Tuberculous Meningitis Research Articles

Comparative evaluation of intensified short course regimen and standard regimen for adults TB meningitis: a protocol for an open label, multi-center, parallel arms, randomized controlled superiority trial (INSHORT trial)

BackgroundDespite several incremental improvements in the management of tuberculous meningitis (TBM), the mortality rates remain high. In spite of national and international guidelines, variation in the choice, dose, and duration of drugs exist between countries and clinicians. We propose to evaluate a shorter and more effective regimen containing agents with augmented intracerebral drug exposure and anti-inflammatory approaches to improve disability-free survival among patients with TBM. Our strategy incorporates the various developments in the field of TBM over the last two decades and only few trials have evaluated a composite of these strategies in the overall outcomes of TBM.MethodsAn open label, parallel arms, randomized controlled superiority trial will be conducted among 372 participants across 6 sites in India. Eligible participants will be randomly allocated in 1:1:1 ratio into one of the three arms. The intervention arm consists of 2 months of high-dose rifampicin (25 mg/kg), moxifloxacin (400 mg), pyrazinamide, isoniazid, aspirin (150 mg), and steroids followed by rifampicin, isoniazid, and pyrazinamide for 4 months. The second intervention arm includes all the drugs as per the first arm except aspirin and the patients in the control arm will receive treatment according to the National TB Elimination Program guidelines. All participants will be followed up for 1 year after the treatment. DiscussionCurrent WHO regimens have agents with poor central nervous system drug exposure and is too long. It does not reflect the accumulating evidence in the field. We propose a comprehensive clinical trial incorporating the emerging evidence accrued over the last two decades to shorten the duration and improve the treatment outcomes. This multi-centric trial may generate crucial evidence with policy and practice implications in the treatment of TBM.Trial registrationClinical Trial Registry India CTRI/2023/05/053314. Registered on 31 May 2023 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=ODYzMzg=&Enc=&userName=CTRI/2023/05/053314). ClinicalTrials.gov NCT05917340. Registered on 6 August 2023 (https://classic.clinicaltrials.gov/ct2/show/NCT05917340).Protocol versionVersion 1.3 dated 12 July 2023.

Dancing Out of Step: A Case of Tuberculous Meningitis Disguised as Childhood Chorea

Dancing Out of Step: A Case of Tuberculous Meningitis Disguised as Childhood Chorea

The spectrum of intracranial arteriopathies and ischemic strokes in pediatric tubercular meningitis- a tri-centric study from eastern India.

The spectrum of intracranial arteriopathies and ischemic strokes in pediatric tubercular meningitis- a tri-centric study from eastern India.

Neuroimaging Changes and Treatment Outcome of Tubercular Meningitis- Experiences 22 Cases in a Tertiary Care Center

Background: Tuberculous meningitis (TBM) is caused by Mycobacterium tuberculosis (M. tuberculosis) and is the most common form of central nervous system (CNS) tuberculosis (TB).The prevalence of TB meningitis remains largely underestimated because clinical manifestations are nonspecific in early stages of the disease. Prompt diagnosis is critical for initiating appropriate therapy, facilitating measures to prevent dissemination of this highly contagious disease and to combat fatal complication in children Aims: To evaluate the role of neuroimaging changes and treatment outcome of tubercular meningitis. Methods: This prospective hospital-based cohort study was conducted in Department of Paediatric Neurology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, during January 2022 to December 2022. Children age belonged to 1 month to 10 year diagnosed as TBM during study period were enrolled in this study. Detailed history, clinical examination, CSF analysis and other relevant investigations were done. Data were recorded in standard questionnaire. Statistical analyses of the results were obtained by using window-based computer software devised with Statistical Packages for Social Sciences (SPSS-22). Results: Total 22 diagnosed case of TBM was enrolled and evaluated. Among them two third (63.63%) children were in 5-10 year age group. Male (59%) were outnumbered than female (36.36 %).Male female ratio was 1.6:1. More than half (59%) of patients came from urban area. All of the patients were vaccinated. Cent percent (100%) patients were presented with fever followed by headache (77.27%), sign of meningeal irritation (54.54%), vomiting (54.54%) and seizures (50%). Most common complication was hemiparesis (45.45%) followed by cranial nerve palsy (40.90%), visual problem (9.09%) and hydrocephalus (4.54%). Abnormal neuroimaging changes were found in 100% cases. Common findings were hydrocephalus (40.90%), tubercloma (36.36%), basilar enhancement (18.18%), Benign enlargement of subdural space & cerebellar hyperintensity (9%) and thalamic infract was present in 4.54% cases. Anti TB and steroid treatment were given in 100% cases and among them18.18% cases were required shunt procedure. More than one-third cases (40.90%) were completely normal without any no sequelae. Among abnormal sequelae found in two third (59%) cases. Speech impairment (36.36%) was most common followed by GDD (18.18%), hemiparesis (13.63%), quadriparesis (9.09%) and epilepsy in 9.09% cases. Conclusion: In our study all children of TBM were presented with fever followed by other predominant clinical features headache, vomiting, seizures and   sign of meningeal irritation.  Abnormal neuroimaging changes were found in all cases. Common findings were  basilar enhancement, hydrocephalus, tubercloma, benign enlargement of subdural space & cerebellar hyper intensity and thalamic infract. After treatment more than one-third cases were completely normal without any no sequelae. J Bangladesh Coll Phys Surg 2024; 42: 214-218

