TB PCR in the early diagnosis of tuberculous meningitis: evaluation of the Roche semi-automated COBAS Amplicor MTB test with reference to the manual Amplicor MTB PCR test. .

SETTING: Cecilia Makiwane Hospital, Mdantsane, Eastern Cape, Republic of South Africa. OBJECTIVE: To assess the role of the semi-automated Roche COBAS AMPLICOR(TM)Mycobacterium tuberculosis PCR test in the diagnosis of tuberculous meningitis (TBM). DESIGN: Eighty-three specimens of cerebrospinal fluid (CSF) were collected prospectively from 69 patients with suspected TBM. The COBAS AMPLICOR TB PCR test was compared with the manual AMPLICOR(TM)TB PCR test, clinical and cerebrospinal fluid (CSF) findings, direct ZN smear and radiometric TB culture. RESULTS: CSF from 7/40 (17.5%) patients treated for TBM were positive by TB COBAS AMPLICOR(TM). The sensitivity of the test was not significantly different (p=0.375) from the manual TB AMPLICOR(TM)PCR test. The comparative sensitivities of the TB COBAS AMPLICOR(TM)PCR and the manual AMPLICOR PCR for detecting cases of definite and probable TBM from CSF collected within 9 days of commencing antituberculosis treatment were 40% and 60% respectively. All 29 patients not treated for TBM were negative by COBAS AMPLICOR(TM), giving a specificity of 100%. CONCLUSION: The COBAS AMPLICOR(TM)TB PCR test is a rapid and highly specific diagnostic test for TBM. However, there was a non-significant trend favouring slightly greater sensitivity using the manual AMPLICOR(TM)TB PCR test.     

Detection of M. tuberculosis in clinical samples of diversified nature by IS6110 based PCR

Performance of the polymerase chain reaction technique based on IS6110 sequence was evaluated in clinical samples obtained from pulmonary and extrapulmonary cases of tuberculosis. One hundred and seventy two samples were processed for detection of M. tuberculosis by ZN stained smear examination, LJ medium culture, BACTEC radiometric culture and PCR tests amplifying 123bp region of IS6110 sequence. A significant difference was seen in the sensitivities of different tests, the figures being 83% for PCR test, 35.2% for smear examination, 47.16% for LJ culture and 53.45% for BACTEC culture (p < 0.05). However, no significant difference was found as far as specificity was concerned. PCR test sensitivity in. pulmonary and extrapulmonary clinical samples were 90.14% and 77.27% respectively and found to be significantly higher (p < 0.05) when compared with those of other tests. The mean detection time for M. tuberculosis was 24.03 days by LJ medium culture, 12.89 days by BACTEC culture and less than one day by PCR test. PCR based on IS6100 sequence is highly sensitive method for the early diagnosis of pulmonary and extrapulmonary tuberculosis.     

Polymerase chain reaction of pleural biopsy is a rapid and sensitive method for the diagnosis of tuberculous pleural effusion

BACKGROUND: Tuberculous pleural effusion occurs in 30% of patients with tuberculosis (TB). Rapid diagnosis of a tuberculous pleural effusion would greatly facilitate the management of many patients. Polymerase chain reaction (PCR) has been used to detect Mycobacterium tuberculosis in pleural fluid with highly variable sensitivity. OBJECTIVE: To improve our laboratory diagnosis of tuberculous pleural effusion. METHODS: We applied PCR to detect DNA specific for M tuberculosis in 33 of the studied pleural biopsy specimens using an IS986-based primer that was specific for mycobacterium complex, and compared it to the results of pleural fluid and biopsy cultures performed on either Lowenstein-Jensen (LJ) medium or BACTEC 12B liquid medium (Becton Dickinson Microbiology Systems; Cockeysville, MD), Ziehl-Neelsen (ZN) staining, and histopathology in 45 patients with pleural effusion. RESULTS: Of the 45 patients with pleural effusion who were studied, 26 patients received diagnoses of tuberculous pleural effusion that had been confirmed by either culture and or histopathology, 10 patients received diagnoses of exudative effusion due to causes other than TB, and 9 patients received diagnoses of transudative effusion. Histopathology of the pleural biopsy specimen had a sensitivity of 53.8%. The sensitivity of the ZN staining of pleural fluid and biopsy specimens was 0.0% and 3.8%, respectively. The sensitivity of the culture on both BACTEC 12B liquid medium and LJ medium was higher in pleural biopsy specimens (92.3%) than in pleural fluid specimens (15.4%; p > 0.001). The improvements of the BACTEC culture system improved and shortened the detection time of M tuberculosis in pleural biopsy specimens. PCR of pleural biopsy specimens had 90% sensitivity and 100% specificity. The positive predictive value and the negative predictive value for pleural biopsy specimen cultures were 100% and 90.5% vs 100% and 86.7% for pleural biopsy specimen PCRs. CONCLUSION: The overall accuracy of PCR of pleural biopsy was similar to the results of pleural biopsy culture, however, PCR of the pleural biopsy was much faster in reaching diagnosis. PCR of pleural biopsy is a useful method when used in combination with the BACTEC culture system and histopathologic examination of pleural biopsy to reach a rapid diagnosis of tuberculous pleural effusion.     

