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dc.contributor.advisorSabiiti, Wilber
dc.contributor.advisorGillespie, S. H.
dc.contributor.authorMusisi, Emmanuel
dc.description.abstractTuberculosis (TB) is a difficult disease to treat, requiring a minimum of six months on a combination of four antibiotics. This thesis reports the first systematic evaluation of the St Andrews' developed RNA-based tuberculosis-Molecular Bacterial Load Assay (TB-MBLA) for its accuracy to diagnose tuberculosis and measure treatment response in comparison to current standard-of-care tests. Presumptive TB patients were enrolled in Uganda and assessed for TB using TB-MBLA versus Xpert MTB/RIF Ultra (Xpert-Ultra) and stained smear fluorescent microscopy (SSM-FM) using sputum MGIT culture as the gold standard and reference test. Out of the 210 presumptive cases, 129 (61.4%) participants tested TB positive on the Xpert-Ultra in the sputum cohort and they were enrolled into the treatment arm and consequently monitored for six months. At baseline, 6/210 (2.9%) sputum MGIT culture results were indeterminate due to contamination, and they were excluded from the calculation of the sensitivity, specificity, and predictive values. Sensitivity for TB-MBLA and Xpert-Ultra (95%CI) was 99%(95-100) which was higher compared to 76%(65-83) for SSM-FM. TB-MBLA specificity at 90%(83-96) was higher than the 76%(68-86) for Xpert-Ultra but less than 98%(93-100) for SSM-FM. In the treatment follow-up arm, TB positivity rates reduced for all tests. TB-MBLA positivity reduction was consistent with that of the MGIT culture but different from that of Xpert-Ultra which occurred remarkably slower. Consequently, 31 participants were still Xpert-Ultra positive at the end treatment course. Three-month post treatment follow-up of the 31 Xpert-Ultra positive cases revealed no TB both clinically and on TB-MBLA and MGIT tests. In the stool cohort, TB-MBLA detected TB in 57/100 participants including 49 who were confirmed positive for pTB on sputum MGIT culture. Fifty-seven percent (57%) of the indeterminate stool culture were positive on TB-MBLA. The findings prove that TB-MBLA's potential utility as both a diagnostic and treatment monitoring tool of TB in research and routine healthcare.en_US
dc.description.sponsorship"This Ph.D. was funded on the European and Developing Countries Clinical trials Partnership (EDCTP-2) PanACEA II (Grant number: TR1A2015-1102), Makerere University Research and innovation Fund (MakRIF), the University of St Andrews, St Leonards Scholarship; the Infectious Diseases Institute through the Health and Innovation Impact project, the Lung MicroCHIP (Grant number: U01 HL098964), K24 (Grant number: K24 HL087713), and the Scottish Funding Council (SCF)-Global Challenges Research Fund (GCRF). Practical execution of this work would not have been possible without the financial support from the mentioned sponsors, to whom I am incredibly grateful."--Fundingen
dc.publisherUniversity of St Andrews
dc.subject.lcshTuberculosis--Molecular aspectsen
dc.titleEvaluation of the tuberculosis-molecular bacterial load assay for tuberculosis diagnosis and monitoring response to standard anti-tuberculosis therapyen_US
dc.contributor.sponsorEuropean and Developing Countries Clinical Trials Partnership (EDCTP). PanACEA IIen_US
dc.contributor.sponsorMakerere University Research and Innovation Fund (MakRIF)en_US
dc.contributor.sponsorUniversity of St Andrews. St Leonard's College Scholarshipen_US
dc.contributor.sponsorScottish Funding Councilen_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.rights.embargoreasonEmbargo period has ended, thesis made available in accordance with University regulationsen

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