Sensitivity and specificity of an index for the diagnosis of TB meningitis in patients in an urban teaching hospital in Malawi

Tuberculous (TB) meningitis is difficult to diagnose and has a high mortality rate, particularly when presentation is delayed. A diagnostic index developed in Vietnam, an area of low-HIV seroprevalence, has been proposed as a means to differentiate TB meningitis from acute bacterial meningitis using clinical and laboratory features. We applied this index over a 4-month period to adults presenting with meningitis to an urban teaching hospital in Malawi, where HIV seroprevalence is 70% among medical inpatients. Eighty-five consecutive eligible patients were studied. Nine had TB meningitis, 64 bacterial meningitis and 12 cryptococcal meningitis. The sensitivity of the diagnostic index for predicting TB meningitis was 78%, with a specificity of 43%, too low to be used in the diagnosis of TB meningitis in this setting. This finding is likely to be generalizable to other southern African countries with similarly high-HIV seroprevalences.     

Rapid diagnosis of Mycobacterium tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T-cells.

SETTING: Hospital in-patients with suspected tuberculous meningitis (TBM), predominantly in India. OBJECTIVE: To determine whether interferon-gamma (IFN-gamma) secreting Mycobacterium tuberculosis antigen-specific T-cells are present in the cerebrospinal fluid (CSF) of patients with TBM and to evaluate the feasibility of CSF enzyme-linked immunospot (ELISpot) for the diagnosis of active TBM. DESIGN: Prospective blinded hospital-based study. RESULTS: The overnight ELISpot assay detected M. tuberculosis antigen-specific IFN-gamma secreting T-cells in CSF from nine of 10 prospectively recruited patients with TBM, and zero of seven control patients with meningitis of other aetiology. This corresponds to a diagnostic sensitivity of 90% (95%CI 56-100) and specificity of 100% (95%CI 59-100). CONCLUSION: This pilot study demonstrates proof-of-principle for a new T-cell-based diagnostic test for TBM which is rapid, sensitive and specific.     

新型隐球菌性脑膜炎与结核性脑膜炎的临床鉴别

目的 探讨新型隐球菌性脑膜炎与结核性脑膜炎的鉴别要点。 方法 回顾分析19例隐球菌性脑膜炎及50例结核性脑膜炎患者的临床表现、脑脊液改变和头颅CT或MRI特点。 结果 隐球菌性脑膜炎延误诊断时间为（2.3±1.7）个月,合并颅外结核病26.3%,合并慢性基础病36.8%,颅神经损害发生率5.3%,颅内压（320.0±57.7）mmH₂O,脑脊液葡萄糖含量（1.2±0.8）mmol/L, PCR-TB阳性率0,抗结核抗体阳性率10.5%,红细胞沉降率（42.1±31.2）mm/1h、头颅CT或MRI检查阳性发现率57.9%等方面与结核性脑膜炎存在差异。而2者在临床症状、脑脊液白细胞数、蛋白、氯化物、腺苷脱氨酶含量和头颅CT或MRI表现等方面差异无统计学意义。 结论 隐球菌性脑膜炎临床表现不典型,与结脑不易鉴别,容易误诊。但提高对隐球菌性脑膜炎的认识,并行多项指标检测有利于早期诊断。     

Tuberculous meningitis and miliary tuberculosis in young children

OBJECTIVES: To document the clinical and diagnostic features of tuberculous meningitis (TBM) in young children with and without concomitant miliary tuberculosis (TB). METHODS: A retrospective comparative study. RESULTS: Of 104 children with TBM, 32 (31%), median age 17.0 months, had a miliary appearance on chest radiograph; 72 (69%), median age 30.5 months, had TBM only (P = 0.04). Mediastinal adenopathy was noted in 27 (84%) of the children with miliary TB and 33 (46%) of those with TBM only (P = 0.0005). The mean cerebrospinal fluid (CSF) lymphocyte and polymorphonuclear counts of all children (no significant differences between groups) were 137 x 10(6)/l and 38 x 10(6)/l and the mean protein and glucose concentrations were 1.45 g/l and 0.72 mmol/l, respectively. Polymorphonuclear leukocytes were predominant in the CSF of 17% of children, in 16% the CSF glucose was > 2.2 mmol/l and in 26% the CSF protein was < 0.8 g/l. On Mantoux testing 37 (65%) of 57 children with TBM only and 12 (48%) of 25 children with TBM and miliary TB had an induration of > or = 10 mm (P = 0.23). Ten children (10%) died, five (7%) who had TBM only and five (16%) who had TBM and miliary TB. CONCLUSION: Children with TBM and miliary TB were younger and more likely to have mediastinal adenopathy on chest radiography than those with TBM only. Diagnostic features and investigations in both groups may be misleading at times.     

