Linezolid manifests a rapid and dramatic therapeutic effect for patients with life-threatening tuberculous meningitis.
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ABSTRACT:
SUBMITTER: Sun F
PROVIDER: S-EPMC4187991 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis (TB) and the most severe form of extrapulmonary TB. It often presents with non-specific symptoms initially and has a high mortality and disability rate. With good central nervous system penetration, linezolid is recommended for treating drug-resistant, severe, or refractory tuberculous meningitis in China. Despite the benefits of linezolid on TBM treatment, the adverse effects of long-term therapy, such as myelosuppression, peripheral neuritis, and optic neuritis, are notable and can be severe and even life-threatening, leading to discontinuation and compromising treatment expectations. Contezolid is a novel oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021, which has a more favorable safety profile than linezolid in terms of myelosuppression and monoamine oxidase inhibition. Here we first report a case of TBM in a patient who was intolerant to antituberculosis treatment with linezolid and achieved good efficacy and safety results after the compassionate use of contezolid. Given the widespread use of linezolid in TB treatment and the potential risks for long-term use, multi-center prospective controlled clinical trials in TB and TBM patients are needed to investigate the appropriate use of contezolid further.
| S-EPMC10621037 | biostudies-literature
Project description: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.
| S-EPMC6440448 | 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:Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with <20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.
| S-EPMC11005362 | biostudies-literature
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