宏基因组二代测序技术和Gene Xpert MTB/RIF对肺结核的诊断价值
Diagnostic Value of Metagenomic Next-Generation Sequencing and Gene Xpert MTB/RIF in Pulmonary Tuberculosis
DOI: 10.12677/ACM.2023.13122685, PDF,   
作者: 陈淑芳*, 姜淑娟#:山东大学齐鲁医学院,山东 济南;山东第一医科大学附属省立医院,呼吸与危重症医学科,山东 济南;李 晶*:山东省公共卫生临床中心,呼吸与危重症医学科,山东 济南;王骏仁:山东第一医科大学附属省立医院,呼吸与危重症医学科,山东 济南
关键词: 结核分枝杆菌Gene Xpert MTB/RIF宏基因组二代测序诊断Mycobacterium tuberculosis Gene Xpert MTB/RIF Metagenomic Next-Generation Sequencing Diagnosis
摘要: 目的:对比抗酸涂片、结核分枝杆菌培养、结核分枝杆菌及利福平耐药基因检测(Gene Xpert MTB/RIF)和宏基因组二代测序技术(metagenomic next-generation sequencing, mNGS)对肺结核诊断的临床价值。方法:回顾分析2021年3月至2023年4月在山东省公共卫生临床中心就诊的175名疑似肺结核患者的临床资料,所有纳入病例均进行痰抗酸涂片、肺泡灌洗液抗酸涂片、痰培养、肺泡灌洗液培养、肺泡灌洗液Gene Xpert MTB/RIF和mNGS检查。比较抗酸涂片、结核杆菌培养、Gene Xpert MTB/RIF和mNGS诊断肺结核的阳性率。结果:175名疑似结核患者共确诊结核126例,灌洗液Gene Xpert MTB/RI敏感度为77.8%,灌洗液mNGS检查阳性率为85.7%高于痰培养法(46.0%)、灌洗液培养法(57.1%),对于涂片阴性的结核患者Gene Xpert MTB/RIF和mNGS检查阳性率高于培养法(P < 0.05)。结论:mNGS及Gene Xpert MTB/RIF在诊断肺结核方面具有重要意义,极大提高了涂片阴性检出率。
Abstract: Objective: To compare the diagnostic efficacy of acid-fast smear of Mycobacterium tuberculosis, Gene Xpert MTB/RIF and metagenomic next-generation sequencing (mNGS) in pulmonary tuberculosis. Methods: The clinical data of 175 patients with suspected pulmonary tuberculosis attending the Public Health Clinical Center of Shandong Province from March 2021 to April 2023 were retrospec-tively analyzed, and all the included cases underwent sputum antacid smear, alveolar lavage fluid antacid smear, sputum culture, alveolar lavage fluid culture, alveolar lavage fluid Gene Xpert MTB/RIF, and mNGS. Positive rates of antacid smear, Mycobacterium tuberculosis culture, Gene Xpert MTB/RIF and mNGS for the diagnosis of tuberculosis were compared. Results: A total of 126 cases of TB were diagnosed in 175 patients with suspected TB. The sensitivity of Gene Xpert MTB/RIF in lavage fluid was 77.8%, and the positivity rate of mNGS in lavage fluid was 85.7%, which was higher than that of sputum culture method (46.0%) and lavage culture method (57.1%), and the positivity rate of Gene Xpert MTB/RIF and mNGS was higher than that of culture method (P < 0.05) in smear-negative patients with TB. For smear-negative TB patients, Gene Xpert MTB/RIF and mNGS were more positive than culture method (P < 0.05) Conclusion: mNGS and Gene Xpert MTB/RIF are important in the diagnosis of TB, and greatly increase the detection rate of smear-negative TB.
