Tuberculous Meningitis Research Articles

Migration of the anal distal end due to ventriculoperitoneal shunt placement: an atypical case report of a 9-month-old infant with tuberculous meningitis and review of the literature.

Ventriculoperitoneal shunt (VPS) represents one of the most classic and widely used treatments for hydrocephalus in pediatric patients. Migration and externalization of the distal end of the catheter through the rectum are extremely rare complications of intestinal perforation with devastating consequences such as meningitis or peritonitis due to enteric bacteria that are significantly life-threatening. Besides, one of the biggest topics with that is that it can happen without producing symptoms, like the patient we present in this case report, which further masks the condition and puts the patient's life more at risk. We present a case of a 9-month-old infant patient, with a history of prematurity, tuberculous meningitis (TBM), and hydrocephalus, who came to ED with a functional VPS and the distal end of the catheter protruding outside the rectum for 7days, without presenting neurological or intestinal symptoms accompanying. One of the parameters that guided the diagnosis and made us suspicious of asymptomatic intestinal perforation (IP) was the background of TMB. The patient was immediately transferred to the OR where both ends of the shunt were removed: in the first instance, the shunt tube was disconnected through the abdomen, thus withdrawing through the anus, and subsequently, the proximal end of the catheter was exteriorized. In turn, the intestinal fistula was successfully repaired laparoscopically, and prophylactic antibiotic treatment was early administered. On the 6th postop day, a shunt was internalized, and a child was discharged on postop day 15 without complications with alarm guidelines. The authors of this article strongly suggest that (1) anal extrusion of catheters is an uncommon complication but real: for this reason, its development should be considered in all patients with VPS, especially in infants. (2) The patients are often asymptomatic since false tracts can form around the catheter protecting it from spillage, and thus can be removed without complications. (3) Special care should be taken in patients with conditions that increase the risk of developing IP, such as TMB.

Infectious Diseases: What You May Have Missed in 2023.

In 2023, published research on COVID-19 remains prominent. The aim of this article is to highlight important developments in infectious disease evidence unrelated to COVID-19 that were published in 2023. The literature was screened for sound new evidence relevant to internal medicine specialists and subspecialists whose focus of practice is not infectious diseases. The highlighted publications relate to various organisms and patient populations. One article provides insight into the updated guidelines for the diagnosis and management of infective endocarditis. Several articles address the management of sepsis and bacteremia: comparison of cefepime versus piperacillin-tazobactam, ceftobiprole for the treatment of complicated Staphylococcus aureus bacteremia, and early switch from intravenous to oral antibiotics in patients with gram-negative bacteremia. Another article examines differences in all-cause mortality in patients with Clostridioides difficile infection who receive different treatments. Additional articles provide evidence about the treatment of patients with HIV infection: the utility of preexposure prophylaxis to prevent HIV infection, the efficacy of pitavastatin in reducing cardiovascular disease, and the efficacy of dexamethasone for the treatment of tuberculous meningitis in persons with HIV.

Role of Pulse Methylprednisolone in Children with Vasculitis Due to Tubercular Meningitis (P4-13.004)

Role of Pulse Methylprednisolone in Children with Vasculitis Due to Tubercular Meningitis (P4-13.004)

Atypical Presentation of Tuberculous Meningitis—Challenges in Diagnosis: A Case Report

Atypical Presentation of Tuberculous Meningitis—Challenges in Diagnosis: A Case Report

An umbrella review of the diagnostic value of next-generation sequencing in infectious diseases.

An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs). This umbrella analysis aimed to assess the potential risk of bias in existing SRs and to summarize the published diagnostic values of NGS in different IDs. We searched PubMed, Embase, and the Cochrane Library until September 2023 for SRs assessing the diagnostic validity of NGS for IDs. Two investigators independently determined review eligibility, extracted data, and evaluated reporting quality, risk of bias, methodological quality, and evidence certainty in the included SRs. Eleven SRs were analyzed. Most SRs exhibited a moderate level of reporting quality, while a serious risk of bias was observed in all SRs. The diagnostic performance of NGS in detecting pneumocystis pneumonia and periprosthetic/prosthetic joint infection was notably robust, showing excellent sensitivity (pneumocystis pneumonia: 0.96, 95% CI 0.90-0.99, very low certainty; periprosthetic/prosthetic joint infection: 0.93, 95% CI 0.83-0.97, very low certainty) and specificity (pneumocystis pneumonia: 0.96, 95% CI 0.92-0.98, very low certainty; periprosthetic/prosthetic joint infection: 0.95, 95% CI 0.92-0.97, very low certainty). NGS exhibited high specificity for central nervous system infection, bacterial meningoencephalitis, and tuberculous meningitis. The sensitivity to these infectious diseases was moderate. NGS demonstrated moderate sensitivity and specificity for multiple infections and pulmonary infections. This umbrella analysis indicates that NGS is a promising technique for diagnosing pneumocystis pneumonia and periprosthetic/prosthetic joint infection with excellent sensitivity and specificity. More high-quality original research and SRs are needed to verify the current findings.

