Tuberculous Meningitis In Children Research Articles

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.

Navigating complex care pathways-healthcare workers' perspectives on health system barriers for children with tuberculous meningitis in Cape Town, South Africa.

Tuberculous meningitis (TBM) occurs when tuberculosis (TB) bacilli disseminate and seed into the meninges, triggering a severe inflammatory response that often leads to brain infarction. It is the most severe and debilitating form of childhood TB with high mortality, and children who survive TBM often suffer lifelong physical and neuro-disability resulting in emotional, social, and economic burdens for families. In the early stages the symptoms may be non-specific and so the diagnosis is often made late when the patient already has significant brain injury. To facilitate earlier diagnosis, it is important to understand how patients are evaluated. This study aimed to chart health systems for paediatric TBM care at both primary healthcare (PHC) and hospital level in Cape Town, South Africa. We conducted fourteen in-depth interviews and eight days of semi-structured observations of patient flow across eight healthcare facilities. We found that children with TBM navigate multiple levels of care categorised into pre-admission and primary care, hospital admission and inpatient care, and post-discharge follow-up care. Healthcare workers identified the following health system barriers along the TBM care pathway for children: limited post-training and mentorship opportunities to manage TBM, overburdened facilities, time constraints, lack of recognition of TBM symptoms, delays in referral between PHC and hospital, lack of standardized diagnostic algorithms, limited diagnostic tests and a lack of child-friendly, easy-to-administer treatment. Regular and compulsory training on TB and TBM in children, including continuous mentoring and support to healthcare workers working in child health and TB services in high TB-burden settings, can facilitate early recognition of symptoms and rapid referral for diagnosis. Algorithms outlining referral criteria for patients with possible TBM at both PHC facilities and district level hospitals can guide healthcare providers and facilitate timely referral between different levels of healthcare services. An integrated data system and alert functions could flag multiple healthcare visits and improve communication between different healthcare facilities during diagnosis and treatment. Children and families affected by TBM are an especially vulnerable sub-population requiring high priority attention and support.

Relevance and challenges of neuroimaging for childhood tuberculous meningitis diagnosis in a resource-constraint country: A case report and literature review

Objective: Tuberculous meningitis (TBM) may be an undiagnosed cause of childhood mortality or neurologic sequelae. Cranial computed tomography (CT) scan remains a relevant diagnostic and prognostic tool amidst negative cerebrospinal fluid or sputum findings for tuberculous meningitis (TBM) diagnosis. Delays in diagnosis and treatment increase morbidity in resource-constraint countries.&#x0D; Case report: A seven-year-old boy was referred with three weeks history of fever, progressive body weakness, aphasia and unconsciousness (three days). He had right cranial nerve III palsy, generalized hypertonia, and hyperreflexia in right lower limbs. All tuberculosis tests were negative except the cranial CT findings of leptomeningeal enhancement with basilar involvement and evidence of obstructive hydrocephalus. He was managed with anti-tuberculous drugs, prednisolone, ventriculoperitoneal shunt, and physiotherapy, and made a significant recovery after a year of anti-tuberculosis treatment.&#x0D; Conclusion: The cranial CT scan findings facilitate TBM diagnosis for which prompt treatment commencement is crucial for a good outcome.

Development of clinical-based scoring system to diagnose tuberculous meningitis in children

ObjectiveDiagnosing tuberculous meningitis (TBM) in children is challenging due to the low sensitivity with time delay of bacterial culture techniques and the lack of brain imaging facilities in many low-...

Diagnosis and Management of Tuberculous Meningitis in Children- an Update

UPDATE ON THE DIAGNOSIS AND MANAGEMENT OF TUBERCULOUS MENINGITIS IN CHILDREN: Ronald van Toorn, Regan Solomons Seminars in Pediatric Neurology Volume 21, Issue 1, March 2014, Pages 12-18 Tuberculous meningitis (TBM), the most devastating manifestation of tuberculosis, is often missed or overlooked because of nonspecific symptoms and difficulties in diagnosis. It continues to be an important cause of neurologic handicap in resource-poor countries. Owing to the suboptimal performance of diagnostic tests of TBM, diagnosis relies on thorough history, clinical examination, and relevant investigations. The development of affordable, accurate diagnostic tests for TBM in resource-poor settings remains a priority. Short intensified treatment is safe and effective in both human immunodeficiency virus (HIV)-infected and HIV-uninfected children. Treatment of tuberculous hydrocephalus depends on the level of the cerebrospinal fluid obstruction. Corticosteroids reduce risk of neurodisability and death in HIV-uninfected children. Thalidomide should be considered in children compromised by tuberculosis abscesses and tuberculous-related optochiasmic arachnoiditis. In resource-poor countries, home-based TBM treatment after initial in-hospital stabilization is feasible in carefully selected patients. Early diagnosis and treatment of TBM is the single most important factor determining outcome.

