Subscribe to RSS
DOI: 10.1055/a-2612-2417
Neue Methoden der Tuberkulose-Diagnostik
New methods of tuberculosis diagnosticsAuthors

Trotz bewährter Testverfahren bleiben viele Tuberkuloseerkrankungen unerkannt – mit gravierenden Folgen für die Betroffenen und die öffentliche Gesundheit. Dieser Beitrag gibt einen Überblick über neue diagnostische Methoden, die das Potenzial haben, die Tuberkulose-Diagnostik schneller, präziser und breiter verfügbar zu machen.
Abstract
Tuberculosis remains the leading cause of death by a single infectious agent worldwide, with over 10 million cases annually. Despite global efforts, delayed or missed diagnoses continue to fuel transmission and mortality, particularly in resource-limited settings. This review outlines both the current diagnostic standards – microscopy, culture, and nucleic acid amplification tests – and highlights promising innovations aimed at improving diagnosis of tuberculosis disease. Novel approaches include stool polymerase chain reaction (PCR), CRISPR (clustered regularly interspaced short palindromic repeats)-based detection of circulating cell-free DNA (cfDNA), transcriptomic signatures, molecular bacterial load assay (MBLA), lipoarabinomannan (LAM) detection in urine or sputum, and non-invasive sampling techniques using exhaled breath condensate, face masks or oral swabs. Furthermore, advancements in imaging technologies and AI (artificial intelligence)-based tools may enhance diagnostic accuracy. Together, these developments have the potential to accelerate and simplify tuberculosis diagnostics in the future.
-
Tuberkulose stellt eine der bedeutendsten Infektionskrankheiten weltweit dar. Millionen Erkrankungen werden nicht erkannt, u.a. wegen unzureichender Diagnostik und begrenzter Ressourcen.
-
Klassische Verfahren wie Mikroskopie, Kultur und Nukleinsäureamplifikationstests (NAT) sind zwar etablierte Standardmethoden, weisen jedoch Einschränkungen auf.
-
Der Nachweis von cfDNA im Blut erlaubt eine hochsensitive Diagnostik und zeigt Potenzial für die Therapie-Überwachung, insbesondere bei Menschen, die mit HIV leben.
-
MBLA weist ribosomale RNA lebender Mykobakterien nach und kann den Krankheitsverlauf und das Therapie-Ansprechen schneller als die Kultur abbilden.
-
Stuhl-PCR, Zungen- und Wangenabstriche, modifizierte Atemschutzmasken sowie Atemkondensat eröffnen neue Möglichkeiten, besonders bei Kindern und Menschen, die nicht in der Lage sind, Sputum zu produzieren.
-
LAM kann in Sputum oder Urin nachgewiesen werden; dies ist besonders relevant bei Menschen mit HIV-Infektion und schlechtem Immunstatus.
-
PET/CT, POCUS und CAD können als Ergänzung dienen. KI-Systeme erreichen eine hohe Befundqualität und werden von der WHO empfohlen.
Schlüsselwörter
Diagnostik der Tuberkulose - CRISPR-basierter cfDNA-Nachweis - Molecular Bacterial Load Assay (MBLA) - Lipoarabinomannan (LAM) - Nicht-invasive DiagnostikKeywords
Tuberculosis diagnosis - CRISPR-based cfDNA detection - Molecular bacterial load assay (MBLA) - Lipoarabinomannan (LAM) - Non-invasive diagnosisPublication History
Article published online:
29 September 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
Literatur
- 1 World Health Organization. Global tuberculosis report 2024. Accessed August 28, 2025 at: https://www.who.int/teams/global-programme-on-tuberculosis-and-lung-health/tb-reports/global-tuberculosis-report-2024
- 2 Cross GB, OʼDoherty J, Chang CC. et al. Does PET-CT Have a Role in the Evaluation of Tuberculosis Treatment in Phase 2 Clinical Trials?. J Infect Dis 2024; 229: 1229-1238
- 3 Belard S, Taccari F, Kumwenda T. et al. Point-of-care ultrasound for tuberculosis and HIV-revisiting the focused assessment with sonography for HIV-associated tuberculosis (FASH) protocol and its differential diagnoses. Clin Microbiol Infect 2024; 30: 320-327
