Diagnosis Of TBM Research Articles

Clinico-epidemiological profile of 75 cases of TB meningitis in children and adoloscents

BackgroundNeurological involvement is one of the deadliest forms of tuberculosis especially in pediatric population. AimTo study the clinico-epidemiological profile of 75 cases of pediatric TB meningitis and its co-relation with CBNAAT/TRUENAT positivity. Study designProspective study in children and adolescents less than 18 years in Tertiary Health care centre in New Delhi. Subjects and methods75 Children and adolescents less than 18 years with Probable TBM as per NTEP guidelines were enrolled. Clinical, Radiological and CSF analysis were carried out in all the patients. Results75 children were enrolled out of which 61% were females. The most common symptom at presentation was fever followed by loss of appetite and weight loss. Neck rigidity was present in 66% cases followed by posturing in 25% cases. 46% patients presented in Stage 2. Tuberculin skin test was positive in 16% cases and 20% patients had evidence of pulmonary TB on chest Xray. Hydrocephalous was the most common finding in neuroimaging present in 61% cases. In majority of the cases, CSF analysis revealed pleocytosis with lymphocyte predominance, low glucose and high protein values. Nucleic amplification tests (CBNAAT/TRUENAT) were positive in 33% cases and 4 out of 75 were detected to have rifampicin resistance. There was no co-relation identified between Stage at presentation, tuberculin positivity and CSF analysis with CBNAAT/TRUENAT positivity. Six patients expired within 2 weeks of presentation. ConclusionThe diagnosis of TBM is a composite of clinical, radiological and CSF analysis parameters. Being a paucibacillary sample, the yield of TB bacilli in NAAT studies remains moderately low. Moreover, detection of TB bacilli in CBNAAT/TRUENAT is independent of the CSF cytological and biochemical profile, and is also independent of the Stage of TBM.

Evaluation of seegene anyplex MTB/NTM real-time detection assay for diagnosis of tuberculous meningitis

BackgroundTuberculous meningitis (TBM) is a common central nervous system infectious disease. Polymerase chain reaction (PCR) assay is a useful method for the rapid diagnosis of TBM. The Seegene Anyplex MTB/NTM real-time detection assay has good sensitivity and specificity for detection of tuberculosis in respiratory specimens, though, data regarding other specimens are lacking. This study aims to define the diagnostic role of Seegene Anyplex MTB/NTM real-time detection assay in TBM in adults.MethodsThis was a retrospective study of 367 adults with symptomatic community acquired meningitis between December 2013 and December 2019. Cerebrospinal fluid (CSF) had been sent for conventional diagnosis, including culture to identify Mycobacterium tuberculosis, and Seegene Anyplex MTB/NTM real-time detection assay. Other diagnostic examinations were performed as necessary.ResultsOf the 367 patients in the study, 37 were diagnosed with TBM (14 with definite TBM and 23 with probable TBM). Between the total TBM cases (n = 37) and non-TBM cases (n = 330), clinical sensitivity was 32.4% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 93.0%. Between the definite TBM cases (n = 14) and non-TBM cases (n = 330), clinical sensitivity was 50.0% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 97.9%.ConclusionDue to lack of sensitivity, we suggest Seegeen Anyplex MTB/NTM real-time detection assay should not be used to rule out TBM but is useful for definite diagnosis.

A New Scoring System to Differentially Diagnose and Distinguish Tuberculous Meningitis and Bacterial Meningitis in South China.

BackgroundTuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis, and is characterized by high morbidity and mortality. Unfortunately, it is difficult to distinguish TBM from bacterial meningitis (BM) based on clinical features alone. The latest diagnostic tests and neuroimaging methods are still not available in many developing countries. This study aimed to develop a simple diagnostic algorithm based on clinical and laboratory test results as an early predictor of TBM in South China.MethodsA retrospective study was conducted to compare the clinical and laboratory characteristics of 114 patients with TBM and 47 with BM. Multivariate logistic regression analysis was performed on the characteristics of independently predicted TBM to develop a new diagnostic rule.ResultsFive characteristics were predictive of a diagnosis of TBM: duration of symptoms before admission; tuberculous symptoms; white blood cell (WBC) count, total cerebrospinal fluid WBC count, and cerebrospinal fluid chloride concentration. The sensitivity and specificity of the new scoring system developed in this study were 81.6 and 93.6%, respectively.ConclusionThe new scoring system proposed in this study can help physicians empirically diagnose TBM and can be used in countries and regions with limited microbial and radiological resources.

