Test offers hope of tuberculosis breakthrough

A blood test that can tell doctors whether someone is likely to develop the active and dangerous form of tuberculosis has become a realistic possibility.

Scientists believe they have finally found a way that could distinguish the 10 per cent of people infected with TB who will go on to develop the full-blown disease from the 90 per cent of healthy carriers who have the latent form of the lung infection.

It would mean that doctors could concentrate on treating the one in 10 infected people who are at high risk of becoming seriously ill, rather than attempting to give potent anti-TB drugs to everyone who is shown to be infected with the TB bacterium.

About two million people worldwide die each year from TB, mostly in the developing world, but the disease has also made a come-back in developed countries. In Britain 9,153 cases were recorded in 2009, the largest annual increase (5.5 per cent) since 2005, with nine out of 10 cases occurring in ethnic minorities.

The researchers, led by Anne O'Garra of the Medical Research Council's National Institute for Medical Research in London, found a "genetic signature" in the blood of people with active TB which could be used as the basis of a diagnostic test.

The study in the journal Nature also found the same genetic signature – evidence of certain infection-related genes being activated – in 10 per cent of people with the latent form of the disease. However, further work needs to be done to assess whether this 10 per cent will be the same 10 per cent of latent patients who go on to develop active TB, Dr O'Garra said.

"As an immunologist, what most intrigued me was that approximately a third of the world has been exposed or infected with the TB bacterium but only 10 per cent of these people get sick and the question is why – what determines when people get active tuberculosis?" Dr O'Garra said.

"What we've described is a distinct blood gene signature in active TB patients, and intriguingly this is absent in other infectious diseases and also in healthy individuals. But it is present in latent TB individuals, but only in 10 per cent of these individuals," she said.

The study involved a wide range of ethnic groups in London, where 3,500 cases of TB were diagnosed last year, about 40 per cent of all UK cases. More than 400 participants took part in the study, which also involved analysing the blood of TB patients in Cape Town in South Africa.

"By doing the study in London we were able to involve individuals with a really wide range of backgrounds and diverse ethnicity and thus make our findings more widely available to this global disease," said Matthew Berry, a consultant in respiratory medicine.

The blood signature found in active TB patients is independent of ethnicity, age and sex, and appears to reflect the severity and extent of the disease. The signature also disappears after successful treatment, Dr Berry said.

"What such a test would enable is very targeted treatment. Instead of trying to treat everyone with latent TB you could focus all of your efforts on that 10 per cent who would develop the disease," he said.

The genetic signature shows that certain genes in specialised blood cells called neutrophils have been turned on by the action of a molecule in the immune system known as type-1 interferon, which can aggravate bacterial infections, Dr O'Garra said. "Finding these molecules expressed in TB suggests that they may be contributing to make the disease worse," she said.

Robert Wilkinson of the University of Cape Town said that the existing diagnostic test for TB has not changed for 125 years. "We're excited by the study because it gives us greater insight into how tissue damage might occur in tuberculosis. It also raises the prospect of developing a diagnostic test or a way of learning who is most at risk of TB," he said.

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