Single-cell transcriptome reveals highly complement activated microglia cells in association with pediatric tuberculous meningitis

BackgroundTuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear.MethodsWe performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis. ResultsWe revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6. DiscussionWe proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb-infected tissues.

An 11-month-old boy with tuberculous meningitis presenting as progressive limb weakness, fever, developmental retardation, and loss of consciousness: a case report

BackgroundTuberculous meningitis (TBM) accounts for about 1% of all tuberculosis cases and about 5% of extrapulmonary tuberculosis cases. However, it poses major importance because approximately half of those affected die or become severely disabled. Herein, the successful treatment of an 11-month-old boy with progressive limb weakness, fever, developmental retardation, and loss of consciousness due to tuberculosis, was reported.Case presentationAn 11-month-old (Iranian Turk) boy was referred to Loghman Hakim hospital for progressive limb weakness and loss of previously attained developmental milestones for the past 2 months. He also had persistent fever and loss of consciousness for about 14 to 21 days. Before being referred to our center, the patient had been diagnosed with hydrocephalus at another center due to possible acute bacterial meningitis based on a CT scan and MRI imaging. On physical examination, anterior fontanel bulging and neck stiffness were observed on the admission. His body temperature and heart rate were 38.1 C and 86 beats per minute (bpm), respectively. He had left 6 cranial nerve palsy and spastic quadriparesis with a power of grade 3/5. Other systemic examinations were normal. Endoscopic third ventriculostomy (ETV) (and leptomeningeal biopsy) revealed diffuse thickening of the floor and lateral walls of the 3rd ventricle and also a cobblestone appearance in the form of multiple white patchy lesions was detected on the floor of the 3rd ventricle. CSF analysis and polymerase chain reaction confirmed the TB meningitis. During hospitalization, a temporary EVD (external ventricular drain) was initially inserted. Eventually, defervescence was denoted 5–6 days after initiation of anti-TB medications, and a permanent ventriculoperitoneal shunt was inserted due to hydrocephalus. Gradually his truncal and limb tone and motor function improved, as did his emotional responses to his parents and ability to eat. The patient can walk without help in the 15th month following the operation and resolved hydrocephalus demonstrated on follow-up imaging.ConclusionOver half of treated TB meningitis patients die or suffer severe neurological sequelae, mainly due to late diagnosis. Hence, early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome.

The application value of cerebrospinal fluid immunoglobulin in tuberculous meningitis.

In clinical practice, physicians can determine the physical conditions of patients based on the levels of cerebrospinal fluids (CSFs) IgG, IgM, and IgA. Higher levels of CSFs IgG, IgM, and IgA suggest more possibility of tuberculous meningitis and worse prognosis and magnetic resonance imaging manifestations.

