Stratification of antimicrobial treatment for TB by WGS
Research type
Research Study
Full title
Stratification of antimicrobial treatment for TB by whole bacterial genome sequencing directly from sputum
IRAS ID
165650
Contact name
Judith Breuer
Contact email
Sponsor organisation
Joint Research Office, University College London Hospitals
Clinicaltrials.gov Identifier
Z6364106/2015/01/20, UCL Data Protection Registration Number
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
The aim of this study is to compare present diagnostic methods with a method we have developed for sequencing Mycobacterium tuberculosis (Mtb) genomes directly from sputum, for detecting and monitoring antimicrobial resistance (AMR) in clinical samples. Rising AMR is making it harder to control the spread of tuberculosis (TB); in the UK resistance to at least one first-line antibiotic is found in 7.8% of cases. Strains that are resistant to the two key drugs, rifampicin and isoniazid, have increased in the UK in the last decade, and are both difficult and expensive to treat. A major barrier to controlling resistant Mtb is the difficulty of promptly detecting and monitoring AMR. Bacterial culture is slow, taking at least 4 weeks; molecular tests while rapid are less sensitive than culture and provide information on only a few targets. This results in most patients being treated empirically. This is sub-optimal as many drug resistant strains may not respond adequately to empirical treatment, and this may inadvertently lead to further resistance emerging.
Whole genome sequencing (WGS) provides simultaneous and comprehensive data on AMR genotype. We have developed a pipeline for automated WGS and analysis of Mtb directly from sputum. Preliminary data on 24 smear-positive sputa has demonstrated an 83% success rate with 20 fully AMR-annotated genomes recovered. Possible turnaround times of 48-72 hours from sample receipt offer the potential for targeted treatment within a clinically relevant timeframe.
This is a small pilot study which is funded for one year by the NIHR UCLH BRC. The study will obtain sputum samples from patients attending one of six participating NHS clinics. Research samples will be obtained at the same time as diagnostic samples and the feasibility of using WGS for the comprehensive detection of Mtb AMR, in comparison to other methods, will be assessed. Additional bioinformatic analyses will be carried out on the whole genome sequences without further cost which will enable the investigation of additional evolutionary questions regarding the genetic diversity of Mtb.REC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
15/EM/0091
Date of REC Opinion
23 Feb 2015
REC opinion
Further Information Favourable Opinion