宏基因组二代测序对疑似骨关节结核患者的诊断价值

doi:10.19982/j.issn.1000-6621.20240486

中国防痨杂志 ›› 2025, Vol. 47 ›› Issue (2): 175-180.doi: 10.19982/j.issn.1000-6621.20240486

宏基因组二代测序对疑似骨关节结核患者的诊断价值

严广璇¹, 王雪钰², 王宇津², 兰汀隆¹(), 聂文娟²()

¹首都医科大学附属北京胸科医院骨科,北京市结核病胸部肿瘤研究所,北京 101149
²首都医科大学附属北京胸科医院结核一科,北京市结核病胸部肿瘤研究所,北京 101149

收稿日期:2024-11-04 出版日期:2025-02-10 发布日期:2025-02-08
通信作者: 聂文娟,Email:94642975@qq.com; 兰汀隆,Email:ltl_dy@163.com
基金资助:
临床医学发展专项“扬帆3.0”计划项目(ZLRK202331);北京市卫生健康委员会研究型病房卓越临床研究计划(BRWEP2024W042160109)

Diagnostic value of using metagenomic second-generation sequencing on suspected osteoarticular tuberculosis patients

Yan Guangxuan¹, Wang Xueyu², Wang Yujin², Lan Tinglong¹(), Nie Wenjuan²()

¹Department of Orthopedics, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China
²Department Ⅰ of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China

Received:2024-11-04 Online:2025-02-10 Published:2025-02-08
Contact: Nie Wenjuan,Email:94642975@qq.com; Lan Tinglong,Email:ltl_dy@163.com
Supported by:
Clinical Medicine Development Special Project “Sailing” Plan Project(ZLRK202331);Beijing Municipal Health Commission Research Ward Excellent Clinical Research Program(BRWEP2024W042160109)

摘要/Abstract

摘要：

目的: 探讨宏基因组二代测序(metagenomics next-generation sequencing,mNGS)技术在疑似骨关节结核患者中的诊断价值。方法: 回顾性分析2019年1月至2023年1月在首都医科大学附属北京胸科医院就诊的疑似骨关节结核患者176例(包括57例骨关节结核患者和119例非结核性骨关节疾病患者),所有研究对象同时行BACTEC MGIT 960液体培养(简称“MGIT 960培养”)、GeneXpert MTB/RIF检测(简称“Xpert”检测)和mNGS检测。分析三种检测方法的阳性预测值、阴性预测值、敏感度及特异度。结果: mNGS检测疑似骨关节结核患者病灶标本结果中,化脓性细菌80例(45.5%)、分枝杆菌73例(41.5%)、真菌22例(12.5%)、放线菌1例(0.6%)。73例分枝杆菌中结核分枝杆菌57例,占32.4%。mNGS、Xpert和MGIT 960培养阳性预测值分别为87.7%(95%CI:77.6%~93.7%)、100.0%(95%CI:93.5%~100.0%)、100.0%(95%CI:89.4%~100.0%),mNGS、Xpert和MGIT 960培养的阴性预测值分别为94.1%(95%CI:88.9%~97.0%)、98.3%(95%CI:93.8%~99.6%)和83.2%(95%CI:78.5%~87.1%)。mNGS与Xpert 检测的敏感度分别为87.7%(95%CI:76.3%~94.9%)、96.5%(95%CI:87.9%~99.6%),高于MGIT 960培养[57.9%(95%CI:44.1%~70.9%)]。mNGS、Xpert和MGIT 960培养的特异度分别为94.1%(95%CI:88.3%~97.6%)、100.0%(95%CI:96.9%~100.0%)、100.0%(95%CI:96.9%~100.0%)。结论: mNGS在疑似骨关节结核患者中具有较高的诊断价值。

关键词: 结核,骨关节, 分子诊断技术, 评价研究

Abstract:

Objective: To explore the diagnostic value of metagenomic next-generation sequencing (mNGS) in patients with suspected osteoarticular tuberculosis. Methods: Retrospective analysis was conducted on data of 176 suspected osteoarticular tuberculosis patients (including 57 patients with osteoarticular tuberculosis and 119 patients with non-tuberculous osteoarticular disease) admitted to Beijing Chest Hospital, Capital Medical University from January 2019 to January 2023. Samples of all subjects were simultaneously subjected to BACTEC MGIT 960 liquid culture (referred to as “MGIT 960 culture”), GeneXpert MTB/RIF detection (referred to as “Xpert” detection) and mNGS detection, then positive predictive value, negative predictive value, sensitivity and specificity of those three methods were analyzed. Results: Results of mNGS detection showed that 80 cases (45.5%) were infected with purulent bacteria, 73 cases (41.5%) with mycobacteria, 22 cases (12.5%) with fungi, and 1 case (0.6%) with actinomyces. Among the 73 mycobacteria cases, 57 (32.4%) were Mycobacterium tuberculosis. The positive predictive values of mNGS, Xpert and MGIT 960 culture were 87.7% (95%CI: 77.6%-93.7%), 100.0% (95%CI: 93.5%-100.0%), 100.0% (95%CI: 89.4%-100.0%), respectively, while their negative predictive values were 94.1% (95%CI: 88.9%-97.0%), 98.3% (95%CI: 93.8%-99.6%) and 83.2%(95%CI:78.5%-87.1%), respectively. The sensitivities of mNGS and Xpert were 87.7% (95%CI: 76.3%-94.9%) and 96.5% (95%CI: 87.9%-99.6%), respectively, higher than those of MGIT 960 culture (57.9%, 95%CI: 44.1%-70.9%). The specificities of mNGS, Xpert and MGIT 960 cultures were 94.1% (95%CI: 88.3%-97.6%), 100.0% (95%CI: 96.9%-100.0%) and 100.0% (95%CI: 96.9%-100.0%), respectively. Conclusion: mNGS has a high diagnostic value in patients with suspected osteoarticular tuberculosis.

Key words: Tuberculosis,osteoarticular, Molecular diagnostic techniques, Evaluation studies

中图分类号:

R529.2

严广璇, 王雪钰, 王宇津, 兰汀隆, 聂文娟. 宏基因组二代测序对疑似骨关节结核患者的诊断价值[J]. 中国防痨杂志, 2025, 47(2): 175-180. doi: 10.19982/j.issn.1000-6621.20240486

Yan Guangxuan, Wang Xueyu, Wang Yujin, Lan Tinglong, Nie Wenjuan. Diagnostic value of using metagenomic second-generation sequencing on suspected osteoarticular tuberculosis patients[J]. Chinese Journal of Antituberculosis, 2025, 47(2): 175-180. doi: 10.19982/j.issn.1000-6621.20240486