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis

BackgroundIn regions endemic for tuberculosis and brucellosis, distinguishing between tuberculous meningitis (TBM) and brucella meningitis (BM) poses a substantial challenge. This study investigates the clinical and paraclinical characteristics of patients with TBM and BM.MethodsAdult patients diagnosed with either TBM or BM who were admitted to two referral hospitals between March 2015 and October 2022, were included, and the characteristics of the patients were analyzed.ResultsSeventy patients formed the study group, 28 with TBM and 42 with BM, were included. TBM patients had a 2.06-fold (95% CI: 1.26 to 3.37, P-value: 0.003) higher risk of altered consciousness and a 4.80-fold (95% CI: 1.98 to 11.61, P-value: < 0.001) higher risk of extra-neural involvement as compared to BM patients. Cerebrospinal fluid (CSF) analysis revealed a significantly higher percentage of polymorphonuclear leukocytes (PMN) in TBM compared to BM (Standardized mean difference: 0.69, 95% CI: 0.18 to 1.20, P-value: 0.008). Neuroimaging findings indicated higher risks of hydrocephalus (P-value: 0.002), infarction (P-value: 0.029), and meningeal enhancement (P-value: 0.012) in TBM compared to BM. Moreover, TBM patients had a 67% (95% CI: 21% to 131%, P-value:0.002) longer median length of hospital stay and a significantly higher risk of unfavorable outcomes (Risk ratio: 6.96, 95% CI: 2.65 to 18.26, p < 0.001).ConclusionsOur study emphasizes that TBM patients displayed increased frequencies of altered consciousness, PMN dominance in CSF, extra-neural involvement, hydrocephalus, meningeal enhancement, and brain infarction. The findings emphasize the diagnostic difficulties and underscore the importance of cautious differentiation between these two conditions to guide appropriate treatment strategies.

A comparison of clinical features between neurobrucellosis and tuberculous meningitis

BackgroudThis study aims to compare the clinical manifestations, imaging findings, routine tests, biochemistry indicators and cerebrospinal fluid cytology between neurobrucellosis and tuberculous meningitis. The objective is to evaluate the similarities and differences of these two diseases and improve early diagnosis.MethodsA comprehensive evaluation was conducted by comparing clinical data, imaging results, routine tests findings, biochemistry indicators and cerebrospinal fluid cytology of patients admitted to the Department of Neurology, the Second Hospital of Hebei Medical University from 2019 to 2021. Statistical analysis was applied to identify significant differences and similarities between the two diseases.ResultsPreliminary analysis demonstrated both diseases commonly present with symptoms such as fever, headache. However, there were no statistical differences between neurobrucellosis and tuberculous meningitis in early clinical data, imaging results, routine tests findings, biochemistry indicators. Further analysis indicates there is a statistically significantly difference in the lymphocyte ratio and neutrophil ratio in the cerebrospinal fluid between the two groups.ConclusionsNeurobrucellosis and tuberculous meningitis share similarities in early clinical manifestations, imaging findings and initial cerebrospinal fluid parametes, making early-stage differentiation challenging. The ratio of lymphocytes and neutrophil in the cerebrospinal fluid and a detailed medical history investigation can provide clues for early clinical diagnosis. So the examination of CSF cytology might be a potential to distinguish these two diseases and become a powerful tool in the future.

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.

Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies.

Tuberculous meningitis (TBM) presents a critical neurologic emergency characterized by high mortality and morbidity rates, necessitating immediate therapeutic intervention, often ahead of definitive microbiological and molecular diagnoses. The primary hurdle in effective TBM treatment is the blood-brain barrier (BBB), which significantly restricts the delivery of anti-tuberculous medications to the central nervous system (CNS), leading to subtherapeutic drug levels and poor treatment outcomes. The standard regimen for initial TBM treatment frequently falls short, followed by adverse side effects, vasculitis, and hydrocephalus, driving the condition toward a refractory state. To overcome this obstacle, intrathecal (IT) sustained release of anti-TB medication emerges as a promising approach. This method enables a steady, uninterrupted, and prolonged release of medication directly into the cerebrospinal fluid (CSF), thus preventing systemic side effects by limiting drug exposure to the rest of the body. Our review diligently investigates the existing literature and treatment methodologies, aiming to highlight their shortcomings. As part of our enhanced strategy for sustained IT anti-TB delivery, we particularly seek to explore the utilization of nanoparticle-infused hydrogels containing isoniazid (INH) and rifampicin (RIF), alongside osmotic pump usage, as innovative treatments for TBM. This comprehensive review delineates an optimized framework for the management of TBM, including an integrated approach that combines pharmacokinetic insights, concomitant drug administration strategies, and the latest advancements in IT and intraventricular (IVT) therapy for CNS infections. By proposing a multifaceted treatment strategy, this analysis aims to enhance the clinical outcomes for TBM patients, highlighting the critical role of targeted drug delivery in overcoming the formidable challenges presented by the blood-brain barrier and the complex pathophysiology of TBM.

