Top

Published in:

Open Access 01-12-2024 | Research

Combining interferon-γ release assays and metagenomic next-generation sequencing for diagnosis of pulmonary tuberculosis: a retrospective study

Authors: Yanyan Liu, Miaohong Fang, Chenxi Yuan, Yi Yang, Liang Yu, Yasheng Li, Lifen Hu, Jiabin Li

Published in: BMC Infectious Diseases | Issue 1/2024

Abstract

Background

Rapid diagnosis of pulmonary tuberculosis (PTB) is urgently needed. We aimed to improve diagnosis rates by combining tuberculosis-interferon (IFN)-γ release assays (TB-IGRA) with metagenomic next-generation sequencing (mNGS) for PTB diagnosis.

Methods

A retrospective study of 29 PTB and 32 non-TB patients from our hospital was conducted between October 2022 and June 2023. Samples were processed for TB-IGRA and mNGS tests according to the manufacturer’s protocol.

Results

The levels of IFN-γ release in PTB patients were significantly higher than those in non-TB patients (604.15 ± 112.18 pg/mL, and 1.04 ± 0.38 pg/mL, respectively; p < 0.0001). Regarding presenting symptoms or signs, cough and thoracalgia were less common in PTB patients than in non-TB patients (p = 0.001 and p = 0.024, respectively). Total protein and albumin levels in the sera of PTB patients were significantly elevated compared to non-TB patients (p = 0.039 and p = 0.004, respectively). The area under the ROC curve (AUC) for TB-IGRA in PTB diagnosis was 0.939. With an optimal IFN-γ cut-off value of 14.3 pg/mL (Youden’s index 0.831), sensitivity was 86.2% and specificity was 96.9%. ROC curve analysis for mNGS and TB-IGRA combined with mNGS showed AUCs of 0.879 and 1, respectively. The AUC of TB-IGRA combined with mNGS was higher than that of TB-IGRA and mNGS alone.

Conclusions

TB-IGRA combined with mNGS may be an effective method for diagnosing tuberculosis, and can be used in the clinical diagnosis of PTB.

Available only for authorised users

Furin J, Cox H, Pai M, Tuberculosis. Lancet. 2019;393(10181):1642–56. https://doi.org/10.1016/S0140-6736(19)30308-3.CrossRefPubMed

Chakaya J, Khan M, Ntoumi F, et al. Global tuberculosis report 2020 - reflections on the global TB burden, treatment and prevention efforts. Int J Infect Dis. 2021;113(Suppl 1):S7–12. https://doi.org/10.1016/j.ijid.2021.02.107.CrossRefPubMedPubMedCentral

Chaw L, Chien LC, Wong J, et al. Global trends and gaps in research related to latent tuberculosis infection. BMC Public Health. 2020;20(1):352. https://doi.org/10.1186/s12889-020-8419-0.CrossRefPubMedPubMedCentral

Park MY, Kim YJ, Hwang SH, et al. Evaluation of an immunochromatographic assay kit for rapid identification of Mycobacterium tuberculosis complex in clinical isolates. J Clin Microbiol. 2009;47(2):481–4. https://doi.org/10.1128/JCM.01253-08.CrossRefPubMed

Kontsevaya I, Cabibbe AM, Cirillo DM, et al. Update on the diagnosis of tuberculosis. Clin Microbiol Infect. 2023;S1198–743X(23):340–3. https://doi.org/10.1016/j.cmi.2023.07.014.CrossRef

Alonzi T, Repele F, Goletti D. Research tests for the diagnosis of tuberculosis infection. Expert Rev Mol Diagn. 2023;23(9):783–95. https://doi.org/10.1080/14737159.2023.2240230.CrossRefPubMed

Li K, Hu Q, Liu J, Liu S, He Y. Effects of sputum bacillary load and age on GeneXpert and traditional methods in pulmonary tuberculosis: a 4-year retrospective comparative study. BMC Infect Dis. 2023;23(1):831. https://doi.org/10.1186/s12879-023-08832-6.CrossRefPubMedPubMedCentral

Dai Y, Feng Y, Xu R, et al. Evaluation of interferon-gamma release assays for the diagnosis of tuberculosis: an updated meta-analysis. Eur J Clin Microbiol Infect Dis. 2012;31(11):3127–37. https://doi.org/10.1007/s10096-012-1674-y.CrossRefPubMed

Slater M, Tran MC, Platt L, et al. In vitro immunomodulation for enhancing T cell-based diagnosis of Mycobacterium tuberculosis infection. Diagn Microbiol Infect Dis. 2015;83(1):41–5. https://doi.org/10.1016/j.diagmicrobio.2015.05.007.CrossRefPubMedPubMedCentral

10.