文章引用:陈淑芳, 李晶, 王骏仁, 姜淑娟. 宏基因组二代测序技术和Gene Xpert MTB/RIF对肺结核的诊断价值[J]. 临床医学进展, 2023, 13(12): 19093-19100. https://doi.org/10.12677/ACM.2023.13122685

参考文献

[1] Abel, L., El-Baghdadi, J., Bousfiha, A.A., Casanova, J.L. and Schurr, E. (2014) Human Genetics of Tuberculosis: A Long and Winding Road. Philosophical Transactions of the Royal Society B: Biological Sciences, 369, Article ID: 20130428. [Google Scholar] [CrossRef] [PubMed]
[2] Furin, J., Cox, H. and Pai, M. (2019) Tuberculosis. The Lancet, 393, 1642-1656. [Google Scholar] [CrossRef
[3] Bagcchi, S. (2023) WHO’s Global Tuberculosis Report 2022. The Lancet Microbe, 4, E20. [Google Scholar] [CrossRef
[4] Boldi, M.O., Denis-Lessard, J., Neziri, R., et al. (2023) Per-formance of Microbiological Tests for Tuberculosis Diagnostic according to the Type of Respiratory Specimen: A 10-Year Retrospective Study. Frontiers in Cellular and Infection Microbiology, 13, Article 1131241. [Google Scholar] [CrossRef] [PubMed]
[5] Lavania, S., Das, R., Dhiman, A., et al. (2018) Aptamer-Based TB Antigen Tests for the Rapid Diagnosis of Pulmonary Tuberculosis: Potential Utility in Screening for Tuberculosis. ACS Infectious Diseases, 4, 1718-1726. [Google Scholar] [CrossRef] [PubMed]
[6] 丁彩红, 王余余, 王庆, 等. Xpert MTB/RIF Ultra快速诊断涂阴肺结核的临床价值[J]. 解放军医学杂志, 2023, 48(7): 761-767.
[7] Shi, C.L., Han, P., Tang, P.J., et al. (2020) Clinical Metagenomic Sequencing for Diagnosis of Pulmonary Tuberculosis. Journal of Infection, 81, 567-574. [Google Scholar] [CrossRef] [PubMed]
[8] Chen, P., Sun, W. and He, Y. (2020) Comparison of Metagenomic Next-Generation Sequencing Technology, Culture and GeneXpert MTB/RIF Assay in the Diagnosis of Tuberculosis. Journal of Thoracic Disease, 12, 4014-4024. [Google Scholar] [CrossRef] [PubMed]
[9] 中华人民共和国国家卫生和计划生育委员会. 肺结核诊断标准(WS 288-2017) [J]. 新发传染病电子杂志, 2018, 3(1): 59-61.
[10] 卫生部疾病预防控制局. 中国结核病防治规划实施工作指南2008年版[M]. 北京: 中国协和医科大学出版社, 2009.
[11] 宋敏, 陆普选, 方伟军, 等. 2022年WHO全球结核病报告:全球与中国关键数据分析[J]. 新发传染病电子杂志, 2023, 8(1): 87-92.
[12] Wang, Q., Guo, S., Wei, X., et al. (2022) Global Prevalence, Treatment and Outcome of Tuberculosis and COVID-19 Coinfection: A Sys-tematic Review and Meta-Analysis (From November 2019 to March 2021). BMJ Open, 12, e059396. [Google Scholar] [CrossRef] [PubMed]
[13] Kim, J., Tran, V. T., Oh, S., et al. (2021) Clinical Trial: Mag-netoplasmonic ELISA for Urine-Based Active Tuberculosis Detection and Anti-Tuberculosis Therapy Monitoring. ACS Central Science, 7, 1898-1907. [Google Scholar] [CrossRef] [PubMed]
[14] Togun, T., Kampmann, B., Stoker, N.G. and Lipman, M. (2020) Anticipating the Impact of the COVID-19 Pandemic on TB Patients and TB Control Programmes. Annals of Clinical Mi-crobiology and Antimicrobials, 19, Article No. 21. [Google Scholar] [CrossRef] [PubMed]
[15] Campelo, T.A., Cardoso de Sousa, P.R., Nogueira, L.L., et al. (2021) Revisiting the Methods for Detecting Mycobacterium tuberculosis: What Has the New Millennium Brought thus Far? Access Microbiology, 3, Article ID: 000245. [Google Scholar] [CrossRef] [PubMed]
[16] Huang, Y., Ai, L., Wang, X., et al. (2022) Review and Updates on the Diagnosis of Tuberculosis. Journal of Clinical Medicine, 11, Article 5826. [Google Scholar] [CrossRef] [PubMed]
[17] Simner, P.J., Doerr, K.A., Steinmetz, L.K. and Wengenack, N.L. (2016) Mycobacterium and Aerobic Actinomycete Culture: Are Two Medium Types and Extended Incubation Times Necessary? Journal of Clinical Microbiology, 54, 1089-1093. [Google Scholar] [CrossRef
