结核与肺部疾病杂志 ›› 2021, Vol. 2 ›› Issue (1): 8-12.doi: 10.3969/j.issn.2096-8493.2021.01.003
收稿日期:
2021-02-10
出版日期:
2021-03-30
发布日期:
2021-03-24
通信作者:
韩利军
E-mail:2301617255@qq.com
基金资助:
Received:
2021-02-10
Online:
2021-03-30
Published:
2021-03-24
Contact:
HAN Li-jun
E-mail:2301617255@qq.com
摘要:
结核性脑膜炎(tuberculous meningitis,TBM)是常见的中枢神经系统结核病,早期诊断和及时治疗是改善TBM患者预后的关键。由于传统的结核分枝杆菌检测方法阳性率低、耗时长,临床缺乏有效的快速检测手段,导致TBM的早期确诊非常困难。作者针对TBM脑脊液分子检测技术的现状、最新研究进展,以及所面临的问题进行评价和讨论,为指导结核病临床工作提供参考。
韩利军, 赵雪瑶. 结核性脑膜炎脑脊液分子检测技术概述[J]. 结核与肺部疾病杂志, 2021, 2(1): 8-12. doi: 10.3969/j.issn.2096-8493.2021.01.003
HAN Li-jun, ZHAO Xue-yao. Molecular detection technologies for diagnosing tuberculous meningitis using cerebrospinal fluid[J]. Journal of Tuberculosis and Lung Disease, 2021, 2(1): 8-12. doi: 10.3969/j.issn.2096-8493.2021.01.003
表1
脑脊液分子检测方法的比较
比较项目 | GeneXpert | GeneXpert MTB/RIF Ultra | LAMP | 熔解曲线技术 | 线性探针技术 |
---|---|---|---|---|---|
检测原理 | 实时荧光定量PCR | 实时荧光定量PCR | 等温扩增技术 | 探针-熔解曲线技术 | 探针-反向杂交技术 |
检测位点 | rpoB[ | IS6110、IS1081、 ropB[ | IS6110、gyrB[ | rpoB、katG、inhA、oxyR、abpC、gyrA[ | rpoB、katG、inhA[ |
报告时间 | 2h[ | 2h[ | 1h[ | 72h[ | 6h[ |
检测内容 | 结核分枝杆菌复合群,利福平耐药性[ | 结核分枝杆菌复合群,利福平耐药性[ | 结核分枝杆菌复合群[ | 结核分枝杆菌复合群,异烟肼、利福平、乙胺丁醇、氟喹诺酮类药品耐药性[ | 结核分枝杆菌复合群,异烟肼、利福平的耐药性(2代还可检测氟喹诺酮类及二线注射类药品的耐药性)[ |
敏感度 | 23%~52%[ | 89.40%[ | 43.2%~82%[ | 12.9%[ | 96.15%[ |
特点 | 需专门的仪器,手动操作简便,可检测利福平耐药性,结果可靠[ | 需专门的仪器,手动操作简便,可检测利福平耐药性,结果可靠,较GeneXpert检测阈值低[ | 操作简便,对实验室及检测人员要求低[ | 可检测多种药物耐药性,但脑脊液相关检测数据较少,难以评价其实用性 | 可检测多种药物耐药性,操作复杂,对实验室及检测人员要求高[ |
WHO是 否推荐 | 是[ | 是[ | 推荐应用于痰液检测,肺外结核的检测有待进一步研究[ | 否 | 仅推荐应用于痰液检测[ |
[1] | 中华医学会结核病学分会结核性脑膜炎专业委员会. 2019中国中枢神经系统结核病诊疗指南. 中华传染病杂志, 2020,38(7):400-408. doi: 10.3760/cma.j.cn311365-20200606-00645. |
[2] |
Nurwidya F, Handayani D, Burhan E, et al. Molecular Diagnosis of Tuberculosis. Chonnam Med J, 2018,54(1):1-9. doi: 10.4068/cmj.2018.54.1.1.
doi: 10.4068/cmj.2018.54.1.1 URL pmid: 29399559 |
[3] | 中华医学会结核病学分会临床检验专业委员会. 结核病病原学分子诊断专家共识. 中华结核和呼吸杂志, 2018,41(9):688-695. doi: 10.3760/cma.j.issn.1001-0939.201 8.09.008. |
[4] |
Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med, 2010,363(11):1005-1015. doi: 10.1056/NEJMoa0907847.
doi: 10.1056/NEJMoa0907847 URL pmid: 20825313 |
[5] |
Patel VB, Theron G, Lenders L, et al. Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study. PLoS Med, 2013,10(10):e1001536. doi: 10.1371/journal.pmed.1001536.
