Tuberculous Meningitis Research Articles

Comparative Efficacy of Adjuvant Rifampicin, Levofloxacin, and Their Combination in Tuberculous Meningitis With and Without HIV Co-infection: A Systematic Review and Meta-Analysis

Comparative Efficacy of Adjuvant Rifampicin, Levofloxacin, and Their Combination in Tuberculous Meningitis With and Without HIV Co-infection: A Systematic Review and Meta-Analysis

Systematic review of tuberculous meningitis in high-risk populations: mortality and diagnostic disparities.

Aim: Tuberculous meningitis (TBM) is one of the most severe clinical forms of tuberculosis (TB). Since epidemiological studies can contribute to TB control, we conducted a review and meta-analysis of epidemiological publications of adults TBM cases in countries with high incidence of TB.Materials & methods: The search resulted in 11,855 articles, in which 21 ultimately were included in our review and 15 in our meta-analysis.Results: TBM mortality was 25% with death rates of 70% in Africa. The review showed different and non-concordant diagnostic techniques and treatment schemes.Conclusion: Adults living in the African region are at high risk of death from TBM, highlighting an urgent need of guidelines to support diagnosis and treatment, and ultimately, to reduce mortality.

Systemic Inflammation Predict Neurological Functional Outcome in Patients with Tuberculous Meningitis: A Multicenter Retrospective Cohort Study in China.

The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment. Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels. A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14-1.33; P<0.001), and poor outcome (OR=1.34; 95% CI, 1.26-1.45; P<0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42-1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49-2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification. Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.

Extrahepatic Portal Vein Obstruction in Children.

Extrahepatic portal vein obstruction is the most common cause of portal hypertension in children. This study aimed to evaluate the causes, clinical, laboratory and endoscopic findings, treatment approaches, long-term results, and prognosis of extrahepatic portal vein obstruction in children. We retrospectively evaluated 82 patients who were followed up with the diagnosis of extrahepatic portal vein obstruction at Gazi University Pediatric Gastroenterology clinic between January 1, 2011, and October 31, 2021. Among our patients, 58.5% were male, median age at presentation was 36 months (range, 1 month to 6 years), and the follow-up period was 2 years (range, 1-14 years). The most common reasons for admission were gastrointestinal bleeding and splenomegaly. All patients diagnosed with incidentally detected obstruction were children under 5 years of age. The most frequently detected risk factors were history of umbilical vein catheterization (50%) and presence of procoagulant status (31%). Esophageal varices (94.8%), variceal bleeding (73.2%), hypersplenism (64.6%), and growth failure (13.4%) were the most common complications. Weight and/or height z-scores were lower in children with esophageal varices, variceal bleeding, and hypersplenism. Endoscopic treatments were more frequently applied to those with splenomegaly, thrombocytopenia, red color sign, and esophageal variceal bleeding. Rates of splenomegaly, hypersplenism, esophageal variceal bleeding, advanced varicose veins, and portal biliopathy were higher in patients who underwent portosystemic shunt surgery than in patients who did not undergo it. Morbidity and mortality rates of variceal bleeding in extrahepatic portal vein obstruction were lower than bleeding seen in cirrhotic prehepatic portal hypertension. In our study, no patients died from extrahepatic portal vein obstruction-related complications. One patient died from tuberculous meningitis.

Modulating sonic hedgehog (SHH) pathway to create a rapid CNS-TB model: Facilitating drug discovery

