Current situation and prospect of laboratory diagnosis of tuberculous meningitis

doi:10.3969/j.issn.1000-6621.2020.05.006

Abstract

Abstract:

Tuberculous meningitis (TBM) is the most serious and common form of central nervous system tuberculosis. Rapid diagnosis and timely treatment are the key to improve the prognosis and survival rate of patients. However, the definite diagnosis of TBM is still extremely difficult due to the lack of effective detection methods. This article discussed the current situation, the latest progress as well as the problems and challenges of TBM laboratory diagnosis, and called for cooperation to further strengthen the research on laboratory diagnosis of TBM.

Key words: Tuberculosis,meningeal, Laboratory techniques and procedures, Early diagnosis, Problem-based learning, Research progress

LI Zi-hui, ZHANG Zong-de. Current situation and prospect of laboratory diagnosis of tuberculous meningitis[J]. Chinese Journal of Antituberculosis, 2020, 42(5): 442-448. doi: 10.3969/j.issn.1000-6621.2020.05.006

References 81

[1]	World Health Organization . Global tuberculosis report 2019. Geneva: World Health Organization, 2019.
[2]	Jain SK, Tobin DM, Tucker EW , et al. Tuberculous meningitis: a roadmap for advancing basic and translational research. Nat Immunol, 2018,19(6):521-525. doi: 10.1038/s41590-018-0119-x URL pmid: 29777209
[3]	Ducomble T, Tolksdorf K, Karagiannis I , et al. The burden of extrapulmonary and meningitis tuberculosis: an investigation of national surveillance data, Germany, 2002 to 2009. Euro Surveill, 2013,18(12):20436. URL pmid: 23557944
[4]	Thwaites GE, van Toorn R, Schoeman J . Tuberculous meningitis: more questions, still too few answers. Lancet Neurol, 2013,12(10):999-1010. doi: 10.1016/S1474-4422(13)70168-6 URL
[5]	Pang Y, An J, Shu W , et al. Epidemiology of extrapulmonary tuberculosis among inpatients, China, 2008—2017. Emerg Infect Dis, 2019,25(3):457-464. doi: 10.3201/eid2503.180572 URL pmid: 30789144
[6]	Gomes T, Reis-Santos B, Bertolde A , et al. Epidemiology of extrapulmonary tuberculosis in Brazil: a hierarchical model. BMC Infect Dis, 2014,14:9. doi: 10.1186/1471-2334-14-9 URL pmid: 24400848
[7]	Wang YY, Xie BD . Progress on diagnosis of tuberculous meningitis. Methods Mol Biol, 2018,1754:375-386. doi: 10.1007/978-1-4939-7717-8_20 URL pmid: 29536453
[8]	Thakur R, Goyal R, Sarma S . Laboratory diagnosis of tuberculous meningitis-is there a scope for further improvement? J Lab Physicians, 2010,2(1):21-24. doi: 10.4103/0974-2727.66705 URL pmid: 21814402
[9]	Rufai SB, Singh A, Singh J , et al. Diagnostic usefulness of Xpert MTB/RIF assay for detection of tuberculous meningitis using cerebrospinal fluid. J Infect, 2017,75(2):125-131. doi: 10.1016/j.jinf.2017.04.010 URL pmid: 28501491
[10]	何红彦, 殷智晔, 李敬 , 等. 结核性脑膜炎患者中几种病原诊断检测技术的应用. 中国感染与化疗杂志, 2016,16(3):336-339.
[11]	刘锐, 张焕, 陈素丽 , 等. Xpert MTB/RIF在早期诊断结核性脑膜炎中的临床应用价值. 国际检验医学杂志, 2017,38(19):2660-2662.
[12]	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.
[13]	Caws M, Dang TM, Torok E , et al. Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis. PLoS One, 2007,2(11):e1173. doi: 10.1371/journal.pone.0001173 URL pmid: 18000545
[14]	高建超, 柳晓金, 齐海亮 , 等. 噬菌体生物扩增法与常规方法对结核性脑膜炎诊断意义对比分析. 现代预防医学, 2014,41(22):4112-4113, 4123.