The diagnostic performance of GeneXpert MTB/RIF in tuberculosis meningitis: A multicentre accuracy study

To evaluate the performance of GeneXpert MTB/RIF (Xpert) for tuberculous meningitis (TBM) and to identify additional indicators to improve diagnostic accuracy. An accuracy study was conducted. During 2011-2019, 243 TBM with 140 non-TBM in three TB-designated facilities in China were enrolled. Microbiological evidence of M tuberculosis (Mtb) in CSF was used as the reference. Additional indicators were identified by Boosted-Classification and Regression Tree (CART), the improvement of diagnostic performance was evaluated by ROC. The diagnostic sensitivity of Xpert was 71.1 % for definite TBM, and 5.5 % for probable/possible TBM. The positive rate of Xpert was improved with cerebrospinal fluid (CSF) increasing volume and was associated with CSF color (yellow). The additional indicators obtained by CART were CSF lactate and glucose and increased the sensitivity to 96.1 % (definite TBM) and 84.6 % (probable/possible TBM). The diagnostic performance of Xpert was satisfactory in definite TBM and would significantly be improved by the additional use of CSF lactate and glucose.

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.

Resource-limited settings like India need a simple, quick, and temperature-independent point-of-care diagnostic test that can diagnose tuberculous meningitis (TBM) at the earliest. A prospective study was carried out at a tertiary care center in North India wherein 50 subjects suspected of TBM were recruited and followed up for six months between January 2019 and December 2020. The aim was to evaluate the performance of loop-mediated isothermal amplification (TB-LAMP) in diagnosing TBM as compared to a composite reference standard (CRS), mycobacteria growth indicator tube 960 (MGIT 960) culture, and GeneXpert®. Out of 50 patients, 32 were TBM cases (64%), and 18 were non-TBM cases (36%). The sensitivity of TB-LAMP and GeneXpert® for TBM diagnosis against CRS was 53% (17/32) for both, and the specificity was 78% (14/18) and 89% (16/18), respectively. On comparing TB-LAMP against GeneXpert® for TBM diagnosis, the two methods had almost perfect agreement (Cohen's kappa=0.83) with statistical significance (p<0.001). The performance of TB-LAMP assay is comparable to GeneXpert® in diagnosing TBM, and it may be used as a substitute for CSF GeneXpert® in resource-limited settings.

TB LAMP assay, a beneficial tool for the diagnosis of Tubercular meningitis in resource-limited settings.

Tubercular meningitis (TBM) is a serious public health problem in developing countries as it leads to significant mortality and residual neurological sequelae. The estimated mortality due to TBM in India is 1.5 per 100,000 population. In resource-limited settings, only the Ziehl-Neelsen (ZN) stain, which has very little sensitivity, is available. The World Health Organization recommended the Loop Mediated Isothermal Amplification (TB LAMP) assay for pulmonary tuberculosis only. We evaluated this test for tubercular meningitis as well. In a cross-sectional study of 2-year duration, we have taken 239 cerebrospinal fluid samples from suspected cases of tubercular meningitis patients. ZN staining along with Mycobacteria Growth Indicator Tube (MGIT) TB culture, Xpert MTB/RIF Ultra assay, and commercial TB LAMP assay were performed for each sample. Out of 239 samples, 40 samples (16.73%) were found TB LAMP assay positive, 48 samples (20.08%) were found Xpert ultra-assay positive, 12 samples (5.02%) were MGIT TB culture positive and acid-fast bacillus smear positive in ten samples (4.18 %). Out of 12 MGIT-positive samples, all samples (100%) were TB LAMP and Xpert ultra positive and one sample (8.33%) was ZN smear positive. In 199 negative samples from the TB LAMP assay, eight samples were positive by Xpert, none by MGIT TB culture and AFB smear. Sensitivity and specificity were found as 100% and 87.66%, respectively, for the TB LAMP assay. TB LAMP assay is a rapid, cost-effective, sensitive, and specific test for tubercular meningitis infection in resource-limited settings.

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

&lt;b&gt;Background:&lt;/b&gt; 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.&lt;br /&gt; &lt;b&gt;Materials &amp;amp; methods:&lt;/b&gt; 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.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; 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&amp;lt;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).&lt;br /&gt; &lt;b&gt;Conclusions:&lt;/b&gt; 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.