New Blood Tests for TB Show Exposure to Disease While Tuberculin Skin Tests Do Not


Two new interferon-gamma blood test assays to detect latent tuberculosis infection (LTBI) showed customers were exposed to a supermarket employee in Holland who had smear-positive tuberculosis, while traditional tuberculin skin tests (TST) did not, according to a large contact study.

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, MD, PhD, of the Department of Pulmonology at Diakonessenhuis Utrecht in The Netherlands, and eight associates recruited 785 supermarket customers who had not received BCG vaccine against tuberculosis, the immunizing agent prepared from Calmette-Guéren bacillus. 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 the infected employee, who had been contagious since February 2004. The large-scale contact investigation began in January 2005.

One-third of the worlds population is believed to harbor latent TB infection, or LTBI, said Bossink. Approximately 5 to 15 percent 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.

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 Food and Drug Administration (FDA) for use in the United States. The other has been approved for use in Europe.

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 Bossink. TST results were not associated with any measure of exposure to the index case in the supermarket.

The researchers 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 assay, slightly over 80 percent (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 percent.

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 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, he added. The clinical significance of this finding merits further study if the blood tests are to replace the TST and be used for therapeutic decisions.

In an editorial on the research in the same issue of the journal, Madhukar Pai, MD, PhD, and Dick Menzies, MD, MSc, of McGill University in Montreal, Canada, wrote: The key question is whether the two new IGRAs are better than the TST in predicting the development of TB disease, and thus identifying persons who will benefit most from latent TB infection (LTBI) therapy. There is abundant evidence, from numerous large-scale cohorts and randomized trials, regarding the prognosis of untreated persons with positive TST results; this remains the greatest advantage of the TST.

What is urgently needed is similar longitudinal studies of cohorts who have been tested with IGRA (ideally both IGRAs) and the TST, they continued. However, in almost all low-incidence, high-income countries, it would be ethically impossible not to treat persons with evidence of LTBI. Moreover, in high-incidence countries, where treatment of LTBI is not the current standard of care, it would seem unethical to test for a condition without plans to offer appropriate treatment. However, this should not be a problem. Almost everyone would agree that individuals with concordant positive TST and IGRA are likely to have LTBI and they will never inform the question as to which test predicts active TB better. Thus, such patients can and should be managed appropriately. However, individuals with discordant results (TST+/IGRA- or vice versa) will be informative regarding the risk of development of active disease without treatment. In addition, because the clinical interpretation, and therefore management is unclear for persons with such discordant results, equipoise exists. Therefore, close observation without treatment is reasonable and ethical.

Source: American Thoracic Society (ATS)    

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