Rapid detection of Mycobacterium tuberculosis from sputum specimens using the FASTPlaqueTB test.

OBJECTIVES: To determine the performance of the FASTPlaqueTB test, based on bacteriophage amplification technology, by comparison with the BACTEC 460 TB culture system, the L?wenstein-Jensen (LJ) medium culture method and Ziehl-Neelsen (ZN) staining. METHODS: Of 400 sputum specimens studied in our laboratory, 19 were excluded due to contaminant growth. The FASTPlaqueTB test was performed according to the manufacturer's instructions. RESULTS: Only 42 of the 381 specimens examined were positive on at least one test: 30 were positive with ZN staining, 34 with LJ medium, 36 with the FASTPlaqueTB test and 39 with BACTEC 460 TB. The combination of BACTEC 460 TB and LJ medium culture was considered the gold standard. The sensitivity and specificity were 70.7% and 99.7% for ZN staining, 87.8% and 100% for the FASTPlaqueTB test, 82.9% and 100% for LJ, and 95.1% and 100% for BACTEC 460 TB. CONCLUSIONS: The FASTPlaqueTB test is useful in the rapid diagnosis of TB.     

Diagnosis of tuberculous meningitis: clinical and laboratory parameters.

BACKGROUND: Confirming the clinical suspicion of tuberculous meningitis (TBM) has always been problematic. Whilst smear and culture positivity are diagnostic, these tests have low sensitivity. The polymerase chain reaction (PCR) assay has given variable results. AIM: This study attempted to improve the diagnostic yield by: (a) increasing the cerebrospinal fluid (CSF) volumes; (b) testing the yield from three specimens of CSF assumed to represent lumbar, cervico-thoracic cord, and base of brain CSF samples; (c) undertaking PCR assays using multiple primer sets; and (d) using real-time PCR. METHOD: Patients suspected of having cranial or spinal meningeal tuberculosis were entered into the study. Three aliquots of CSF were subjected to smear, culture, and conventional and real-time PCR. Three sets of primers - IS6110, MPB64, and PT8/9 - were used. Patients were retrospectively classified into four categories: 'definite TB' (culture positive), 'probable TB' (clinical and other tests suggestive of TB), 'not TB', and 'uncertain diagnosis'. RESULTS: A total of 68 patients were studied. There were 20 patients classified as definite TB, 24 probable TB, 17 not TB, and seven uncertain diagnosis. Forty-eight of 57 (84.2%) patients tested were HIV seropositive. The IS6110 PCR was positive in 27 patients which included 18/20 culture positive cases, six in the probable TB group, and three in the not TB group. The MPB64 and PT8/9 primers did not increase the yield. Real-time PCR was positive in seven additional patients. Combining the definite and probable TB, the sensitivity of all PCR assays was 70.5% (31/44) and specificity 87.5% (21/24). CONCLUSION: Targeting multiple sites of the TB genome using conventional PCR did not increase the number of positive cases. Real-time PCR was more sensitive. However, all the current techniques are still too insensitive to confidently exclude the diagnosis on laboratory grounds.     