结核性脑膜炎100例临床分析

目的探讨成人结核性脑膜炎的临床特点、脑脊液改变、影像学特点、诊治方法及其转归。方法回顾性分析1982年1月至2003年12月间在北京协和医院确诊或临床诊断为结核性脑膜炎的100例住院患者的临床资料。结果100例结核性脑膜炎患者中,男性49例,女性51例;年龄（31±11）岁。70％为慢性病程（11．1±9．2）周。13例确诊病例,脑脊液结核杆菌培养阳性,或开颅脑活检病理证实为结核性肉芽肿或粟粒样结核;87例为临床诊断病例。临床表现以发热（97％）,头痛（92％）、意识障碍（71％）和脑膜刺激征多见（77％）,44例伴颅神经损害,以动眼神经和外展神经受损为主。35例X线胸片有活动性肺结核表现,肺外活动性结核12例,陈旧性肺结核18例。腰穿示颅内压增高者占86％,脑脊液呈非化脓性改变,白细胞增高以淋巴细胞为主,蛋白质明显增高,葡萄糖显著下降。52例患者头颅影像学有异常发现,脑室扩张、交通性脑积水和脑梗死最常见。全部病例均接受抗结核治疗,9例行侧脑室外引流术。81例患者病情好转,4例因合并开放性肺结核转结核病院治疗,8例自动出院,死亡7例。结论慢性脑膜炎若伴发肺结核或肺外结核者应高度疑诊结核性,鉴别诊断和诊断性抗结核治疗有效有助诊断。脑脊液涂片和（或）培养抗酸杆菌／结核分枝杆菌阳性,以及脑活检为诊断的金标准。早期诊断、早期治疗是改善本病预后的关键。     

Diagnosing tuberculous meningitis – have we made any progress?

Tuberculous meningitis (TBM) comprises a significant proportion of TB cases globally and causes substantial morbidity and mortality, especially in children and HIV‐infected patients. It is a challenging condition to diagnose due to its non‐specific clinical presentation and the limited sensitivity of existing laboratory techniques. Smear microscopy and culture are the most widely available diagnostic tools yet are negative in a significant proportion of TBM cases. Simplified and more affordable nucleic acid amplification tests (NAATs) are increasing in use in resource‐limited settings but have not been optimised for cerebrospinal fluid (CSF) samples. Novel diagnostic methods such as CSF interferon‐gamma release assays and various biomarkers have been developed but require further evaluation to establish their utility as diagnostic tools. There is an urgent need for further research into optimal diagnostic strategies to decrease the morbidity and mortality as a result of delayed or missed diagnosis of TBM. In this review, we discuss current and novel diagnostic tests in TBM and areas where future research should be prioritised.     

Adenosine deaminase from the cerebrospinal fluid for the diagnosis of tuberculous meningitis: A meta-analysis

Objective

To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of patients' age groups and cutoffs of measured adenosine deaminase.

Methods

Systematic review and meta-analysis of relevant studies retrieved from PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effect model.

Results

Overall, 43 studies with 1653 patients with TBM and 3417 controls without were included. Pooled results showed that adenosine deaminase in CSF is associated with satisfactory diagnostic efficacy for TBM, with a pooled sensitivity of 0.86 (95% confidence interval [CI]: 0.82–0.90), specificity of 0.89 (95% CI: 0.86–0.91), positive likelihood ratio of 7.70 (95% CI: 6.16–9.63), and negative likelihood ratio of 0.15 (95% CI: 0.12–0.20). The pooled receiver operating characteristic (AUC) was 0.94 (95% CI: 0.91–0.96), suggesting good performance. Subgroup analyses showed good diagnostic efficacies of adenosine deaminase in CSF for both adults (AUC 0.95) and children (AUC 0.96) with TBM. AUCs indicating the diagnostic accuracies of adenosine deaminase in CSF for TBM were 0.93 for studies with cutoffs <10 U/L and and 0.94 for a cutoff =10 U/L, but only 0.90 for studies with cutoffs >10 U/L.

Conclusions

Measuring adenosine deaminase of CSF shows satisfactory diagnostic efficacy for TBM in children and adults, particularly if using a cutoff ≤10 U/L.     

