningitis |
| title_full_unstemmed | Investigations into HIV-associated tuberculous meningitis |
| title_short | Investigations into HIV-associated tuberculous meningitis |
| title_sort | investigations into hiv associated tuberculous meningitis |
| url | http://hdl.handle.net/11427/9304 |
| work_keys_str_mv | AT maraissuzaan investigationsintohivassociatedtuberculousmeningitis |