doi: 10.1371/journal.pmed.1001536 URL pmid: 24167451 |
[6] | 杨元利, 张永峰, 刘元, 等. Gene Xpert MTB/RIF技术对成年人结核性脑膜炎诊断价值的研究. 中国防痨杂志, 2017,39(9):980-984. doi: 10.3969/j.issn.1000-6621.2017.09.016. |
[7] |
Bahr NC, Tugume L, Rajasingham R, et al. Improved diagnostic sensitivity for tuberculous meningitis with Xpert(®) MTB/RIF of centrifuged CSF. Int J Tuberc Lung Dis, 2015,19(10):1209-1215. doi: 10.5588/ijtld.15.0253.
doi: 10.5588/ijtld.15.0253 URL pmid: 26459535 |
[8] |
Bahr NC, Nuwagira E, Evans EE, et al. Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study. Lancet Infect Dis, 2018,18(1):68-75. doi: 10.1016/S1473-3099(17)30474-7.
doi: 10.1016/S1473-3099(17)30474-7 URL pmid: 28919338 |
[9] |
Metcalf T, Soria J, Montano SM, et al. Evaluation of the GeneXpert MTB/RIF in patients with presumptive tuberculous meningitis. PLoS One, 2018,13(6):e0198695. doi: 10.1371/journal.pone.0198695.
doi: 10.1371/journal.pone.0198695 URL pmid: 29912907 |
[10] |
Siddiqi OK, Birbeck GL, Ghebremichael M, et al. Prospective Cohort Study on Performance of Cerebrospinal Fluid (CSF) Xpert MTB/RIF, CSF Lipoarabinomannan (LAM) Lateral Flow Assay (LFA), and Urine LAM LFA for Diagnosis of Tuberculous Meningitis in Zambia. J Clin Microbiol, 2019,57(8):e00652-19. doi: 10.1128/JCM.00652-19.
doi: 10.1128/JCM.00652-19 URL pmid: 31189584 |
[11] | 张瑞雪, 龙铟, 冯国栋, 等. Xpert MTB/RIF对结核性脑膜炎诊断的临床评价. 中华检验医学杂志, 2016,39(6):442-447. doi: 10.3760/cma.j.issn.1009-9158.2016.06.011. |
[12] | 金慧芳, 刘鑫. 脑脊液Gene Xpert MTB/RIF检测和结核杆菌快速培养辅助诊断结核性脑膜炎的价值比较. 临床内科杂志, 2018,35(8):529-530. doi: 10.3969/j.issn.1001-9057.2018.08.007. |
[13] | World Health Organization. WHO consolidated guidelines on tuberculosis. Module 3: Diagnosis—Rapid diagnostics for tuberculosis detection. Geneva: World Health Organization, 2020. |
[14] | 王赛赛, 马艳, 刘洋. 脑脊液检测在结核性脑膜炎早期诊断中的研究进展. 中国防痨杂志, 2019,41(1):95-101. doi: 10.3969/j.issn.1000-6621.2019.01.019. |
[15] |
Kohli M, Schiller I, Dendukuri N, et al. Xpert MTB/RIF Ultra and Xpert MTB/RIF assays for extrapulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev, 2021, 1: CD012768. doi: 10.1002/14651858.CD012768.pub3.
doi: 10.1002/14651858.CD011302.pub3 URL pmid: 33461239 |
[16] | 孙雯雯, 肖和平. 环介导等温扩增技术早期诊断结核性脑膜炎的研究. 中国防痨杂志, 2016,38(12):1102-1108. doi: 10.3969/j.issn.1000-6621.2016.12.018. |
[17] |
Nagdev KJ, Kashyap RS, Parida MM, et al. Loop-mediated isothermal amplification for rapid and reliable diagnosis of tuberculous meningitis. J Clin Microbiol, 2011,49(5):1861-1865. doi: 10.1128/JCM.00824-10.
doi: 10.1128/JCM.00824-10 URL |
[18] |
Modi M, Sharma K, Sharma M, et al. Multitargeted loop-mediated isothermal amplification for rapid diagnosis of tuberculous meningitis. Int J Tuberc Lung Dis, 2016,20(5):625-630. doi: 10.5588/ijtld.15.0741.
doi: 10.5588/ijtld.15.0741 URL pmid: 27084816 |
[19] | 樊丽超, 陈宇, 朱雅娟, 等. 脑脊液环介导等温扩增和GeneXpert MTB/RIF在结核性脑膜炎早期诊断中的效能分析. 中国现代医生, 2020,58(17):128-131. |
[20] | 冉燕, 赵建军, 张建勇, 等. 利福平耐药实时荧光定量核酸扩增检测技术及环介导等温扩增技术在结核性脑膜炎的诊断价值. 实用医学杂志, 2020,36(24):3416-3419. doi: 10.3969/j.issn.1006-5725.2020.24.022. |
[21] | 刘威, 李奉京, 黄留玉, 等. 基于颜色判定的LAMP方法快速检测结核分枝杆菌. 中国医疗器械信息, 2014,20(10):7-10, 25. |
[22] |
Pang Y, Dong H, Tan Y, et al. Rapid diagnosis of MDR and XDR tuberculosis with the MeltPro TB assay in China. Sci Rep, 2016,6:25330. doi: 10.1038/srep25330.