Tuberculous meningitis, a severe complication of Mycobacterium tuberculosis (M. tb) infection, involves the dissemination of bacilli in the brain. This study explored the role of the sonic hedgehog (SHH) signaling pathway in regulating blood-brain barrier (BBB) integrity, M. tb invasion into the central nervous system (CNS), and disease progression of Central Nervous System Tuberculosis (CNS-TB) in a Balb/c mouse model. The modulation of the SHH pathway using agonist Purmorphamine (PUR) and antagonist Cyclopamine (CYC) revealed that CYC treatment led to a rapid and extensive invasion of M. tb in the brain, with bacterial loads increasing by 99 % compared to the untreated-infected group. In contrast, PUR reduced M. tb loads by 50 % and delayed disease progression. Histopathological analysis showed that CYC exacerbated inflammation and immune cell infiltration, while PUR mitigated these responses. Immunohistochemistry demonstrated that CYC caused severe BBB breakdown and reactive gliosis, while PUR partially attenuated this response. Further analysis revealed that CYC upregulated Matrix Metalloproteinase-9 (MMP-9) secretion, a key contributor to BBB disruption. These findings highlight the critical role of the SHH pathway in maintaining BBB integrity and regulating the immunopathological response during CNS-TB, opening up future scope for drug discovery. This Cyclopamine-induced model of rapid M. tb invasion and chronic inflammation provides a new tool for studying CNS-TB pathogenesis and evaluating potential therapeutic interventions targeting the SHH signaling axis. Significance statementUnderstanding how tuberculosis (TB) infection can spread to the brain is crucial, as this “central nervous system TB” (CNS-TB) is a serious and potentially life-threatening health complication. However, studying CNS-TB in humans is very difficult. Animal models are needed to better understand how TB gets into the brain and the resulting damage. This study in mice showed that blocking a signaling pathway called Sonic Hedgehog (SHH) allowed TB to rapidly spread to the brain, damaging the blood-brain barrier and causing severe inflammation. In contrast, activating the SHH pathway helped protect the brain from TB invasion. These findings provide important insights that could lead to new ways to prevent or treat this dangerous form of TB.

Navigating the Dual Threat: Cryptococcal and Tubercular Co-infections in PLHIV

Co-infections of Cryptococcosis and tuberculosis (TB) represent a significant clinical challenge, particularly in people living with HIV, due to their compounded impact on an already compromised immune system. Cryptococcus neoformans and Mycobacterium tuberculosis exploit immune dysfunction, often resulting in severe, disseminated infections with overlapping clinical symptoms, which complicates diagnosis and delays appropriate treatment. A 55-year-old HIV-positive male, recently initiated on ART (TLD regimen) was admitted with fever, headache, vomiting, irritability, and altered behavior. Poor adherence to ART and a CD4 count of 210 cells/cumm raised concerns about a CNS opportunistic infection, possibly cryptococcal meningitis and immune reconstitution inflammatory syndrome (IRIS). Examination revealed fever, irritability, neck stiffness, and positive Kernig's signs. Cryptococcal antigen was positive, and imaging suggested both cryptococcal and tubercular meningitis. Bronchoalveolar lavage confirmed tuberculosis. The patient was treated with liposomal amphotericin B, fluconazole, and rifampicin-sparing antitubercular therapy. After showing clinical improvement, he was discharged with dual therapy and stabilized after 3 weeks of hospitalization. Our findings emphasize the importance of comprehensive clinical guidelines and multidisciplinary management to address the complexities of treating this co-infection. Our case review underscores the need for integrated

Deciphering Familiar Conundrum of Cerebral Salt Wasting Syndrome vs Syndrome of Inappropriate Secretion of Antidiuretic Hormone and Establishing Role of Hyponatremia in Patients of Tuberculous Meningitis as a Predictor of Outcome.