Frequency of Hydrocephalus in Cases of Tuberculous Meningitis

Aim: To determine the frequency of hydrocephalus in cases of Tuberculous meningitis Methods: This was a cross sectional study conducted during 01-07-16 to 31-12-2017 at Department of Medicine, Sheikh Zayed Hospital, Rahim Yar Khan. The cases of tuberculosis meningitis of age range of 15 to 50 years of either gender with tuberculous meningitis were included in this study. The diagnosis of TBM was made on the basis of combination of clinical symptoms and laboratory data. The symptoms were fever, weight loss and neck rigidity with or without fits. These cases then underwent CSF analysis under aseptic measures. The findings to label TBM on CSF were low glucose (< 40 mg/dl), increased protein content (> 100 mg/dl) and high WBC count with predominance of lymphocytes. The cases of TBM were divided according to standard BMRC scale into three stages. The cases with bacterial meningitis, having any SOL in brain and those with any previous history of neurosurgery were excluded from this study. Then these cases underwent CT brain in the same institute and diagnosis of Hydrocephalus was made when any of the ventricle is dilated more than 25% of the baseline. Results: In this study there were total 93 cases of TBM with mean age of 37.11±08.67years. There were 54(58.06%) males and 39(41.94%) females. Maximum cases were seen in stage II of TBM which affected 65 (69.89%) cases. Hydrocephalus was seen in 61(65.59%) of the cases as shown in figure 01. Hydrocephalus was significantly high in male gender as compared to females where it affected 39(72.22%) of cases with p value of 0.03. It was also more common in cases that had age group 15-29 years affecting 40(67.79%) of cases with p= 0.86. Hydrocephalus was also significantly high in cases with stage II and III of TB affecting 66.15% and 77.27% of cases respectively with p= 0.01. Conclusion: Hydrocephalus is very common in cases of TBM and it is significantly high in male gender and stage II and III of TBM. Key words: TBM, Hydrocephalus

Metagenomic next generation sequencing for the diagnosis of tuberculosis meningitis: A systematic review and meta-analysis.

BackgroundTuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die. The current study aimed to assess the accuracy of metagenomic next generation sequencing (mNGS) for TBM, and to identify a new test for the early diagnosis of TBM.MethodsWe searched for articles published in Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data up to June 30, 2020 for studies that assessed the efficacy of mNGS for the diagnosis of TBM. Then, the accuracy between mNGS and a composite reference standard (CRS) in these articles was compared using the meta-analysis approach.ResultsFour independent studies with 342 samples comparing mNGS and a CRS were included in this study. The sensitivity of mNGS for TBM diagnosis ranged from 27% to 84%. The combined sensitivity of mNGS was 61%, and the I2 value was 92%. Moreover, the specificity of mNGS for TBM diagnosis ranged from 96% to 100%. The combined specificity of mNGS was 98%, and the I2 value was 74%. The heterogeneity between studies in terms of sensitivity and specificity was significant. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for TBM was 0.98.ConclusionsThe sensitivity of mNGS for TBM diagnosis was moderate. Furthermore, the specificity was extremely high, and the AUC of the SROC indicated a very good diagnostic efficacy. mNGS could be used as an early diagnostic method for TBM, however, the results should be treated with caution for the heterogeneity between studies was extremely significant.Systematic review registrationINPLASY202070100.