Research progress on specific and non-specific immune effects of BCG and the possibility of BCG protection against COVID-19.

Bacille Calmette-Guérin (BCG) is the only approved vaccine for tuberculosis (TB) prevention worldwide. BCG has an excellent protective effect on miliary tuberculosis and tuberculous meningitis in children or infants. Interestingly, a growing number of studies have shown that BCG vaccination can induce nonspecific and specific immunity to fight against other respiratory disease pathogens, including SARS-CoV-2. The continuous emergence of variants of SARS-CoV-2 makes the protective efficiency of COVID-19-specific vaccines an unprecedented challenge. Therefore, it has been hypothesized that BCG-induced trained immunity might protect against COVID-19 infection. This study comprehensively described BCG-induced nonspecific and specific immunity and the mechanism of trained immunity. In addition, this study also reviewed the research on BCG revaccination to prevent TB, the impact of BCG on other non-tuberculous diseases, and the clinical trials of BCG to prevent COVID-19 infection. These data will provide new evidence to confirm the hypotheses mentioned above.

Risk factors of poor developmental outcome in children with tuberculous meningitis.

Neurodevelopmental delay is a significant long-term complication of childhood tuberculous meningitis (TBM). The objective of this study was to assess risk factors for neurodevelopmental delay in children with TBM. We conducted a retrospective cohort study of children diagnosed with TBM at Tygerberg Hospital, Cape Town, South Africa, over a 30-year period between 1985 and 2015. We assessed the relationship between demographic, clinical, laboratory and neuro-imaging characteristics, and cognitive impairment at the conclusion of anti-tuberculous treatment. Poor outcome was defined as moderate-to severe cognitive impairment. A total of 327 TBM patients were included, 71 (21.7%) suffered a poor outcome. Multivariate analysis revealed that decreased level of consciousness (adjusted OR (aOR): 4.68; 95%CI: 2.43-13.88; p = 0.005), brainstem dysfunction (aOR: 3.20; 95%CI: 1.70-6.00; p < 0.001), and radiological infarction (aOR: 3.47; 95%CI: 1.87-6.45; p < 0.001) were associated with a poor developmental outcome. Left hemispherical (single and multiple) stroke and bilateral stroke were associated with poor developmental outcomes. Certain neurological signs as well as radiological infarct characteristics are important predictors of poor developmental outcome. Anticipation of the likely level of cognitive impairment at diagnosis allows more accurate prognostication and prompt institution of supportive and rehabilitative measures, after the acute illness.

Validation of host cerebrospinal fluid protein biomarkers for early diagnosis of tuberculous meningitis in children: a replication and new biosignature discovery study

Purpose: The diagnosis of tuberculous meningitis (TBM) in children is often delayed due to diagnostic difficulties. New tools are urgently needed to improve the diagnosis of the disease in this vulnerable group. The present study aimed to validate the accuracy of recently identified host cerebrospinal (CSF) biomarkers as candidates for the diagnosis of TBM in children. Materials and methods: We collected CSF samples from 87 children aged 3 months to 13 years, that were consecutively admitted at a tertiary hospital in Cape Town, South Africa, on suspicion of having TBM. We evaluated the concentrations of 67 selected host protein biomarkers using a multiplex platform. Results: Previously identified 3-marker (VEGF-A + IFN-γ + MPO) and 4-marker (IFN-γ + MPO + ICAM-1 + IL-8) signatures diagnosed TBM with AUCs of 0.89 (95% CI, 0.81–0.97) and 0.87 (95% CI, 0.79–0.95) respectively; sensitivities of 80.6% (95% CI, 62.5–92.5%) and 81.6% (95% CI, 65.7–92.3%), and specificities of 86.8% (71.9–95.6%) and 83.7% (70.4–92.7%) respectively. Furthermore, a new combination between the analytes (CC4b + CC4 + procalcitonin + CCL1) showed promise, with an AUC of 0.98 (95% CI, 0.94–1.00). Conclusions: We have shown that the accuracies of previously identified candidate CSF biomarkers for childhood TBM was reproducible. Our findings augur well for the future development of a simple bedside test for the rapid diagnosis of TBM in children.

