Standardized Methods for Enhanced Quality and Comparability of Tuberculous Meningitis Studies.
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ABSTRACT:
SUBMITTER: Marais BJ
PROVIDER: S-EPMC5399942 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Tuberculous meningitis (TBM), the most severe manifestation of tuberculosis, has poorly understood immunopathology and high mortality and morbidity despite antituberculous therapy. This calls for accelerated clinical and basic science research in this field. As TBM disproportionally affects poorer communities, studies are often performed in resource-limited environments, creating challenges for data collection and harmonisation. Comparison of TBM studies has been hampered by variation in sampling strategies, study design and choice of study endpoints. Based on literature review and expert consensus, this paper provides firstly, practical recommendations to enable thorough diagnostic, pathophysiological and pharmacokinetic studies using clinical samples, and facilitates better data aggregation and comparisons across populations and settings. Secondly, we discuss clinically relevant study endpoints, including neuroimaging, functional outcome, and cause of death, with suggestions of how these could be applied in different designs for future TBM studies.
| S-EPMC7194504 | biostudies-literature
Project description:Whole blood transcriptional profiles in children with or without tuberculous meningitis (TBM) were compared using RNA-Seq and a biomarker signature driven by inflammasome activation and signaling was identified
2019-08-06 | GSE111459 | GEO
Project description:BackgroundTuberculous meningitis (TBM) is a medical emergency, yet there are no standardized treatment guidelines for the medical or neurosurgical management of these patients and little data on neurocritical care. We conducted an international survey to understand current medical and neurosurgical TBM management and resource availability to provide baseline data needed for future multicenter trials addressing unanswered clinical research questions and the establishment of standardized guidelines.MethodsAn online survey of 77 questions covering medical and neurosurgical TBM management aimed at clinicians/nurses treating TBM was distributed as an anonymous link through email invitation, international organizations' membership distribution, and direct links on organizational webpages or social media. The survey remained open for 5 months. Data were summarized with frequencies and percentages.ResultsThe survey had 222 responses from 43 countries representing 6 continents. Most respondents were from tertiary care facilities, with broad access to medical and neurosurgical resources. There was significant heterogeneity in general supportive care, and TBM-specific management demonstrated considerable divergence from current standard-of-care practices. The lack of standardized guidelines was identified as a major challenge in TBM management. General and neurocritical care were largely absent. Resources for bedside supportive care and noninvasive monitoring were broadly accessible.ConclusionsThese findings suggest that current TBM management could be improved by the establishment of internationally accepted treatment guidelines based on available evidence, and that numerous centers have resources available to participate in future multicenter trials, even for basic interventions, that may further improve patient outcomes globally.
| S-EPMC7652100 | biostudies-literature
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.
2011-07-01 | GSE23074 | GEO
Project description:Cerebrospinal fluid transcriptional profiles in children with tuberculous meningitis (TBM) or other infections were compared using RNA-Seq and a biomarker signature driven by NMDA-receptor activation was identified
2019-08-06 | GSE122377 | GEO
Project description:Tuberculous meningitis is one of the fatal forms of extra pulmonary disease associated with high mortality and severe neurological defects in affected individuals. We have carried out transcriptome level analysis using whole human genome microarrays to identify differential expression of genes between tuberculous meningitis and normals. In our gene expression analysis, we found 2,434 genes that were differentially erexpressed with 2 or more than 2 fold changes between tuberculous meningitis compared to normal cases. Most of the genes encoded many of the proteins, which involves metabolism, energy pathways, cell growth and/or maintenance, transport and cell communication and signal transduction. We have performed immunohistochemistry for the validation of some of the novel candidates identified in our microarray studies.!Series_overall_design = Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups. Present study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis and four head injury cases were used as controls. We have used 4X44K arrays from agilent plaform. To validate our microarray results, we have done Immunohistochemistry on 15 TBM cases with control groups.!Series_type = Expression profiling by array
2011-06-30 | E-GEOD-23074 | biostudies-arrayexpress
Project description:Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury. Here we review the steps from primary infection to cerebral disease, factors that contribute to the virulence of the organism and the vulnerability of the host and discuss the immune response and the clinical manifestations arising. Priorities for future research directions are suggested.
| S-EPMC6355360 | biostudies-literature
Project description:BackgroundCognitive impairment is reported as a common complication in adult tuberculous meningitis (TBM), yet few studies have systematically assessed the frequency and nature of impairment. Moreover, the impact of impairment on functioning and medication adherence has not been described.MethodsA cognitive test battery (10 measures assessing 7 cognitive domains) was administered to 34 participants with human immunodeficiency virus (HIV)-associated TBM 6 months after diagnosis. Cognitive performance was compared with that a comparator group of 66 people with HIV without a history of tuberculosis. A secondary comparison was made between participants with TBM and 26 participants with HIV 6 months after diagnosis of tuberculosis outside the central nervous system (CNS). Impact on functioning was evaluated, including through assessment of medication adherence.ResultsOf 34 participants with TBM, 16 (47%) had low performance on cognitive testing. Cognition was impaired across all domains. Global cognitive performance was significantly lower in participants with TBM than in people with HIV (mean T score, 41 vs 48, respectively; P < .001). These participants also had lower global cognition scores than those with non-CNS tuberculosis (mean global T score, 41 vs 46; P = .02). Functional outcomes were not significantly correlated with cognitive performance in the subgroup of participants in whom this was assessed (n = 19).ConclusionsLow cognitive performance following HIV-associated TBM is common. This effect is independent of, and additional to, effects of HIV and non-CNS tuberculosis disease. Further studies are needed to understand longer-term outcomes, clarify the association with treatment adherence, a key predictor of outcome in TBM, and develop context-specific tools to identify individuals with cognitive difficulties in order to improve outcomes in TBM.
