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The study was published in the journal The Lancet Regional Health – Europe and led by Martina Sester, Professor of Immunology at Saarland University, and Christoph Lange, medical director at the Research Center Borstel, Leibniz Lung Center.
The following text has been machine translated.
Tuberculosis, commonly known as consumption, was one of the deadliest diseases for a long time. It was only after Robert Koch discovered its pathogen, Mycobacterium tuberculosis, in 1882 that the disease could be effectively combated with new antibiotics. In the Western world, tuberculosis is no longer a major problem, although an estimated 25 per cent of all people worldwide carry the pathogen. In most cases, however, it remains inactive, and in the rare cases where active tuberculosis does develop, it can usually be effectively treated with medication.
Tuberculosis can, however, be problematic for immunocompromised individuals, for example after organ transplantation or in HIV-infected individuals. 'The bacterium can multiply much more easily in immunocompromised patients,' Martina Sester points out. It is therefore particularly important for people with weakened immune systems to know whether they are at risk of active tuberculosis. The professor of immunology has therefore worked with numerous colleagues in eleven European countries to investigate how reliable the current 'gold standard' tuberculosis test is, especially in immunocompromised individuals.
The QuantiFERON-TB Gold Plus test, or QFT+ for short, is currently the method of choice for doctors who want to determine whether someone is carrying the pathogen or even has active tuberculosis. 'This test is an indirect test, which means that it measures whether or not there has already been an immune response to the pathogen in the body,' says Martina Sester, explaining how it works. In other words, it does not detect the pathogen itself, but rather the immune system's response to it. If the immune system is weakened, either deliberately to prevent rejection of a donor organ or by an immune system-weakening pathogen such as HIV, the immune response to the tuberculosis pathogen is also weaker. 'The QFT+ test can therefore more often produce false negative results,' concludes Martina Sester.
In their large-scale study, Sester and her colleagues examined over 2,600 patients between 2015 and 2019 to determine how reliable the QFT+ test is for detecting infection with mycobacteria and tuberculosis. Follow-up observations were also conducted to determine how well the test is suited to assessing the risk of developing tuberculosis. 1,788 people were selected from one of five groups with weakened immune systems: people who had undergone organ transplants, stem cell transplants, or who had rheumatoid arthritis, chronic renal failure or HIV infection. A further 861 immunocompetent individuals served as a control group. The patients were treated at 21 medical centres in eleven European countries. 'This makes it the largest multicentre study of its kind ever conducted,' says Martina Sester.
'The QFT+ test has been shown to be insufficiently reliable to be used on its own to diagnose active disease. Furthermore, the test has very low predictive value for future disease,' explains Martina Sester. Even after two years, there were no cases of active tuberculosis in either the positive or negative test groups – even when the QFT+ test was positive and no preventive treatment was given. 'Only a few HIV-positive individuals developed active tuberculosis in isolated cases,' says Martina Sester, citing the only exception to this observation.
'There are better tests than the QFT+ test for diagnosing tuberculosis. It does not meet the requirements set by the World Health Organisation (WHO) for a tuberculosis test,' concludes Christoph Lange. 'The QFT+ test is also insufficient to reliably predict the individual risk of tuberculosis in low-incidence countries. In future, additional risk factors – such as HIV status, immune status and origin – should be given greater weight in the decision to prescribe preventive treatment.'
The study was conducted as part of the TBnet tuberculosis research network. TBnet is a Europe-wide network of doctors and scientists dedicated to clinical research, training and networking in the field of tuberculosis. Founded in 2006, TBnet has more than 500 members from over 70 countries. Its aim is to improve the diagnosis, treatment and prevention of tuberculosis, especially in its multi-resistant forms. TBnet organises multicentre studies, develops consensus-based guidelines and promotes young talent through courses, academies and scholarships. TBnet works closely with European and international partners such as the WHO and the DZIF. In addition to scientific work, TBnet attaches great importance to knowledge transfer and regular exchange, for example at annual symposia or webinars. Through research, training and networking, TBnet contributes significantly to improving the care and control of tuberculosis in Europe and beyond.
https://www.tbnet.eu/
Publication:
Sester, M., Altet-Gomez, N., Andersen, Å.B., Arias-Guillén, M., Avsar, K., Bakken Kran, A.-M., Bothamley, G., Nordholm Breschel, A.C., Brown, J., Chesov, D., Ciobanu, N., Cirillo, D.M., Crudu, V., de Souza Galvao, M., Dilektasli, A.G., Dominguez, J., Duarte, R., Dyrhol-Riise, A.M., Goletti, D., Hoffmann, H., Ibraim, E., Kalsdorf, B., Krawczyk, M., Kunst, H., Lange, B., Lipman, M., Matteelli, A., Milkiewicz, P., Neyer, D., Nitschke, M., Oral, H.B., Palacios-Gutiérrez, J.J., Petruccioli, E., Raszeja-Wyszomirska, J., Ravn, P., Rupp, J., Spohn, H.-E., Toader, C., Villar-Hernandez, R., Wagner, D., van Leth, F., Martinez, L., Pedersen, O.S., and Lange, C. Diagnostic accuracy and predictive value of the QuantiFERON-TB gold plus assay for tuberculosis in immunocompromised individuals: a prospective TBnet study. The Lancet Regional Health - Europe 2025; 57:101416.
Further information:
Prof. Dr. Martina Sester
Email: martina.sester(at)uks.eu