Evaluation of Loop-Mediated Isothermal Amplification Assay in Diagnosing Tuberculous Meningitis

Evaluation of Loop-Mediated Isothermal Amplification Assay in Diagnosing Tuberculous Meningitis

Predictions of Bedaquiline Central Nervous System Exposure in Patients with Tuberculosis Meningitis Using Physiologically based Pharmacokinetic Modeling.

The use of bedaquiline as a treatment option for drug-resistant tuberculosis meningitis (TBM) is of interest to address the increased prevalence of resistance to first-line antibiotics. To this end, we describe a whole-body physiologically based pharmacokinetic (PBPK) model for bedaquiline to predict central nervous system (CNS) exposure. A whole-body PBPK model was developed for bedaquiline and its metabolite, M2. The model included compartments for brain and cerebrospinal fluid (CSF). Model predictions were evaluated by comparison to plasma PK time profiles following different dosing regimens and sparse CSF concentrations data from patients. Simulations were then conducted to compare CNS and lung exposures to plasma exposure at clinically relevant dosing schedules. The model appropriately described the observed plasma and CSF bedaquiline and M2 concentrations from patients with pulmonary tuberculosis (TB). The model predicted a high impact of tissue binding on target site drug concentrations in CNS. Predicted unbound exposures within brain interstitial exposures were comparable with unbound vascular plasma and unbound lung exposures. However, unbound brain intracellular exposures were predicted to be 7% of unbound vascular plasma and unbound lung intracellular exposures. The whole-body PBPK model for bedaquiline and M2 predicted unbound concentrations in brain to be significantly lower than the unbound concentrations in the lung at clinically relevant doses. Our findings suggest that bedaquiline may result in relatively inferior efficacy against drug-resistant TBM when compared with efficacy against drug-resistant pulmonary TB.

HIV–A prognostic factor of tuberculous meningitis: A retrospective cohort study among adults in peninsular Malaysia

<b>Background:</b> Tuberculous meningitis is a major public health issue, despite showing low incidence, tuberculous meningitis causes substantial mortality. For better clinical management, identification of prognostic factors is crucial to reduce health risk of Malaysian society. Therefore, the aim of this study was to determine the prognostic factors of adult tuberculous meningitis in peninsular Malaysia.<br /> <b>Materials & methods:</b> Initially, a retrospective cohort study and one-year of follow-up period was carried out. In addition, a total of 217 adult tuberculous meningitis patients treated or had follow-up in four tertiary hospitals in peninsular Malaysia were recruited. Cox proportional hazards regression was employed to perform multivariable analysis.<br /> <b>Results:</b> The overall survival probability of adult tuberculous meningitis was 36.8% with median survival time 244 days. Significant prognostic factors were Glasgow coma scale score (aHR=0.71, 95% CI=0.65, 0.76; p<0.001), HIV status (aHR=1.94, 95% confidence interval [CI]=1.19, 3.15; p=0.008), headache (aHR=0.48, 95% CI=0.31, 0.76; p=0.002) and meningeal enhancement (aHR=0.47, 95% CI=0.30, 0.74; p=0.001), nausea (aHR=2.21, 95% CI=1.33, 3.66; p=0.002), and vomit (aHR=0.58, 95% CI=0.36, 0.93; p=0.023).<br /> <b>Conclusions:</b> Evidently, the survival of among adults with tuberculous meningitis was low. Since HIV positive has a significant influence in mortality; early screening, diagnosis, and prompt treatment in this subgroup of patients play a key role in survival.