[15]	Fu X, Ding M, Zhang N , et al. Mycobacteriophages: an important tool for the diagnosis of Mycobacterium tuberculosis (Review). Mol Med Rep, 2015,12(1):13-19. doi: 10.3892/mmr.2015.3440 URL pmid: 25760591
[16]	Thwaites GE, Chau TT, Farrar JJ . Improving the bacteriological diagnosis of tuberculous meningitis. J Clin Microbiol, 2004,42(1):378-379. doi: 10.1128/jcm.42.1.378-379.2004 URL pmid: 14715783
[17]	Chen P, Shi M, Feng GD , et al. A highly efficient Ziehl-Neelsen stain: identifying de novo intracellular Mycobacterium tuberculosis and improving detection of extracellular M.tuberculosis in cerebrospinal fluid. J Clin Microbiol, 2012,50(4):1166-1170. doi: 10.1128/JCM.05756-11 URL pmid: 22238448
[18]	Gupta R, Talwar P, Khurana S , et al. Diagnostic accuracy of nucleic acid amplification based assays for tuberculous meningitis: A meta-analysis. J Infect, 2018,77(4):302-313. doi: 10.1016/j.jinf.2018.04.017 URL pmid: 29758242
[19]	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 URL pmid: 29912907
[20]	Sun WW, Sun Q, Yan LP , et al. The application of IS6110-baced loop-mediated isothermal amplification (LAMP) in the early diagnosis of tuberculous meningitis. Oncotarget, 2017,8(34):57537-57542. doi: 10.18632/oncotarget.15734 URL pmid: 28915693
[21]	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 URL pmid: 27084816
[22]	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 URL pmid: 21411583
[23]	Gupta R, Thakur R, Gupta P , et al. Evaluation of Geno Type MTBDRplus line probe assay for early detection of drug resis-tance in tuberculous meningitis patients in India. J Glob Infect Dis, 2015,7(1):5-10. doi: 10.4103/0974-777X.150882 URL pmid: 25722613
[24]	Liu Q, Li GL, Chen C , et al. Diagnostic Performance of the GenoType MTBDRplus and MTBDRsl Assays to Identify Tuberculosis Drug Resistance in Eastern China. Chin Med J (Engl), 2017,130(13):1521-1528. doi: 10.4103/0366-6999.208248 URL pmid: 28639565
[25]	Lawn SD, Kerkhoff AD, Vogt M , et al. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infect Dis, 2012,12(3):201-209. doi: 10.1016/S1473-3099(11)70251-1 URL
[26]	Patel VB, Singh R, Connolly C , et al. Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting. PLoS One, 2010,5(12):e15664. doi: 10.1371/journal.pone.0015664 URL pmid: 21203513
[27]	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 URL pmid: 31189584
[28]	Cox JA, Lukande RL, Kalungi S , et al. Accuracy of lipoarabinomannan and Xpert MTB/RIF testing in cerebrospinal fluid to diagnose tuberculous meningitis in an autopsy cohort of HIV-infected adults. J Clin Microbiol, 2015,53(8):2667-2673. doi: 10.1128/JCM.00624-15 URL pmid: 26063865
[29]	Bahr NC, Tugume L, Boulware DR . A word of caution in considering the use of the lipoarabinomannan lateral flow assay on cerebrospinal fluid for detection of tuberculous meningitis. J Clin Microbiol, 2016,54(1):241-242. doi: 10.1128/JCM.02753-15 URL pmid: 26719583
[30]	中华医学会结核病学分会, 《中华结核和呼吸杂志》. γ-干扰素释放试验在中国应用的建议. 中华结核和呼吸杂志, 2014,37(10):744-747.
