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The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus

Thesis (DMed (Medicine. Internal Medicine))-University of Stellenbosch, 2005.

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Main Author: Reuter, Helmuth
Other Authors: Doubell, Anton F.
Format: Thesis
Language:English
Published: Stellenbosch : University of Stellenbosch 2008
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access_status_str Open Access
author Reuter, Helmuth
author2 Doubell, Anton F.
author_browse Doubell, Anton F.
Reuter, Helmuth
author_facet Doubell, Anton F.
Reuter, Helmuth
author_sort Reuter, Helmuth
collection Thesis
dc_rights_str_mv University of Stellenbosch
description Thesis (DMed (Medicine. Internal Medicine))-University of Stellenbosch, 2005.
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institution Stellenbosch University (South Africa)
language English
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license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository
publishDate 2008
publishDateRange 2008
publishDateSort 2008
publisher Stellenbosch : University of Stellenbosch
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spelling oai:scholar.sun.ac.za:10019.1/1411 The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus Reuter, Helmuth Doubell, Anton F. Burgess, Lesley J. University of Stellenbosch. Faculty of Health Sciences. Dept. of Medicine. Internal Medicine. HIV infections Tuberculosis -- Immunological aspects Tuberculosis -- Treatment Mycobacterium tuberculosis Dissertations -- Internal medicine Theses -- Internal medicine Thesis (DMed (Medicine. Internal Medicine))-University of Stellenbosch, 2005. Mycobacterium tuberculosis (M. tuberculosis) accounts for more adult deaths than any other infectious agents. The present study included 162 patients with tuberculous pericarditis; 50% of the tuberculous pericarditis patients studied were human immunodeficiency virus (HIV) positive, compared to only 4.2% of patients who presented with non-tuberculous pericardial effusions. A steady year-to-year rise in HIV prevalence was observed in this 6-year study. Although the prognosis of pericardial tuberculosis (TB) is excellent with appropriate medical treatment, untreated pericardial TB has a mortality of 80-85%. It is thus important to diagnose tuberculous pericarditis efficiently. Traditionally, the diagnosis of pericardial TB is established by positive mycobacterial culture and/or histological evidence of necrotising granulomatous inflammation of the pericardium. Our study confirmed the insensitivity of pericardial fluid culture and pericardial biopsy in the diagnosis of pericardial TB, and at the time of clinical decision-making, results were usually not available. To overcome these difficulties, we explored various alternative strategies and this resulted in two diagnostic tools, namely a diagnostic rule and a diagnostic algorithm or classification tree. By means of classification and regression tree analysis, we allocated a weighted diagnostic index to each of five independently predictive features (fever, night sweats, weight loss, serum globulin >40 g/L and peripheral blood leukocyte count <10x109/L). A total diagnostic index of 6 or more corresponded to 82-86% sensitivity and 76-87% specificity for a diagnosis of tuberculous pericarditis. When possible, pericardial fluid should be aspirated to determine adenosine deaminase (ADA) levels and pericardial differential leukocyte counts. Fluid should also be sent for Gram stain and culture. The proposed diagnostic classification tree utilises the independently predictive attributes of pericardial adenosine deaminase levels, pericardial fluid lymphocyte/neutrophil ratios, peripheral leukocyte counts and the HIV status. Applying this prediction model to our entire data set of 233 patients resulted in 96% sensitivity and 97% specificity for the correct diagnosis of tuberculous pericarditis. Generally, patients were critically ill at the time of enrolment; 90% of tuberculous pericarditis presented with echocardiographic features of cardiac tamponade. Echoguided percutaneous pericardiocentesis with an indwelling catheter and intermittent daily aspiration was highly effective and safe. It is likely that the combination of this drainage technique and the early initiation of anti-tuberculous chemotherapy contributed to the almost complete absence of constriction in the patients studied, and our data do not support the routine use of adjunctive corticosteroids in patients with tuberculous pericarditis. Tuberculous exudates result from a Th1 mediated immune response characterised by lymphocyte dominance, significantly elevated levels of gamma-interferon (IFN-γ) and undetectable levels of interleukin-4 (IL-4). IFN-γ levels were not influenced by HIV status in spite of the severely diminished pericardial CD4+ lymphocyte counts observed in this study. It is thus likely that in HIV positive patients IFN-γ production is partly maintained by activated CD8+ T cells, which were significantly elevated in HIV positive patients compared to HIV negative tuberculous pericarditis patients. This finding underlines the importance of IFN-γ in the human immune response against M. tuberculosis. We also demonstrated that the presence of ADA in pericardial fluids reflects the activity of the cellular immune response. Both IFN-γ and ADA can be utilised as sensitive and specific diagnostic tools for pericardial TB. Doctoral 2008-07-28T07:49:44Z 2010-06-01T08:21:00Z 2008-07-28T07:49:44Z 2010-06-01T08:21:00Z 2005-12 Thesis http://hdl.handle.net/10019.1/1411 en University of Stellenbosch application/pdf Stellenbosch : University of Stellenbosch
spellingShingle HIV infections
Tuberculosis -- Immunological aspects
Tuberculosis -- Treatment
Mycobacterium tuberculosis
Dissertations -- Internal medicine
Theses -- Internal medicine
Reuter, Helmuth
The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
title The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
title_full The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
title_fullStr The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
title_full_unstemmed The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
title_short The immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
title_sort immunopathogenesis and treatment of tuberculous pericardial effusions in a population with a high prevalence of infection with the human immunodeficiency virus
topic HIV infections
Tuberculosis -- Immunological aspects
Tuberculosis -- Treatment
Mycobacterium tuberculosis
Dissertations -- Internal medicine
Theses -- Internal medicine
url http://hdl.handle.net/10019.1/1411
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