Utilization of Truenat chips in defining XDR, pre-XDR and MDR in tuberculous meningitis

Setting and objectiveTo develop and evaluate newer molecular tests that identify drug resistance according to contemporary definitions in Tuberculous meningitis (TBM), the most severe form of EPTB. Design93 cerebrospinal fluid (CSF) specimens [41 culture-positive and 52 culture-negative], were subjected to Truenat MTB Plus assay along with chips for rifampicin, isoniazid, fluoroquinolones and bedaquiline resistance. The performance was compared against phenotypic drug susceptibility testing (pDST), Line probe assay (LPA) and gene sequencing. ResultsAgainst pDST, Truenat chips had a sensitivity and specificity of 100%; 94.47%, 100%; 94.47%, 100%; 97.14% and 100%; 100%, respectively for rifampicin, isoniazid, fluoroquinolones and bedaquiline. Against LPA, all Truenat chips detected resistant isolates with 100% sensitivity; but 2 cases each of false-rifampicin and false-isoniazid resistance and 1 case of false-fluoroquinolone resistance was reported. Truenat drug chips gave indeterminate results in ∼25% cases, which were excluded. All cases reported indeterminate were found to be susceptible by pDST/LPA. ConclusionThe strategic drug resistance chips of Truenat Plus assay can contribute greatly to TB elimination by providing rapid and reliable detection of drug resistance pattern in TBM. Cases reported indeterminate require confirmation by other phenotypic and genotypic methods.

Stereotypy and Parkinsonism in tubercular meningitis: Expanding the spectrum

Abstract Movement disorders associated with tubercular meningitis have been reported, ranging from tremors to chorea. Stereotypy is a rare manifestation following tubercular meningitis. Here we report a rare case of a 29-year-old man who developed stereotypy and parkinsonism following tubercular meningitis. The stereotypy was in the form of rotatory movements of the right upper limb, which were repetitive, purposeless, non-goal directed, present for most of the day, and partially suppressible. In addition, it was associated with severe generalized parkinsonism. This report expands the spectrum of movement disorders seen in tubercular meningitis.

Acute ischemic stroke in tuberculous meningitis.

The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Performance of metagenomic next-generation sequencing in cerebrospinal fluid for diagnosis of tuberculous meningitis.

Purpose. Metagenomic next-generation sequencing (mNGS) has been widely used in the diagnosis of infectious diseases, while its performance in diagnosis of tuberculous meningitis (TBM) is incompletely characterized. The aim of this study was to assess the performance of mNGS in the diagnosis of TBM, and illustrate the sensitivity and specificity of different methods.Methods. We retrospectively recruited TBM patients between January 2021 and March 2023 to evaluate the performance of mNGS on cerebrospinal fluid (CSF) samples, in comparison with conventional microbiological testing, including culturing of Mycobacterium tuberculosis (MTB), acid-fast bacillus (AFB) stain, reverse transcription PCR and Xpert MTB/RIF.Results. Of the 40 enrolled, 34 participants were diagnosed with TBM, including 15(44.12 %) definite and 19(55.88 %) clinical diagnosis based upon clinical manifestations, CSF parameters, brain imaging, pathogen evidence and treatment response. The mNGS method identified sequences of Mycobacterium tuberculosis complex (MTBC) in 11 CSF samples. In patients with definite TBM, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of mNGS were 78.57, 100, 100, 66.67 and 85 %, respectively. Compared to conventional diagnostic methods, the sensitivity of mNGS (78.57 %) was higher than AFB (0 %), culturing (0 %), RT-PCR (60 %) and Xpert MTB/RIF (14.29 %).Conclusions. Our study indicates that mNGS of CSF exhibited an overall improved sensitivity over conventional diagnostic methods for TBM and can be considered a front-line CSF test.

Clinical characteristic, common sites, and geographical distribution of pediatric tuberculosis patients in Southwest China.

The data report of a large sample, dynamic epidemiology, and characteristic analysis of pediatric tuberculosis (TB) in Southwest China is not clear. Herein, we conducted descriptive dynamic epidemiology, characteristic analysis and geographical distribution study of pediatric TB inpatients in Southwest China for more than 20 years. Patients with pediatric TB were recruited from October 2002 to September 2022 in Southwest of China based on etiology or clinical confirmation. Extract hospitalization medical record information for each patient. The geographical distribution chart of cases is used to display the trend of case flow segmented every 5 years. Among 3,024 pediatric TB patients with an average age of 9.11 ± 4.39, 17.49% (529) had pulmonary tuberculosis (PTB), 9.06% (274) had extrapulmonary tuberculosis (EPTB), and 73.45% (2,221) had combined TB. The most common form of EPTB is disseminated TB (28.98%), followed by TB lymphadenitis (20.56%), pleural TB (19.72%), and TB meningitis (19.68%). Children aged 0-4 years had a high risk of TB meningitis and a severe symptoms, while children in the elderly age group had a high risk of pleural TB. In the past 20 years, hospitalized TB pediatric cases mainly came from Sichuan, Tibet, Qinghai, Yunnan and other places. The number of patients from ethnic minorities, especially Tibetans, showed an upward trend on a yearly basis (χ2 = 401.43, P < 0.001). Public health investment and effective management in pediatric TB should be further strengthened.