Introduction: Hyponatremia is one of the most common electrolyte abnormalities [35-71%] associated with tuberculous meningitis [TBM]. It is an independent predictor of patient outcome. Cerebral salt wasting syndrome [CSWS] and syndrome of inappropriate secretion of antidiuretic hormones [SIADH] are two common causes of hyponatremia in patients with TBM. This study targets patients with tuberculous meningitis to provide a detailed analysis of hyponatremia in TBM patients and it’s predictive value in terms of outcome and also describes the distinguishing features of CSWS and SIADH. Materials and methods: This was a clinical, prospective study of 31 patients with TBM in which various parameters were analysed . Serial sodium levels were recorded on the day of admission, day 2, 7 and 28. Patients with hyponatremia were divided into CSWS and SIADH. Results: In this study, 24[77.42%] patients had hyponatremia. In 14 [58%], hyponatremia was due to CSWS and in 10[42%] of the patients with hyponatremia it was SIADH. Hyponatremia was related to disease severity, GCS score, hospital stay, ventilator stay and patient outcome. CSWS was more strongly associated with disease severity than SIADH. Conclusion: Hyponatremia is a common electrolyte imbalance in patients with TBM and a direct and valid predictor of disease outcome. CSWS should be differentiated from SIADH due to the different treatment strategies.

Paroxysmal Sympathetic Hyperactivity in Childhood Tuberculous Meningitis: A New Association.

We sought to estimate the prevalence and clinical characteristics of paroxysmal sympathetic hyperactivity (PSH) in childhood tuberculous meningitis. Hospital records of children (6 months to 14 years) with tuberculous meningitis were retrospectively analyzed from September 2019 through January 2022. In September 2019, the first case of paroxysmal sympathetic hyperactivity in tuberculous meningitis was identified in our division. Since then, all admitted children with tuberculous meningitis have been screened for paroxysmal sympathetic hyperactivity using the Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM). Paroxysmal sympathetic hyperactivity is suspected when any of the following are present: recurrence of fever after initial defervescence, episodic posturing, dystonia, or unexplained tachycardia. Outcome at 3 months was prospectively scored according to the Pediatric Cerebral Performance Category score. Forty-one hospital records of children with tuberculous meningitis were analyzed, and 6 of them had paroxysmal sympathetic hyperactivity (probable paroxysmal sympathetic hyperactivity, 5/6; possible paroxysmal sympathetic hyperactivity, 1/6). Paroxysmal sympathetic hyperactivity appeared after a mean duration of 17 weeks (range: 12-25 weeks) from the diagnosis of tuberculous meningitis in 4 of 6 children and at 4 weeks in 2 of 6 children. Children with tuberculous meningitis who developed paroxysmal sympathetic hyperactivity were younger (median age: 5 years) compared with the nonparoxysmal sympathetic hyperactivity tuberculous meningitis cohort (median age: 10 years). A high proportion of children who developed paroxysmal sympathetic hyperactivity had hydrocephalus at presentation (5 of 6 [83.3%] vs 12 of 35 [34.3%], P = .035). Hospital stay was significantly prolonged in children with probable paroxysmal sympathetic hyperactivity (mean: 71.2 ± 26.8 days) compared with tuberculous meningitis without paroxysmal sympathetic hyperactivity (mean: 20.8 ± 11.6 days; P < .0001). Paroxysmal sympathetic hyperactivity is a late complication of tuberculous meningitis observed in 14.6% cases and should be anticipated in children with reappearance of fever or neurologic worsening without any apparent cause.

Brain and spinal arachnoiditis in a patient with neurocysticercosis: Case report

Introduction: Arachnoiditis is a chronic inflammatory process of the arachnoid layer and subarachnoid space, and many possible etiologies can cause it, including infectious diseases. Case report: A patient with brain and spinal arachnoiditis was diagnosed and managed on the basis of clinical suspicion as tuberculous meningitis, but when he finished corticosteroids he presented neurological worsening, and after serum western blot immunoassay of T. solium positive, a possible racemose neurocysticercosis was diagnosed and treated. Conclusion: Doctors should consider the importance of nontuberculous etiologies in countries where both neurocysticercosis and tuberculosis are endemic, especially when exist arachnoiditis with cranial basal involvement.