Detection of tuberculous meningitis by various microbiological modalities at a tertiary care hospital in north India

Tuberculous meningitis is a common infection of the CNS, posing significant diagnostic and management challenges. Death in TBM patients is strongly associated with delay in diagnosis and treatment. Since, any single conventional or automated method for diagnosis of TBM has limited sensitivity; the main objectives of this study was – 1. Detect TBM by a combination of Direct Microscopy by ZN Staining, Culture by solid (LJ) and liquid media (BacT/Alert), besides GeneXpert (RT-PCR) in clinically suspected cases.; 2. Evaluate the role ofGeneXpert for detection of Mycobacterium tuberculosis in CSF and demonstrate the sensitivity, specificity, PPV and NPV of GeneXpert in comparison with a set composite reference standard. This was a prospective cross-sectional study carried out by the Department of Microbiology, GMC, Srinagar, from August ’17 to September ’19 CSF samples of 450 patients suspected of TBM were included in the study. CSF volume <0.1ml was excluded. A composite reference standard was devised which comprised of culture, ZN staining and empirical diagnosis. The samples were tested by ZN staining, solid culture, liquid culture and GeneXpert MTB/RIF using proper protocols. Patient details were obtained on a preformed proforma. Of the 450 suspected patients, 10% had Definitive TBM. The median age was 35 years with an almost equal male to female ratio. The sensitivities of ZN staining, Solid culture, liquid culture and Gene Xpert were 3%, 38%, 76% and 63% respectively. The specificity was 100% for all these tests, 95% CI being, 99-100%. The NPV was 84.02%, 100%, 91% and 93.6% whereas, the PPV was 84.89%, 100%, 100% and 99.1% respectively. Rifampicin resistance was positive in 2%. 95% cases had a very low bacillary load and 2.2% patients showed low and medium bacillary load. 12% patients had concomitant pulmonary TB and 10% with other forms of extrapulmonary TB. Gene/Xpert as a frontline diagnostic tool, is a game changer. It abridges presumptive prescribing of tuberculosis treatment. Speedy detection of TBM especially in smear negative cases and detection of drug resistance in the paucibacillary CSF improves outcome for patients with TBM /MDR TBM. However, additional tests, with better sensitivity are required and we must make the best use of the tests we have by testing adequate volumes (5 -10ml) of CSF.

Safety diagnosis of TBM for tunnel excavation and its effect on engineering

Since the development of tunnel construction technology, different tunnel excavation technologies have also been derived for different conditions. The safety diagnosis before the TBM mining method is particularly important. With the technology of safety diagnosis, the excavation process has the following effects on the tunnel engineering work. Great guarantee. The purpose of this paper is to study the excavation process of tunnel machinery for safety diagnosis before mining by TBM. It mainly includes step excavation method, full-section excavation method, guide pit excavation method and other technologies. This article uses a city subway construction project as an example to discuss in-depth the study of tunnel machinery excavation technology before the safety diagnosis of the mining method. The specific project is a city subway line with a total length of about 25.464 km and a total of 22 stations, including 9 transfer station. Based on field engineering experiments, the problems encountered in tunnel mechanical excavation are studied. The experimental data show that the results obtained through engineering tests can guarantee the safe and stable construction of the tunnel project, and the safety rate can reach 90%. The experimental results show that the obtained results can ensure the safety of tunnel mechanical excavation.

Diagnostic accuracy of droplet digital PCR analysis of cerebrospinal fluid for tuberculous meningitis in adult patients