[31]	Qin L, Zhang L, Zhang Y , et al. Diagnostic value of T-cell interferon-gamma release assays on cerebrospinal fluid for tuberculous meningitis. PLoS One, 2015,10(11):e0141814. doi: 10.1371/journal.pone.0141814 URL pmid: 26545256
[32]	Pan L, Liu F, Zhang J , et al. Interferon-gamma release assay performance of cerebrospinal fluid and peripheral blood in tuberculous meningitis in China. Biomed Res Int, 2017,2017:8198505. doi: 10.1155/2017/8198505 URL pmid: 28316991
[33]	Lu D, Chen C, Yu S , et al. Diagnosis of tuberculous meningitis using a combination of peripheral blood T-SPOT.TB and cerebrospinal fluid interferon-gamma detection methods. Lab Med, 2016,47(1):6-12. doi: 10.1093/labmed/lmv010 URL pmid: 26732776
[34]	Park KH, Cho OH, Lee EM , et al. T-cell-based assays on cerebrospinal fluid and PBMCs for rapid diagnosis of TB meningitis in non-HIV patients. Eur Respir J, 2012,39(3):768-770. doi: 10.1183/09031936.00098111 URL pmid: 22379149
[35]	Patel VB, Singh R, Connolly C , et al. Cerebrospinal T-cell responses aid in the diagnosis of tuberculous meningitis in a human immunodeficiency virus- and tuberculosis-endemic population. Am J Respir Crit Care Med, 2010,182(4):569-577. doi: 10.1164/rccm.200912-1931OC URL pmid: 20442433
[36]	Vidhate MR, Singh MK, Garg RK , et al. Diagnostic and prognostic value of Mycobacterium tuberculosis complex specific interferon gamma release assay in patients with tuberculous meningitis. J Infect, 2011,62(5):400-403. doi: 10.1016/j.jinf.2011.03.009 URL pmid: 21457728
[37]	Tuon FF, Higashino HR, Lopes MI , et al. Adenosine deaminase and tuberculous meningitis--a systematic review with meta-analysis. Scand J Infect Dis, 2010,42(3):198-207. doi: 10.3109/00365540903428158 URL pmid: 20001225
[38]	Pormohammad A, Riahi SM, Nasiri MJ , et al. Diagnostic test accuracy of adenosine deaminase for tuberculous meningitis: A systematic review and meta-analysis. J Infect, 2017,74(6):545-554. doi: 10.1016/j.jinf.2017.02.012 URL pmid: 28366687
[39]	Chakravorty S, Simmons AM, Rowneki M , et al. The new Xpert MTB/RIF Ultra: Improving detection of Mycobacterium tuberculosis and resistance to rifampin in an assay suitable for point-of-care testing. mBio, 2017,8(4):e00812-17. doi: 10.1128/mBio.00812-17 URL pmid: 28851844
[40]	World Health Organization . WHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MTB/RIF Ultra compared to Xpert MTB/RIF. Geneva: World Health Organization, 2017.
[41]	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 URL pmid: 28919338
[42]	Wang G, Wang S, Jiang G , et al. Xpert MTB/RIF Ultra improved the diagnosis of paucibacillary tuberculosis: A prospective cohort study. J Infect, 2019,78(4):311-316. doi: 10.1016/j.jinf.2019.02.010 URL pmid: 30796951
[43]	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
[44]	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 URL pmid: 30814264
[45]	Pormohammad A, Nasiri MJ, McHugh TD , et al. A systema-tic review and meta-analysis of the diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis. J Clin Microbiol, 2019,57(6):e01113-18. doi: 10.1128/JCM.01113-18 URL pmid: 30944198
[46]	Haldar S, Sankhyan N, Sharma N , et al. Detection of Mycobacterium tuberculosis GlcB or HspX antigens or devR DNA impacts the rapid diagnosis of tuberculous meningitis in children. PLoS One, 2012,7(9):e44630. doi: 10.1371/journal.pone.0044630 URL pmid: 22984534
[47]	Jain RK, Nayak AR, Husain AA , et al. Mycobacterial dormancy regulon protein Rv2623 as a novel biomarker for the diagnosis of latent and active tuberculous meningitis. Dis Markers, 2013,35(5):311-316. doi: 10.1155/2013/309816 URL pmid: 24167379