Cerebrospinal fluid-induced stable and reproducible SERS sensing for various meningitis discrimination assisted with machine learning

Cerebrospinal fluid (CSF)-based pathogen or biochemical testing is the standard approach for clinical diagnosis of various meningitis. However, misdiagnosis and missed diagnosis always occur due to the shortages of unusual clinical manifestations and time-consuming shortcomings, low sensitivity, and poor specificity. Here, for the first time, we propose a simple and reliable CSF-induced SERS platform assisted with machine learning (ML) for the diagnosis and identification of various meningitis. Stable and reproducible SERS spectra are obtained within 30 s by simply mixing the colloidal silver nanoparticles (Ag NPs) with CSF sample, and the relative standard deviation of signal intensity is achieved as low as 2.1%. In contrast to conventional salt agglomeration agent-induced irreversible aggregation for achieving Raman enhancement, a homogeneous and dispersed colloidal solution is observed within 1 h for the mixture of Ag NPs/CSF (containing 110–140 mM chloride), contributing to excellent SERS stability and reproducibility. In addition, the interaction processes and potential enhancement mechanisms of different Ag colloids-based SERS detection induced by CSF sample or conventional NaCl agglomeration agents are studied in detail through in-situ UV–vis absorption spectra, SERS analysis, SEM and optical imaging. Finally, an ML-assisted meningitis classification model is established based on the spectral feature fusion of characteristic peaks and baseline. By using an optimized KNN algorithm, the classification accuracy of autoimmune encephalitis, novel cryptococcal meningitis, viral meningitis, or tuberculous meningitis could be reached 99%, while an accuracy value of 68.74% is achieved for baseline-corrected spectral data. The CSF-induced SERS detection has the potential to provide a new type of liquid biopsy approach in the fields of diagnosis and early detection of various cerebral ailments.

Diagnostic Prediction Model for Tuberculous Meningitis: An Individual Participant Data Meta-Analysis.

No accurate and rapid diagnostic test exists for tuberculous meningitis (TBM), leading to delayed diagnosis. We leveraged data from multiple studies to improve the predictive performance of diagnostic models across different populations, settings, and subgroups to develop a new predictive tool for TBM diagnosis. We conducted a systematic review to analyze eligible datasets with individual-level participant data (IPD). We imputed missing data and explored three approaches: stepwise logistic regression, classification and regression tree (CART), and random forest regression. We evaluated performance using calibration plots and C-statistics via internal-external cross-validation. We included 3,761 individual participants from 14 studies and nine countries. A total of 1,240 (33%) participants had "definite" (30%) or "probable" (3%) TBM by case definition. Important predictive variables included cerebrospinal fluid (CSF) glucose, blood glucose, CSF white cell count, CSF differential, cryptococcal antigen, HIV status, and fever presence. Internal validation showed that performance varied considerably between IPD datasets with C-statistic values between 0.60 and 0.89. In external validation, CART performed the worst (C = 0.82), and logistic regression and random forest had the same accuracy (C = 0.91). We developed a mobile app for TBM clinical prediction that accounted for heterogeneity and improved diagnostic performance (https://tbmcalc.github.io/tbmcalc). Further external validation is needed.

Kinetic Determination of Cerebrospinal Fluid Adenosine Deaminase Activity for the Diagnosis of Tuberculous Meningitis.

Tuberculous meningitis (TBM) is a common infectious disease of the central nervous system. Detection of cerebrospinal fluid (CSF) adenosine deaminase (ADA) activity for the diagnosis of TBM has a relatively high accuracy. Most previous reports determined ADA levels by following the colorimetric method of Giusti (endpoint assay). Recently, a Diazyme ADA assay kit was developed to determine CSF ADA levels. This study aimed to define the cutoff value of CSF ADA that is diagnostic for TBM with the Diazyme ADA assay kit. Adults with meningitis were included in the study. The diagnostic properties of CSF ADA for TBM as determined by the Diazyme ADA assay kit were assessed by the receiver operating characteristic curve, area under the curve, sensitivity, specificity, and likelihood ratios. There were 97 patients enrolled in the study, comprising 15 cases of TBM and 82 cases of non-TBM meningitis. The median CSF ADA activity level in the TBM group was significantly higher than in the non-TBM group (P = 0.002), with a mean difference of 14.5 U/L (95% CI: 5.3-23.8 U/L). A CSF ADA level of 6.1 U/L was the best cutoff value to differentiate between the TBM and non-TBM groups, with a sensitivity of 53.33%, a specificity of 89.02%, a positive likelihood ratio of 4.86, a negative likelihood ratio of 0.52, and an area under the curve of 0.75. A CSF ADA level of 6.1 U/L determined by the Diazyme ADA assay kit could be used as a diagnostic tool in the early diagnosis of TBM.