Tuberculous Meningitis in Children: Treatment Outcomes at Discharge and Its Associated Factors in Eastern Ethiopia: A Five Years Retrospective Study.

BackgroundTuberculous meningitis is a serious public health problem, particularly in low-income countries. It is associated with high rates of mortality and morbidity. The outcome of tuberculous meningitis in children is not well documented in Ethiopia, particularly in eastern Ethiopia. This study aimed to determine the treatment outcomes of tuberculous meningitis at discharge and its associated factors in eastern Ethiopia.MethodsAn institutional-based retrospective cross-sectional study was conducted on 121 children who were admitted and treated for tuberculous meningitis between January 2017 and December 2021. Data were collected using a pretested checklist, coded and entered into EpiData version 3.1, and analyzed using Statistical Package for the Social Sciences (SPSS) version 25. Factors associated with treatment outcomes were identified using multivariable logistic regression analyses. The association was described using the adjusted odds ratio (AOR) at a 95% confidence interval (CI). Finally, statistical significance was set at a p-value <0.05.ResultsOf the 121 medical records of children, 33.9% (95% CI:25–42%) died. Among the survivors, 28.1% were discharged with neurological sequelae and the remains (38.0%) were discharged with normal outcomes. In multivariable analyses, nutritional status (AOR=2.87; 95% CI:1.04–7.94), duration of illness (AOR = 0.33; 95% CI: 0.15–0.86), hydrocephalus (AOR=3.78; 95% CI:1.08–13.34), and stage-III Tuberculous Meningitis (AOR = 5.29; 95% CI:1.88–14.84) were identified as significantly associated factors with poor clinical outcomes.ConclusionThe treatment outcomes for tuberculous meningitis in children are unfavorable. Two-thirds of children had poor treatment outcomes. Malnutrition, disease stage, hydrocephalus, and illness duration were associated with poor treatment outcomes at discharge. Health workers in primary health care should be aware of the importance of early screening, diagnosis, and treatment to improve clinical outcomes and reduce associated mortality and disability. In practice, more attention should be paid to children with malnutrition and hydrocephalus.

Comparative Effectiveness of Regimens for Drug-Susceptible Tuberculous Meningitis in Children and Adolescents: A Systematic Review and Aggregate-Level Data Meta-Analysis.

BackgroundBefore August 2021, the only regimen recommended by the World Health Organization (WHO) to treat pediatric drug-susceptible tuberculous meningitis was a 12-month regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide (2HRZE/10HR). The comparative effectiveness of shorter regimens is unknown.MethodsTo inform a WHO guideline update, we undertook a systematic review and meta-analysis to evaluate outcomes from regimens of 6- to less than 12-months’ duration that included, at a minimum, isoniazid, rifampicin, and pyrazinamide. We included studies that applied rigorous diagnostic criteria and reported outcomes for ≥10 children or adolescents. Using generalized linear mixed models, we estimated the random effects pooled proportions of patients with key outcomes.ResultsOf 7 included studies, none compared regimens head-to-head. Three studies (724 patients) used a 6-month intensive regimen, which includes isoniazid and rifampicin at higher doses, pyrazinamide, and ethionamide instead of ethambutol (6HRZEto). Outcomes for this versus the 12-month regimen (282 patients, 3 studies) were, respectively, as follows: death, 5.5% (95% confidence interval [CI], 2.1%–13.4%) vs 23.9% (95% CI, 17.5%–31.7%); treatment success (survival with or without sequelae), 94.6% (95% CI, 73.9%–99.1%) vs 75.4% (95% CI, 68.7%–81.1%); and neurological sequelae among survivors, 66.0% (95% CI, 55.3%–75.3%) vs 36.3% (95% CI, 30.1%–43.0%). Relapse did not occur among 148 patients followed-up for 2 years after completing the 6-month intensive regimen.ConclusionsOur findings are limited by the small number of studies and substantial potential for confounding. Nonetheless, the 6HRZEto regimen was associated with high treatment success and is now recommended by WHO as an alternative to the 12-month regimen.

