Acute ischemic stroke in tuberculous meningitis.

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

Epidemiology of tuberculosis among children in Beijing, China, 2012-2021.

Data on epidemiology trends of paediatric tuberculosis (TB) are limited in China. So, we investigated the clinical and epidemiological profiles in diagnosed TB disease and TB infection patients at Beijing Children's Hospital. Of 3 193 patients, 51.05% had pulmonary TB (PTB) and 15.16% had extrapulmonary TB (EPTB). The most frequent forms of EPTB were TB meningitis (39.05%), pleural TB (29.75%), and disseminated TB (10.33%). PTB patients were significantly younger and associated with higher hospitalization frequency. Children aged 1-4 years exhibited higher risk of PTB and TB meningitis, and children aged 5-12 years had higher risk of EPTB. The proportion of PTB patients increased slightly from 40.9% in 2012 to 65% in 2019, and then decreased to 17.8% in 2021. The percentage of EPTB cases decreased from 18.3% in 2012 to 15.2% in 2019, but increased to 16.4% in 2021. Among EPTB cases, the largest increase was seen in TB meningitis. In conclusion, female and young children had higher risk of PTB in children. TB meningitis was the most frequent forms of EPTB among children, and young children were at high risk of TB meningitis. The distribution of different types of EPTB differed by age.

Mortality and sequelae of tuberculous meningitis in a high-resource setting: A cohort study, 1990-2017.

INTRODUCTION: Tuberculous meningitis (TBM), the most serious form of tuberculosis, results in high mortality and long-term disability in low-resource countries. We investigated temporal trends in mortality and sequelae in a high-resource low-incidence country. METHODS: We performed a retrospective cohort study of all adult patients with TBM at two third-level teaching hospitals in Barcelona (Spain), between January 1990 and December 2017, assessing temporal trends in mortality and sequelae after 12 months over four consecutive 7-year time windows. Rates observed across the four periods were adjusted for covariates. RESULTS: Of the 135 cases included, all but one started tuberculosis (TB) treatment and 120 (89.6%) received rifampicin, isoniazid, and pyrazinamide, with or without ethambutol. The probability of being alive at month 12 was 81.8%, with no differences among the four periods: in comparison with the 1990-1996 period, the adjusted hazard ratios and 95% confidence intervals (CI) were 2.55 (0.71-9.25), 0.70 (0.13-3.85), and 1.29 (0.28-5.91) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. Sequelae were present in 28.3% at month 12, with no differences across the four periods in the adjusted analysis: in comparison with the 1990-1996 period, the odds ratios and 95% CIs were 0.80 (0.09-7.22); 1.94 (0.21-17.96), and 2.42 (0.25-23.07) for the 1997-2003, 2004-2010, and 2011-2017 periods respectively. CONCLUSION: This study shows that TBM still causes high mortality and disability even in a high-resource low-incidence TB setting and without improvement over time.

Clinical characteristics of tuberculous meningitis in older patients compared with younger and middle-aged patients: a retrospective analysis.

BACKGROUND: Few studies have analyzed the clinical characteristics and adverse factors affecting prognosis in older patients with tuberculous meningitis (TBM). This study aimed to compare the clinical characteristics of TBM in older patients with those in younger and middle-aged patients. METHODS: This single-center retrospective study extracted data on the clinical features, cerebrospinal fluid changes, laboratory results, imaging features, and outcomes of patients with TBM from patient medical records and compared the findings in older patients (aged 60 years and older) with those of younger and middle-aged patients (aged 18-59 years). RESULTS: The study included 197 patients with TBM, comprising 21 older patients aged 60-76 years at onset, and 176 younger and middle-aged patients aged 18-59 years at onset. Fever was common in both older (81%) and younger and middle-aged patients (79%). Compared with younger and middle-aged patients, older patients were more likely to have changes in awareness levels (67% vs. 40%), peripheral nerve dysfunction (57% vs. 29%), changes in cognitive function (48% vs. 20%), and focal seizures (33% vs. 6%), and less likely to have headache (71% vs. 93%), neck stiffness on meningeal stimulation (38% vs. 62%), and vomiting (47% vs. 68%). The Medical Research Council staging on admission of older patients was stage II (52%) and stage III (38%), whereas most younger and middle-aged patients had stage I (33%) and stage II (55%) disease. Neurological function evaluated on the 28th day of hospitalization was more likely to show poor prognosis in older patients than in younger and middle-aged patients (76% vs. 25%). Older patients had significantly higher red blood cell counts and blood glucose levels, and significantly lower serum albumin and sodium levels than those in younger and middle-aged patients. The cerebrospinal fluid protein levels, nucleated cell counts, glucose levels, and chloride levels did not differ significantly by age. CONCLUSION: In patients with TBM, older patients have more severe clinical manifestations, a higher incidence of hydrocephalus and cerebral infarction, and longer hospital stays than younger and middle-aged patients. Older patients thus require special clinical attention.