Role of cerebrospinal fluid adenosine deaminase measurement in the diagnosis of tuberculous meningitis: an updated systematic review and meta-analysis.

Tuberculous meningitis (TBM) can be difficult to diagnose. Elevated cerebrospinal fluid (CSF) adenosine deaminase (ADA) is often seen in TBM, but its reliability has been questioned. A previous meta-analysis in 2017 had demonstrated the diagnostic utility of CSF ADA in TBM versus non-TBM. We sought to update this meta-analysis with more recent studies, to determine whether CSF ADA could be used to aid in the early recognition of TBM. Electronic searches were performed in PubMed and Scopus on studies published from 2016 to 2022. Ten additional studies were identified and added to 20 studies (from 2000 to 2016) from a previous meta-analysis. Meta-analysis was conducted using the random effects method, estimating the pooled diagnostic odds ratio (DOR) for elevated CSF ADA in the diagnosis of TBM. Of the 30 studies included, 16/30 (53.3%) used the Giusti method for measuring ADA. Fourteen (46.7%) studies used an ADA cut-off of 10 IU/L, and 11 (36.7%) studies used an even lower cut-off. The pooled DOR for elevated CSF ADA in the diagnosis of TBM was 45.40 (95% confidence interval [CI] 31.96-64.47, I2 = 44%). When only studies using the Giusti method were considered, DOR was 44.21 (95% CI 28.37-68.91, I2 = 40%). Among the studies that used a cut-off of 10 IU/L, DOR was 58.09 (95% CI 33.76-99.94, I2 = 41%). Studies remain heterogeneous but demonstrate that CSF ADA can differentiate TBM from non-TBM. In line with most studies, CSF ADA >10 IU/L supports the diagnosis of TBM in a patient with compatible symptoms and high-risk epidemiology.

Design of RNA Polymerase Inhibitors as Therapeutics for Tuberculous Meningitis.

Tuberculosis is an infectious disease caused by Mycobacterium tuber-culosis. The current treatment protocols for pulmonary tuberculosis are quite effective, even though the treatment requires 3-6 months. The current treatment protocols for extrapulmonary tuberculosis are based on the same drugs that are used for pulmonary tuberculosis. However, the success rates are much lower for certain types of extrapulmonary tuberculosis, such as tubercu-lous meningitis. Tuberculous meningitis is one of the very few diseases attributable to bacteria that have a very high short-term mortality rate among diagnosed patients, even after treatment with antibiotics that are effective for pulmonary tuberculosis. For example, rifampicin is highly effective for the treatment of pulmonary tuberculosis, but its effectiveness for the treatment of tuberculous meningitis is much lower. The reason for the lower effectiveness of rifampicin against tuberculous meningitis is that it has low Blood-Brain Barrier (BBB) permeability, which results in lower concentrations of the drug at the required sites in the central nervous system. In this work, ligands having increased BBB permeability and pharmacokinetic and pharmacodynamic properties, either similar to or better than that of rifampicin, have been de-signed. The BBB permeability of the designed molecules was assessed by using pkCSM, a ma-chine-learning model. Pharmacokinetic properties, drug-likeness, and synthesizability were as-sessed by using SWISS-MODEL. The binding affinity of the designed drugs was assessed by using AutoDock Vina. A customized scoring function, StWN score, was used for a quantitative weighted assessment of all the properties of interest to rank the designed molecules. In this study, drug-like ligands have been designed that have been predicted to have high BBB permeability as well as high affinity for RNA polymerase  ofMycobacterium tuberculosis. The best ligands generated by the tools employed were selected as potential drugs to address the current need for better options for the treatment of tuberculous meningitis.

