Press Releases 2023

Prevention of tuberculosis: Diagnostic tests put to the test

An international team of researchers with the participation of the Research Center Borstel, Leibniz Lung Center, has compared established diagnostic methods that predict the future occurrence of tuberculosis. The results have now been published in the journal EClinicalMedicine.

The tuberculin skin test (TST) and the interferon-gamma release assay (IGRA) are both tests for predicting the future risk of tuberculosis in risk groups. However, they work in slightly different ways.

The TST involves injecting a small amount of a substance called tuberculin into the skin on the forearm. If a person has had contact with the tuberculosis bacteria, the immune system reacts to the tuberculin and causes a hard, raised area (induration) at the injection site. The size of the induration is measured 48 to 72 hours after the injection to determine the likelihood of contact with tuberculosis bacteria.

IGRAs, on the other hand, are blood tests that measure the level of interferon-gamma, a substance produced by the immune system in response to antigens from the tuberculosis bacteria.

A major advantage of blood tests over skin tests is that they are less likely to give false-positive results in people who have been vaccinated with the Bacille Calmette Guerin (BCG) vaccine or who have been exposed to non-tuberculous mycobacteria. IGRAs should also be more specific for infection with tuberculosis bacteria and are less influenced by prior BCG vaccination. The TST may give false positive results in people who have been vaccinated with BCG or have been exposed to mycobacteria from the environment.

The skin test is much less expensive and does not require laboratory infrastructure. It is better to use in poorer countries where tuberculosis is more common.

In an international group of researchers led by Dr Yohhei Hamada from the University College of London, researchers from the Borstel Research Centre, Leibniz Lung Centre and the Tuberculosis Network European Trialsgroup (TBNET) conducted a comprehensive systematic review and meta-analysis of the scientific literature. They examined data from 13 studies with a total of 32 034 participants. One third of the people came from countries with a high incidence of tuberculosis.

The predictive power of both tests was higher in countries with low tuberculosis incidence rates than in countries with high tuberculosis incidence rates. The absolute differences in positive and negative predictive values between TST and IGRA were small. If the test result was negative, tuberculosis did not occur in the future in >99% of cases for both tests. However, the positive predictive value of both tests was low in countries with low tuberculosis incidence. Only 2-3% of people with positive TST or IGRA results later developed tuberculosis.

In summary, the authors found little difference in the performance of the two tests, much less than previously thought. They conclude that the choice of test should be made taking into account the available options. The future occurrence of tuberculosis is inadequately predicted by both tests. "In Germany, the IGRA has now become established; in other countries where IGRAs are not available, the TST is a comparable alternative. It is important to think about preventive therapy for tuberculosis in risk groups," says Professor Christoph Lange from the Research Centre Borstel, Leibniz Lung Centre.

Literature: Hamada Y, et al. Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis. EClinicalMedicine. 2023 Jan 5;56:101815. doi: 10.1016/j.eclinm.2022.101815. PMID: 36636295; PMCID: PMC9829704.


Prof. Dr. med. Dr. h.c. Christoph Lange 
Medical Director, Research Center Borstel, Leibniz Lung Center 
Professor of Respiratory Medicine & International Health, University of Lübeck
Parkallee 35
D-23845 Borstel

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