Pai M, Behr M. Latent Mycobacterium tuberculosis infection and interferongamma release assays. Microbiol Spectr. 2016;4(5). https://doi.org/10.1128/microbiolspec.TBTB2-0023-2016.2.

11.

Higuchi K, Kawabe Y, Mitarai S, et al. Comparison of performance in two diagnostic methods for tuberculosis infection. Med Microbiol Immunol. 2009;198(1):33–7. https://doi.org/10.1007/s00430-008-0102-5.CrossRefPubMed

12.

Ai L, Feng P, Chen D, et al. Clinical value of interferon-γ release assay in the diagnosis of active tuberculosis. Exp Ther Med. 2019;18(2):1253–7. https://doi.org/10.3892/etm.2019.7696.CrossRefPubMedPubMedCentral

13.

Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet. 2019;20(6):341–55. https://doi.org/10.1038/s41576-019-0113-7.CrossRefPubMedPubMedCentral

14.

Chen H, Liang Y, Wang R, et al. Metagenomic next-generation sequencing for the diagnosis of Pneumocystis Jirovecii Pneumonia in critically pediatric patients. Ann Clin Microbiol Antimicrob. 2023;22(1):6. https://doi.org/10.1186/s12941-023-00555-5.CrossRefPubMedPubMedCentral

15.

Diao Z, Han D, Zhang R, Li J. Metagenomics next-generation sequencing tests take the stage in the diagnosis of lower respiratory tract infections. J Adv Res. 2021;38:201–12. https://doi.org/10.1016/j.jare.2021.09.012.CrossRefPubMedPubMedCentral

16.

Xing XW, Yu SF, Zhang JT, et al. Metagenomic next-generation sequencing of Cerebrospinal Fluid for the diagnosis of cerebral aspergillosis. Front Microbiol. 2021;12:787863. https://doi.org/10.3389/fmicb.2021.787863.CrossRefPubMedPubMedCentral

17.

Miao Q, Ma Y, Wang Q, et al. Microbiological Diagnostic performance of Metagenomic Next-generation sequencing when Applied to Clinical Practice. Clin Infect Dis. 2018;67(suppl2):S231–40. https://doi.org/10.1093/cid/ciy693.CrossRefPubMed

18.

Li Y, Bian W, Wu S, et al. Metagenomic next-generation sequencing for Mycobacterium tuberculosis complex detection: a meta-analysis. Front Public Health. 2023;11:1224993. https://doi.org/10.3389/fpubh.2023.1224993.CrossRefPubMedPubMedCentral

19.

Zhou X, Wu H, Ruan Q, et al. Clinical evaluation of diagnosis efficacy of active Mycobacterium tuberculosis complex infection via Metagenomic Next-Generation sequencing of direct clinical samples. Front Cell Infect Microbiol. 2019;9:351. https://doi.org/10.3389/fcimb.2019.00351.CrossRefPubMedPubMedCentral

20.

Zhu N, Zhou D, Li S. Diagnostic accuracy of Metagenomic Next-Generation sequencing in Sputum-Scarce or smear-negative cases with suspected pulmonary tuberculosis. Biomed Res Int. 2021;2021:9970817. https://doi.org/10.1155/2021/9970817.CrossRefPubMedPubMedCentral

21.

Shi CL, Han P, Tang PJ, et al. Clinical metagenomic sequencing for diagnosis of pulmonary tuberculosis. J Infect. 2020;81(4):567–74. https://doi.org/10.1016/j.jinf.2020.08.004.CrossRefPubMed

22.

Sun W, Lu Z, Yan L. Clinical efficacy of metagenomic next-generation sequencing for rapid detection of Mycobacterium tuberculosis in smear-negative extrapulmonary specimens in a high tuberculosis burden area. Int J Infect Dis. 2021;103:91–6. https://doi.org/10.1016/j.ijid.2020.11.165.CrossRefPubMed

23.

Jin Y, Hu S, Feng J, Ni J. Clinical value of metagenomic next-generation sequencing using spinal tissue in the rapid diagnosis of spinal tuberculosis. Infect Drug Resist. 2023;16:3305–13. https://doi.org/10.2147/idr.S410914.CrossRefPubMedPubMedCentral

24.

Satta G, Lipman M, Smith GP, et al. Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? Clin Microbiol Infect. 2018;24(6):604–9. https://doi.org/10.1016/j.cmi.2017.10.030.CrossRefPubMed

25.