Performance of Xpert® MTB/RIF and Xpert® Ultra for the diagnosis of tuberculous meningitis in children.

OBJECTIVE: To assess Xpert® MTB/RIF (Xpert) and Xpert® MTB/RIF Ultra (Ultra) performance in diagnosing pediatric tuberculous meningitis (TBM).METHODS: We conducted a study among children with suspected meningoencephalitis in Pune, India. Clinical, radiological, laboratory, and treatment data were analyzed to classify disease as definite, probable, possible or no TBM, using microbiologic or composite reference standards. We tested cerebrospinal fluid (CSF) either using Xpert or Ultra and estimated test performance characteristics.RESULTS: Of 341 participants, 149 (43.7%) were tested using Ultra and 192 (56.3%) with Xpert. Ultra had higher sensitivity (50% vs. 18%), lower specificity (91% vs. 99%), poor positive predictive value (PPV) (13% vs. 75%), and higher negative predictive value (NPV) (99% vs. 93%) than Xpert using the composite reference standard, with similar results by the microbiologic reference standard. Of 10 participants with trace positivity on Ultra, none met clinical TBM definitions.CONCLUSION: This is the first study to report on diagnostic performance of Ultra in pediatric TBM, which showed higher sensitivity and NPV than Xpert. For children presenting with nonspecific clinical features, Ultra is a promising diagnostic test. Further studies are required to define its optimal clinical use, including interpretation of trace positive results.

Tuberculous Meningitis in Children: A Forgotten Public Health Emergency.

Tuberculous meningitis (TBM) remains a major cause of morbidity and mortality in children with tuberculosis (TB), yet there are currently no estimates of the global burden of pediatric TBM. Due to frequent non-specific clinical presentation and limited and inadequate diagnostic tests, children with TBM are often diagnosed late or die undiagnosed. Even when diagnosed and treated, 20% of children with TBM die. Of survivors, the majority have substantial neurological disability with significant negative impact on children and their families. Surveillance data on this devastating form of TB can help to quantify the contribution of TBM to the overall burden, morbidity and mortality of TB in children and the epidemiology of TB more broadly. Pediatric TBM usually occurs shortly after primary infection with Mycobacterium tuberculosis and reflects ongoing TB transmission to children. In this article we explain the public health importance of pediatric TBM, discuss the epidemiology within the context of overall TB control and health system functioning and the limitations of current surveillance strategies. We provide a clear rationale for the benefit of improved surveillance of pediatric TBM using a TB care cascade framework to support monitoring and evaluation of pediatric TB, and TB control more broadly. Considering the public health implications of a diagnosis of TBM in children, we provide recommendations to strengthen pediatric TBM surveillance and outline how improved surveillance can help us identify opportunities for prevention, earlier diagnosis and improved care to minimize the impact of TBM on children globally.

Treatment Outcomes of Childhood Tuberculous Meningitis in a Real-World Retrospective Cohort, Bandung, Indonesia

We retrospectively evaluated clinical features and outcomes in children treated for tuberculous meningitis (TBM) at Hasan Sadikin Hospital, Bandung, Indonesia, during 2011–2020. Among 283 patients, 153 (54.1%) were <5 years of age, and 226 (79.9%) had stage II or III TBM. Predictors of in-hospital death (n = 44 [15.5%]) were stage III TBM, hydrocephalus, male sex, low-income parents, seizures at admission, and lack of bacillus Calmette-Guérin vaccination. Predictors of postdischarge death (n = 18 [6.4%]) were hydrocephalus, tuberculoma, and lack of bacillus Calmette-Guérin vaccination. At treatment completion, 91 (32.1%) patients were documented to have survived, of whom 33 (36.3%) had severe neurologic sequelae and 118 (41.7%) had unknown outcomes. Predictors of severe neurologic sequelae were baseline temperature >38°C, stage III TBM, and baseline motor deficit. Despite treatment, childhood TBM in Indonesia causes substantial neurologic sequelae and death, highlighting the importance of improved early diagnosis, better tuberculosis prevention, and optimized TBM management strategies.

The Sensitivity of Diagnostic Criteria of Marais S, et al. in Confirmed Childhood Tuberculous Meningitis.

