Interferon-Gamma Blood Test Assays Detect Latent Tuberculosis

Two new interferon-gamma blood test assays to detect latent tuberculosis infection (LTBI) showed that people had smear-positive tuberculosis, while traditional tuberculin skin tests (TST) were negative, according to a large contact study.

TSTs are based on a skin reaction to injection, scratching, or puncturing the skin with a purified protein derivative of tuberculosis bacterium. Swelling and redness indicate a positive result. In the new blood tests, two interferon-gamma release assays (IGRAs) measure response to an antigen highly specific for Mycobacterium tuberculosis. One of the blood tests, QuantiFeron-TB Gold, has received approval from the U.S. Food and Drug Administration (FDA) for use in the United States. The other has been approved for use in Europe.

Results from these tests were published in the second issue for March 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Ailko Bossink, M.D., Ph.D., from the Department of Pulmonology at Diakonessenhuis Utrecht (The Netherlands) and eight associates, recruited 785 supermarket customers who had not received Calmette-Guéren bacillus (BCG) vaccine against tuberculosis-- the immunizing agent prepared from Calmette-Guéren bacillus, since TST results are not accurate in those vaccinated with BCG.

All individuals in the study cohort were recruited from over 20,000 customers who had shopped at the supermarket for more than 10 months. Many had numerous contacts with an infected employee, who had been contagious since February 2004. The large-scale contact investigation began in January 2005.

One-third of the world's population is believed to harbor latent TB infection, or LTBI, said Dr. Bossink. Approximately five to 15% of immunocompetent persons with LTBI will develop TB disease. In countries with a low-incidence of TB, the tracing and targeted treatment of individuals with LTBI constitutes the major pillar of TB control.

For the study, researchers selected 469 customers randomly on the day that their TST was administered and 316 with a TST result of more than 0 mm. Among the 785 study participants, TST results were associated with age, whereas positive interferon-gamma blood test assay results were significantly associated with cumulative shopping time, said Dr. Bossink. TST results were not associated with any measure of exposure to the index case in the supermarket.

The scientists noted that positive TST responses largely reflected delayed type hypersensitivity due to remote infection with M. tuberculosis acquired before the source case at the supermarket became infectious.

Among the 759 shoppers who had valid results from both interferon-gamma blood assays, slightly over 80% (608) were concordant negative with both blood tests, while 72 were concordant positive and 79 were discordant. Overall agreement between the two tests was 89.6%.

Although the interferon-gamma blood tests are now considered more specific and show a better correlation with exposure than TST, it has not been demonstrated whether they provide a valid basis for therapeutic decisions regarding treatment, said Dr. Bossink. The risk of TB disease in the presence of a positive test result had not been established.
Notably, positive interferon-gamma blood assays were observed in a significant proportion of recently exposed contacts with a negative TST result, The clinical significance of this finding merits further study if the blood tests are to replace the TST and be used for therapeutic decisions.


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