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DNA sequencing has TB in its sights

16 September 2013
Appeared in BioNews 722

Scientists have shown how to map tuberculosis (TB) outbreaks using DNA sequencing, an advance that could lead to quicker, more effective responses to the potentially lethal bug.

Currently when an outbreak occurs, public health bodies rely on patients volunteering information about their movements and social circle to help identify others at risk and tailor a response. They will also perform a 'DNA fingerprinting' technique on the isolated bacteria to try and link diagnosed cases.

Both approaches are problematic. TB often afflicts the most precarious members of Western societies – illegal drug users and clandestine immigrants, for example – who can be reluctant to share information with authorities.

And DNA fingerprinting has considerable limitations, says Dr Tim Walker of the John Radcliffe Hospital in Oxford. Dr Walker is a TB researcher and first author on a recent paper in Lancet Infectious Diseases demonstrating the effectiveness of whole genome sequencing (WGS) - where nearly the entirety of the bacterium's DNA code is analysed - in mapping TB outbreaks.

'Currently, each TB sample gets a fingerprint in a reference laboratory and these results are sent to the public health consultants', explains Dr Walker. 'When the public health team gets matching fingerprints, they may start an epidemiological investigation. But fingerprinting can only rule out transmission between cases and not reliably confirm it. So considerable resources may be invested looking for links between patients that don't exist'.

'WGS offers much, much greater resolution', Dr Walker continues. 'You're looking at less than one percent of the genome with a fingerprint whereas you can analyse about 92 percent of the genome with WGS'.

In the paper in Lancet Infectious Diseases, researchers performed WGS on TB samples from 254 patients in the Midlands. By looking at how the genetic code of each sample differed they were able to create a map showing chains of infection between patients. They accurately predicted which cases were isolated and how outbreaks spread.

The paper also identified patients known as 'super-spreaders', who are particularly prolific in infecting others. Such information could be highly valuable during TB outbreaks as it would enable public health officials to ensure that the patients most likely to spread the infection were being treated.

WGS offers advantages over the current approach in many scenarios, says Dr Walker: 'Take the situation where there's a TB outbreak among people from the same immigrant group scattered across several cities. Has the outbreak occurred in the UK and spread because people are regularly meeting socially or has the TB been acquired in the country of origin and carried by a number of individuals?'

'The public health response would depend on the answer to that question. Correctly deployed, WGS would enable much quicker and more efficient targeting of that response'.

A recent report from Public Health England highlighted that 'despite considerable efforts to improve TB prevention, treatment and control, the incidence of TB in the UK remains high compared to most other Western European countries'. Nearly 9,000 people contracted TB in the UK in 2012.

It seems likely that WGS will play a prominent role in the country's battle with the bug. 'The vision is that WGS does more than just replace DNA fingerprinting', says Dr Walker, 'and actually replaces all the tests in the lab as it becomes sufficiently cost-effective. So you'd be able to identify both the species of TB and its drug resistance profile on analysis of the bacterial genome'.

Dr Walker is involved in a pilot study to assess the feasibility and reliability of this approach which will begin in October at the John Radcliffe Hospital.

Dr Walker was talking about his work prior to his presentation 'How whole genome sequencing can help us understand the epidemiology of M. tuberculosis' at the British Society for Genetic Medicine's annual conference, held at the Liverpool Arena and Convention Centre on Monday 16 September 2013.

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