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.     

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.     

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.     

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.     

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.     

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。     

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。     

Evaluations of MTD and Amplicor Mycobacterium for direct detection of Mycobacteria from clinical specimens]

MTD (GEN-PROBE AMPLIFIED MYCOBACTERIUM TUBERCULOSIS DIRECT TEST) for Mycobacterium tuberculosis, and Amplicor Mycobacterium for Mycobacteria (AMP-M. tb for M. tuberculosis, AMP-M. av for M. avium and AMP-M. in for M. intracellulare) were used for the detection of relevant Mycobacterium. Their sensitivity and specificity were evaluated. Total 244 clinical specimens including 164 sputa were examined by the above two tests. The results were compared with those obtained by the conventional methods. Of 244 samples, number of the M. tuberculosis positive samples by microscopy, cultural test, MTD and AMP-M. tb were 32, 33, 38 and 35, respectively. Among 33 culture positive samples, 25 were MTD positive and 26 were AMP-M. tb positive. Therefore, sensitivity of MTD and AMP-M. tb were 75.8% and 78.8%, and their specificity were 93.8% and 95.7%, respectively. When only sputa were used for the tests as the clinical specimens, both sensitivity of MTD and AMP-M. tb were increased to 94.4%. For MAC, positive samples of M. avium complex by culture, M. avium by AMP-M. av and M. intracellulare by AMP-M. in were 13, 16, and 8, respectively. Sensitivity and specificity of AMP-M. av/M. in were 100% and 95.2%, respectively. Clinical findings of the patients whose MTD tests were positive but negative by culture were reexamined. Three of 9 specimens were also positive in AMP-M. tb. From the records of the isolations of tubercle bacilli or other important pathogens from the other kind of clinical specimens, smear tests and patients' response to tuberculosis chemotherapy, four of 9 specimens were confirmed as true positive, three were suspected as positive, and two other specimens were false positive which might be caused by contamination. From these observations, it could be concluded that MTD and AMP-M. tb are more sensitive than conventional culture method, and MTD is more sensitive than AMP-M. tb but needs more careful treatment to avoid the contamination.     

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.     

Molecular analysis of Mycobacterium tuberculosis causing multidrug-resistant tuberculosis meningitis.

SETTING: Tertiary referral hospitals in southern Vietnam. OBJECTIVE: Molecular characterisation of multidrug-resistant (MDR) tuberculous meningitis (TBM). DESIGN: Mycobacterium tuberculosis isolates from the cerebrospinal fluid (CSF) of 198 Vietnamese adults were compared with 237 isolates from patients with pulmonary tuberculosis (PTB) matched for age, sex and residential district. Isolates resistant to isoniazid or rifampicin (RMP) were sequenced in the rpoB and katG genes, inhA promoter and oxyR-ahpC intergenic regions. RESULTS: While drug resistance rates were lower in the CSF (2.5% MDR) than pulmonary isolates (5.9% MDR), the difference was not significant. The most commonly mutated codons were 531, 526 and 516 in rpoB and 315 in katG. Four novel triple mutants in rpoB were identified. CONCLUSION: RMP resistance is a good surrogate marker for MDR-TBM in this setting. However, probes directed against these three codons would have a maximum sensitivity of only 65%. A rapid phenotypic detection test may be more applicable for the diagnosis of MDR-TBM.     

Penicillinase ELISA for detection of tubercular antigen in tuberculosis.

Stick sandwich enzyme linked immunosorbent assay (ELISA) using rabbit anti PPD-RT 23 immunoglobulins and enzyme penicillinase has been explored for detection of tubercular antigen in sera and CSF samples of pulmonary tuberculosis and tubercular meningitis (TBM) respectively. The analysis of sera showed 73.3% of pulmonary tuberculosis cases, 16.2% of healthy controls and 44.4% of Hansen's disease positive for tubercular antigen. The accuracies of positive and negative predictive values were 69% and 82% respectively. The analysis of CSF samples showed the presence of tubercular antigen in 76.4% of TBM, 16.6% of pyogenic meningitis cases, 19.4% of neurological diseases other than meningitis and 16.1% non-neurological disease controls. The accuracies of positive and negative predictive values were 48% and 94% respectively. Hence this simple test using economical and indigenous reagents can be applied for the diagnosis of pulmonary and extra-pulmonary tuberculosis.     

