Abstract
Nucleic acid amplification tests (NAATs) were performed selectively as an initial diagnostic test for pulmonary tuberculosis (TB) in Taiwan. We assessed whether expanded use of Xpert MTB/RIF assay as an initial diagnostic test made positive contribution to the management of TB. Patients who had NAATs as an initial diagnostic test requested by clinician were classified as group A. Those who did not were randomized in a 1:1 ratio into group B who had an immediate Xpert test by intervention and group C who had usual care. 6835 patients were enrolled. Comparing group B and group C, the proportion of patients diagnosed with active TB (3.1% vs 2.7%, p = 0.336), the proportion of patients died before anti-TB treatment (2.3% vs 5.1%. p = 0.318), the median interval between submitting sputum and initiation of anti-TB treatment (7.0 days, interquartile range 3.0–25.0 vs 6.0 days, interquartile range 2.0–23.0, p = 0.589), and the proportion of TB patients with treatment success (73.8% vs 81.8%, p = 0.657) were not significantly different. There is no evidence that expanded use of Xpert MTB/RIF test as an initial diagnostic test for pulmonary TB among cases with a relatively low pretest probability of TB has positive influence on TB control in Taiwan.
Trial Registration: ClinicalTrials.gov. Number NCT04433195 (date: 16/06/2020).
Data availability
All data and materials generated or analyzed during this study are included in this published article/as supplementary information files. The trial protocol and data underlying this article will be shared on reasonable request to the corresponding author.
References
World Health Organization. Global tuberculosis report 2024. 1–50 (World Health Organization, 2024).
World Health Organization. Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children. Policy update. World Health Organization Document WHO/HTM/TB/2013.16, 1–89 (2013).
Reischl, U., Lehn, N., Wolf, H. & Naumann, L. Clinical evluation of the automated COBAS AMPLICOR MTB assay for testing respiratory and nonrespiratory specimens. J. Clin. Microbiol. 36, 2853–2860 (1998).
Boehme, C. C. et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: A multicentre implementation study. Lancet 377, 1495–1505 (2011).
Huang, W. C. et al. Performance of nucleic acid amplification tests in patients with presumptive pulmonary tuberculosis in Taiwan. Infect. Dis. Ther. 11, 871–885. https://doi.org/10.1007/s40121-022-00610-2 (2022).
World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: diagnosis. Rapid diagnostics for tuberculosis detection. Third edition. Vol. Licence: CC BY-NC-SA 3.0 IGO 1–160 (World Health Organization, 2024).
Lee, P. H. et al. Impact of universal drug susceptibility testing and effective management of multidrug-resistant tuberculosis in Taiwan. PLoS ONE 14, e0214792. https://doi.org/10.1371/journal.pone.0214792 (2019).
Chiang, C.-Y. et al. Taiwan guidelines for TB diagnosis and treatment. (Taiwan Centers for Disease Control, 2022).
Feng, J. Y. et al. Nucleic acid amplification tests reduce delayed diagnosis and misdiagnosis of pulmonary tuberculosis. Sci. Rep. 12, 12064. https://doi.org/10.1038/s41598-022-16319-8 (2022).
Chiang, C. Y. et al. Incremental yield of serial sputum examinations in the diagnosis of pulmonary tuberculosis in Taiwan: Findings of a pragmatic trial. J. Microbiol. Immunol. Infect. 56, 1245–1252. https://doi.org/10.1016/j.jmii.2023.09.006 (2023).
Cox, H. S. et al. Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: A pragmatic randomised trial. PLoS Med 11, e1001760. https://doi.org/10.1371/journal.pmed.1001760 (2014).
Durovni, B. et al. Impact of replacing smear microscopy with Xpert MTB/RIF for diagnosing tuberculosis in Brazil: A stepped-wedge cluster-randomized trial. PLoS Med 11, e1001766. https://doi.org/10.1371/journal.pmed.1001766 (2014).
Chiang, C. Y., Lee, J. J., Yu, M. C., Lin, T. P. & Luh, K. T. Tuberculosis-related deaths without treatment. Int. J. Tuberc. Lung Dis. 13, 1563–1565 (2009).
Wu, M. H., Chiang, C. Y., Jou, R., Chang, S. Y. & Luh, K. T. External quality assessment of sputum smear microscopy in Taiwan. Int. J. Tuberc. Lung Dis. 13, 606–612 (2009).
Wu, M. H., Chiang, C. Y., Deng, Y. M., Wang, T. F. & Jou, R. Proficiency of drug susceptibility testing for Mycobacterium tuberculosis in Taiwan, 2007–2011. Int. J. Tuberc. Lung Dis. 17, 113–119 (2013).
