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Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies

With an estimated third of all tuberculosis (TB) cases being missed, the need to develop rapid, simple and accurate diagnostic tests is critical. The last five years has seen an unprecedented activity in the development of a range of new tests. However, a major concern is that not all marketed TB te...

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Main Author: Moodley, Vineshree Mischka
Other Authors: Nicol, Mark P
Format: Thesis
Language:English
Published: Division of Medical Microbiology 2017
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access_status_str Open Access
author Moodley, Vineshree Mischka
author2 Nicol, Mark P
author_browse Moodley, Vineshree Mischka
Nicol, Mark P
author_facet Nicol, Mark P
Moodley, Vineshree Mischka
author_sort Moodley, Vineshree Mischka
collection Thesis
description With an estimated third of all tuberculosis (TB) cases being missed, the need to develop rapid, simple and accurate diagnostic tests is critical. The last five years has seen an unprecedented activity in the development of a range of new tests. However, a major concern is that not all marketed TB tests have been assessed rigorously, particularly in terms of diagnostic accuracy, robustness under operational conditions in the field, and practical usefulness. This dissertation comprises a compilation of diagnostic clinical studies of novel point-of-care tests, namely a chemiresistive "TB breath-analyser"; a lipoarabinomannan (LAM) urine dipstick, and an adaptation of the Xpert®MTB/RIF assay for use on blood. Lastly, there is a modification of the sputum collection device (SCD) to enable specimen processing without the requirement of a biosafety cabinet. The chemiresistive sensor, which detects volatile organic compounds released by Mycobacterium tuberculosis in a patient's breath, demonstrated a high sensitivity (100%) and specificity (92%) for distinguishing patients with active TB from healthy controls. However, sensitivity (74%) and specificity (63%) were lower when the culture-negative participant group was compared to the culture-positive participants. The test shows potential as a useful screening test for TB with further refinement of the sensor technology. The LAM dipstick was shown to be useful in hospitalised HIV-infected patients with CD4 T-cell counts <200 cells/μL reinforcing the data from other studies. Although the blood Xpert®MTB/RIF assay showed some utility in diagnosis of TB in hospitalised patients with very advanced HIV, given the poor sensitivity and specificity, and the requirement for specialised equipment as well as a large volume of blood for testing, it is unlikely that Xpert®MTB/RIF testing on blood will contribute much over other existing diagnostics in resource-limited settings. Finally, the redesigned SCD offers a solution to biosafety concerns with minimal impact on patient acceptability and clinical care.
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language eng
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license_str Not specified — see source repository
provenance_str_mv Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository
publishDate 2017
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publisher Division of Medical Microbiology
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spelling oai:open.uct.ac.za:11427/25439 Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies Moodley, Vineshree Mischka Nicol, Mark P Dorman, Susan E Pathology Medical Microbiology With an estimated third of all tuberculosis (TB) cases being missed, the need to develop rapid, simple and accurate diagnostic tests is critical. The last five years has seen an unprecedented activity in the development of a range of new tests. However, a major concern is that not all marketed TB tests have been assessed rigorously, particularly in terms of diagnostic accuracy, robustness under operational conditions in the field, and practical usefulness. This dissertation comprises a compilation of diagnostic clinical studies of novel point-of-care tests, namely a chemiresistive "TB breath-analyser"; a lipoarabinomannan (LAM) urine dipstick, and an adaptation of the Xpert®MTB/RIF assay for use on blood. Lastly, there is a modification of the sputum collection device (SCD) to enable specimen processing without the requirement of a biosafety cabinet. The chemiresistive sensor, which detects volatile organic compounds released by Mycobacterium tuberculosis in a patient's breath, demonstrated a high sensitivity (100%) and specificity (92%) for distinguishing patients with active TB from healthy controls. However, sensitivity (74%) and specificity (63%) were lower when the culture-negative participant group was compared to the culture-positive participants. The test shows potential as a useful screening test for TB with further refinement of the sensor technology. The LAM dipstick was shown to be useful in hospitalised HIV-infected patients with CD4 T-cell counts <200 cells/μL reinforcing the data from other studies. Although the blood Xpert®MTB/RIF assay showed some utility in diagnosis of TB in hospitalised patients with very advanced HIV, given the poor sensitivity and specificity, and the requirement for specialised equipment as well as a large volume of blood for testing, it is unlikely that Xpert®MTB/RIF testing on blood will contribute much over other existing diagnostics in resource-limited settings. Finally, the redesigned SCD offers a solution to biosafety concerns with minimal impact on patient acceptability and clinical care. 2017-09-28T05:24:46Z 2017-09-28T05:24:46Z 2017 Doctoral Thesis Doctoral PhD http://hdl.handle.net/11427/25439 eng application/pdf Division of Medical Microbiology Faculty of Health Sciences University of Cape Town
spellingShingle Pathology
Medical Microbiology
Moodley, Vineshree Mischka
Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies
thesis_degree_str Doctoral
title Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies
title_full Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies
title_fullStr Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies
title_full_unstemmed Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies
title_short Improving point-of-care diagnosis of tuberculosis: development and evaluation of novel technologies
title_sort improving point of care diagnosis of tuberculosis development and evaluation of novel technologies
topic Pathology
Medical Microbiology
url http://hdl.handle.net/11427/25439
work_keys_str_mv AT moodleyvineshreemischka improvingpointofcarediagnosisoftuberculosisdevelopmentandevaluationofnoveltechnologies