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01/30/2025 16:45

Molecular Bacterial Load Assay: New method can rapidly and accurately predict the effectiveness of tuberculosis therapy

Britta Weller Presse- und Öffentlichkeitsarbeit
Forschungszentrum Borstel, Leibniz Lungenzentrum

    Emerging drug-resistant strains are posing significant challenges to the global fight against tuberculosis (TB) and it is a critical task to detect treatment failure as early as possible. Researchers from the Marius Nasta Institute (MNI) and the Research Center Borstel, Leibniz Lung Center (FZB) have now evaluated a new test for the early detection of changes in the bacterial load of Mycobacterium tuberculosis, which provides an indication of treatment success within hours. The results of the study have now been published in the Journal of Infection.

    TB is a bacterial infection caused by Mycobacterium tuberculosis. It primarily affects the lungs and remains one of the world’s deadliest infectious diseases, particularly in its drug-resistant forms. Current methods for tracking pulmonary TB, the most common form of the disease, rely on sputum smear microscopy, DNA amplification tests, and cultures of M. tuberculosis. However, these approaches have notable limitations: Microscopy, while quick and cost-effective, struggles to distinguish between live and dead bacteria and has low sensitivity. DNA amplification tests, such as GeneXpert, may yield false positive results for patients who have successfully completed treatment. Cultures, considered the gold standard, are accurate but require weeks for results.

    As part of a research project between the Research Center Borstel, Leibniz Lung Center and the Marius Nasta Institute (MNI) in Bucharest, Romania, medical doctoral student Marit Neumann from the University of Lübeck worked for two years to evaluate a new test for the early detection of changes in the bacterial load in patients infected with drug-resistant M. tuberculosis.

    This test, the so-called Molecular Bacterial Load Assay (MBLA) represents a novel innovative tool for monitoring TB treatment. The assay measures M. tuberculosis 16S rRNA, a marker of viable bacteria, through reverse transcriptase PCR. “Unlike traditional methods, MBLA provides results in hours instead of weeks, streamlining the monitoring process, which is extremely important for drug-resistant TB,” says Marit Neumann, first author of the study.

    To validate this test for tracking the treatment response of patients with drug-resistant TB, researchers at the Research Centre Borstel have conducted a study on patients in Romania with multidrug-resistant (MDR/RR) and extensively drug-resistant (pre-XDR/XDR) TB. Patients in this cohort were monitored weekly by microscopy, GeneXpert, culture and MBLA, providing rich data for a comparative analysis.

    “MBLA demonstrated excellent concordance with culture results, particularly in the early stages of treatment. In contrast to all other diagnostic tests, MBLA was able to clearly identify early changes in bacterial load in drug-resistant patients during treatment,” summarizes Marit Neumann the results. “Hence, the MBLA assay offers a culture-free alternative with comparable accuracy to microscopy and superior precision over DNA amplification tests like GeneXpert.

    The findings underline MBLA’s potential to transform TB management by significantly reducing time-to-results to evaluate treatment response. This tool is poised to improve patient care and accelerate the evaluation of new anti-TB drugs in early-phase clinical trials.

    About this project:

    This research was conducted as an international collaborative effort to enhance diagnostic tools for TB management and to address the urgent need for faster, more accurate treatment monitoring methods. This project is part of a cooperation between the Research Center Borstel and the Marius Nasta Institute (MNI) in Bucharest, Romania. Scientists from Borstel have been cooperating for years with colleagues from Romania in TB research as part of a partnership between the German Center for Infection Research (DZIF) and the MNI. The MNI is the largest lung clinic in the EU, treating many hundreds of patients with pulmonary tuberculosis each year. The study was funded by the DZIF as a doctoral thesis by the first author and supervised by Dr. Christoph Hölscher and PD Dr. Barbara Kalsdorf in Borstel.


    Contact for scientific information:

    Dr. Christoph Hölscher
    Leiter der Forschungsgruppe „Infektionsimmunologie“
    Forschungszentrum Borstel, Leibniz Lungenzentrum
    Telefon: +49 4537 / 188-5860
    Mail: choelscher@fz-borstel.de


    Original publication:

    Marit Neumann, Maja Reimann, Dumitru Chesov, Cristina Popa, Antonela Dragomir, Oana Popescu, Roxana Munteanu, Alexandra Hölscher, Isobella Honeyborne, Jan Heyckendorf, Christoph Lange, Christoph Hölscher, Barbara Kalsdorf 2025 „The molecular bacterial load assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif“, Journal of Infection, Volume 90, Issue 2, https://doi.org/10.1016/j.jinf.2024.106399


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    Journalists, Scientists and scholars
    Biology, Medicine
    transregional, national
    Research results
    English


     

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