Transforming Tuberculosis control

TB's genetic 'family tree' holds the key to tackling outbreaks quickly and effectively

Transforming Tuberculosis control

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New genetic sequencing techniques can map the 'family tree' of a Tuberculosis (TB) outbreak allowing the spread of disease to be tackled quickly and effectively.

Researchers, led by the Oxford Biomedical Research Centre, the Health Protection Agency in Birmingham and the Wellcome Trust Sanger Institute in Cambridge, have pioneered the whole genome sequencing (WGS) method through a study of 254 TB cases in the Midlands.

The method, published in the Lancet Infectious Diseases, compares the genetic information from the TB germs of each patient to determine with a high degree of accuracy whether cases are isolated, or if there is an outbreak of the potentially fatal disease.

By genetically mapping the spread of infection it can also show who has given the disease to whom and help identify potential 'super spreaders' before any information has been collected from patients.

Armed with this data, public health bodies can assess how much transmission is taking place and thereby target efforts quickly, efficiently and effectively to where it is needed most.

"This will result in a major rebalancing of the public health approach to the spread of TB."

"It will make them far more focused on where the problems are and make them more efficient and effective."

Lead investigator Professor Tim Peto, at the Oxford Biomedical Research Centre

Co-investigators Drs. Grace Smith and Philip Monk, senior members of the HPA TB control programme, described the research as a 'revolution in TB control', adding "at present you have to put a lot of work into contact tracing to find links between cases. This is extremely difficult particularly when people often lead such chaotic lives.

"By identifying so-called super spreaders we can target our work effectively. In terms of the public health management of TB, that is a major paradigm shift."

TB cases in the UK remain relatively low. However, the number of cases has risen slightly over the past decade, with 8,963 cases reported in 2011 (source: Health Protection Agency). Many cases are isolated, but there have been numerous outbreaks across the country over recent years.

Current practice sees public health bodies depend on people with TB volunteering information about their movements, family and friends, to identify further cases and piece together the potential spread of the disease. Until now this approach has been aided by limited genetic typing techniques that are only able to rule out transmission between cases, and not reliably confirm transmission.

The process of identifying outbreaks has therefore been time consuming, relying on the information people are able to give and occasionally throwing up 'false connections', leading to wasted effort by health bodies.

By sequencing the whole genome the new technique allows linking of cases and the mapping of outbreaks, and has the ability to predict the existence of undiagnosed cases.

"We are very pleased to have been able to work with the teams in Oxford and and Birmingham on this important study. We hope that this will contribute to the introduction of WGS into routine analysis of TB transmission, which we believe will become increasingly valuable for clinical practice in the future."

Dr Julian Parkhill, investigator from the Wellcome Trust Sanger Institute

WGS is used to measure the genetic distance between TB strains to accurately link cases before any additional patient data has been collected. By analysing the evolving pattern of mutations it is possible to work out the direction of transmission and identify potential 'super-spreaders'.

"This work gives a level of certainty you could never have before about who belongs to a transmission chain."

"The information is in the germ, and it speaks for itself."

Professor Tim Peto

Notes to Editors
  • Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study.

    Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G et al.

    The Lancet. Infectious diseases 2013;13;2;137-46


Medical Research Council, Wellcome Trust, National Institute for Health Research, and the Health Protection Agency.

Participating Centres
  • Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
  • Department of Statistics, University of Oxford, Oxford, UK
  • West Midlands Public Health Laboratory, Health Protection Agency, Heart of England NHS Foundation Trust, Birmingham, UK
  • Heartlands Hospital and Birmingham Chest Clinic, Heart of England NHS Foundation Trust, Birmingham, UK
  • Oxford National Institute of Health Research Biomedical Research Centre, John Radcliffe Hospital, Headington, Oxford, UK
  • School of Immunity and Infection, University of Birmingham, Birmingham, UK
  • Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge
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