| S-EPMC9989126 | biostudies-literature
Project description:BackgroundTuberculous meningitis is a serious form of tuberculosis (TB) that affects the meninges that cover a person's brain and spinal cord. It is associated with high death rates and with disability in people who survive. Corticosteroids have been used as an adjunct to antituberculous drugs to treat people with tuberculous meningitis, but their role has been controversial.ObjectivesTo evaluate the effects of corticosteroids as an adjunct to antituberculous treatment on death and severe disability in people with tuberculous meningitis.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register up to the 18 March 2016; CENTRAL; MEDLINE; EMBASE; LILACS; and Current Controlled Trials. We also contacted researchers and organizations working in the field, and checked reference lists.Selection criteriaRandomized controlled trials that compared corticosteroid plus antituberculous treatment with antituberculous treatment alone in people with clinically diagnosed tuberculous meningitis and included death or disability as outcome measures.Data collection and analysisWe independently assessed search results and methodological quality, and extracted data from the included trials. We analysed the data using risk ratios (RR) with 95% confidence intervals (CIs) and used a fixed-effect model. We performed an intention-to-treat analysis, where we included all participants randomized to treatment in the denominator. This analysis assumes that all participants who were lost to follow-up have good outcomes. We carried out a sensitivity analysis to explore the impact of the missing data.Main resultsNine trials that included 1337 participants (with 469 deaths) met the inclusion criteria.At follow-up from three to 18 months, steroids reduce deaths by almost one quarter (RR 0.75, 95% CI 0.65 to 0.87; nine trials, 1337 participants, high quality evidence). Disabling neurological deficit is not common in survivors, and steroids may have little or no effect on this outcome (RR 0.92, 95% CI 0.71 to 1.20; eight trials, 1314 participants, low quality evidence). There was no difference between groups in the incidence of adverse events, which included gastrointestinal bleeding, invasive bacterial infections, hyperglycaemia, and liver dysfunction.One trial followed up participants for five years. The effect on death was no longer apparent at this time-point (RR 0.93, 95% CI 0.78 to 1.12; one trial, 545 participants, moderate quality evidence); and there was no difference in disabling neurological deficit detected (RR 0.91, 95% CI 0.49 to 1.69; one trial, 545 participants, low quality evidence).One trial included human immunodeficiency virus (HIV)-positive people. The stratified analysis by HIV status in this trial showed no heterogeneity, with point estimates for death (RR 0.90, 95% CI 0.67 to 1.20; one trial, 98 participants) and disability (RR 1.23, 95% CI 0.08 to 19.07; one trial, 98 participants) similar to HIV-negative participants in the same trial.Authors' conclusionsCorticosteroids reduce mortality from tuberculous meningitis, at least in the short term.Corticosteroids may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death, and the CI for the relative effect includes possible harm. However, this small possible harm is unlikely to be quantitatively important when compared to the reduction in mortality.The number of HIV-positive people included in the review is small, so we are not sure if the benefits in terms of reduced mortality are preserved in this group of patients.
| S-EPMC4916936 | biostudies-literature
Project description:BackgroundThe differential diagnosis between tuberculous meningitis (TBM) and bacterial meningitis (BM) remains challenging in clinical practice. This study aimed to establish a diagnostic model that could accurately distinguish TBM from BM.MethodsPatients with TBM or BM were recruited between January 2017 and January 2021 at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The detection for indicators involved in cerebrospinal fluid (CSF) and T-SPOT assay were performed simultaneously. Multivariate logistic regression was used to create a diagnostic model.ResultsA total of 174 patients (76 TBM and 98 BM) and another 105 cases (39 TBM and 66 BM) were enrolled from Qiaokou cohort and Caidian cohort, respectively. Significantly higher level of CSF lymphocyte proportion while significantly lower levels of CSF chlorine, nucleated cell count, and neutrophil proportion were observed in TBM group when comparing with those in BM group. However, receiver operating characteristic (ROC) curve analysis showed that the areas under the ROC curve (AUCs) produced by these indicators were all under 0.8. Meanwhile, tuberculosis-specific antigen/phytohemagglutinin (TBAg/PHA) ratio yielded an AUC of 0.889 (95% CI, 0.840-0.938) in distinguishing TBM from BM, with a sensitivity of 68.42% (95% CI, 57.30%-77.77%) and a specificity of 92.86% (95% CI, 85.98%-96.50%) when a cutoff value of 0.163 was used. Consequently, we successfully established a diagnostic model based on the combination of TBAg/PHA ratio, CSF chlorine, CSF nucleated cell count, and CSF lymphocyte proportion for discrimination between TBM and BM. The established model showed good performance in differentiating TBM from BM (AUC: 0.949; 95% CI, 0.921-0.978), with 81.58% (95% CI, 71.42%-88.70%) sensitivity and 91.84% (95% CI, 84.71%-95.81%) specificity. The performance of the diagnostic model obtained in Qiaokou cohort was further validated in Caidian cohort. The diagnostic model in Caidian cohort produced an AUC of 0.923 (95% CI, 0.867-0.980) with 79.49% (95% CI, 64.47%-89.22%) sensitivity and 90.91% (95% CI, 81.55%-95.77%) specificity.ConclusionsThe diagnostic model established based on the combination of four indicators had excellent utility in the discrimination between TBM and BM.
| S-EPMC8632769 | biostudies-literature