Hristea���ּ�����˽������Ĥ���벡������Ĥ���ٴ���ֵ�о�

??Abstract??Objective To investigate the applicability of Hristea diagnostic scoring in differentiated diagnosis between viral meningitis (VM) and tuberculous meningitis (TBM).Methods The study was performed retrospectively in resident patients with TBM (n=87) or VM (n=76) in our hospital.The prediction of TBM was determined by Hristea diagnostic scoring using parameters such as duration of symptoms before admission??neurological stages??cerebrospinal fluid (CSF)/blood glucose ratio and CSF protein concentrations.The diagnostic value of the scoring was assessed by calculating the area under the receiver operating characteristic (ROC) curves.Results The Hristea scores of all parameters were significantly different between TBM and VM patients.The sensitivity??specificity??positive predictive value and negative predictive value of Hristea scoring for TBM were 89.7%??86.8%??88.6% and 88.0%??respectively.The area under the ROC curve value for the diagnostic scoring was 0.92.Conclusion Hristea diagnostic scoring is helpful in early diagnosis and differential diagnosis of TBM and VM??and the usefulness of the scoring should be validated in larger series.     

结核性脑膜炎评分系统对儿童结核性脑膜炎的诊断价值

目的 评价结核性脑膜炎(TBM)评分系统对儿童TBM与病毒性脑炎进行鉴别的价值。方法 回顾性分析2010年1月1日至2017年12月31日天津市儿童医院呼吸科收住院的确诊及临床诊断TBM的患儿102例(TBM组),以及同期病毒性脑炎患儿125例(病毒性脑炎组)。TBM评分系统采用包括临床表现、脑脊液检测结果、影像学表现、肺结核或肺外结核的其他表现进行综合评分来诊断TBM(分值越高,越支持TBM诊断;评分≥12分可以临床诊断TBM)。采用病例对照研究的方法,比较该评分系统诊断TBM的敏感度及特异度;同时比较该评分系统与结核菌素皮肤试验(TST)、γ干扰素释放试验(IGRA)及脑脊液病原学检测敏感度的差异。结果 TBM组患儿中,16例(15.69%,16/102)脑脊液病原学检测阳性,确诊为TBM患儿;其余86例(84.31%,86/102)TBM患儿经评分系统评估,分值为(13.25±2.22)分,明显高于病毒性脑炎组患儿的评分[(3.79±2.48)分],差异有统计学意义(t=29.97,P<0.001)。86例患儿中,76例患儿TBM评分≥12分,判断为临床诊断TBM患儿;TBM诊断的敏感度为90.20%(92/102),特异度为100.00%(102/102)。脑脊液病原学检查中,抗酸杆菌染色的敏感度为15.69%(16/102),结核分枝杆菌培养的敏感度为10.78%(11/102),DNA检测的敏感度为16.47%(14/85),均明显低于TBM评分系统(χ ²值分别为113.65、128.66、100.64,P值均<0.001)。免疫学检查方法中,TST的敏感度为50.00%(51/102),特异度为99.20%(124/125);IGRA的敏感度为72.55%(74/102),特异度为99.20%(124/125);敏感度均明显低于TBM评分系统(χ ²值分别为39.31、10.48,P值均<0.001)。 结论 TBM评分系统对TBM诊断价值较好,其敏感度明显高于脑脊液抗酸染色、脑脊液结核分枝杆菌培养、脑脊液DNA检测、TST及IGRA等检测方法。     

31例非典型结核性脑膜炎临床疗效观察

目的总结非典型结核性脑膜炎（结脑）的诊断方法,提高临床认识,避免误诊,及早治疗。方法结合临床表现、脑脊液、影像学检查以及免疫学,回顾性分析31例非典型结脑临床资料。结果 31例患者经临床表现、脑脊液、影像学及免疫学,临床诊断结脑,给予诊断性抗结核治疗,30例恢复正常好转出院,1例自动出院。结论对非典型结脑的患者应反复行脑脊液及头部核磁共振检查。排除其他颅内感染性病变,尽早做诊断性抗结核治疗,避免病情加重减少并发症的发生。     

Diagnostic utility of cerebrospinal fluid studies in patients with clinically suspected tuberculous meningitis.