ObjectivesTuberculous meningitis (TBM) is difficult to diagnose. Digital PCR (dPCR) is a novel method which can quantify trace nucleic acids. This study sought to evaluate the diagnostic accuracy of dPCR analysis of cerebrospinal fluid (CSF) for TBM. MethodsWe collected CSF specimens from hospitalized TBM and non-TBM patients. Total CSF DNA was purified and the concentrations of Mycobacterium tuberculosis insert sequence 6110 (IS6110) and gyrase subunit B (gyrB) were quantified using droplet dPCR. The receiver operating characteristic curves of dPCR were established and the diagnostic performances were obtained. We also compared the sensitivity of dPCR with routine diagnostic tests. ResultsA total of 101 patients were recruited, 68 of whom suffered from TBM (26 definite, 34 probable and eight possible TBM) and 33 from non-TBM. The sensitivity of IS6110-dPCR assay for total TBM was higher than that of gyrB-dPCR assay (57.4% (44.8–69.3%) vs. 22.1% (12.9–33.8%)), and there was no significant difference for specificity between them (97.0% (84.2–99.9%) vs. 100% (89.4–100.0%)). The sensitivity of IS6110-dPCR in definite TBM was higher than that in probable and possible TBM (73.1% vs. 52.9% and 25.0%, respectively). IS6110-dPCR assay showed a higher sensitivity than smear microscopy (53.3% vs. 6.7%), mycobacterial culture (50.0% vs. 12.5%), IS6110-quantitative PCR (53.1% vs. 21.9%) and Xpert MTB/RIF (70.4% vs. 29.6%). Long anti-tuberculosis treatment time was found to be significantly associated with negative dPCR results. ConclusionCSF IS6110-dPCR assay is a rapid and sensitive molecular test, which has the potential to be used to enhance the diagnosis of TBM.

OC 8277 IDENTIFICATION OF NEW CEREBROSPINAL FLUID AND BLOOD-BASED BIOMARKERS FOR THE DIAGNOSIS OF TUBERCULOUS MENINGITIS IN CHILDREN

BackgroundTuberculous meningitis (TBM) is the most severe form of extrapulmonary tuberculosis (TB). It mostly affects young children and results in high morbidity and mortality, mainly due to diagnostic delay. There is an urgent need for new tests for the earlier and accurate diagnosis of the disease. We previously identified a 3-marker cerebrospinal fluid (CSF) biosignature (VEGF, IL-13, and LL-37) with potential to diagnose TBM. In the present study, we show that CSF and blood-based biosignatures may be useful in the diagnosis of TBM.MethodsCSF and serum samples were consecutively collected from 47 children that were admitted to the Tygerberg Academic Hospital in Cape Town, South Africa, on suspicion of having TBM. Using a multiplex platform, the concentrations of 69 host markers were evaluated in the CSF and serum samples from all the study participants, followed by statistical analysis to ascertain the usefulness of these biomarkers as diagnostic candidates for TBM disease.ResultsOut of the 47 study participants, 23 (48.9%) were finally diagnosed with TBM and 6 (12.8%) were infected with HIV. Several CSF and serum biomarkers showed potential individually as diagnostic candidates for TBM as ascertained by area under the receiver operator characteristics curve (AUC). However, the main findings of our study were the identification of a four-marker CSF biosignature which diagnosed TBM with an AUC of 0.97 (95% CI, 0.92–1.00), and a 3-marker serum biosignature which diagnosed TBM with an AUC of 0.84 (95% CI, 0.73–0.96). We also validated a previously identified 3-marker CSF biosignature (VEGF, IL13 and LL37) in the study.ConclusionCSF and serum biosignatures may be useful in the diagnosis of TBM in children. Our findings require further validation in larger, multi-site studies after which the biosignatures may be incorporated into point-of-care diagnostic tests for TBM.

Structural switching electrochemical DNA aptasensor for the rapid diagnosis of tuberculous meningitis.

BackgroundTuberculous meningitis (TBM) is the most devastating manifestation of extra-pulmonary tuberculosis. About 33% of TBM patients die due to very late diagnosis of the disease. Conventional diagnostic methods based on signs and symptoms, cerebrospinal fluid (CSF) smear microscopy or liquid culture suffer from either poor sensitivity or long turnaround time (up to 8 weeks). Therefore, in order to manage the disease efficiently, there is an urgent and unmet need for a rapid and reliable diagnostic test.MethodsIn the current study, to address the diagnostic challenge of TBM, a highly rapid and sensitive structural switching electrochemical aptasensor was developed by combining the electrochemical property of methylene blue (MB) with the molecular recognition ability of a ssDNA aptamer. To demonstrate the clinical diagnostic utility of the developed aptasensor, a blinded study was performed on 81 archived CSF specimens using differential pulse voltammetry.ResultsThe electrochemical aptasensor developed in the current study can detect as low as 10 pg HspX in CSF background and yields a highly discriminatory response (P<0.0001) for TBM and not-TBM categories with ~95% sensitivity and ~97.5% specificity and has the ability to deliver sample-to-answer in ≤30 minutes.ConclusionIn summary, we demonstrate a new aptamer-based electrochemical biosensing strategy by exploiting the target-induced structural switching of H63 SL-2 M6 aptamer and electroactivity of aptamer-tagged MB for the detection of HspX in CSF samples for the diagnosis of TBM. Further, the clinical utility of this sensor could be extended for the diagnosis of other forms of tuberculosis in the near future.

