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Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples

Background: Tuberculosis (TB) is now the leading cause of death from infectious disease. Rapid screening and diagnostic methods for TB are urgently required. Rapid development of metagenomics next-generation sequencing (mNGS) in recent years showed promising and satisfying application of mNGS in sev...

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Autores principales: Zhou, Xian, Wu, Honglong, Ruan, Qiaoling, Jiang, Ning, Chen, Xinchang, Shen, Yaojie, Zhu, Yi-Min, Ying, Yue, Qian, Yi-Yi, Wang, Xuyang, Ai, Jing-Wen, Zhang, Wen-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813183/
https://www.ncbi.nlm.nih.gov/pubmed/31681628
http://dx.doi.org/10.3389/fcimb.2019.00351
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author Zhou, Xian
Wu, Honglong
Ruan, Qiaoling
Jiang, Ning
Chen, Xinchang
Shen, Yaojie
Zhu, Yi-Min
Ying, Yue
Qian, Yi-Yi
Wang, Xuyang
Ai, Jing-Wen
Zhang, Wen-Hong
author_facet Zhou, Xian
Wu, Honglong
Ruan, Qiaoling
Jiang, Ning
Chen, Xinchang
Shen, Yaojie
Zhu, Yi-Min
Ying, Yue
Qian, Yi-Yi
Wang, Xuyang
Ai, Jing-Wen
Zhang, Wen-Hong
author_sort Zhou, Xian
collection PubMed
description Background: Tuberculosis (TB) is now the leading cause of death from infectious disease. Rapid screening and diagnostic methods for TB are urgently required. Rapid development of metagenomics next-generation sequencing (mNGS) in recent years showed promising and satisfying application of mNGS in several kinds of infectious diseases. However, research directly evaluating the ability of mNGS in TB infection is still scarce. Methods: We conducted an adult prospective study in mainland China to evaluate the diagnostic performance of mNGS for detection of Mycobacterium tuberculosis complex (MTB) in multiple forms of direct clinical samples compared with GeneXpert MTB/RIF assay (Xpert), traditional diagnostic methods, and the clinical final diagnosis. Results: Of 123 patients presenting with suspected active TB infection between June 1, 2017, and May 21, 2018, 105 patients underwent synchronous tuberculous testing with culture, Xpert, and mNGS on direct clinical samples including sputum, cerebrospinal fluids, pus, etc. During follow-up, 45 of 105 participants had clinical final diagnosis of active TB infection, including 13 pulmonary TB cases and 32 extrapulmonary TB cases. Compared to clinical final diagnosis, mNGS produced a sensitivity of 44% for all active TB cases, which was similar to Xpert (42%) but much higher than conventional methods (29%). With only one false-positive result, mNGS had a specificity of 98% in our study. mNGS yielded significantly much higher sensitivity in pre-treatment samples (76%) than post-treatment ones (31%) (P = 0.005), which was also true for Xpert and conventional methods. Combining Xpert and mNGS together, the study identified 27 of 45 active TB cases (60%), including all 13 conventional method-identified cases, and the result reached statistical significance compared to conventional methods (McNemar-test P < 0.001). Conclusions: mNGS had a similar diagnostic ability of MTB compared with Xpert and showed potential for a variety of clinical samples. Combined mNGS and Xpert showed an overall superior advantage over conventional methods and significantly improved the etiology diagnosis of both MTB and other pathogens. The result that anti-TB treatment significantly reduced diagnostic efficacy of culture, Xpert, and mNGS highlighted the importance of collecting samples before empirical treatment.
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spelling pubmed-68131832019-11-01 Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples Zhou, Xian Wu, Honglong Ruan, Qiaoling Jiang, Ning Chen, Xinchang Shen, Yaojie Zhu, Yi-Min Ying, Yue Qian, Yi-Yi Wang, Xuyang Ai, Jing-Wen Zhang, Wen-Hong Front Cell Infect Microbiol Cellular and Infection Microbiology Background: Tuberculosis (TB) is now the leading cause of death from infectious disease. Rapid screening and diagnostic methods for TB are urgently required. Rapid development of metagenomics next-generation sequencing (mNGS) in recent years showed promising and satisfying application of mNGS in several kinds of infectious diseases. However, research directly evaluating the ability of mNGS in TB infection is still scarce. Methods: We conducted an adult prospective study in mainland China to evaluate the diagnostic performance of mNGS for detection of Mycobacterium tuberculosis complex (MTB) in multiple forms of direct clinical samples compared with GeneXpert MTB/RIF assay (Xpert), traditional diagnostic methods, and the clinical final diagnosis. Results: Of 123 patients presenting with suspected active TB infection between June 1, 2017, and May 21, 2018, 105 patients underwent synchronous tuberculous testing with culture, Xpert, and mNGS on direct clinical samples including sputum, cerebrospinal fluids, pus, etc. During follow-up, 45 of 105 participants had clinical final diagnosis of active TB infection, including 13 pulmonary TB cases and 32 extrapulmonary TB cases. Compared to clinical final diagnosis, mNGS produced a sensitivity of 44% for all active TB cases, which was similar to Xpert (42%) but much higher than conventional methods (29%). With only one false-positive result, mNGS had a specificity of 98% in our study. mNGS yielded significantly much higher sensitivity in pre-treatment samples (76%) than post-treatment ones (31%) (P = 0.005), which was also true for Xpert and conventional methods. Combining Xpert and mNGS together, the study identified 27 of 45 active TB cases (60%), including all 13 conventional method-identified cases, and the result reached statistical significance compared to conventional methods (McNemar-test P < 0.001). Conclusions: mNGS had a similar diagnostic ability of MTB compared with Xpert and showed potential for a variety of clinical samples. Combined mNGS and Xpert showed an overall superior advantage over conventional methods and significantly improved the etiology diagnosis of both MTB and other pathogens. The result that anti-TB treatment significantly reduced diagnostic efficacy of culture, Xpert, and mNGS highlighted the importance of collecting samples before empirical treatment. Frontiers Media S.A. 2019-10-18 /pmc/articles/PMC6813183/ /pubmed/31681628 http://dx.doi.org/10.3389/fcimb.2019.00351 Text en Copyright © 2019 Zhou, Wu, Ruan, Jiang, Chen, Shen, Zhu, Ying, Qian, Wang, Ai and Zhang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Zhou, Xian
Wu, Honglong
Ruan, Qiaoling
Jiang, Ning
Chen, Xinchang
Shen, Yaojie
Zhu, Yi-Min
Ying, Yue
Qian, Yi-Yi
Wang, Xuyang
Ai, Jing-Wen
Zhang, Wen-Hong
Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples
title Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples
title_full Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples
title_fullStr Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples
title_full_unstemmed Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples
title_short Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples
title_sort clinical evaluation of diagnosis efficacy of active mycobacterium tuberculosis complex infection via metagenomic next-generation sequencing of direct clinical samples
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813183/
https://www.ncbi.nlm.nih.gov/pubmed/31681628
http://dx.doi.org/10.3389/fcimb.2019.00351
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