Correlation between culture of Mycobacterium tuberculosis and IgG antibody to Mycobacterium tuberculosis antigen-5 in the cerebrospinal fluid of patients with tuberculous meningitis

A retrospective study was made of the correlation between culture of Mycobacterium tuberculosis and detection of IgG antibody to M. tuberculosis antigen-5 in cerebrospinal fluid (CSF) by means of an enzyme linked immunosorbent assay (ELISA). Mycobacterium tuberculosis was cultured from the CSF in 14 of 70 patients with a clinical diagnosis of tuberculous meningitis (TBM). IgG antibody to M. tuberculosis antigen-5 was demonstrated in significant titres (80-640) in all 14 culture-positive patients. Thus, positive correlation was observed between culture of M. tuberculosis and detection of IgG antibody in the CSF. As a result of this observation, the CSF from 56 culture-negative patients with a clinical diagnosis TBM was specifically investigated for the detection of IgG antibody to M. tuberculosis antigen-5 and the findings were correlated with those of culture-positive patients. The assay was positive in 34 of 56 patients, the antibody titre ranging between 80 and 640. In the CSF of 70 patients with non-tuberculous neurological diseases, the assay was negative at a dilution of 1 in 80. Thus, detection of IgG antibody to M. tuberculosis antigen-5 by indirect ELISA carried 100% specificity and 60.7% sensitivity for a tuberculous aetiology in culture-negative patients with TBM. The results of this study suggest that indirect ELISA for IgG antibody to M. tuberculosis antigen-5 in CSF holds definite promise in diagnosis of TBM, particularly when repeated cultures of CSF are negative for M. tuberculosis.     

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.     

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。     

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。     

Efficiency of polymerase chain reaction for the diagnosis of tuberculous meningitis

The early diagnosis of tuberculous meningitis (TBM) is very important. In this study, the efficiency of the polymerase chain reaction (PCR), one of the most reliable and sensitive DNA-based assays, was compared with conventional methods (acid-fast microscopy and culture) for the detection of M. tuberculosis in cerebrospinal fluid(CSF) specimens from patients suspected of TBM. Of the 29 CSF specimens from highly-probable TBM patients (based on clinical features), 25 were positive by PCR (86.2%), whereas only one of 29 was acid-fast microscopy (AFM) positive (3.4%), and 5 out of 29 were culture-positive (17.2%). No positive results were found by AFM, culture or PCR in the non-tuberculous control group. The results of this study indicate that the application of PCR should be extremely useful in the diagnosis of TBM.     

Detection of antibody to Mycobacterium tuberculosis protein antigens in the cerebrospinal fluid of patients with tuberculous meningitis

Antibodies against Mycobacterium tuberculosis antigens were detected by enzyme-linked immunosorbent assay in cerebrospinal fluid (CSF) samples obtained from 442 patients with tuberculous meningitis (TBM) and 102 control patients. Antibodies were found in the CSF of 87% of patients with clinical (culture-negative) TBM, 72% of patients with culture-positive TBM, and 65% of patients with autopsy-proven TBM. That anti-M. tuberculosis antibodies were detected in the CSF of patients with clinically diagnosed cases more frequently than in patients with culture-positive cases suggests that the detection of antibodies in CSF tends to decrease as bacillary load increases. Of the patients with clinical TBM who were coinfected with human immunodeficiency virus (HIV), 70% exhibited anti-M. tuberculosis antibody in CSF, which suggests that antibody responses in this group were substantially weaker than those in HIV-negative patients with clinical TBM. Some groups showed a stronger response to certain antigens, which suggests that antigen recognition patterns may be specific for the stage of disease.     

Comparison of the BACTEC MGIT 960 with L?wenstein-Jensen medium for recovery of mycobacteria from clinical specimens.

SETTING: Taiwan Provincial Chronic Disease Control Bureau. OBJECTIVE: To evaluate the rate of recovery and the mean time to detection (TTD) of mycobacteria in clinical specimens with two culture systems, the BACTEC MGIT 960 and L?wenstein-Jensen (LJ) medium. DESIGN: We studied 365 specimens, collected from 166 patients. Specimens were processed with standard N-acetyl-L-cysteine (NALC)-NaOH method, then inoculated onto BACTEC MGIT 960 and onto LJ slants. RESULTS: A total of 124 mycobacterial isolates (114 Mycobacterium tuberculosis and 10 non-tuberculous mycobacteria) were detected. The recovery rates were 94% (117/124) with BACTEC MGIT 960 and 75.8% (94/124) with LJ. The rates of contamination for each of the systems were 5.5% with BACTEC MGIT 960 and 4.1% with LJ. The TTDs for mycobacteria were 10.7 days with BACTEC MGIT 960 and 30.6 days with LJ. Excluding the non-tuberculous mycobacteria, the TTDs for M. tuberculosis were 11.1 days with BACTEC MGIT 960 and 30.7 days with LJ. The difference in TTD between smear-positive and smear-negative specimens for either mycobacteria (10.0 vs 12.6 days; P = 0.06) or M. tuberculosis (10.1 vs 12.7 days; P = 0.06) with BACTEC MGIT 960 was not statistically significant. CONCLUSION: The BACTEC MGIT 960 system can expedite the recovery of mycobacteria in culture. Combined with conventional solid medium, it also increases the overall recovery of mycobacteria in culture.     