BackgroundTo establish the sensitivity of the diagnostic criteria published by Marais and co-workers in 2010 for childhood tuberculous meningitis (TBM), a retrospective study on children with confirmed TBM was conducted.MethodsBetween January 2006 and December 2019, children consecutively diagnosed with TBM were recruited retrospectively at our center. TBM was defined in cases where any of the following criteria were met: the presence of acid-fast bacilli (AFB) in cerebrospinal fluid (CSF) microscopy, CSF nucleic acid amplification test (NAAT, +), or M.tuberculosis cultured from CSF. The demographic and clinical features of all enrolled patients were recorded including clinical characteristics, CSF findings, cerebral imaging features, and other evidence of TB.ResultsA total of 30 children with confirmed diagnosis of TBM over an 14-year period were recruited. The mean age of patients was 7.2 ± 5.1 years and 16 (53.3%) were male. The estimated mean diagnostic score was 12.7 ± 2.4. Twenty-three (76.7%; 95% CI: 59.1–88.2%) patients were classified as “probable TBM” according to the Marais criteria and 7 (23.3%; 95% CI: 11.8–40.9%) as “possible TBM.” Further statistical analysis revealed significant differences in CSF scores between probable and possible TBM groups. Other variables reported at a relatively low frequency, such as symptoms and imaging features, made little contribution to TBM diagnosis according to the Marais criteria.ConclusionChildhood TBM could be effectively identified by the criteria defined by Marais et al. However, further revision is required to ensure that the system is more sensitive and easier to perform in practice.

The Impact of Hyponatremia on the Severity of Childhood Tuberculous Meningitis.

Introduction: Hyponatremia and/or hypoglycorrhachia are commonly encountered biochemical derangements during the acute stage of childhood tuberculous meningitis (TBM). Few studies have explored the correlation between these derangements and the staging of TBM disease (severity), or explored their role as biomarkers for vascular ischemic events, hydrocephalus, or seizures.Methods: We aimed to identify the prevalence and the correlation between serum hyponatremia (mild, moderate and severe) and/or hypoglycorrhachia in relation to clinical TBM features such as stage of disease, seizures and stroke in children diagnosed with definite and probable TBM, between 1985 and 2015, at Tygerberg Hospital, Cape town, South Africa.Results: The prevalence of hyponatremia was 344 out of 481 (71.5%) patients; 169 (49.1%) had mild hyponatremia, 146 (42.4%) moderate hyponatremia and 29 (8.4%) severe hyponatremia. Children with severe hyponatremia had higher frequency of stroke [odds ratio (OR) 4.36, 95% confidence interval (CI) 1.24–15.35; p = 0.01], brainstem dysfunction (OR 7.37, 95% CI 2.92–18.61; p < 0.01), cranial nerve palsies (OR 2.48, 95% CI 1.04–5.91; p = 0.04) and non-communicating hydrocephalus (OR 2.66, 95% CI 1.09–6.44; p = 0.03). Children with moderate hyponatremia and mild hyponatremia compared to those without hyponatremia similarly were more likely to exhibit signs of brainstem dysfunction (OR 1.91, 95% CI 1.11–3.28; p = 0.02) and hydrocephalus (OR 3.18, 95% CI 1.25–8.09; p = 0.01), respectively. On multivariable analysis only brainstem dysfunction was significantly associated with severe hyponatremia [adjusted odds ratio (aOR) 4.46, 95% CI 1.62–12.30; p < 0.01]. Children with hypoglycorrhachia compared to normoglycorrhachia were more likely to have had longer symptom duration prior to admission (OR 1.87, 95% CI 1.09–3.20; p = 0.02), non-communicating hydrocephalus (OR 1.64, 95% CI 0.99–2.71; p = 0.05), higher cerebrospinal white cell counts (OR 3.00, 95% CI 1.47–6.12; p < 0.01) and higher CSF protein concentrations (OR 2.51, 95% CI 1.49–4.20; p < 0.01). On multivariable analysis raised CSF protein concentration >1 g/L was significantly associated with hypoglycorrhachia (aOR 2.52, 95% CI 1.44–4.40; p < 0.01). Death rates did not differ by sodium level category or presence of hypoglycorrachia, however an increasing trend of children that had demised was noted the more severe the sodium category.Conclusion: Hyponatremia and/or hypoglycorrhachia occur in more than two-thirds of children with TBM. Severe TBM disease complications such as brainstem dysfunction was associated with moderate hyponatremia, while severe hyponatremia was associated with brainstem dysfunction, stroke, cranial nerve palsies and non-communicating hydrocephalus. Cerebrospinal fluid (CSF) glucose depletion correlated with non-communicating hydrocephalus and increased CSF inflammation.

