15 november 2012

TB outbreaks in the Midlands mapped using DNA sequencing

Source: Oxford University Hospitals NHS Trust

Mycobacterium tuberculosis bacteria
Sequencing the entire DNA of TB bacteria can track outbreaks of the disease.

A new study has demonstrated how DNA sequencing techniques can map tuberculosis (TB) outbreaks, allowing the spread of disease to be tackled more quickly and effectively.

Researchers in Oxford and at the Health Protection Agency in Birmingham have pioneered the method – which read outs the entire DNA code of the TB-causing bacteria – through a study of 254 TB cases in the Midlands. The results are published today in the journal Lancet Infectious Diseases.

The team used whole genome sequencing techniques to compare the genetic information from the TB bacteria of each patient. This allowed them to determine with a high degree of accuracy whether cases were isolated, or if there was an outbreak of the potentially fatal disease.

By genetically mapping the spread of infection, the method can 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 target efforts quickly, efficiently and effectively to where it is needed most.

Professor Tim Peto led the research at the NIHR Oxford Biomedical Research Centre, a partnership between the University of Oxford and the Oxford University Hospitals NHS Trust. He said: '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.'

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

Professor Tim Peto

TB cases in the UK remain relatively low. However, the number of cases has risen slightly over the past decade, with almost 9,000 cases reported in 2011. Many cases are isolated but there have been numerous outbreaks across the country over recent years.

Public health bodies currently 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. It also occasionally throws up false connections, leading to wasted effort by health bodies.

By sequencing the whole genome of the TB bacteria, the new technique allows outbreaks to be mapped by linking cases together, and it has the ability to predict the existence of undiagnosed cases.

Dr Philip Monk, a consultant in public health at the Health Protection Agency, described the research as a 'revolution in TB control'.

He added: '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.'

The whole genome sequencing method measures 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 in the DNA of the TB bacteria, it is possible to work out the direction of transmission and identify potential super-spreaders.

Professor Peto of the Nuffield Department of Clinical Medicine at Oxford University said: '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.'

The study was funded by the Medical Research Council, Wellcome Trust, National Institute for Health Research and the Health Protection Agency.