Clinical profiles and related factors in tuberculosis patients with positive sputum smear mycobacterium tuberculosis tests

The aim of this study was to explore the related factors linked to the development and infectivity of tuberculosis. This was achieved by comparing the clinical characteristics of patients with pulmonary tuberculosis (TB) who tested positive in smear Mycobacterium tuberculosis tests with this who tested negative in smear mycobacterium tests but positive in sputum Gene Xpert tests. We gathered clinical data of 1612 recently hospitalized patients diagnosed with pulmonary tuberculosis who tested positive either in sputum Gene-Xpert test or sputum smear Mycobacterium tuberculosis tests. The data was collected from January 1, 2018 to August 5, 2023, at Sichuan Provincial People's Hospital. We conducted separately analyzes and comparisons of the clinical characteristics between the two groups of patients, aiming to discussed the related factors influencing the development and infectivity of tuberculosis. In comparison to the GeneXpert positive group, the sputum smear positive group exhibited a higher proportion of elderly patients (aged 75–89) and individuals classified as underweight (BMI < 18.5 kg/m2). Furthermore, this group was more prone to experiencing symptoms such as weight loss, coughing and sputum production, hemoptysis, shortness of breath, and difficulty breathing. Moreover, they are also more likely to develop extrapulmonary tuberculosis, such as tuberculous meningitis, tuberculous pleurisy, and tuberculous peritonitis. These clinical features, when present, not only increase the likelihood of a positive result in sputum smear tests but also suggest a high infectivity of pulmonary tuberculosis. Elderly individuals (aged 75 to 89) who are underweight (BMI < 18.5 kg/m2), display symptom of cough, expectoration, hemoptysis and dyspnea-particularly cough and expectoration-and those with extra pulmonary tuberculosis serve as indicators of highly infectious pulmonary tuberculosis patients. These patients may present with more severe condition, carrying a higher bacteria, and being more prone to bacterial elimination. Identification of these patients is crucial, and prompt actions such as timely and rapid isolation measures, cutting off transmission routes, and early empirical treatment of tuberculosis are essential to control the development of the disease.

Utility of Cerebrospinal Fluid Unstimulated Interferon-Gamma (IRISA-TB) as a Same-Day Test for Tuberculous Meningitis in a Tuberculosis-Endemic, Resource-Poor Setting.

Tuberculous meningitis (TBM) mortality is high and current diagnostics perform suboptimally. We evaluated the diagnostic performance of a DNA-based assay (GeneXpert Ultra) against a new same-day immunodiagnostic assay that detects unstimulated interferon-gamma (IRISA-TB). In a stage 1 evaluation, IRISA-TB was evaluated in biobanked samples from Zambia (n = 82; tuberculosis [TB] and non-TBM), and specificity in a South African biobank (n = 291; non-TBM only). Given encouraging results, a stage 2 evaluation was performed in suspected TBM patients from Zimbabwe and Malawi (n = 668). Patients were classified as having definite, probable or possible TBM, or non-TBM based on their microbiological results, cerebrospinal fluid (CSF) chemistry, and whether they received treatment. In the stage 1 evaluation, sensitivity and specificity of IRISA-TB were 75% and 87% in the Zambian samples, and specificity was 100% in the South African samples. In the stage 2 validation, IRISA-TB sensitivity (95% confidence interval [CI]) was significantly higher than Xpert Ultra (76.2% [55.0%-89.4%] vs 25% [8.9%-53.3%]; P = .0048) when trace readouts were considered negative. Specificity (95% CI) was similar for both assays (91.4% [88.8%-93.4%] vs 86.9% [83.4%-89.8%]). When the Xpert Ultra polymerase chain reaction product was verified by sequencing, the positive predictive value of trace readouts in CSF was 27.8%. Sensitivity of IRISA-TB was higher in human immunodeficiency virus (HIV)-infected versus uninfected participants (85.8% vs 66.7%). As a same-day rule-in test, IRISA-TB had significantly better sensitivity than Xpert Ultra in a TB/HIV-endemic setting. An immunodiagnostic approach to TBM is promising, and further studies are warranted.