Lv D, Liu Y, Guo F, et al. Combining interferon-γ release assays with lymphocyte enumeration for diagnosis of Mycobacterium tuberculosis infection. J Int Med Res. 2020;48(6):300060520925660. https://doi.org/10.1177/0300060520925660.CrossRefPubMed

26.

Tan Y, Tan Y, Li J, et al. Combined IFN-γ and IL-2 release assay for detect active pulmonary tuberculosis: a prospective multicentre diagnostic study in China. J Transl Med. 2021;19(1):289. https://doi.org/10.1186/s12967-021-02970-8.CrossRefPubMedPubMedCentral

27.

Zhang B, Xiao L, Qiu Q, et al. Association between IL-18, IFN-γ and TB susceptibility: a systematic review and meta-analysis. Ann Palliat Med. 2021;10(10):10878–86. https://doi.org/10.21037/apm-21-2582.CrossRefPubMed

28.

Goletti D, Delogu G, Matteelli A, Migliori GB. The role of IGRA in the diagnosis of tuberculosis infection, differentiating from active tuberculosis, and decision making for initiating treatment or preventive therapy of tuberculosis infection. Int J Infect Dis. 2022;124(Suppl 1):S12–9. https://doi.org/10.1016/j.ijid.2022.02.047.CrossRefPubMed

29.

Ji L, Lou YL, Wu ZX, et al. Usefulness of interferon-γ release assay for the diagnosis of sputum smear-negative pulmonary and extra-pulmonary TB in Zhejiang Province, China. Infect Dis Poverty. 2017;6(1):121. https://doi.org/10.1186/s40249-017-0331-1.CrossRefPubMedPubMedCentral

30.

Boyd AE, Ashcroft A, Lipman M, Bothamley GH. Limited added value of T-SPOT.TB blood test in diagnosing active TB: a prospective bayesian analysis. J Infect. 2011;62(6):456–61. https://doi.org/10.1016/j.jinf.2011.04.003.CrossRefPubMedPubMedCentral

Title: Combining interferon-γ release assays and metagenomic next-generation sequencing for diagnosis of pulmonary tuberculosis: a retrospective study
Authors: Yanyan Liu
Miaohong Fang
Chenxi Yuan
Yi Yang
Liang Yu
Yasheng Li
Lifen Hu
Jiabin Li
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: BMC Infectious Diseases / Issue 1/2024
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-024-10206-5

Survival of hospitalised COVID-19 patients in Hawassa, Ethiopia: a cohort study

Open Access
COVID-19
Research

Association between serum carotenoids and bacterial vaginosis infection among American women

Open Access
Research

Early predictors of delayed radiographic resolution of lobar pneumonia caused by Mycoplasma pneumoniae in children: a retrospective study in China

Open Access
Pneumonia
Research

Urine biomarkers individually and as a consensus model show high sensitivity and specificity for detecting UTIs

Open Access
Urinary Tract Infection
Research

Correction: Whole-genome sequencing of non-typeable Haemophilus influenzae isolated from a tertiary care hospital in Surabaya, Indonesia

Open Access
Correction

Development and validation of a clinical and laboratory-based nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome

Open Access
Thrombocytopenia
Research

Keynote series | Spotlight on menopause

Menopause
Video Series

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the broader systemic effects of menopause, so you can help patients in your clinics through the transition.

Launching: Thursday 12th December 2024

Prof. Martha Hickey

Dr. Claudia Barth

Dr. Samar El Khoudary

Developed by: Springer Medicine

Keynote webinar | Spotlight on adolescent vaping

Live
Webinar | 29-01-2025 | 18:00 (CET)

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Watch it live: Wednesday 29th January, 18:00-19:30 CET

Prof. Ann McNeill

Dr. Debbie Robson

Benji Horwell

Developed by: Springer Medicine

Join the webinar

Keynote webinar | Spotlight on modern management of frailty

Frailty in Geriatric Patients
On-demand webinar

Frailty has a significant impact on health and wellbeing, especially in older adults. Our experts explain the factors that contribute to the development of frailty and how you can manage the condition and reduce the risk of disability, dependency, and mortality in your patients.

Prof. Alfonso Cruz-Jentoft

Prof. Barbara C. van Munster

Prof. Mirko Petrovic

Developed by: Springer Medicine

Watch now

A quick guide to ECGs

Electrocardiography
Training Course

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date.

PD Dr. Carsten W. Israel

Developed by: Springer Medizin

Start the cases

At a glance: The STEP trials

Obesity
Clinical Trial Summary

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote series | Spotlight on menopause

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content