OBJECTIVE: To compare yields of cerebrospinal fluid (CSF) studies in the diagnosis of tuberculosis meningitis (TBM). DESIGN: Prospective laboratory study, Kenyatta National Hospital, Kenya. STUDY POPULATION: Consecutive patients with 1) headache, neck stiffness and altered consciousness for more than 14 days, 2) above features plus evidence of tuberculosis elsewhere in the body, and 3) on standard antimeningitic drugs for one week without response, were included. Those with contraindications to lumbar puncture, confirmed causes of meningitis (except TB) and on anti-tuberculosis treatment were excluded. METHODS: CSF cell counts, glucose and protein were assayed. CSF was stained on ZN, cultured on LJ and BACTEC and subjected to PCR and LCR for Mycobacterium tuberculosis DNA sequences. Positive tests for M. tuberculosis were classified as definite and the rest as probable TBM. RESULTS: Fifty-eight patients with a mean age of 33.0 years were recruited. Mean CSF cell count was 71/microl and CSF lymphocyte count up 67%. Mean CFS protein and glucose were 2.10 g/l and 2.05 mmol/l, respectively. BACTEC was positive in 20 cases, LJ 12, LCR eight, and PCR and ZN one each. Twenty-six patients had definite and 32 probable TBM. Patients with definite TBM had significantly higher CSF protein, lower CSF glucose, higher CSF cell count and lower CSF lymphocytes. CONCLUSION: TBM can be confirmed in half of clinically suspected cases. More sensitive tests for confirmation of TBM are required.     

HIV-associated tuberculous meningitis--diagnostic and therapeutic challenges

HIV-associated tuberculous meningitis (TBM) poses significant diagnostic and therapeutic challenges and carries a dismal prognosis. In this review, we present the clinical features and management of HIV-associated TBM, and compare this to disease in HIV-uninfected individuals. Although the clinical presentation, laboratory findings and radiological features of TBM are similar in HIV-infected and HIV-uninfected patients, some important differences exist. HIV-infected patients present more frequently with extra-meningeal tuberculosis and systemic features of HIV infection. In HIV-associated TBM, clinical course and outcome are influenced by profound immunosuppression at presentation, emphasising the need for earlier diagnosis of HIV infection and initiation of antiretroviral treatment.     

结核性与隐球菌性脑膜炎的鉴别诊断

目的　探讨结核性脑膜炎（结脑）和隐球菌性脑膜炎（隐脑） 的临床和脑脊液鉴别要点。方法　回顾性调查并比较１９８３ 年２ 月～１９９７ 年１２ 月收治的５３ 例结脑和５５ 例隐脑患者的临床表现和特效治疗前的脑脊液（ＣＳＦ） 结果。结果　９％ 的结脑和４９％ 的隐脑以头痛为首发症状,结脑和隐脑发生视力改变、听力下降、肢体瘫痪的比例分别为３％ 和３６ ％ ,２％ 和１６ ％ ,１９％ 和０ ;视神经乳头水肿的发生率分别为１５％ 和６６％ ,且隐脑患者多为中、重度水肿。发生脑疝的比例分别为１１ ％ 和２９％ 。９０％ 的隐脑和１１％ 的结脑患者ＣＳＦ压力＞４００ ｍｍ Ｈ２Ｏ。３６％ 的隐脑患者ＣＳＦ中蛋白质含量正常,有升高者大部分为轻度升高,＞２ ｇ／Ｌ者仅占９％ ,而结脑均有蛋白质含量升高,且４５％ 的患者＞２ ｇ／Ｌ。结论　患者具有下列特征时考虑隐脑可能性大：起病时以头痛为主而不伴发热,听力损害出现早,中、重度视神经乳头水肿,ＣＳＦ压力显著升高,蛋白含量正常等。而感染中毒症状突出,ＣＳＦ中蛋白含量明显升高,特别是＞２ ｇ／Ｌ时,结脑的可能性较大。     

脑脊液标志物在结核性脑膜炎诊断中的研究进展

结核性脑膜炎(tuberculous meningitis, TBM)患者早期的临床表现和影像学变化均不具有特异性,且缺乏有效的实验室诊断方法,致使其诊断异常困难。早期诊断TBM对于患者的及时治疗和改善预后至关重要。脑脊液(cerebrospinal fluid, CSF)中存在多种生物标志物,对TBM早期诊断具有一定的潜在价值。本文主要针对CSF中宿主诊断生物标志物用于TBM诊断的研究进展及挑战进行综述和讨论。     

Efficacy of Xpert MTB/RIF Ultra in diagnosing tuberculosis meningitis: A systematic review and meta-analysis