Mortality in hospitalized patients with tuberculous meningitis

BackgroundTo evaluate the mortality in hospitalized patients with tuberculous meningitis and describe factors associated with an increased risk of mortality.MethodsRetrospective study of hospitalized patients with tuberculous meningitis between 2006 and 2015 in Peru performing a generalized linear regression to identify factors predictive of in-hospital mortality.ResultsOf 263 patients, the median age was 35 years, 72.6% were men, 38% were positive for HIV upon admission, 24% had prior TB infections and 2.3% had prior MDR-TB infections. In-hospital mortality was 30.4% of all study patients with a final diagnosis of TBM. When multivariable analysis was applied, significant associations with in-hospital mortality were seen among patients with HIV (RR 2.06; Confidence Interval 95% (95% CI) 1.44–2.94), BMRC II (RR 1.78; 95% CI 1.07–2.97), BMRC III (RR 3.11; 95% CI 1.78–5.45) and positive CSF cultures (RR 1.95; 95% CI 1.39–2.74).ConclusionsIn-hospital mortality is higher among patients with HIV infections, age over 40 years, positive CSF TB culture and BMRC stage II or III.

Diagnostic accuracy of nucleic acid amplification based assays for tuberculous meningitis: A meta-analysis

Numerous in-house and commercial nucleic acid amplification tests (NAAT) have been evaluated using variable reference standards for diagnosis of TBM but their diagnostic potential is still not very clear. We conducted a meta-analysis to assess the diagnostic accuracy of different NAAT based assays for diagnosing TBM against 43 data sets of confirmed TBM (n = 1066) and 61 data sets of suspected TBM (n = 3721) as two reference standards. The summary estimate of the sensitivity and the specificity were obtained using the bivariate model. QUADAS-2 tool was used to perform the Quality assessment for bias and applicability. Publication bias was assessed with Deeks' funnel plot. Studies with confirmed TBM had better summary estimates as compared to studies with clinically suspected TBM irrespective of NAAT and index tests used. Among in-house assays, MPB as the gene target had best summary estimates in both confirmed [sensitivity:90%(83-95), specificity:97-%(87-99), DOR:247 (50-1221), AUC:99%(97-100), PLR:38.8-(6.6-133), NLR:0.11(0.05-0.18), I2 = 15%] and clinically suspected [sensitivity:69%(47-85), specificity:96%(90-98), DOR:62(16.8-232), AUC:94%(92-97), PLR:16.9(6.5-36.8), NLR:0.33(0.16-0.56), I2:15.3%] groups. GeneXpert revealed good diagnostic accuracy only in confirmed TBM group [sensitivity = 57%(38-74), specificity = 98%(89-100), DOR = 62(7-589), AUC = 87%(79-96), PLR = 33.2(3.8-128), NLR = 0.45(0.26-0.68), I2 = 0%]. This meta-analysis identified potential role of MPB gene among in-house assays and GeneXpert as commercial assay for diagnosing TBM.