[18] Zhu, N., Zhou, D. and Li, S. (2021) Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Sputum-Scarce or Smear-Negative Cases with Suspected Pulmonary Tuberculosis. BioMed Research International, 2021, Article ID: 9970817. [Google Scholar] [CrossRef] [PubMed]
[19] Cao, W.F., Leng, E.L., Liu, S.M., et al. (2023) Recent Ad-vances in Microbiological and Molecular Biological Detection Techniques of Tuberculous Meningitis. Frontiers in Mi-crobiology, 14, Article 1202752. [Google Scholar] [CrossRef] [PubMed]
[20] Boehme, C.C., Nicol, M.P., Nabeta, P., et al. (2011) 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. The Lancet, 377, 1495-1505. [Google Scholar] [CrossRef
[21] Acharya, B., Acharya, A., Gautam, S., et al. (2020) Ad-vances in Diagnosis of Tuberculosis: An Update into Molecular Diagnosis of Mycobacterium tuberculosis. Molecular Biology Reports, 47, 4065-4075. [Google Scholar] [CrossRef] [PubMed]
[22] Steingart, K.R., Schiller, I., Horne, D.J., et al. (2014) Xpert® MTB/RIF Assay for Pulmonary Tuberculosis and Rifampicin Resistance in Adults. Cochrane Database of Systematic Reviews, No. 1, CD009593. [Google Scholar] [CrossRef
[23] 高春景, 杨洋, 阚宗卫, 等. Xpert MTB/RIF对结核菌利福平耐药的诊断价值及rpoB基因突变特点的分析[J]. 临床肺科杂志, 2021, 26(5): 723-727.
[24] Kumar, M., Kumar, G., Kumar, R., et al. (2023) A Comparative Analysis of Microscopy, Culture, and the Xpert Mycobacterium tu-berculosis/Rifampicin Assay in Diagnosing Pulmonary Tuberculosis in Human Immunodeficiency-Positive Individuals. Cureus, 15, e42962. [Google Scholar] [CrossRef] [PubMed]
[25] Rajendran, P., Padmapriyadarsini, C., Nair, S., et al. (2023) Newer TB diagnostics: An Update. Indian Journal of Tuberculosis, 70, 372-375. [Google Scholar] [CrossRef] [PubMed]
[26] 赵素娥, 高欣, 刘胜岗, 等. 肺泡灌洗液宏基因组二代测序对疑似肺结核的诊断价值[J]. 临床肺科杂志, 2022, 27(5): 722-725, 743.
[27] Huang, Z., Zhang, C., Hu, D., et al. (2019) Diagnosis of Osteoarticular Tuberculosis via Metagenomic Next-Generation Sequencing: A Case Report. Experimental and Therapeutic Medicine, 18, 1184-1188. [Google Scholar] [CrossRef] [PubMed]
[28] Wei, P., Wu, L., Li, Y., et al. (2022) Metagenomic Next-Generation Sequencing for the Detection of Pathogenic Microorganisms in Patients with Pulmonary Infection. American Journal of Translational Research, 14, 6382-6388.
[29] Zhou, X., Wu, H., Ruan, Q., et al. (2019) Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Di-rect Clinical Samples. Frontiers in Cellular and Infection Microbiology, 9, Article 351. [Google Scholar] [CrossRef] [PubMed]
[30] Xu, P., Yang, K., Yang, L., et al. (2022) Next-Generation Meta-genome Sequencing Shows Superior Diagnostic Performance in Acid-Fast Staining Sputum Smear-Negative Pulmonary Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease. Frontiers in Microbiology, 13, Article 898195. [Google Scholar] [CrossRef] [PubMed]
[31] Liu, B.B., Tian, Q., Wang, P., et al. (2022) Evaluating the Diag-nostic Value of Using Metagenomic Next-Generation Sequencing on Bronchoalveolar Lavage Fluid and Tissue in Infec-tious Pathogens Located in the Peripheral Lung Field. Annals of Palliative Medicine, 11, 1725-1735. [Google Scholar] [CrossRef] [PubMed]
[32] 孙雯雯, 顾瑾, 范琳. 宏基因组二代测序对不同类型结核病的诊断价值[J]. 中华结核和呼吸杂志, 2021, 44(2): 96-100.
[33] Li, Z., Wang, J., Xiu, X., et al. (2023) Evaluation of Dif-ferent Diagnostic Methods for Spinal Tuberculosis Infection. BMC Infectious Diseases, 23, Article No. 695. [Google Scholar] [CrossRef] [PubMed]