Post-tuberculosis sequelae in children and adolescents: a systematic review.

In 2020, an estimated total of 155 million people had survived tuberculosis. Among this number, a sizable proportion have considerable post-tuberculosis morbidity, as shown for the adult population. This systematic review aims to identify the spectrum and prevalence of post-tuberculosis sequelae in children and adolescents. Four databases were systematically searched from database inception to Feb 7, 2022, for literature on post-treatment outcomes of tuberculosis acquired during childhood. Of the 4613 identified publications, 71 studies were included in this systematic review. Studies on cohorts with comparably rare (most of which were extrapulmonary) tuberculosis presentations, such as spinal tuberculosis and tuberculous meningitis were over-represented; however, no study assessed long-term sequelae in a cohort with an average childhood tuberculosis spectrum. The descriptive analysis includes long-term outcomes of 3529 paediatric patients 1 month to 36 years after confirmed (47%) or clinical (53%) tuberculosis. In a considerable proportion of children, a broad spectrum of post-tuberculosis sequelae were identified, ranging from radiological residua after pulmonary tuberculosis, to disabling deformities after musculoskeletal and cutaneous tuberculosis, to somatic and psychosocial impairment after tuberculous meningitis. A better understanding and comprehensive assessment of post-tuberculosis sequelae in children are needed to improve tuberculosis care beyond antituberculous treatment.

Microbiological diagnosis and mortality of tuberculosis meningitis: Systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) which is caused by Mycobacterium tuberculosis poses a significant public health global treat. Tuberculosis meningitis (TBM) accounts for approximately 1% of all active TB cases. The diagnosis of Tuberculosis meningitis is notably difficult due to its rapid onset, nonspecific symptoms, and the difficulty of detecting Mycobacterium tuberculosis in cerebrospinal fluid (CSF). In 2019, 78,200 adults died of TB meningitis. This study aimed to assess the microbiological diagnosis TB meningitis using CSF and estimated the risk of death from TBM. METHODS: Relevant electronic databases and gray literature sources were searched for studies that reported presumed TBM patients. The quality of included studies was assessed using the Joanna Briggs Institute Critical Appraisal tools designed for prevalence studies. Data were summarized using Microsoft excel ver 16. The proportion of culture confirmed TBM, prevalence of drug resistance and risk of death were calculated using the random-effect model. Stata version 16.0 was used perform the statistical analysis. Moreover, subgroup analysis was conducted. RESULTS: After systematic searching and quality assessment, 31 studies were included in the final analysis. Ninety percent of the included studies were retrospective studies in design. The overall pooled estimates of CSF culture positive TBM was 29.72% (95% CI; 21.42-38.02). The pooled prevalence of MDR-TB among culture positive TBM cases was 5.19% (95% CI; 3.12-7.25). While, the proportion of INH mono-resistance was 9.37% (95% CI; 7.03-11.71). The pooled estimate of case fatality rate among confirmed TBM cases was 20.42% (95%CI; 14.81-26.03). Based on sub group analysis, the pooled case fatality rate among HIV positive and HIV negative TBM individuals was 53.39% (95%CI; 40.55-66.24) and 21.65% (95%CI;4.27-39.03) respectively. CONCLUSION: Definite diagnosis of TBM still remains global treat. Microbiological confirmation of TBM is not always achievable. Early microbiological confirmation of TBM has great importance to reduce mortality. There was high rate of MDR-TB among confirmed TBM patients. All TB meningitis isolates should be cultured and drug susceptibility tested using standard techniques.

The rare manifestations in tuberculous meningoencephalitis: a review of available literature.

Aim: Tuberculous meningitis is an infectious disease of the central nervous system caused by Mycobacterium tuberculosis (M. tuberculosis). It mainly involves the meninges and brain parenchyma, as well as the spinal cord and meninges; Disability and mortality rates are high. In recent years, due to the increase of drug-resistant tuberculosis patients, population mobility and the prevalence of acquired immune deficiency syndrome, the incidence rate of tuberculosis has increased significantly, and tuberculous meningitis has also increased.Methods: At present, tuberculosis is still a worldwide infectious disease that seriously threatens human health, especially in underdeveloped and developing countries. China is the largest developing country in the world with a large population.Results: The situation of tuberculosis prevention and control is grim. Its disability rate is the highest in tuberculosis infection. In addition to the common non-specific manifestations, tuberculous meningoencephalitis may also have rare manifestations of stroke, hearing loss and visual loss.Conclusion: Understanding and timely improvement of corresponding examinations and targeted treatment will help improve the prognosis of patients.

An unusual presentation of gross cerebral vascular dilatation in a TB/HIV co-infected individual.