[48]	Song F, Sun X, Wang X , et al. Early diagnosis of tuberculous meningitis by an indirect ELISA protocol based on the detection of the antigen ESAT-6 in cerebrospinal fluid. Ir J Med Sci, 2014,183(1):85-88. doi: 10.1007/s11845-013-0980-4 URL pmid: 23864405
[49]	Dhiman A, Haldar S, Mishra SK , et al. Generation and application of DNA aptamers against HspX for accurate diagnosis of tuberculous meningitis. Tuberculosis (Edinb), 2018,112:27-36. doi: 10.1016/j.tube.2018.07.004 URL pmid: 30205966
[50]	Das R, Dhiman A, Mishra SK , et al. Structural switching electrochemical DNA aptasensor for the rapid diagnosis of tuberculous meningitis. Int J Nanomedicine, 2019,14:2103-2113. doi: 10.2147/IJN.S189127 URL pmid: 30988611
[51]	Dhiman A, Kumar C, Mishra SK , et al. Theranostic application of a novel G-quadruplex-forming DNA aptamer targeting malate synthase of Mycobacterium tuberculosis. Mol Ther Nucleic Acids, 2019,18:661-672. doi: 10.1016/j.omtn.2019.09.026 URL pmid: 31704587
[52]	Tang XL, Wu SM, Xie Y , et al. Generation and application of ssDNA aptamers against glycolipid antigen ManLAM of Mycobacterium tuberculosis for TB diagnosis. J Infect, 2016,72(5):573-586. doi: 10.1016/j.jinf.2016.01.014 URL pmid: 26850356
[53]	Tang XL, Zhou YX, Wu SM , et al. CFP10 and ESAT6 aptamers as effective Mycobacterial antigen diagnostic reagents. J Infect, 2014,69(6):569-580. doi: 10.1016/j.jinf.2014.05.015 URL pmid: 24968239
[54]	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 URL pmid: 31551954
[55]	Liu L, Zhang WJ, Zheng J , et al. Exploration of novel cellular and serological antigen biomarkers in the ORFeome of Mycobacterium tuberculosis. Mol Cell Proteomics, 2014,13(3):897-906. doi: 10.1074/mcp.M113.032623 URL pmid: 24447912
[56]	Serra-Vidal MM, Latorre I, Franken KL , et al. Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis. Front Microbiol, 2014,5:517. doi: 10.3389/fmicb.2014.00517 URL pmid: 25339944
[57]	Adekambi T, Ibegbu CC, Cagle S , et al. Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response. J Clin Invest, 2015,125(5):1827-1838. doi: 10.1172/JCI77990 URL pmid: 25822019
[58]	Marin ND, Paris SC, Rojas M , et al. Functional profile of CD4⁺ and CD8⁺T cells in latently infected individuals and patients with active TB . Tuberculosis (Edinb), 2013,93(2):155-166. doi: 10.1016/j.tube.2012.12.002 URL pmid: 23332142
[59]	Pollock KM, Whitworth HS, Montamat-Sicotte DJ , et al. T-cell immunophenotyping distinguishes active from latent tuberculosis. J Infect Dis, 2013,208(6):952-968. doi: 10.1093/infdis/jit265 URL pmid: 23966657
[60]	Tonaco MM, Moreira JD, Nunes FFC , et al. Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis. Immunol Lett, 2017,192:52-60. doi: 10.1016/j.imlet.2017.10.014 URL pmid: 29106984
[61]	Won EJ, Choi JH, Cho YN , et al. Biomarkers for discrimination between latent tuberculosis infection and active tuberculosis disease. J Infect, 2017,74(3):281-293. doi: 10.1016/j.jinf.2016.11.010 URL pmid: 27871809
[62]	Wu J, Wang S, Lu C , et al. Multiple cytokine responses in discriminating between active tuberculosis and latent tuberculosis infection. Tuberculosis (Edinb), 2017,102:68-75. doi: 10.1016/j.tube.2016.06.001 URL pmid: 28061954
[63]	Kwon JS, Park JH, Kim JY , et al. Diagnostic usefulness of cytokine and chemokine levels in the cerebrospinal fluid of patients with suspected tuberculous meningitis. Am J Trop Med Hyg, 2019,101(2):343-349. doi: 10.4269/ajtmh.18-0947 URL pmid: 31264559
[64]	Kataria J, Rukmangadachar LA, Hariprasad G , et al. Two dimensional difference gel electrophoresis analysis of cerebrospinal fluid in tuberculous meningitis patients. J Proteomics, 2011,74(10):2194-2203. doi: 10.1016/j.jprot.2011.06.020 URL