Characterization of mycobacterium isolates from pulmomary tuberculosis suspected cases visiting Tuberculosis Reference Laboratory at Ethiopian Health and Nutrition Research Institute,Addis Ababa Ethiopia:a cross sectional study

Objective:To characterize mycobaclerium isolates from pulmomary tuberculosis suspected cases visiting National Tuberculosis Reference Laboratory at Ethiopian Health and Nutrition Research Institute,for diagnosis of pulmonary tuberculosis from January 4 to February 22.2010 with total samples of 263.Methods:Sputum specimens were collected and processed:the deposits were cultured.Por culturing Lowenstein Jensen medium(LJ) and Mycobacteria Growth Indicator Tube(BACTEC MGIT 960) were used.Capilia Neo was used for detecting NTM isolates from isolates of BACTEC MGIT960.In Armauer Hansen Research Institute,Addis Ababa Ethiopia,Deletion typing PCR method for species identification(from confirmed Mycobacterium tuberculosis complex(MTBC) isolates by Capilia Neo) uas done.Results:Out of 263 enrolled in the study.124 and 117 ol them were positive for mycobaeterium growth by BACTEC MGIT 960 and 1.1 culture method,respectively.From BACTEC MGIT 960 positive media of 124 isolates.117 were randomly taken to perform Capilia TB Neo lest.From these 7(6%) of them were found to be NTM and 110(94%) were MTBC.From these 110 MTBC isolates,81 of them were randomly taken and run by the deletion typing RD9 PCR method of molecular technique.Out of these 78(96.3%) were found to be species of Mycobacterium tuberculosis and 3(3.7%) were found to be not in the MTBC.Regarding the types of methods of culture media.Mycobacteria Growth Indicator Tube(BACTEC MGIT 960) method was found to have excellent agreement(with kappa value ol 0.78) with the routine method of LJ.Conclusions:Pulmonary tuberculosis suspected cases visiting the National Tuberculosis Reference Laboratory at EHNR1 that were confirmed to be pulmonary tuberculosis are caused by the species of Mycobacterium tuberculosis.hence treatment regimen including pyrazinamide can be applied to the patients as the first choice in the study area in Addis Ababa.Ethiopia.There is indication of the presence of NTM in patients visiting the tuberculosis reference laboratory and this is important because NTM is known lo cause pulmonary disease similar with sign and symptom ol pulmonary tuberculosis but different in treatment.BACTEC MGIT 960 has excellent agreement with LJ media but it has high tendency of having high contamination rale unless a better decontamination method is designed.     

Comparative study of PCR, smear examination and culture for diagnosis of cutaneous tuberculosis

Diagnosis of tuberculosis (TB), especially cutaneous TB by conventional laboratory method is unreliable and time consuming. We assessed the utility of Polymerase Chain Reaction (PCR) test vis a vis other laboratory tests in 37 clinical samples of skin biopsy from equal number of patients with different variants of cutaneous TB. The PCR test amplifying 165bp region of 65kDa antigen coding gene specific for M. tuberculosis was performed on skin biopsy samples obtained from cases with a strong clinical evidence of cutaneous TB. The samples were also subjected to other laboratory tests e.g. smear examination, conventional (LJ based culture) and rapid BACTEC culture and histopathological examination for mycobacteria. Significant difference (p<0.05) was observed in the sensitivity of PCR test vis-a-vis other tests e.g. smear examination, LJ and BACTEC culture. PCR test showed a higher sensitivity than histopathological examination but the difference was not found to be statistically significant (p>0.05). PCR test showed the maximum positivity of 79.4% followed by histopathology (73.5%), BACTEC culture (47.5%), LJ media culture (29.4%) and smear examination (5.8%). The sensitivity and specificity of PCR test employing culture as the "gold standard" were 95.2% and 100%. The mean time taken for a positive result in different tests were less than 24 hours for smear examination, 1 day for PCR test, 23.42 days for BACTEC culture and 38.02 days for LJ culture. These results show that PCR amplification of 165bp region of 65kDa antigen coding gene of M. tuberculosis is a rapid and sensitive test for diagnosis of cutaneous TB using skin biopsy samples.     

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.     