Urinary metabolic characterization of advanced tuberculous meningitis cases in a South African paediatric population.

Tuberculous meningitis (TBM) is a severe form of tuberculosis with high neuro-morbidity and mortality, especially among the paediatric population (aged ≤12years). Little is known of the associated metabolic changes. This study aimed to identify characteristic metabolic markers that differentiate severe cases of paediatric TBM from controls, through non-invasive urine collection. Urine samples selected for this study were from two paediatric groups. Group 1: controls (n = 44): children without meningitis, no neurological symptoms and from the same geographical region as group 2. Group 2: TBM cases (n = 13): collected from paediatric patients that were admitted to Tygerberg Hospital in South Africa on the suspicion of TBM, mostly severely ill; with a later confirmation of TBM. Untargeted 1H NMR-based metabolomics data of urine were generated, followed by statistical analyses via MetaboAnalyst (v5.0), and the identification of important metabolites. Twenty nine urinary metabolites were identified as characteristic of advanced TBM and categorized in terms of six dysregulated metabolic pathways: 1) upregulated tryptophan catabolism linked to an altered vitamin B metabolism; 2) perturbation of amino acid metabolism; 3) increased energy production-metabolic burst; 4) disrupted gut microbiota metabolism; 5) ketoacidosis; 6) increased nitrogen excretion. We also provide original biological insights into this biosignature of urinary metabolites that can be used to characterize paediatric TBM patients in a South African cohort.

Urinary markers of Mycobacterium tuberculosis and dysbiosis in paediatric tuberculous meningitis cases undergoing treatment

BackgroundThe pathogenesis of tuberculous meningitis (TBM) involves infection by Mycobacterium tuberculosis in the meninges and brain. However, recent studies have shown that the immune response and inflammatory processes triggered by TBM can have significant effects on gut microbiota. Disruptions in the gut microbiome have been linked to various systemic consequences, including altered immunity and metabolic dysregulation. Inflammation caused by TBM, antibiotic treatment, and changes in host immunity can all influence the composition of gut microbes. This complex relationship between TBM and the gut microbiome is of great importance in clinical settings. To gain a deeper understanding of the intricate interactions between TBM and the gut microbiome, we report innovative insights into the development of the disease in response to treatment. Ultimately, this could lead to improved outcomes, management strategies and quality of life for individuals affected by TBM.MethodWe used a targeted liquid chromatography–tandem mass spectrometry (LC-MS/MS) approach to investigate metabolites associated with gut metabolism in paediatric participants by analysing the urine samples collected from a control group (n = 40), and an experimental group (n = 35) with confirmed TBM, which were subdivided into TBM stage 1 (n = 8), stage 2 (n = 11) and stage 3 (n = 16).FindingsOur metabolomics investigation showed that, of the 78 initially selected compounds of microbiome origin, eight unique urinary metabolites were identified: 2-methylbutyrlglycine, 3-hydroxypropionic acid, 3-methylcrotonylglycine, 4-hydroxyhippuric acid, 5-hydroxyindoleacetic acid, 5-hydroxyhexanoic acid, isobutyrylglycine, and phenylacetylglutamine as urinary markers of dysbiosis in TBM.ConclusionThese results – which are supported by previous urinary studies of tuberculosis – highlight the importance of gut metabolism and of identifying corresponding microbial metabolites as novel points for the foundation of improved management of TBM patients.

Targeted sequencing from cerebrospinal fluid for rapid identification of drug-resistant tuberculous meningitis.

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.

Marked IDO2 expression and activity related to autophagy and apoptosis in brain tissue of fatal tuberculous meningitis

In about 1% of tuberculosis (TB) patients, Mycobacterium tuberculosis (M. tuberculosis) can disseminate to the meninges, causing tuberculous meningitis (TBM) with mortality rate up to 60%.Chronic granulomatous inflammation (non-necrotizing and necrotizing) in the brain is the histological hallmark of TBM. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and the generated kynurenine metabolites exert major effector functions relevant to TB granuloma functioning. Here we have assessed immunohistochemically IDO1 expression and activity and its effector function and that of its isoform, IDO2, in post-mortem brain tissue of patients that demised with neurotuberculosis. We also related these findings to brain tissue of fatal/severe COVID-19. In this study, IDO1 and IDO2 were abundantly expressed and active in tuberculoid granulomas and were associated with the presence of M. tuberculosis as well as markers of autophagy and apoptosis. Like in fatal/severe COVID-19, IDO2 was also prominent in specific brain regions, such as the inferior olivary nucleus of medulla oblongata and cerebellum, but not associated with granulomas or with M. tuberculosis. Spatially associated apoptosis was observed in TBM, whereas in fatal COVID-19 autophagy dominated. Together, our findings highlight IDO2 as a potentially relevant effector enzyme in TBM, which may relate to the symptomology of TBM.