Aneurysmal dilatation secondary to HIV vasculitis is well described being more common in patients under 45 years of age with advanced stage HIV infection (CD4 < 200 cells/µl). Tuberculous meningitis is far more common than previously anticipated with centres in Cape Town publishing that more than half of all cases of adult meningitis were secondary to tuberculosis. But aneurysmal dilatation of the cerebral vessels is exceedingly rare complication in this population. We report a 14-year-old male presenting to Robert Mangaliso Sobukwe Hospital in South Africa, with a first seizure and Tuberculous Meningitis. The patient was lost to follow-up with subsequent representation 2 years later with worsening clinical picture and imaging revealing marked anterior circulation aneurysmal dilatation. The patient was newly diagnosed as being HIV positive giving uncertainty of the aetiology of his vascular malformations. Aneurysmal dilatation in HIV associated cerebral vasculitis is rare. It is more frequently encountered in young adults with advanced disease who are severely immunocompromised. Tuberculous involvement in the central nervous system is thought to be due to secondary reactivation of quiescent foci of micro infection. Aneurysmal dilatation in the setting of Tuberculous Meningitis is infrequently reported in medical literature.

Neuromeningeal tuberculosis in HIV-negative patients: a retrospective study in Rabat, Morocco.

Neuro-Meningeal Tuberculosis (NMT) is a severe infection of the central nervous system which causes a public health problem in Morocco and in several countries in the world. In order to describe the epidemiological, clinical, paraclinical and outcome among NMT patients without HIV, we carried out a retrospective study at the neurology department of the Military Hospital of Rabat in Morocco, over a period of 17 years (2000-2017). Forty patients were included with a mean age of 44 years (± 18) and a sex ratio of 1.66. A history evoking the possibility of tuberculous origin was found in 8 patients (20%). Febrile confusion was the most common clinical manifestation and was observed in 22 patients (55%) followed by febrile meningeal syndrome in 12 patients (30%). The main abnormalities noted in brain magnetic resonance imaging (MRI) were: hydrocephalus in 13 cases (32.5%), intra-cranial tuberculomas in 10 patients (25%) and leptomeningitis in 9 cases (22.5%). Cerebrospinal fluid study found clear aspect in 29 patients (75%), direct acid fast bacilli smear examination was positive in 4 patients (10%) and positive culture in 4 patients (10%). The Polymerase chain reaction (PCR) study returned positive in 6 patients (35%) of the 17 patients tested. The outcome was good in 18 patients (45%) while 19 patients suffered from neurological sequelae (47.5%) and 3 cases of death recorded (7.5%). Febrile confusion was the most reported manifestation in our patients. Subacute onset of symptoms was the most predominant feature in our patients as reported in the literature. Our results are consistent with the literature and confirm the severity of this infectious disease, even in HIV-negative patients.

Global Frequency and Clinical Features of Stroke in Patients With Tuberculous Meningitis: A Systematic Review.

Importance: Stroke in tuberculous meningitis (TBM) is associated with significant morbidity and mortality. Objective: To determine the country-specific, regional, and overall prevalence of stroke among patients with TBM, including their clinical manifestations, stroke locations, and outcomes. Evidence Review: This systematic review searched records in MEDLINE by PubMed, Scopus, and EMBASE until July 2020 for relevant articles on the occurrence and characteristics of stroke in TBM. Randomized clinical trials and cohort studies that included a population of patients with TBM were analyzed for clinical manifestations, type of stroke, area of stroke, vascular territory, and outcomes. Studies that did not report the occurrence of stroke, reported as abstract only with no full-texts available, and articles not in English were excluded. The country-specific, regional, and overall frequencies of stroke among patients with TBM were determined; secondary analysis enumerated the summary estimates of the clinical presentations, common locations of stroke, and outcomes. The Murad tool was used to assess methodological quality. Findings: From 852 articles identified, 71 studies involving 2194 patients with stroke in TBM were included. The sample size for each study ranged from 17 to 806 patients. The frequency of stroke in TBM showed an estimate of 0.30 (95% CI, 0.26-0.33). The most common clinical manifestations were fever and headache. The lateral striate, middle cerebral, and medial striate arteries were typically affected. The basal ganglia, cortex and lobar, and internal capsule were the frequently involved areas of the brain. The pooled proportions of mortality and poor outcomes were 0.22 (95% CI, 0.16-0.29) and 0.51 (95% CI, 0.37-0.66), respectively. Conclusions and Relevance: The results of this systematic review suggest that stroke is considerably frequent among patients with TBM. The reported frequencies of stroke in TBM and its clinical features vary across the studies and populations.

The epidemiological profile of meningitis among adults in a South African district hospital.