doi: 10.1038/srep25330 URL pmid: 27149911 |
[23] | 吴剑, 石学萍, 刘艳. 溶解曲线技术在结核性脑膜炎临床诊断中的价值评价. 新疆医学, 2020,50(5):423-425, 428. |
[24] |
Kaviyil JE, Ravikumar R. Diagnosis of tuberculous meningitis: Current scenario from a Tertiary Neurocare Centre in India. Indian J Tuberc, 2017,64(3):183-188. doi: 10.1016/j.ijtb.2017.01.005.
doi: 10.1016/j.ijtb.2017.01.005 URL pmid: 28709486 |
[25] |
Gupta R, Thakur R, Gupta P, et al. Evaluation of Geno Type MTBDRplus Line Probe Assay for Early Detection of Drug Resistance in Tuberculous Meningitis Patients in India. J Glob Infect Dis, 2015,7(1):5-10. doi: 10.4103/0974-777X.150882.
doi: 10.4103/0974-777X.150882 URL pmid: 25722613 |
[26] | 张梦瑶, 任建发, 陈亚南, 等. 脑脊液宏基因组二代测序技术及其在中枢神经系统感染性疾病诊断中的应用进展. 山东医药, 2020,60(27):86-90. doi: 10.3969/j.issn.1002-266X.2020.27.024. |
[27] | 辛子凯, 邹月丽, 范佳, 等. 脑脊液二代测序确诊中枢神经系统李斯特菌感染二例. 中华医学杂志, 2019,99(25):1989-1990. doi: 10.3760/cma.j.issn.0376-2491.2019.25.018. |
[28] | 赵伟丽, 乌依罕, 李红芳, 等. 伪狂犬病毒脑炎临床观察与脑脊液二代测序鉴定. 中华医学杂志, 2018,98(15):1152-1157. doi: 10.3760/cma.j.issn.0376-2491.2018.15.006. |
[29] |
Piantadosi A, Kanjilal S, Ganesh V, et al. Rapid Detection of Powassan Virus in a Patient With Encephalitis by Metagenomic Sequencing. Clin Infect Dis, 2018,66(5):789-792. doi: 10.1093/cid/cix792.
doi: 10.1093/cid/cix792 URL pmid: 29020227 |
[30] |
Wang S, Chen Y, Wang D, et al. The Feasibility of Meta-genomic Next-Generation Sequencing to Identify Pathogens Causing Tuberculous Meningitis in Cerebrospinal Fluid. Front Microbiol, 2019,10:1993. doi: 10.3389/fmicb.2019.01993.
doi: 10.3389/fmicb.2019.01993 URL pmid: 31551954 |
[31] |
Xing XW, Zhang JT, Ma YB, et al. Metagenomic Next-Generation Sequencing for Diagnosis of Infectious Encephalitis and Meningitis: A Large, Prospective Case Series of 213 Patients. Front Cell Infect Microbiol, 2020,10:88. doi: 10.3389/fcimb.2020.00088.
doi: 10.3389/fcimb.2020.00088 URL pmid: 32211343 |
[32] |
Gomathi NS, Singh M, Singh UB, et al. Multicentric validation of indigenous molecular test TruenatTM MTB for detection of Mycobacterium tuberculosis in sputum samples from presumptive pulmonary tuberculosis patients in comparison with re-ference standards . Indian J Med Res, 2020,152(4):378-385. doi: 10.4103/ijmr.IJMR_2539_19.
doi: 10.4103/ijmr.IJMR_2539_19 URL pmid: 33380702 |
[33] |
Li Z, Pan L, Lyu L, et al. Diagnostic accuracy of droplet digital PCR analysis of cerebrospinal fluid for tuberculous meningitis in adult patients. Clin Microbiol Infect, 2020,26(2):213-219. doi: 10.1016/j.cmi.2019.07.015.
URL pmid: 31336201 |
[34] |
Park JH, Jin CE, Koo B, et al. A Simple Microfluidic Assay for Diagnosing Tuberculous Meningitis in HIV-Uninfected Patients. J Clin Microbiol, 2019,57(5):e01975-18. doi: 10.1128/JCM.01975-18.
doi: 10.1128/JCM.01975-18 URL pmid: 30814264 |
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