Predictors of neurologic deficit on discharge and in-hospital mortality of pediatric tuberculous meningitis patients with hydrocephalus who undergo ventriculoperitoneal shunting

Objective: To determine predictors of neurologic deficit on discharge and in-hospital mortality among TBM patients with hydrocephalus who undergo VPS insertion. Methods: This was a retrospective cross-sectional study from January 2005–December 2015. The diagnosis of TBM were based on a combination of clinical features, CSF findings, and neuroimaging appearances. Results: Eighty-three children with TBM who underwent VPS. Their median age was 3 years old, and 61.45% were males. Nearly half of the patients were underweight. A previous and family histories of PTB was reported in 15.66% and 19.28%, respectively. The majority of patients admitted were Stage II (78.31%). More than half had increased CSF protein, and reduced sugar and WBC on analysis. Basilar enhancement in 15.58% and infarction in 3.95% of the patients were noted by neuroimaging. CUS showed rim/halo, increased periventricular echogenicity, and flattened sulci. Duration from onset of symptoms to detection of hydrocephalus was less than two weeks in 26% of Stage II and 41% of Stage III. The duration of altered sensorium prior surgery was less than 24 h for most of the patients across stages. More than half of patients in Stage III with severe hydrocephalus and GCS below 8. The mRS distribution among the Stage II patients; 6.15% normal, 72.31% with neurologic deficit, 10.77% severely debilitated, and 10.77% expired while in Stage III; 47.06% with deficits, 11.76% severely debilitated, and 41.18% expired. Patients whose CSF protein and severe hydrocephalus were poor mRS scores on discharge (95% CI 1.1044 to 7.6062, p = 0.031). Conclusion: TBM affects mainly children less than 5 years of age and is still a serious public health problem. CSF protein and the severity of hydrocephalus are strongly associated with high mortality rate.

Cerebrospinal fluid adenosine deaminase and its dynamic changes in tuberculous meningitis

Objective: To explore the diagnostic value of cerebrospinal fluid (CSF) adenosine deaminase (ADA) level in tuberculous meningitis. Methods: We retrospectively analyzed 139 patients (73 males, 66 females) who visited Beijing Chest Hospital for suspected TBM from January 2010 to June 2015. Of them, 99 patients were diagnosed to have TBM, with 45 males and 54 females, and a mean age of (33±15) years. Forty patients were diagnosed as having Non-TBM, with 28 males and 12 females, and a mean age of (35±18) years. All patients underwent lumbar puncture, and CSF ADA, routine, biochemical and bacteriological tests were performed. Thirty-five TBM patients reviewed CSF ADA test after treatment for 4 weeks, 8 weeks and 6 months. Results: The level of CSF ADA in TBM group was higher than that in the non-TBM group, the difference being statistically significant (5.6 U/L vs 2.3 U/L, P=0.000). When the cut-off value of the CSF ADA was 3.8 U/L , the sensitivity and specificity for diagnosis of TBM were 60.6% (95%CI 50.3%-70.1%) and 87.5% (95%CI 72.4%-95.3%), respectively, and the area under the ROC curve was 0.734.The CSF ADA level was (6.7±4.2) U/L in the 35 cases of TBM before treatment. After 4 weeks, 8 weeks and 6 months of anti-tuberculosis treatment, the CSF ADA levels were (4.5±3.3) U/L, (3.7±2.7) U/L and (2.0±1.5) U/L, respectively; all significantly decreased as compared to that before treatment (P<0.001). There was no significant change in the ADA level between 8 weeks and 4 weeks (P=0.128). After 6 months of treatment, the level of CSF ADA was significantly lower than those after 4 and 8 weeks' treatment (P<0.001). Conclusions: CSF ADA in TBM patients was significantly higher than in non-TBM patients. The sensitivity of CSF ADA level in the diagnosis of TBM was poor, but the specificity was better. CSF ADA was significantly reduced and showed dynamic changes with effective anti-tuberculosis treatment and maybe helpful in evaluating the effect of treatment.

Role of multiplex polymerase chain reaction in diagnosing tubercular meningitis.

