Bacterial RNA profiling to predict tuberculosis treatment failure (360G-Wellcome-204538_Z_16_Z)

At present there is no way of accurately predicting tuberculosis (TB) treatment failure and relapse to active disease. This results in the over-treatment of many patients, who might safely stop the toxic six-month therapy earlier, and necessitates lengthy and costly clinical trials to assess new therapies, thus creating a bottleneck to progress. This innovative project will test whether the transcriptional response of TB isolated from patient sputa during the first few days of treatment will predict relapse months later. Building on the applicant’s recent study demonstrating that sputa TB mRNA signatures differ between patients and reflect clinical/microbiological measures of disease, this proof-of-concept prospective patient study will for the first time define markers of relapse. TB RNA from patient sputa will be assayed by targeted and genome-wide profiling techniques at diagnosis and at multiple timepoints after the start of drug therapy. RNA yields and gene expression signatures will be analysed to determine key methodological parameters concerning the collection and detection of sputa TB RNA and to assess applicability in the UK and Cameroon. Finally, TB mRNA signatures from relapse and successfully-treated patients will be compared using this novel discovery approach to identify biomarkers that predict relapse, transforming the management of TB.