图/表 2

参考文献 23

[1]	秦世炳. 我国骨关节结核诊治的回顾与展望. 中国防痨杂志, 2014, 36(9):788-792. doi:10.3969/j.issn.1000-6621.2014.09.008.
[2]	王怡婷, 孟祥莉, 付茵, 等. 宏基因组测序应用于结核病防治的研究进展. 中国防痨杂志, 2024, 46(8):976-981. doi:10.19982/j.issn.1000-6621.20240111.
[3]	Acharya A, Panda K, Panigrahi S, et al. Spinal Tuberculosis:An Exhaustive Diagnosis. Int J Mycobacteriol, 2024, 13(1): 96-99. doi:10.4103/ijmy.ijmy_14_24.
[4]	姚晓伟, 刘树仁, 贾晨光, 等. 二代测序技术在骨关节结核临床诊断中的应用价值. 结核与肺部疾病杂志, 2024, 5(1):37-43. doi:10.19983/j.issn.2096-8493.20230094.
[5]	Zhao M, Tang K, Liu F, et al. Metagenomic Next-Generation Sequencing Improves Diagnosis of Osteoarticular Infections From Abscess Specimens: A Multicenter Retrospective Study. Front Microbiol, 2020, 11(9): 2034. doi:10.3389/fmicb.2020.02034.
[6]	Miller S, Naccache SN, Samayoa E, et al. Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid. Genome Res, 2019, 29(5): 831-842. doi:10.1101/gr.238170.118. pmid: 30992304
[7]	Li Y, Sun B, Tang X, et al. Application of metagenomic next-generation sequencing for bronchoalveolar lavage diagnostics in critically ill patients. Eur J Clin Microbiol Infect Dis, 2020, 39(2): 369-374. doi:10.1007/s10096-019-03734-5.
[8]	中华人民共和国国家卫生和计划生育委员会. WS 288—2017肺结核诊断. 结核与肺部疾病杂志, 2024, 5(4):376-378. doi:10.19983/j.issn.2096-8493.2024022.
[9]	Ma Y, Fan J, Li S, et al. Comparison of Lowenstein-Jensen medium and MGIT culture system for recovery of Mycobacterium tuberculosis from abscess samples. Diagn Microbiol Infect Dis, 2020, 96(4): 114969. doi:10.1016/j.diagmicrobio.2019.114969.
[10]	中国防痨协会. 结核病实验室检验规程. 北京: 人民卫生出版社,2015:77-106.
[11]	Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics, 2014, 30(15): 2114-2120. doi:10.1093/bioinformatics/btu170. pmid: 24695404
[12]	Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods, 2012, 9(4): 357-359. doi:10.1038/nmeth.1923. pmid: 22388286
[13]	Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics, 2009, 25(14): 1754-1760. doi:10.1093/bioinformatics/btp324. pmid: 19451168
[14]	Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases. Clin Infect Dis, 2018, 66(5): 778-788. doi:10.1093/cid/cix881. pmid: 29040428
[15]	Li Y, Yao XW, Tang L, et al. Diagnostic efficiency of metagenomic next-generation sequencing for suspected spinal tuberculosis in China: A multicenter prospective study. Front Microbiol, 2022, 13(12): 1018938. doi:10.3389/fmicb.2022.1018938.
[16]	张丽帆, 刘晓清. 诊断试验准确性研究设计及临床应用. 协和医学杂志, 2020, 11(1):96-101. doi:10.3969/j.issn.1674-9081.20190276.
[17]	王雅娟, 曹新益, 刘升明, 等. 宏基因组二代测序和GeneXpert MTB/RIF对结核病诊断价值的Meta分析. 中国防痨杂志, 2022, 44(12):1327-1337. doi:10.19982/j.issn.1000-6621.20220303.
[18]	张淋, 洪城, 李颖, 等. 宏基因组学第二代测序技术对比传统实验室微生物培养在脓毒症病原学诊断中的优势. 中国急救医学, 2022, 42(2):114-120. doi:10.3969/j.issn.1002-1949.2022.02.005.
[19]	黄子达, 张翀景, 张文明, 等. 宏基因组二代测序技术检测病原菌在诊断假体周围感染中的作用. 中华骨科杂志, 2019, 39(15):944-953. doi:10.3760/cma.j.issn.0253-2352.2019.15.005.
[20]	殷楚强, 王海龙, 王亭, 等. 宏基因组二代测序技术在脊柱感染病原微生物诊断中的应用. 中国脊柱脊髓杂志, 2022, 32(2):141-148. doi:10.3969/j.issn.1004-406X.2022.02.07.
[21]	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. 中华结核和呼吸杂志, 2021, 42(2):96-100. doi:10.3760/cma.j.cn112147-20200316-00343.
[22]	姚黎明, 姚晓伟, 贾晨光, 等. 宏基因组二代测序技术对髋/膝关节结核的诊断价值. 中国防痨杂志, 2023, 45(3):292-296. doi:10.19982/j.issn.1000-6621.20220451.
[23]	刘富兵, 王孝宾, 李晶, 等. 高通量测序技术在脊柱感染病原体检测中的初步应用. 中华骨科杂志, 2021, 41(3):149-156. doi:10.3760/cma.j.cn121113-20200715-00449.

检测方法	结核	非结核	敏感度 (%, 95%CI)	特异度 (%, 95%CI)	阳性预测值 (%, 95%CI)	阴性预测值 (%, 95%CI)	阳性似然比 (95%CI)	阴性似然比 (95%CI)
mNGS			87.7 (76.3~94.9)	94.1 (88.3~97.6)	87.7 (77.6~93.7)	94.1 (88.9~97.0)	14.91 (7.22~30.80)	0.13 (0.07~0.26)
阳性	50	7
阴性	7	112
Xpert			96.5 (87.9~99.6)	100.0 (96.9~100.0)	100.0 (93.5~100.0)	98.3 (93.8~99.6)	∞	0.04 (0.01~0.14)
阳性	55	0
阴性	2	119
MGIT 960培养			57.9 (44.1~70.9)	100.0 (96.9~100.0)	100.0 (89.4~100.0)	83.2 (78.5~87.1)	∞	0.42 (0.31~0.57)
阳性	33	0
阴性	24	119

宏基因组二代测序对疑似骨关节结核患者的诊断价值

Diagnostic value of using metagenomic second-generation sequencing on suspected osteoarticular tuberculosis patients

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