Use of the amplified mycobacterium tuberculosis direct test in a public health laboratory: test performance and impact on clinical care

BACKGROUND: The Amplified Mycobacterium tuberculosis Direct Test (MTD; Gen-Probe; San Diego, CA) is a nucleic-acid amplification test for rapid pulmonary tuberculosis (PTB) diagnosis. In a routine public health setting, test accuracy and impact on clinical decisions are unknown. METHODS: Retrospectively, we evaluated MTD accuracy and impact on clinical decisions in a public health setting. To estimate MTD accuracy, mycobacterial culture was used as the "gold standard." To evaluate MTD impact on clinical decisions, concordance of clinician presumptive diagnosis (at time of MTD and smear availability) and definitive diagnosis, and duration of nonindicated tuberculosis therapy were determined for smear-positive PTB suspects in a period of MTD availability (MTD group) and a prior period of MTD nonavailability (non-MTD group). RESULTS: A total of 1,151 respiratory specimens from 638 PTB suspects were analyzed. MTD sensitivity, specificity, positive predictive value, and negative predictive value were 91.7%, 98.7%, 96.7%, and 96.5% overall, respectively; and 98.7%, 97.8%, 98.7%, and 97.8% for smear-positive patients; and 62.2%, 98.9%, 85.2%, and 96.1% for smear-negative patients. In the MTD group, concordance between definitive and clinician presumptive diagnoses was 78% (95% confidence interval [CI], 64 to 88%), similar to that for the non-MTD group (79%; 95% CI, 68.4 to 89.6%). However, concordance between definitive diagnosis and the MTD test was 98% (95% CI, 94.1 to 100%). Median duration of nonindicated tuberculosis treatment was 6 days for the MTD group vs 31 days for the non-MTD group (p = 0.002). CONCLUSION: In this public health setting, MTD was accurate and rapidly detected more than half of the smear-negative PTB cases. For smear-positive PTB suspects, MTD had excellent concordance with definitive diagnosis, but clinicians often inappropriately initiated TB therapy despite a negative MTD result.     

Usefulness of cranial and chest imaging in the diagnosis of tuberculous meningitis among infants and young children

We retrospectively evaluated the clinical and laboratory data of children with tuberculous meningitis (TBM) treated at our hospital from 1990 to 1999 to determine the optimal method of diagnosing TBM. The evaluated diagnostic criteria for TBM were as follows: (1) fever and malaise as symptoms of acute/subacute inflammation, (2) positive cerebrospinal fluid and/or gastric aspirate cultures for Mycobacterium tuberculosis, (3) pleocytosis of cerebrospinal fluid, and (4) a good response to anti-tuberculous therapy. The data for eleven patients (6 boys, 5 girls) with TBM (mean age, 10.7 months) were reviewed. Three patients (27%) were previously vaccinated with BCG. A known contact with tuberculosis was established at the time of admission in four patients (36%). Symptoms related to tuberculosis appeared on the average 14.8 days before the diagnosis. Three patients (27%) were diagnosed as clinical stage I, three (27%) as stage II, and five (46%) as stage III; all patients had fever (100%). With regard to the cerebrospinal fluid examinations, pleocytosis with mononuclear predominance was noted in all patients but one (91%), and mycobacterial staining was positive in three patients (27%). Tuberculin skin test was positive in four out of 10 patients (40%). Mycobacterial staining of gastric aspirate was positive in four patients (36%). Chest radiological examinations showed a swelling of the mediastinal lymphonodes and/or parenchymal infiltration in all patients (100%). A cranial CT examination demonstrated a basal meningeal enhancement in all patients (100%), hydrocephalus in nine patients (82%), and infarction in eight patients (73%). These results suggest that chest and cranial CT examinations are useful adjunct methods for diagnosis of TBM in infants and young children suffering from meningitis with pleocytosis of the cerebrospinal fluid and mononuclear predominance, in addition to conventional methods such as the tuberculin skin test, plain chest radiography, and staining for mycobacteria in body fluids.     

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.     

The clinical evaluation of MTD false-positive & false-negative results]

The usefulness of MTD (Amplified Mycobacterium Tuberculosis Direct Test) for a rapid diagnosis of tuberculosis was evaluated. A total of 400 clinical samples obtained from July, 1995 to June, 1997 were tested by MTD, direct microscopy and culture. The results of MTD and smear/culture were coincident in 387 out of 400 samples. Eight samples (2%) were MTD false-positive (i.e. they were MTD positive but smear and culture negative), and 5 (1.25%) were MTD false-negative (i.e. MTD negative but smear and/or culture positive). Despite a careful review of the clinical data of those patients whose samples showed discrepant results, the reasons of discrepancy were not clear in 2 (0.5%) of the 8 false positives and 3 (0.75%) of the 5 false negatives. In the other cases, the MTD false positives may be accounted for the presence of previous M. tuberculosis infection, the influence of anti-tuberculous medication and so on, and the MTD false negatives are most likely due to the presence of inhibitors (blood, for example) or to the small number of organisms in the specimens. It can be concluded that adequate samples should be obtained, and that MTD should be repeated in case of discrepant results.     

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.     