A comprehensive investigation into the ranges of laboratory tests present in cerebrospinal fluid across various types of meningitis within different age categories

Background. Diagnosing meningitis requires a lumbar puncture to analyze cerebrospinal fluid (CSF) and determine the causative pathogen. Key diagnostic measures include Glucose and Protein concentrations, cell count, differential leukocyte count, Gram stain, culture, and PCR if necessary. Objective. Our analysis assessed patterns in key biomarkers—neutrophils, lymphocytes, cerebrospinal fluid white blood cell count, and CSF/blood Glucose and Protein ratios—across various types of meningitis, including meningococcemia, meningococcal, tuberculous, pneumococcal, aseptic, and other bacterial meningitis. We examined these biomarkers within distinct age categories: children (0-12 years), adults (13-64 years), and the elderly (≥ 65 years). Methods. Descriptive statistics were used to analyze various types of meningitis across different age groups. We assessed the normality of laboratory biomarkers using the Shapiro-Wilk test, and applied Welch ANOVA to explore potential differences in biomarker levels among various types of meningitis. A Games-Howell post hoc test was used to identify specific pairs of meningitis types with statistically significant differences in biomarker levels. Results. The analysis of variance of cerebrospinal fluid biomarkers revealed significant differences in CSF WCC (cells/mm3), Neutrophils (%), Lymphocytes (%), CSF/blood Glucose and Protein ratios in children and adults (p &lt;0.05). However, differences were observed solely in neutrophil levels among elderly subjects. In bacterial meningitis, neutrophil levels increased across all ages, with adults showing higher levels. For meningococcal meningitis, adults had a median neutrophil level of 78.5% [60%, 90%] compared to 57% [24.5%, 85.25%] in children. The CSF white cell count (WCC) median was also higher in adults (339 cells/mm³) compared to children (224 cells/mm³). Viral meningitis cases exhibited higher lymphocyte levels across all age groups, with medians of 69% [34%, 87%] in children, 82% [61%, 93%] in adults, and 77% [55%, 90%] in the elderly. The glucose ratio was lower in bacterial meningitis (&lt;0.3) and higher in viral cases (&gt;0.5). Protein ratios were elevated in bacterial meningitis, indicating increased blood-brain barrier permeability. These results demonstrate a distinct biological profile for different causative agents, modulated by patient age.

A Rare Case of Pyogenic and Tuberculous Co-Infection

CNS co-infections by pyogenic and tuberculosis are uncommon infectious processes, with few cases reported to date. These superadded bacterial infections during CNS tuberculosis present usually atypical clinical manifestations. Bacterial meningitis is a rare but severe complication of patients with spondylodiscitis. CNS tuberculosis has a broad spectrum of disease patterns and a high risk of complications and mortality. Although bacterial infection of the central nervous system (CNS) is a lifethreatening neurological emergency only few papers reported. Here We report a case of 48 year old diabetic male who was diagnosed with Neurotuberculosis with bacterial meningitis and cervical spondylodiscitis and treated with both Antibiotics and Anti-Tuberculous drugs and patient improved symptomatically. Keywords: Bacterial meningitis, TB Meningitis, Cervical Spondylodiscitis, Anti-Tuberculous drugs.