Habib, S. S. et al. Impact of upfront Xpert testing on time to treatment initiation for multidrug-resistant TB. Int. J. Tuberc. Lung Dis. 25, 584–586. https://doi.org/10.5588/ijtld.21.0092 (2021).
Mupfumi, L. et al. Impact of Xpert MTB/RIF on antiretroviral therapy-associated tuberculosis and mortality: a pragmatic randomized controlled trial. Open Forum Infect. Dis. 1, ofu038. https://doi.org/10.1093/ofid/ofu038 (2014).
Yoon, C. et al. Impact of Xpert MTB/RIF testing on tuberculosis management and outcomes in hospitalized patients in Uganda. PLoS ONE 7(11), e48599 (2012).
Sachdeva, K. S. et al. Use of Xpert MTB/RIF in decentralized public health settings and its effect on pulmonary TB and DR-TB case finding in India. PLoS ONE 10, e0126065. https://doi.org/10.1371/journal.pone.0126065 (2015).
Creswell, J. et al. Introducing new tuberculosis diagnostics: The impact of Xpert® MTB/RIF testing on case notifications in Nepal. Int. J. Tuberc. Lung Dis. 19, 545–551 (2015).
Agizew, T. et al. Treatment outcomes, diagnostic and therapeutic impact: Xpert vs. smear. A systematic review and meta-analysis. Int. J. Tuberc. Lung Dis. 23, 82–92. https://doi.org/10.5588/ijtld.18.0203 (2019).
Di Tanna, G. L. et al. Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: Individual patient data meta-analysis. Lancet Glob Health 7, e191–e199. https://doi.org/10.1016/S2214-109X(18)30458-3 (2019).
Trajman, A. et al. Impact on patients’ treatment outcomes of XpertMTB/RIF implementation for the diagnosis of tuberculosis: Follow-up of a stepped-wedge randomized clinical trial. PLoS ONE 10, e0123252. https://doi.org/10.1371/journal.pone.0123252 (2015).
Huh, H. J., Koh, W. J., Song, D. J., Ki, C. S. & Lee, N. Y. Evaluation of the Cobas TaqMan MTB test for the detection of Mycobacterium tuberculosis complex according to acid-fast-bacillus smear grades in respiratory specimens. J Clin Microbiol 53, 696–698 (2015).
Theron, G. et al. Xpert MTB/RIF results in patients with previous tuberculosis: Can we distinguish true from false positive results?. Clin Infect Dis 62, 995–1001. https://doi.org/10.1093/cid/civ1223 (2016).
Theron, G. et al. False-positive Xpert MTB/RIF results in retested patients with previous tuberculosis: Frequency, profile, and prospective clinical outcomes. J. Clin. Microbiol. 56, e01696-e11617. https://doi.org/10.1128/JCM.01696-17 (2018).
Metcalfe, J. Z. et al. Suboptimal specificity of Xpert MTB/RIF among treatment-experienced patients. Eur. Respir. J. 45, 1504–1506 (2015).
Zifodya, J. S. et al. Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive tuberculosis (Review). Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD009593.pub5 (2021).
Xie, Y. L. et al. Xpert MTB/RIF Ultra versus mycobacterial growth indicator tube liquid culture detection of Mycobacterium tuberculosis in symptomatic adults: A diagnostic accuracy study. Lancet Microbe 5, e520–e528. https://doi.org/10.1016/S2666-5247(24)00001-6 (2024).
Acknowledgements
Authors would like to thank Wei-Hsiang Hsu for data collection and management. We also thank Dr. Gwan-Han Shen, who supervised Laboratory No. 114 at Taichung Veterans General Hospital, Taiwan, and passed away in 2014.
Funding
This work was supported by the Taiwan Centers for Disease Control [Grant Number MOHW109-CDC-C-114-000107, MOHW110-CDC-C-114–000104, MOHW111-CDC-C-114-000103], and the National Science and Technology Council, Taiwan [Grant Numbers MOST 110-2314-B-075A-012 and MOST 111-2314-B-005-005-MY3]. The funder had no role in the study design, collection, analysis and interpretation of data, writing of the report, and decision to submit the paper for publication.
Author information
Authors and Affiliations
Contributions
Conception and design of study: CYC. Acquisition of data: WCH, YWH, CBL, STC, CHL, MCY, JJL and CYC. Data analysis and/or interpretation: WCH, YWH, CBL, STC, CHL, MCY, JJL and CYC. Drafting of manuscript and/or critical revision: WCH and CYC. Approval of final version of manuscript: WCH, YWH, CBL, STC, CHL, MCY, JJL and CYC.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Huang, WC., Huang, YW., Lin, CB. et al. Xpert MTB/RIF assay as an initial diagnostic test in pulmonary tuberculosis: a multicenter prospective randomized pragmatic trial. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39022-4
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-026-39022-4
