Browsing by Author "Wilkinson, Katalin"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Open Access
    Immunological analysis of pericardial tuberculosis
    (2011) Matthews, Kerryn; Wilkinson, Katalin; Wilkinson, Robert J; Mayosi, Bongani
    Pericardial tuberculosis (TB) offers a relevant human model to study TB at the site of disease and to determine the effect of HIV-1 infection. 96 Patients with pericardial TB were recruited into this study, 68 of whom were HIV-1 infected. Where clinically indicated, pericardiocentesis was performed to drain pericardial fluid and blood was drawn. The data derived from the study provide novel insight into the immune response in the pericardium to TB infection. Furthermore, HIV-1 infection caused a dysregulation of the immune response.
  • Thumbnail Image
    Item
    Open Access
    Immunological characterization of the HIV-tuberculosis associated immune reconstitution inflammatory syndrome
    (2011) Tadokera, Rabecca; Wilkinson, Robert J; Wilkinson, Katalin
    While the integration of anti-TB and cART therapies is associated with substantial clinical improvement in the majority of patients, HIV-Tuberculosis associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS) has been shown to occur in a significant subset of these patients. TB-IRIS is an inflammatory complication of the combined treatments for HIV-1 and tuberculosis, which is being reported increasingly, particularly in areas endemic to both diseases. This work aimed to characterise the immunopathogenesis of paradoxical HIV-Tuberculosis associated immune reconstitution inflammatory syndrome.
  • Thumbnail Image
    Item
    Open Access
    Investigations into HIV-associated tuberculous meningitis
    (2014) Marais, Suzaan; Wilkinson, Robert J; Meintjes, Graeme; Wilkinson, Katalin
    [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.
  • Thumbnail Image
    Item
    Open Access
  • Thumbnail Image
    Item
    Open Access
    Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children
    (BioMed Central Ltd, 2010) Connell, Tom; Davies, Mary-Ann; Johannisen, Christine; Wood, Kathryn; Pienaar, Sandy; Wilkinson, Katalin; Wilkinson, Robert; Zar, Heather; Beatty, David; Nicol, Mark; Curtis, Nigel; Eley, Brian
    BACKGROUND: Recent interest has focused on the potential use of serial interferon gamma (IFN-gamma) release assay (IGRA) measurements to assess the response to anti-tuberculous (TB) treatment. The kinetics of IFN-gamma responses to Mycobacterium tuberculosis (MTB) antigens in HIV-infected children during treatment have not however been previously investigated. METHODS: IFN-gamma responses to the MTB antigens, ESAT-6, CFP-10 and PPD were measured by an enzyme-linked immunospot assay (IFN-gamma ELISpot) at presentation and at one, two and six months after starting anti-tuberculous treatment in HIV-infected children with definite or probable TB. Responses at different time points were compared using a Mann-Whitney U test with paired data analysed using the Wilcoxon signed rank test. A Fisher's exact or Chi-squared test was used to compare proportions when test results were analysed as dichotomous outcomes. RESULTS: Of 102 children with suspected TB, 22 (21%) had definite TB and 24 (23%) probable TB. At least one follow up IFN-gamma ELISpot assay result was available for 31 (67%) of the 46 children. In children with definite or probable TB in whom the IFN-gamma ELISpot assay result was positive at presentation, anti-tuberculous treatment was accompanied by a significant decrease in both the magnitude of the IFN-gamma response to individual or combined MTB-specific antigens (ESAT-6 median 110 SFCs/106 PBMC (IQR 65-305) at presentation vs. 15 (10-115) at six months, p = 0.04; CFP-10 177 (48-508) vs. 20 (5-165), p = 0.004, ESAT-6 or CFP-10 median 250 SFCs/106 PBMC (IQR 94-508) vs. 25 (10-165), p = 0.004) and in the proportion of children with a positive IFN-gamma ELISpot assay (Fisher's exact test: ESAT-6 15/0 vs 5/11, p = 0.0002, CFP-10 22/0 vs 8/17, p = 0.0001, ESAT-6 or CFP-10 22/0 vs. 9/17, p= 0.002). However almost half of the children had a positive IFN-gamma ELISpot assay after six months of anti-tuberculous treatment. In addition, there was conversion of the IFN-gamma ELISpot assay result during anti-tuberculous therapy in six of 12 children in whom the initial IFN-gamma ELISpot assay was negative. CONCLUSIONS: In HIV-infected children with definite or probable TB, anti-tuberculosis treatment is accompanied by a reduction in the magnitude of the IFN-gamma ELISpot response to MTB-antigens. However, serial IFN-gamma ELISpot measurements appear to have limited clinical utility in assessing a successful response to anti-tuberculous treatment in HIV infected children.
  • Thumbnail Image
    Item
    Open Access
    Studies on in vitro human T cell reactivity to antigens of mycobacterium tuberculosis
    (2010) Gideon, Hannah Priyadarshini; Wilkinson, Robert J; Wilkinson, Katalin
    Studies on Mycobacterium tuberculosis (MTB) antigens are important to improve immunodiagnostics and vaccine efficacy. A novel genome based strategy for antigen discovery is to relate what is highly expressed by bacilli in vivo or in vitro, to what is recognized by human T cells as antigens. As hypoxia is a relevant stimulus that MTB encounters in vivo, whole genome based transcriptional profiles of M. tuberculosis subject to prolonged hypoxia (described as the Enduring hypoxic response (EHR) were analyzed, to guide the discovery of novel potential anitgens, by a combined bioinformatic and empirical approach and to determine evidence of infection stage specific recognition.