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dc.contributor.advisorGillespie, S. H.
dc.contributor.advisorSabiiti, Wilber
dc.contributor.authorMtafya, Bariki Anyamkisye
dc.description.abstractTuberculosis (TB) remains a major public health disease responsible for over 1 million death every year. Effective diagnosis, treatment and monitoring of treatment response are crucial for controlling TB. The gold standard culture does not provide real time results. Routine microscopy and Xpert MTB/RIF tests fail to differentiate viable from dead Mycobacterium tuberculosis which is crucial to clinicians and trialists for treatment monitoring. The TB-MBLA detects the 16S ribosomal RNA of M. tuberculosis as the maker of viability using a quantitative RT-PCR with a promising potential to replace routine culture and microscopy for monitoring. This thesis explored the utility of TB- MBLA for treatment monitoring compared routine methods. Our results show that treatment response measured by TB-MBLA is consistent with resolution of clinical signs and is rapid, accurate with shorter time to result than standard culture. A survey of the healthcare practitioners showed a high level of TB- MBLA acceptability. The NaOH-based decontamination is perquisite step in the processing of sputum for standard TB culture. This study revealed that NaOH reduces viable M. tuberculosis count by a magnitude of 0.66log₁₀ and 0.65log₁₀ eCFU/mL measured by TB-MBLA for H37Rv cultures and sputum samples, respectively. The time to MGIT culture positivity increased by 1.2 days after decontamination of H37Rv cultures. Reduction in viable count compromises the sensitivity of TB tests and may lead to false negative results in later stage of treatment when patient bacterial burden is low. We also show that using fluorescent microscopy (FM) increases the risk of false positive results since most FM positive samples in late-stage treatment were negative by tests of viability, MGIT and TB-MBLA. Results suggest that the TB-MBLA could be applied in high burden settings for monitoring and identifying patients failing TB therapy. Further work is required to develop point of care systems for this assay.en_US
dc.description.sponsorship"This work was funded by government of United Kingdom through the commonwealth doctoral studentship awards (award number TZCS-2016-718), University of St. Andrews and NIMR- Mbeya Medical Research Centre, Tanzania."--Acknowledgementen
dc.relationMtafya, B., Sabiiti, W., Sabi, I., John, J., Sichone, E., Ntinginya, N. E., & Gillespie, S. H. (2019). Molecular bacterial load assay (MBLA) concurs with culture on the NaOH-induced Mycobacterium tuberculosis loss of viability. Journal of Clinical Microbiology, 57, Article e01992-18.
dc.relationSabiiti, W., Mtafya, B. A., Alferes De Lima, D., Dombay, E., Baron, V. O., Azam, K., Orascova, K., Sloan, D. J., & Gillespie, S. H. (2020). A tuberculosis molecular bacterial load assay (TB-MBLA). Journal of Visualized Experiments, 158, Article e60460.
dc.titleExploring the utility and implementability of an innovative method to monitor tuberculosis treatment response in a resource limited high burden settingen_US
dc.contributor.sponsorCommonwealth Scholarship Commission in the United Kingdomen_US
dc.contributor.sponsorUniversity of St Andrewsen_US
dc.contributor.sponsorNational Institute of Medical Research (NIMR). Mbeya Medical Research Center (MMRC)en_US
dc.type.qualificationnamePhD Doctor of Philosophyen_US
dc.publisher.institutionThe University of St Andrewsen_US
dc.rights.embargoreasonThesis restricted in accordance with University regulations. Restricted until 18 November 2022en

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