[65]	Yang Y, Mu J, Chen G , et al. iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis. Int J Mol Med, 2015,35(5):1323-1332. doi: 10.3892/ijmm.2015.2131 URL pmid: 25760060
[66]	Mu J, Yang Y, Chen J , et al. Elevated host lipid metabolism revealed by iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid of tuberculous meningitis patients. Biochem Biophys Res Commun, 2015,466(4):689-695. doi: 10.1016/j.bbrc.2015.08.036 URL pmid: 26348777
[67]	Chen Y, Zhang J, Wang X , et al. HMGB1 level in cerebrospinal fluid as a complimentary biomarker for the diagnosis of tuberculous meningitis. Springerplus, 2016,5(1):1775. doi: 10.1186/s40064-016-3478-5 URL pmid: 27795917
[68]	Shekhawat SD, Purohit HJ, Taori GM , et al. Evaluation of host Hsp(s) as potential biomarkers for the diagnosis of tuberculous meningitis. Clin Neurol Neurosurg, 2016,140:47-51. doi: 10.1016/j.clineuro.2015.11.008 URL pmid: 26638081
[69]	Kalita J, Misra UK, Bhoi SK , et al. Possible role of transforming growth factor beta in tuberculous meningitis. Cytokine, 2017,90:124-129. doi: 10.1016/j.cyto.2016.11.004 URL pmid: 27865204
[70]	Mailankody S, Dangeti GV, Soundravally R , et al. Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier permeability, and treatment outcome in tuberculous meningitis. PLoS One, 2017,12(7):e0181262. doi: 10.1371/journal.pone.0181262 URL pmid: 28704492
[71]	王静, 赵青, 冯国栋 , 等. 白三烯B4在结核性脑膜炎患者脑脊液中的水平及临床意义. 细胞与分子免疫学杂志, 2015,31(8):1108-1111.
[72]	Visser DH, Solomons RS, Ronacher K , et al. Host immune response to tuberculous meningitis. Clin Infect Dis, 2015,60(2):177-187. doi: 10.1093/cid/ciu781 URL pmid: 25301213
[73]	Manyelo CM, Solomons RS, Snyders CI , et al. Application of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden setting. Mediators Inflamm, 2019,2019:7582948. doi: 10.1155/2019/7582948 URL pmid: 31148946
[74]	Pan D, Pan M, Xu YM . Mir-29a expressions in peripheral blood mononuclear cell and cerebrospinal fluid: Diagnostic value in patients with pediatric tuberculous meningitis. Brain Res Bull, 2017,130:231-235. doi: 10.1016/j.brainresbull.2017.01.013 URL pmid: 28109794
[75]	Pan L, Liu F, Zhang J , et al. Genome-wide miRNA analysis identifies potential biomarkers in distinguishing tuberculous and viral meningitis. Front Cell Infect Microbiol, 2019,9:323. doi: 10.3389/fcimb.2019.00323 URL pmid: 31572691
[76]	Mason S, Reinecke CJ, Kulik W , et al. Cerebrospinal fluid in tuberculous meningitis exhibits only the L-enantiomer of lactic acid. BMC Infect Dis, 2016,16:251. doi: 10.1186/s12879-016-1597-9 URL pmid: 27267176
[77]	Mason S, van Furth AM, Mienie LJ , et al. A hypothetical astrocyte-microglia lactate shuttle derived from a ¹H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis . Metabolomics, 2015,11(4):822-837. doi: 10.1007/s11306-014-0741-z URL pmid: 26109926
[78]	Li Z, Du B, Li J , et al. Cerebrospinal fluid metabolomic profiling in tuberculous and viral meningitis: Screening potential markers for differential diagnosis. Clin Chim Acta, 2017,466:38-45. doi: 10.1016/j.cca.2017.01.002 URL pmid: 28063937
[79]	van Laarhoven A, Dian S, Aguirre-Gamboa R , et al. Cerebral tryptophan metabolism and outcome of tuberculous meningitis: an observational cohort study. Lancet Infect Dis, 2018,18(5):526-535. doi: 10.1016/S1473-3099(18)30053-7 URL pmid: 29395996
[80]	Riste M, Hobden D, Pollard C , et al. Diagnosis of tuberculous meningitis with invasive pulmonary sampling. Lancet Infect Dis, 2018,18(1):25-26. doi: 10.1016/S1473-3099(17)30713-2 URL pmid: 29303733
[81]	Marais S, Thwaites G, Schoeman JF , et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis, 2010,10(11):803-812. doi: 10.1016/S1473-3099(10)70138-9 URL pmid: 20822958