Diagnosis of cryptococcal and tuberculous meningitis in a resource‐limited African setting

Objectives Cryptococcal meningitis (CM) and tuberculous meningitis (TBM) are common in HIV‐infected adults in Africa and difficult to diagnose. Inaccurate diagnosis results in adverse outcomes. We describe patterns of meningitis in a Malawian hospital, focusing on features which differentiate CM and TBM with the aim to derive an algorithm using only clinical and basic laboratory data available in this resource‐poor setting. Methods Consecutive patients admitted with meningitis were prospectively recruited, clinical features were recorded and cerebrospinal fluid (CSF) was examined. Results A total of 573 patients were recruited, and 263 (46%) had CSF consistent with meningitis. One hundred and twelve (43%) had CM and 46 (18%) had TBM. CM was associated with high CSF opening pressure and low CSF leukocyte count. Fever, neck stiffness and reduced conscious level were associated with TBM. A diagnostic index was constructed demonstrating sensitivity 83%and specificity 79% for the differentiation of CM and TBM. An algorithm was derived with 92% sensitivity for the diagnosis of CM, but only 58% specificity. Conclusions Although we demonstrate features associated with CM and TBM, a sufficiently sensitive and specific diagnostic algorithm could not be derived, suggesting that the diagnosis of CM and TBM in resource‐limited settings still requires better access to laboratory tools.     

Rapid molecular diagnosis of tuberculous meningitis using the Gen-probe Amplified Mycobacterium Tuberculosis direct test in a large Canadian public health laboratory.

OBJECTIVE: A 5-year retrospective study of the performance of the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) for detecting Mycobacterium tuberculosis complex in cerebrospinal fluid (CSF). Patient data from culture-confirmed cases of tuberculous meningitis (TBM) were also analysed. RESULTS: In total, 311 CSF specimens were tested by the MTD, of which 17 were positive. When compared with culture (gold standard), the sensitivity and specificity of the MTD test were 93.8% and 99.3%, respectively. The positive and negative predictive values for TBM were 88.2%, and 99.7%. Clinical and epidemiological information was requested for all culture-positive TBM patients. These data were used to assess the mortality rate (55.6%) and to determine common factors that could be applied as selection criteria for the appropriate testing of CSF by MTD. CONCLUSION: The study found the MTD test to be a rapid, sensitive and specific test for TBM. A history of immigration from an area endemic for tuberculosis (TB), a history of TB, symptoms of neurological deficits and the results of CSF analyses could be used to appropriately select CSF for MTD testing in order to provide a critical early diagnosis of TBM.     

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。     

Cerebrospinal fluid nitric oxide levels in childhood bacterial meningitis

The role of nitric oxide (NO) in childhood bacterial meningitis was investigated by determining the levels of nitrate/nitrite, stable end products of NO metabolism, in cerebrospinal fluid (CSF). Eighteen children with bacterial meningitis and 18 as a control group were included in the study. Mean (+/- SD) CSF nitrate/nitrite levels were 27.6 +/- 26 micromol/l in the bacterial meningitis group and 3.2 +/- 1.8 micromol/l in the control group (p = 0.0005). We found no correlation between CSF nitrate/nitrite levels and CSF white blood cell count (r = 0.22), protein (r = 0.26) or tumour necrosis factor alpha (TNF-alpha) levels (r = 0.046), but a moderate negative correlation between CSF nitrate/nitrite and glucose levels (r = -0.46).     

Validation of a diagnostic algorithm for adult tuberculous meningitis

Tuberculous meningitis (TBM) remains difficult to diagnose. We prospectively evaluated a diagnostic algorithm for TBM in 205 HIV-negative patients with meningitis and a low CSF glucose. Patients were classified as having TBM or bacterial meningitis (BM) by two diagnostic methods: logistic regression method (LRM) and classification and regression tree (CART). We performed analyses of TBM versus BM and TBM versus non-TBM in all patients and in patients with microbiologically confirmed diagnoses. Diagnostic sensitivities for TBM were 99% (LRM) and 87% (CART). For BM, diagnostic sensitivities were 81.5% (LRM) and 86.5% (CART) in the primary analysis and 86.5% (LRM) and 74% (CART) in the secondary analysis. In microbiologically confirmed cases, similar rates were achieved. These figures are superior to microbiological confirmation rates in routine laboratories and support the use of this algorithm in high-prevalence TB settings with limited diagnostic facilities. Validation in an HIV-endemic setting is required.