Background:This study aimed to assess whether Xpert MTB/RIF Ultra (Xpert Ultra) can effectively diagnose tuberculosis meningitis (TBM) and to simultaneously compare its effectiveness with Xpert in diagnosing TBM in the same population.Methods:On August 12, 2020, Wanfang Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed were searched for studies evaluating the diagnostic accuracy of Xpert Ultra for TBM. Then, we assessed the efficacy of Xpert Ultra against a composite reference standard and culture. If applicable, we also examined the diagnostic efficacy of Xpert in the same population. Heterogeneity was then explored by meta-regression, subgroup, and sensitivity analyses.Results:Six studies containing 601 specimens reported the diagnostic efficacy of Xpert Ultra for TBM, with a composite reference standard. No study had compared the efficacy between Xpert Ultra and culture. The pooled sensitivity of Xpert Ultra was 64% (95% confidence interval [CI]: 45–80), and the I² value was 86% (95% CI: 76–96); its specificity for TBM was consistently 100%. In the same population, 5 studies compared the diagnostic efficacy between Xpert Ultra and Xpert for TBM. The pooled sensitivity of Xpert Ultra and Xpert was 68% (95% CI: 46–84; I² = 87%) and 37% (95% CI: 25–50; I² = 72%), respectively. The studies were significantly heterogeneous in terms of sensitivity but not heterogeneous in specificity.Conclusions:Xpert Ultra was more sensitive than Xpert, but both were specific (100%). Therefore, Xpert Ultra had an excellent diagnostic efficacy for TBM, and it could be the preferred initial test for TBM.     

Role of IS6110 uniplex PCR in the diagnosis of tuberculous meningitis: experience at a tertiary neurocentre.

SETTING: Tuberculous meningitis (TBM) is the commonest form of neurotuberculosis in the Indian subcontinent. Rapid laboratory confirmation of TBM is important for the institution of early treatment and to avoid associated morbidity and mortality. The polymerase chain reaction (PCR) is the most widely applied alternative rapid diagnostic technique for TBM. OBJECTIVE: To evaluate the efficacy of an in-house developed IS6110 uniplex PCR (uPCR) in the diagnosis of TBM. DESIGN: A prospective, blinded study was conducted in a large sample base of 677 cerebrospinal fluid samples from 677 patients with clinically suspected TBM. RESULTS: All culture-positive samples (n = 136) were positive (100%) by the PCR assay. The assay was found to be positive in 70% (n = 541) of the samples with a clinical diagnosis of TBM. The assay had an observed sensitivity of 76.37% (negative predictive value 59.90%) and a specificity of 89.18% (positive predictive value 94.69%). A diagnostic accuracy of 80% (kappa 0.57) was seen in patients with a clinical diagnosis of TBM. Statistical significance was observed, as patients with a clinical diagnosis of TBM were found to be 9.38 times more likely to be PCR-positive (OR 9.38, chi2 = 149.94, P < 0.001). CONCLUSION: The performance of the in-house IS6110 uPCR assay merits its use as a sensitive and specific tool for the rapid diagnosis of TBM.     

The Prognostic Factors of Adult Tuberculous Meningitis

Background: Our aim was to analyze the prognostic factors and therapeutic outcomes of adult tuberculous meningitis (TBM). Patients and Methods: Clinical data of 36 patients with adult TBM were retrospectively identified at our institution over a period of 5 years. Results: 36 adult TBM patients, 23 males and 13 females, aged 16–83 years, were included in this study. The 36 patients were also divided into three groups (stages I, II and III) according to the severity of TBM on admission. Therapeutic outcomes at 3 months were determined using a modified Barthel Index (BI). For the purpose of statistical analysis, the patients were divided into two groups: good outcome (BI ≥ 12) and poor outcome (BI < 12). Positive cerebrospinal fluid (CSF) culture was found in 47% (17/36) of patients and isoniazid-resistant strains were found in 18% (3/17) of culture-proven TBM. We statistically compared clinical manifestations, CSF features and therapeutic results of the two patient groups. Significant prognostic factors included severity of TBM at the time of admission, the presence of headache, fever, hydrocephalus, high CSF protein concentration and high CSF lactate concentration. In stepwise logistic regression analysis, only the presence of hydrocephalus and severity of TBM on admission were strongly associated with therapeutic failure even after adjusting for other potentially confounding factors. Conclusion: In Taiwan, TBM is an important public health issue and the emergence of resistant strains of this disease in recent years presents a therapeutic challenge. Because delay in diagnosis is directly related to poor outcome, early diagnosis and early treatment are essential for survival. Received: July 17, 2000 · Revision accepted: July 16, 2001     