The diagnostic challenge of atypical tuberculous meningitis in children from rural area

Tuberculous meningitis (TBM) is a severe form of Mycobacterium tuberculosis infection, while its diagnosis is still a challenge in children. Here, six children with atypical TBM were retrospectively reviewed and the main findings were displayed as follows. The enrolled cases exhibited non-specific symptoms on admission, mainly including fever ( n = 5), headache ( n = 3), vomiting ( n = 5), and drowsiness ( n = 3), but no typical symptoms of TB infection. Two of them exhibited progressive symptoms under routine treatment. Cerebrospinal fluid (CSF) examinations revealed increased white blood cells and proteins, as well as decreased glucose and chloride in all cases. Chest imaging identified the possibly of pulmonary tuberculous in 2 cases. Cranial CT and MRI revealed neuroimaging abnormality in 1 and 3 cases, respectively. In addition, next-generation sequencing directly supported the diagnosis of TBM in case 5. To sum up, TBM should be highly suspected in children with central nervous system infection, when there are no improvements under routine treatment and/or the presence of progressive symptoms. Timely rechecking of CSF combined with cranial imaging is feasible and valuable for the diagnosis of TBM.

Tuberculous Meningitis in Children: Reducing the Burden of Death and Disability.

Tuberculous meningitis disproportionately affects young children. As the most devastating form of tuberculosis, it is associated with unacceptably high rates of mortality and morbidity even if treated. Challenging to diagnose and treat, tuberculous meningitis commonly causes long-term neurodisability in those who do survive. There remains an urgent need for strengthened surveillance, improved rapid diagnostics technology, optimised anti-tuberculosis drug therapy, investigation of new host-directed therapy, and further research on long-term functional and neurodevelopmental outcomes to allow targeted intervention. This review focuses on the neglected field of paediatric tuberculous meningitis and bridges current clinical gaps with research questions to improve outcomes from this crippling disease.

Optimizing Antimicrobial and Host-Directed Therapies to Improve Clinical Outcomes of Childhood Tuberculous Meningitis.

Optimizing Antimicrobial and Host-Directed Therapies to Improve Clinical Outcomes of Childhood Tuberculous Meningitis.

Clinical significance of dysproteinemic changes in tuberculous meningitis in children

One of the achievements of medical science is the possibility of curing tuberculous meningitis, a previously incurable form of the tuberculous process.

Molecular Methods and Culture in Diagnosis of Tuberculous Meningitis in Children

Objectives: This study aimed to detect the incidence of tuberculous meningitis (TM) in pediatric patients using GenoType MTBDRplus, GenoType MTBDRsl, and Mycobacteria Growth Indicator Tube (MGIT). Additionally, it aimed to evaluate the utility of GeneXpert MTB/RIF assay in the detection of Mycobacterium tuberculosis in comparison to MGIT culture. Methods: Children under or equal to 15 years of age who were clinically suspected of tuberculous meningitis (TBM) were included in the study. Cerebrospinal Fluid (CSF) samples were collected and tested for GeneXpert MTB/RIF assay and MGIT culture. Culture-positive samples were further analyzed using Line Probe Assay (LPA) to detect drug-resistant mycobacteria. Results: Out of 272 CSF samples, 28 (10.3%) samples were positive for MTB, and 5 (17.8%) were MDR-TB. GeneXpert MTB/RIF assay detected 23 (8.4%) MTB cases of which 3 (13%) were rifampicin-resistant. MGIT culture detected the presence of MTB organism in 19 (6.9%) cases, of which 6 (31.6%) were isoniazid-resistant and 2 (10.5%) were rifampicin-resistant by first line LPA. None of the samples had Extensively Drug-Resistant TB (XDR-TB). GeneXpert MTB/RIF assay had 73.6% sensitivity and 96.4% specificity taking MGIT as a gold standard. Conclusion: Total positivity for MTB was seen in 10.3% cases, among which 17.8% were MDR-TB; no XDR-TB was detected in pediatric patients. GeneXpert MTB/RIF assay is a rapid and reliable method for diagnosis of tuberculous meningitis but may miss some cases, so samples should also be cultured in MGIT to enhance yield and for extended sensitivity panel. J Microbiol Infect Dis 2021; 11(3):140-146.