Tuberculous meningitis (TBM) is one of the most serious manifestations of extrapulmonary tuberculosis. Timely and accurate diagnosis provides a favorable prognosis in patients with TBM. The study evaluated the use of multiplex polymerase chain reaction (PCR) in the diagnosis of TBM. A study was conducted on 74 patients clinically suspected with TBM. The cerebrospinal fluid (CSF) specimens were processed for smear microscopy, middle brook 7H9 culture, and multiplex PCR using primers directed against IS6110 gene and 38 kD protein for detection of Mycobacterium tuberculosis. The results were analyzed to assess the role of multiplex PCR in the diagnosis of TBM. A total of 26 (35.1%) patients were diagnosed with TBM. Microscopy was negative in all while culture was positive in two cases only. Comparing with clinical diagnosis and CSF adenosine deaminase levels of ≥10 U/L, multiplex PCR showed sensitivity, specificity, positive predictive value, and negative predictive value of 71.4%, 89.6%, 83.3%, and 81.2%, respectively, in the diagnosis of TBM.

Diagnosis of tuberculous meningitis: Current scenario from a Tertiary Neurocare Centre in India

BackgroundTuberculous meningitis (TBM) is a condition that is caused by Mycobacterium tuberculosis complex and is difficult to diagnose due to the nonspecificity of the presentations. The study analyzed the different modes of diagnosis available in a developing country set up over a period of five years to understand the diagnostic values of the current conventional and automated methods of diagnosis of TBM among the patients suspected with chronic meningitis. MethodsA total of 10,281 cerebrospinal fluid samples (CSF) were collected from suspected chronic meningitis patients, of which 790 samples were from individuals who had clinically suspected TBM. The samples were subjected to CSF cytology and staining, culturing, immunological tests, molecular techniques, and methods for detection of drug resistance. ResultsThe TBM patients were predominantly male, with a mean age of 21–40 years. CSF pleocytosis and lymphocytic predominance were noted. Culture had 40.13% positivity among clinically suspected TBM patients. The multidrug-resistant M. tuberculosis (MDR-TB) constituted 3.14% of the total clinical isolates. With IS6110 PCR, a specificity of 92.86% and sensitivity of 100% are seen with an assay threshold of 30pg/ml. Line probe assay (LPA) using culture isolates had a sensitivity of 97.67% and a specificity of 100%. Direct CSF LPA showed a sensitivity of 96.15% and a specificity of 100%. ConclusionsA combination of techniques that involved culture, cytology, and DNA amplification methods was found to be promising in specific, accurate, and rapid detection of M. tuberculosis in the CSF samples from patients.

Is it possible to differentiate tuberculous and cryptococcal meningitis in HIV-infected patients using only clinical and basic cerebrospinal fluid characteristics?

Tuberculous and cryptococcal meningitis (TBM and CM) are the most common causes of opportunistic meningitis in HIVinfectedpatients from resource-limited settings, and the differential diagnosis is challenging. To compare clinical and basic cerebrospinal fluid (CSF) characteristics between TBM and CM in HIV-infected patients. A retrospective analysis was conducted of clinical, radiological and laboratory records of 108 and 98 HIV-infected patients withculture-proven diagnosis of TBM and CM, respectively. The patients were admitted at a tertiary centre in São Paulo, Brazil. A logisticregression model was used to distinguish TBM from CM and derive a diagnostic index based on the adjusted odds ratio (OR) to differentiatethese two diseases. In multivariate analysis, TBM was independently associated with: CSF with neutrophil predominance (odds ratio (OR) 35.81, 95%confidence interval (CI) 3.80 - 341.30, p=0.002), CSF pleocytosis (OR 9.43, 95% CI 1.30 - 68.70, p=0.027), CSF protein &gt;1.0 g/L (OR 5.13,95% CI 1.38 - 19.04, p=0.032) and Glasgow Coma Scale &lt;15 (OR 3.10, 95% CI 1.03 - 9.34, p=0.044). Nausea and vomiting (OR 0.27, 95% CI0.08 - 0.90, p=0.033) were associated with CM. Algorithm-related area under the receiver operating characteristics curve was 0.815 (95% CI0.758 - 0.873, p&lt;0.0001), but an accurate cut-off was not derived. Although some clinical and basic CSF characteristics appear useful in the differential diagnosis of TBM and CM in HIVinfectedpatients, an accurate algorithm was not identified. Optimised access to rapid, sensitive and specific laboratory tests is essential.