- 4 World Heath Organization. Use of computer-aided detection software for tuberculosis screening: WHO policy statement. Accessed August 28, 2025 at: https://www.who.int/publications/i/item/9789240110373
- 5 Carratalà-Castro L, Munguambe S, Saavedra-Cervera B. et al. Performance of stool-based molecular tests and processing methods for paediatric tuberculosis diagnosis: a systematic review and meta-analysis. Lancet Microbe 2025; 6: 100963
- 6 Sibandze DB, Kay A, Dreyer V. et al. Rapid molecular diagnostics of tuberculosis resistance by targeted stool sequencing. Genome Med 2022; 14: 52
- 7 Huang Z, LaCourse SM, Kay AW. et al. CRISPR detection of circulating cell-free Mycobacterium tuberculosis DNA in adults and children, including children with HIV: a molecular diagnostics study. Lancet Microbe 2022; 3: e482-e492
- 8 Youngquist BM, Saliba J, Kim Y. et al. Rapid tuberculosis diagnosis from respiratory or blood samples by a low cost, portable lab-in-tube assay. Sci Transl Med 2025; 17: eadp6411
- 9 Sweeney TE, Braviak L, Tato CM. et al. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med 2016; 4: 213-224
- 10 Hamada Y, Penn-Nicholson A, Krishnan S. et al. Are mRNA based transcriptomic signatures ready for diagnosing tuberculosis in the clinic? – A review of evidence and the technological landscape. EBioMedicine 2022; 82: 104174
- 11 Musisi E, Wamutu S, Ssengooba W. et al. Accuracy of the tuberculosis molecular bacterial load assay to diagnose and monitor response to anti-tuberculosis therapy: a longitudinal comparative study with standard-of-care smear microscopy, Xpert MTB/RIF Ultra, and culture in Uganda. Lancet Microbe 2024; 5: e345-e354
- 12 Neumann M, Reimann M, Chesov D. et al. The Molecular Bacterial Load Assay predicts treatment responses in patients with pre-XDR/XDR-tuberculosis more accurately than GeneXpert Ultra MTB/Rif. J Infect 2025; 90: 106399
- 13 Hassane-Harouna S, Braet SM, Decroo T. et al. Face mask sampling (FMS) for tuberculosis shows lower diagnostic sensitivity than sputum sampling in Guinea. Ann Clin Microbiol Antimicrob 2023; 22: 81
- 14 Meiwes L, Kontsevaya I, Chesov D. et al. Whispers in the Wind: Face Mask Sampling for Mycobacterium tuberculosis Detection in Children With Pulmonary Tuberculosis. J Infect Dis 2024; 230: 1510-1517
- 15 Steadman A, Andama A, Ball A. et al. New Manual Quantitative Polymerase Chain Reaction Assay Validated on Tongue Swabs Collected and Processed in Uganda Shows Sensitivity That Rivals Sputum-based Molecular Tuberculosis Diagnostics. Clin Infect Dis 2024; 78: 1313-1320
- 16 Khambati N, Moureen KA, Basile FW. et al. Oral Swab Testing With Xpert MTB/RIF Ultra for the Diagnosis of Tuberculosis in Children Aged <5 Years in Uganda: An Exploratory Interim Analysis of Diagnostic Accuracy in the NOD-pedFEND Cohort. Open Forum Infect Dis 2025; 12: ofaf206
- 17 Mosquera-Restrepo SF, Zuberogoïtia S, Gouxette L. et al. A Mycobacterium tuberculosis fingerprint in human breath allows tuberculosis detection. Nat Commun 2022; 13: 7751
- 18 Akinaga A, Takahashi M, Yamazaki T. et al. Development and preliminary evaluation toward a new tuberculosis treatment monitoring tool: the PATHFAST TB LAM Ag assay. J Clin Microbiol 2024; 62: e0062924
- 19 World Health Organization. WHO operational handbook on tuberculosis. Module 3: diagnosis: rapid diagnostics for tuberculosis detection. Accessed August 28, 2025 at: https://www.who.int/publications/i/item/9789240089501
- 20 Budde K, Lange C, Reimann M. et al. A novel method for detecting Lipoarabinomannan in urine with the promise of meeting the WHO target product profile for the diagnosis of tuberculosis. Tuberculosis (Edinb) 2025; 152: 102619