Detection and its clinical significance of IgM antibody in cerebrospinal fluid in patients with tuberculous meningitis

Specific antibody for IgM in cerebrospinal fluid (CSF) of 45 patients with tuberculous meningitis (TBM), 33 patients with non-TBM and 51 control patients was determined by enzyme-linked immunosorbent assay, and compared with specific antibody for IgG. The sensitivity and specificity was 71.1% and 98.8% for IgM antibody, and 88.9% and 96.4% for IgG antibody respectively, but the positive rate of IgM antibody at early stage of TBM was higher than that of IgG antibody. There was a highly significant positive correlation between positive rates of the two types of antibody and contents of protein in CSF. The sensitivity and specificity was 97.8% and 98.8% respectively in detecting both the IgM and IgG antibodies in CSF simultaneously, which can be used as a supplementary method for the diagnosis of TBM.     

AIDS-associated cryptococcal meningitis in Rwanda (1983-1992): epidemiologic and diagnostic features.

OBJECTIVES: to document the trend of AIDS-associated Cryptococcus neoformans meningitis (CM) in Kigali, Rwanda, during 1983-1992, and to highlight some diagnostic and epidemiological features of the disease. METHODS: during the study period, 3476 cerebrospinal fluid (CSF) specimens from 2824 adults (1578 men, 1246 women) were analysed in the Laboratory of Microbiology at the Centre Hospitalier de Kigali, Rwanda, Central Africa, using direct examination, culture and detection of the cryptococcal antigen (CrAg) in the CSF. RESULTS: CM was diagnosed among 549 (19%) patients (347 men, 202 women) and was by far the leading cause of meningitis before Neisseria meningitidis (n=115), Streptococcus pneumoniae (n=68), Mycobacterium tuberculosis (n=26). E. coli, Klebsiella pneumoniae, non-typhoid Salmonella (n=l5) and streptococci (n=4). The number of CM increased from one case in 1983 to 130 new cases in 1992. All 293 tested CM patients had HIV-1 antibodies. The male/female ratio declined from 3.31 during 1983-1987 to 1.58 during 1988-1992. CM showed a seasonal fluctuation, the highest number of infections being observed during the long rainy season. The sensitivity and specificity of the latex test for diagnosing CM was 98% and 99%, respectively. Cryptococcus neoformans var. gattii was cultured from eight (1.6%) of the 499 culture positive patients. CONCLUSION: CM is an important opportunistic infection among AIDS patients in Central Africa. It remains a problematic diagnosis in areas with limited diagnostic facilities.     

Interpretation of mycobacterial antibodies in the cerebrospinal fluid of adults with tuberculous meningitis

Objective Microbiological identification of Mycobacterium tuberculosis is insensitive and slow, and clinical distinction of tuberculous meningitis (TBM) from other subacute or chronic meningoenchephalitides (SACM) is difficult. Successful use of highly specific M. tuberculosis serological assays on cerebrospinal fluid has been reported, but their performance for diagnosis in a tuberculosis endemic country where they would be of most value is unclear. We sought to determine the biological basis for the uncertainty in interpretation of antibody detection in the CSF of TBM patients. Methods We identified prospectively 46 adults with SACM and explored the concordance between TBM diagnosis and detection of highly specific M. tuberculosis antibodies in CSF. The source of antibodies in CSF was explored by evaluating the correlation between antibody titres in CSF with those in serum, or with the albumin quotient. Intrathecal IgG synthesis was assessed by the IgG index. Results Positive antibody titres were more frequent among TBM patients (76%), but were also present in individuals with other SACM (59%). A positive correlation between antibody titres in CSF with those in serum, or with the albumin quotient, supported the leakage of antibodies from plasma to CSF through an increased blood–brain barrier permeability. Intrathecal IgG synthesis was only detected in 35% of the TBM cases. Conclusion Plasma antibodies likely synthesized in response to previous tuberculosis infections were a major source of mycobacterial antibodies in CSF due to leakage through an impaired blood–brain barrier. Interpretation of mycobacterial antibodies in CSF of adults for TBM, however specific, must take into account the contribution of antibodies from plasma, and hence, has questionable use for diagnosis.