The Impact of GeneXpert Cerebrospinal Fluid Testing on Tuberculous Meningitis Diagnosis in Routine Care in Botswana

Abstract Background Tuberculous meningitis (TBM) disproportionately impacts high–HIV prevalence, resource-limited settings where diagnosis is challenging. The GeneXpert platform has utility in TBM diagnosis, but uptake remains limited. In Botswana, before the introduction of GeneXpert, tuberculosis (TB) testing was only available through mycobacterial culture at the National TB Reference Laboratory. Data describing routine use of Xpert MTB/RIF for cerebrospinal fluid (CSF) testing in resource-limited settings are scarce. Methods Electronic records for patients with CSF tested in government facilities in Botswana between 2016 and 2022 were obtained from a central online repository as part of ongoing national meningitis surveillance. Samples were excluded from 1 site where Xpert MTB/RIF is performed universally. The proportion receiving TB-specific investigation on CSF and the number positive for Mycobacterium tuberculosis following increased Xpert MTB/RIF capacity were determined. Results The proportion of CSF samples receiving TB-specific investigation increased from 4.5% (58/1288) in 2016 to 29.0% (201/693) in 2022, primarily due to increased analysis with Xpert MTB/RIF from 0.9% (11/1288) to 23.2% (161/693). There was an overall decline in the annual number of CSF samples analyzed, but the proportion with microbiologically confirmed TBM increased from 0.4% to 1.2%. The proportion of samples tested for TB that were collected from health care facilities &amp;gt;100 km from the National TB Reference Laboratory increased with Xpert MTB/RIF rollout from 65.9% (87/132) to 78.0% (494/633). Conclusions In Botswana, access to TB culture is challenging in remote populations; more accessible near-patient testing using Xpert MTB/RIF increased the number of patients receiving TB-specific testing on CSF and the number of confirmed TBM cases.

Comparative analysis of pediatric pulmonary and extrapulmonary tuberculosis: A single-center retrospective cohort study in Syria

BackgroundTuberculosis (TB) is a global public health challenge, contributing significantly to morbidity and mortality worldwide. This research aims to investigate the epidemiology, clinical characteristics, diagnostic methods, and early mortality rate among pediatric patients with pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) who were admitted to a hospital in Syria. MethodsThis retrospective cohort study was conducted at the University Children's Hospital in Syria, involving pediatric patients diagnosed with TB between January 2013 and January 2023. Data were collected from medical records and encompassed socio-demographic characteristics, diagnostic methods, clinical presentation, chest radiography findings, and patient outcomes. Statistical analysis was performed using SPSS version 25. ResultsA total of 129 patients were included in the study, with 26.4 % diagnosed with PTB and 73.6 % with EPTB. The most common types of EPTB were lymphatic (25.6 %) and gastrointestinal (17.1 %). Patients with PTB and EPTB did not differ significantly in terms of age, weight, or gender. Significant cough was more common in PTB cases (67.6 %), while lymphadenopathy was more prevalent in EPTB cases (48.4 %). Chest X-ray abnormalities were found in 58.1 % of patients, with PTB patients more likely to have abnormal findings (97.1 %). Microbiological confirmation was higher in PTB cases (76.5 %) compared to EPTB cases (25.3 %). The overall mortality rate was 14 %, with higher mortality observed in patients with EPTB (16.8 %), particularly in cases of TB meningitis. ConclusionOur study highlights the epidemiological challenges of TB among hospitalized children, with a focus on the complexities of diagnosing and managing EPTB. We emphasize the urgent need for enhanced diagnostic and management strategies, particularly in conflict zones like Syria, where TB control efforts face significant obstacles. Prompt solutions are imperative to improve outcomes, given the high occurrence of EPTB and its associated mortality rates. Clinical recommendations stress the need for comprehensive contact histories and awareness of varied clinical presentations in pediatric TB diagnosis.