New blood test six times more effective for tuberculosis control

In a landmark study electronically published today in the American Journal of Respiratory and Critical Care Medicine, a blood test for detecting TB infection, QuantiFERON(R)-TB Gold (QFT), has been shown to be six times more accurate than the conventional tuberculin skin test (TST) at predicting which tuberculosis (TB)-exposed individuals will go on to develop TB disease.

This study has important implications for the worldwide effort to eradicate TB, as accurately indentifying TB-infected individuals allows health authorities to treat them before they develop disease, and the greater accuracy of the new test makes this more efficient as well as cheaper and safer.

Globally, up to two billion people are infected with TB. In most cases the TB bacteria is contained by the body's immune system (latent TB infection) without any symptoms of the infection. But 9 million people, most originating from this large pool of individuals with latent TB infection, are reported every year by The World Health Organization as developing active and infectious TB disease.

In the developed world, TB eradication strategies have focused on identifying and treating people with latent TB infection. Until recently the tuberculin skin test (TST; Mantoux test) has been the only test available to detect infected people. However, the TST often produces false-positive results, meaning many uninfected people are offered unneeded preventative treatment for TB. This treatment is for 6 to 9 months and may produce damaging side effects. For improved TB control, a test that accurately detects those truly infected, enabling treatment for only those at risk of developing TB disease, has major implications. The QFT test has now been shown to have this desired characteristic.

In the German city of Hamburg, Dr. Roland Diel and colleagues used both TST and QFT on 601 people who may have been infected by contact with people with TB disease. 40% had a positive TST, but only 11% (66) of the exposed persons were found infected by QFT and offered TB treatment -- 41 declined. Over the next two years 6 people developed TB disease, all were QFT positive and had declined treatment. In the past, all 243 TST positive people would need to have had anti-TB treatment to prevent only 5 of these cases, as one was TST negative. In scientific terms, QFT had a predictive value for developing TB disease of 15%, more than 6 times greater than the 2.3% for the TST.

What does this mean? Using QFT, doctors can now treat only a fraction of the people they would have with the TST, with the knowledge that they are preventing TB disease to at least the same extent, and likely better.

Dr. Lee B. Reichman, Professor of Medicine and Preventive Medicine and Community Health and Executive Director of the New Jersey Medical School Global Tuberculosis Institute in Newark, New Jersey USA comments:

"For many years we have known that active TB is a preventable disease, but we have had an extremely difficult time convincing health professionals and patients to apply and accept well recognized preventive measures because the tuberculin skin test universally used to define risk wasn't selective enough.

This study by Diel and colleagues is really "dynamite" because, for the first time, it documents that by using QFT in place of the skin test, practitioners can focus on a much smaller group who are those most likely to progress to active TB".

These findings have far-reaching economic implications for global and regional TB control, as use of QFT in similar settings will likely result in only one quarter the number of individuals requiring preventive medication as indicated by the current, inaccurate, TST. The adoption of QFT will enable health authorities to confidently focus on individuals who are truly at risk of developing active TB, significantly reducing the costs and risks associated with preventative treatment, and effectively reducing the overall number of cases of tuberculosis disease. For example, in the Hamburg study alone, by using QFT instead of the TST, >45,000 fewer pills would have been needed to treat every test positive person. Worldwide, this can eliminate the cost and side-effects of taking tens of billions of unnecessary tablets, and many millions of X-rays and clinical visits.

References:

Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a wholeblood IFN-a assay for the development of active TB disease. Am J Respir Crit Care Med [Epub ahead of print]. http://ajrccm.atsjournals.org/cgi/content/abstract/200711-1613OCv1

About QuantiFERON(R)-TB Gold (QFT(TM)):

QFT is the first major advance in TB diagnosis since the introduction of the Mantoux or tuberculin skin test (TST) over 100 years ago. The QFT test is based on measurement of a cell mediated immune response in TB-infected individuals. The T-cells of these individuals are sensitized to TB, and respond to stimulation with peptides simulating those expressed by the TB causing bacteria, secreting a cytokine called interferon-a. QFT accurately measures the interferon-a response in a sensitive enzyme assay. Unlike the TST, QFT is unaffected by previous BCG vaccination and most other mycobacteria. QFT requires only one patient visit, is a controlled laboratory test, and provides an objective, reproducible result that is not subject to interpretation based on a patient's relative risk factors for TB exposure. The test has received regulatory and policy approvals in the USA, Japan, Europe and elsewhere.

About Cellestis:

Cellestis is a listed Australian biotechnology company commercializing QuantiFERON(R) technology for diagnosing TB and other diseases worldwide. The Company operates through subsidiaries in the USA, Europe and Australia.