Routine use of Gen-Probe Amplified Mycobacterium Tuberculosis Direct (MTD) test for detection of Mycobacterium tuberculosis with smear-positive and smear-negative specimens.

SETTING: Nucleic acid amplification tests, such as the Amplified Mycobacterium Tuberculosis Direct (MTD) Test, may improve early diagnosis of tuberculosis when used in combination with acid-fast bacilli smear examination with a similar turnaround time. OBJECTIVE: To evaluate the routine use of MTD in respiratory and non-respiratory samples; to investigate the improvement of MTD specificity and positive predictive value by defining an equivocal zone for result interpretation. DESIGN: MTD was performed according to the instructions supplied by the manufacturer. An equivocal zone was included for interpretation of results. Discordant results with culture were resolved by incorporating clinical data and multiple specimen analysis. RESULTS: The overall sensitivities, specificities, and positive and negative predictive values for respiratory specimens (n = 3308) were 90.8, 99.9, 99.1, and 99.2%, respectively. With extra-pulmonary specimens (n = 1350) those values were 67.4, 99.9, 98.2, and 97.9%, respectively. By implementing an equivocal zone, the specificity and positive predictive value of MTD were improved (from 99.1% and 88.6% to 99.9% and 98.9% respectively) without significantly altering other performance characteristics. CONCLUSIONS: Amplification assays cannot yet replace the conventional diagnostic techniques. Nevertheless, MTD is a reliable method for the direct detection of M. tuberculosis in clinical specimens. The number of false-positive results can be limited by defining an equivocal zone.     

Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death.     

Significance of mycobacterial immune complexes (IgG) in the diagnosis of tuberculous meningitis

Setting: Tuberculous meningitis (TBM) has high mortality, especially in children. Early accurate diagnosis and adequate treatment would reduce this mortality. Diagnosis of TBM remains an enigma because of low cerebrospinal fluid (CSF) culture positivity for Mycobacterium tuberculosis and weak clinical correlation with conventional immunoassays.Objective: To evaluate significance of mycobacterial immune complexes (IgG) and anti-mycobacterial antibodies in the diagnosis of TBM.Method: CSF from TBM patients and various types of other neurological (both infectious and non-infectious) and non-neurological cases was studied for the presence of IgG and anti-mycobacterial antibodies using antigen capture (by anti-BCG) and multilayered ELISA (using M. tuberculosis soluble extract), respectivelyResults: IgG in CSF could be detected in 33 of 55 (60%) and anti-mycobacterial antibodies in 30 of 55 (55%) TBM cases. Presence of IgG, anti-mycobacterial antibodies or both could be detected in 45 of 55 (82%) of the TBM cases. Excepting three of the pyogenic meningitis CSF, none of the infectious (49), non-infectious neurological cases (30) and non-neurological controls (32) showed the presence of IgG or anti-mycobacterial antibodies.Conclusion: Detection of IgG along with anti-mycobacterial antibodies aids in diagnosis of a large proportion of TBM cases.     

Evaluating 82 cases of tuberculous meningitis

Tuberculous meningitis (TBM) is not the most common but the most serious clinical form of extrapulmonary tuberculosis. Serious complications resulting from difficulties in diagnosis and treatment of the disease makes it an important health problem. In our study, 82 patients with TBM, followed up in our clinic between January 1998-December 2002, are evaluated with their clinical and laboratory properties. 52% of our patients were females, 48% were males and their ages ranged from 15 to 70 with a mean of 32 years. The diagnosis was based on patients' history, clinical and laboratory properties, cerebrospinal fluid (CSF) findings and radiographic findings. 59% of our patients were grade II clinically, 29% were grade I, and 23% were grade III. Mostly observed complaints were headache (87%) and nausea-vomiting (63%) and fever (45%) and mostly seen physical findings were stiff neck (70%), alterations in consciousness (57%). Pleocytosis in CSF was detected in 94%, low CSF glucose level in 87%, and elevated CSF protein level in 82% of the patients. From CSF samples of 40 patients, out of total 82, Mycobacterium tuberculosis was isolated on Loewenstein-Jensen medium (49%). Nineteen patients had tuberculomas, 13 had basal meningitis, and 11 had hydrocephalus on cranial radiographic studies. 28% had miliary pattern and 26% had active infiltration and cavities on chest roentgenogram. A four-drug antituberculous regimen was administered for 88% of the patients and dexamethasone treatment was administered for 75%; 56 (68.3%) patients recovered from the illness, 14 (17%) patients had slight and 4 (4.9%) patients had serious neurological sequeales and 8 (9.8%) patients died in spite of tuberculous therapy. As a conclusion, TBM is an infectious disease with high morbidity and mortality rates. Various prognosis patterns may be observed according to the clinical grade of the patient on application. When suspected, an early diagnosis and early treatment of the disease are the most important factors which effect complication and mortality rates.