Clinical evaluation of TB diagnostics
File(s)
Author(s)
Park, Mirae
Type
Thesis
Abstract
Tuberculosis is a major global health burden and remains one of the top ten causes of death. There remains a large diagnostic gap between the notified and estimated incident cases. This is from factors including challenges in diagnostic testing.
There is currently a lack of a rapid and accessible test which can identify MTB as well as provide correct drug susceptibility with a sufficient sensitivity.
The main scope of this thesis is to explore the different modalities to improve TB diagnostics and its implications for clinical practice. Evaluating Xpert Ultra using bronchoalveolar lavage samples for sputum negative pulmonary TB and in endobronchial ultrasound guided transbronchial needle aspiration samples for mediastinal lymph node TB, our findings have confirmed the diagnostic accuracies of Xpert Ultra in these non-sputum samples, as the use of Xpert Ultra has not yet been approved by the WHO. A retrospective followed by a multicentre prospective study set in a low incidence country showed the higher sensitivity of Xpert Ultra in comparison to smear microscopy. Trace readings were likely to reflect TB disease.
Whole genome sequencing has been integrated into the national clinical pathway. This thesis has demonstrated the lag time for results to be available in clinical practice. Availability of genotypic drug susceptibility results defined changes in drug regimens, and this thesis highlighted the importance of communication between a central and local laboratory. Furthermore, delays in isoniazid resistance were identified. By exploring new technologies such as Xpert MTB/XDR and next generation sequencing Deeplex Myc-TB, early identification of resistant patterns could potentially reduce delays on correct treatment regimens and ultimately treatment success.
This thesis reflects on the complex diagnostic challenges in identifying MTB and correct drug susceptibilities and how a multi strategy approach could optimise rapid TB diagnostics.
There is currently a lack of a rapid and accessible test which can identify MTB as well as provide correct drug susceptibility with a sufficient sensitivity.
The main scope of this thesis is to explore the different modalities to improve TB diagnostics and its implications for clinical practice. Evaluating Xpert Ultra using bronchoalveolar lavage samples for sputum negative pulmonary TB and in endobronchial ultrasound guided transbronchial needle aspiration samples for mediastinal lymph node TB, our findings have confirmed the diagnostic accuracies of Xpert Ultra in these non-sputum samples, as the use of Xpert Ultra has not yet been approved by the WHO. A retrospective followed by a multicentre prospective study set in a low incidence country showed the higher sensitivity of Xpert Ultra in comparison to smear microscopy. Trace readings were likely to reflect TB disease.
Whole genome sequencing has been integrated into the national clinical pathway. This thesis has demonstrated the lag time for results to be available in clinical practice. Availability of genotypic drug susceptibility results defined changes in drug regimens, and this thesis highlighted the importance of communication between a central and local laboratory. Furthermore, delays in isoniazid resistance were identified. By exploring new technologies such as Xpert MTB/XDR and next generation sequencing Deeplex Myc-TB, early identification of resistant patterns could potentially reduce delays on correct treatment regimens and ultimately treatment success.
This thesis reflects on the complex diagnostic challenges in identifying MTB and correct drug susceptibilities and how a multi strategy approach could optimise rapid TB diagnostics.
Version
Open Access
Date Issued
2025-05-02
Date Awarded
2026-03-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Kon, Onn Min
Satta, Giovanni
Lalvani, Ajit
Hansel, Trevor
Sponsor
National Institute for Health Research (Great Britain)
Grant Number
P68495
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)