Distinctive antibody responses to Mycobacterium tuberculosis in pulmonary and brain infection.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a global health burden. While Mtb is primarily a respiratory pathogen, it can spread to other organs, including the brain and meninges, causing TB meningitis (TBM). However, little is known about the immunological mechanisms that leads to differential disease across organs. Attention has focused on differences in T cell responses in the control of Mtb in the lungs, but emerging data point to a role for antibodies, as both biomarkers of disease control and as antimicrobial molecules. Given an increasing appreciation for compartmentalized antibody responses across the blood brain barrier, here we characterized the antibody profiles across the blood and brain compartments during TBM, and determined whether Mtb-specific humoral immune responses differed between Mtb infection of the lung (pulmonary TB) and TBM. Using a high throughput systems serology approach, we deeply profiled the antibody responses against 10 different Mtb antigens, including lipoarabinomannan (LAM) and purified protein derivative (PPD), in HIV-negative adults with pulmonary TB (n=10) vs TBM (n=60). Antibody studies included analysis of immunoglobulin isotypes (IgG, IgM, IgA) and subclass levels (IgG1-4), the capacity of Mtb-specific antibodies to bind to Fc receptors or C1q, and to activate innate immune effectors functions (complement and NK cells activation, monocyte or neutrophil phagocytosis). Machine learning methods were applied to characterize serum and CSF responses in TBM, identify prognostic factors associated with disease severity, and define the key antibody features that distinguish TBM from pulmonary TB. In individuals with TBM, we identified CSF-specific antibody profiles that marked a unique and compartmentalized humoral response against Mtb, characterized by an enrichment of Mtb-specific antibodies able to robustly activate complement and drive phagocytosis by monocytes and neutrophils, all of which were associated with milder TBM severity at presentation. Moreover, individuals with TBM exhibited Mtb-specific antibodies in the serum with an increased capacity to activate phagocytosis by monocytes, compared to individuals with pulmonary TB, despite having lower IgG titers and Fcγ receptors (FcγR)-binding capacity. Collectively, these data point to functionally divergent humoral responses depending on the site of infection (i.e. lungs vs brain), and demonstrate a highly compartmentalized Mtb-specific antibody response within the CSF during TBM. Moreover, our results suggest that phagocytosis- and complement-mediating antibodies may promote attenuated neuropathology and milder TBM disease.

Role of MicroRNAs as post transcription regulators of matrix metalloproteinases and their association in tuberculous meningitis

Matrix metalloproteinases (MMPs) have a role in driving neuroinflammation in infectious as well as non-infectious diseases; however, recent reports have potentiated the role of microRNAs in regulating MMPs at post-transcriptional levels, leading to dysregulation of crucial MMP functions like tissue remodelling, blood brain barrier integrity, etc. In present study, microRNAs regulating MMPs (MMP2 and MMP3) were selected from database search followed by literature support. Expression of these microRNAs i.e., hsa-miR-495-3p, hsa-miR-132-3p and hsa-miR-21-5p was assessed by RT-PCR and the protein levels of MMPs were assessed by ELISA in the cerebrospinal fluid (CSF) of tuberculous meningitis (TBM) patients, healthy controls (HC) and non-infectious neuroinflammatory disease (NID) patients. The expression of hsa-miR-495-3p and hsa-miR-132-3p showed downregulation in TBM while hsa-miR-21-5p was overexpressed as compared to healthy controls. Moreover, MMP levels were found to be deranged with a significant increase in MMP3 levels in the TBM and NID patients compared to HC group. These observations highlight dysregulated microRNAs (hsa-miR-495-3p, hsa-miR-21-5p and hsa-miR-132-3p) levels might impair the levels of MMPs (MMP2 and MMP3) leading to neuroinflammation in TBM and NID population. These findings can further be applied to target these microRNAs for developing newer treatment modalities for better complication management.

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.