Determination and Validation of a Lower Cut Off Value of Cerebrospinal Fluid Adenosine Deaminase (CSF-ADA) Activity in Diagnosis of Tuberculous Meningitis.

Tuberculous meningitis is an infection of the meninges caused by Mycobacterium tuberculosis. It is one of the most common infectious diseases of the Central Nervous System (CNS) and a major health problem in developing countries like India. If there is delay in diagnosis and initiation of specific treatment, it causes significant morbidity and mortality. CSF-ADA 10 U/l is the standard cut off value that is used for differentiation between Tuberculous (TBM) and Non-Tuberculous Meningitis (non-TBM). To determine and validate a lower cut off value for CSF-ADA for diagnosing TBM in an Indian setting. This was a prospective study involving 85 cases of meningitis whose CSF were analysed and ADA estimated using an enzymatic deamination assay kit. Diagnosis of various types of meningitis was made based on specified diagnostic criteria. The comparison of mean value of CSF- ADA activity of the two types of meningitis was done using two Sample t-test. A p-value of <0.05 was considered as significant. Cut off value to differentiate between TBM and non-TBM meningitis was determined using ROC curve analysis. The CSF-ADA activity of TBM and non-TBM cases was compared. The mean CSF-ADA activity was found to be significantly higher in TBM patients (10.97±4.43; Mean±SD) than in non-TBM patients (5.09±1.53) which was statistically significant with a p-value of <0.001. A cut off value of 6.65 was calculated using ROC curve for the diagnosis of TBM which gave a sensitivity of 85.3% and a specificity of 84.3% for differentiating TBM from non-TBM. The positive predictive value was 78.3% and negative predictive value of 89.5% using the above cut off. The positive likelihood ratio was 5.44 and negative likelihood ratio of 0.17 when this lower cut off value was applied. This study has demonstrated that CSF-ADA can be used as an important diagnostic tool in early diagnosis of TBM using a cut off value of 6.65. This cut off value gave a good sensitivity and specificity in differentiating it from non-TBM.

CD4 count in Tuberculous Meningitis patients with HIV co-infection. - A perfect surrogate marker of disease severity?

Introduction: Tubercular meningitis is frequently associated with HIV infection. There have been no markers identified till today which can indicate severity of Tubercular meningitis. Aim : To test correlation between clinical severity grading and mortality of HIV patients suffering from tubercular meningitis with and to identify surrogate markers of severity of tubercular meningitis. Material and Methods: We carried out retrospective analysis of the data from the clinical records of HIV infected patients with a diagnosis of TBM admitted between June 2010 to Dec 2012. The neurologic status of patients was classified according to the BMRC staging system. Correlation between clinical staging, laboratory parameters was analysed. Results: Of the 44 cases included in the study 35(79%) were male, 11(21%) were female patients. Thirty two patients (72%) of 44 patients were using antiretroviral drugs at the time of admission. CD4 count was found to correlate with the mortality in the study group. But other factors like age or sex of the patient, patients hemoglobin or total leucocyte count, and also CSF protein, sugar or cell count- were not found to correlate with the clinical severity grading or mortality. Conclusion: Only CD4 cell counts correlate with clinical severity grading and mortality of patients with HIV infection suffering from tubercular meningitis.

COMPARATIVE EVALUATION OF ELISA AND DOT-BLOT FOR THE DIAGNOSIS OF TUBERCULOUS MENINGITIS

Tuberculous meningitis is a central nervous system tuberculosis caused by M. tuberculosis. It causes high mortality if delayed in diagnosis and treatment. In this comparative study, Cerebrospinal fluid from TBM and non TBM patients were analyzed by ELISA and Dot-blot for anti-tuberculous antibodies. About 70% of the TBM samples showed positivity by Dot-blot and 72.5% by ELISA. Among the non TBM controls, 2.9% showed positivity by Dot-blot and 4.4% by ELISA. Both methods did not differ significantly as seen by Fisher's exact test (p = 0.50). Thus, Dot-blot could be an easy alternative to ELISA for quick diagnosis of TBM.