Introduction: understanding the epidemiological profile of a disease in a particular region allows for proper planning of public health resources for prevention, early diagnosis and treatment. In this present study, we describe the epidemiological profile of viral, fungal, tuberculous and bacterial meningitis among adults at National District Hospital (NDH), Free State province, over three years period (January 2017 to December 2019). Methods: a retrospective, observational study of all adult meningitis cases, managed at the National District Hospital (NDH) Bloemfontein, Free State Province, South Africa between January 2017 and December 2019. Results: of the 236 case files reviewed, majority (93.2%; n=220) of the patients managed for meningitis were black, as well as males (55.5%; n = 131). Higher incidence was found between the ages 20 to 49 (81.7%). Of those who died, the majority (n = 14; 63.6%) were males, in the age group 40-49 (n = 7; 31.8%), had TB meningitis (n = 12; 54.5%), were HIV positive (n = 20; 90.9%), and had cell count <100 cells/mm3 (n = 10; 45.5%). Conclusion: our study suggests that combining information on patient demography, co-morbidities, clinical presentation, and examination findings can substantially contribute to raising clinical suspicion, leading to swift identification, diagnosis, and treatment of patients.

Global morbidity and mortality of central nervous system tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is the second most common cause of death due to a single infectious agent worldwide after COVID-19. Up to 15% of the cases are extrapulmonary, and if it is located in the central nervous system (CNS-TB), it presents high morbidity and mortality. Still, the global epidemiology of CNS-TB remains unknown. AIM: To estimate the global prevalence and incidence of CNS-TB based on the available literature. METHODS: We systematically searched in MEDLINE, Cochrane Central, Scopus, and LILACS databases (April 2020) and included observational studies evaluating the epidemiology of CNS-TB. Two independent researchers selected and assessed the quality of the studies and extracted relevant data. We performed random-effects model meta-analysis of proportions to estimate the pooled prevalence. The protocol of this study was registered in PROSPERO (CRD 42018103946). RESULTS: We included 53 studies from 28 countries, representing 12,621 patients with CNS-TB. The prevalence of CNS-TB was 2 per 100,000 inhabitants. According to the clinical setting, the prevalence of CNS-TB represented the 13.91% of all cases of meningitis and 4.55% of all cases of TB. The mortality was calculated by tuberculous meningitis due to the lack of data of other presentation, and it rose up to 42.12% in hospitalized patients. The burden of countries' TB, Human Development Index (HDI), and the prevalence of HIV were the most important prevalence moderators, especially in patients with TB. No data on incidence were found. CONCLUSION: The prevalence and mortality of CNS-TB remain high, and TB meningitis is the most frequent presentation. The highest prevalence was reported in developing countries, and its main moderators were the countries' HDI and HIV infection. Our study was limited by high heterogeneity, risk of bias, and potential data under registration from developing countries. The integration of CNS-TB early detection and management into national TB programs and population-based studies from developing countries are needed for better global estimation and response.

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.

Clinical characteristics in 26 children with congenital tuberculosis in Central Southern China: a retrospective study.

BACKGROUND: Congenital tuberculosis (CTB) is relatively rare and most patients are described in case reports. AIM: To investigate the clinical characteristics of CTB in 26 children. METHODS: A retrospective analysis of 26 children with CTB from January 2013 to December 2021 in Changsha Central Hospital in Central Southern China was undertaken. RESULTS: The median age at onset was 25 days (17-33) and within 4 weeks of age in approximately 73% of cases. Of 24 mothers (including two mothers of twins), 18 (75.0%) were asymptomatic during pregnancy, and four were diagnosed with tuberculosis prenatally. The numbers of tuberculous meningitis, tuberculous encephalitis and liver TB were 17 (65.4%), five (19.2%) and four (15.4%), respectively. The main symptoms were fever (n = 18, 69.2%) and cough (n = 16, 61.5%). Positive rates of T-SPOT.TB, acid-fast bacilli smear, culture of Mycobacterium tuberculosis and GeneXpert MTB/RIF test were, respectively, 84.2% (16/19), 42.3% (11/26), 43.5% (10/23) and 83.3% (5/6). Radiograph or computed tomography demonstrated typical pulmonary tuberculous lesions in all cases and the head magnetic resonance imaging (MRI) showed marked meningeal enhancement or parenchymal lesions in seven cases (26.9%). One case had drug-resistant TB. During follow-up, nine cases had varying degrees of liver injury, and one had delayed growth and development. Eight died and 18 recovered satisfactorily. CONCLUSION: Maternal TB status during pregnancy, the epidemiological history, T-SPOT.TB and other TB-related aetiological tests and imaging are important for the early diagnosis and treatment of CTB, and are associated with a favourable outcome. ABBREVIATIONS: AFB: acid-fast bacilli; Amk: amikacin; Cs: cycloserine; CT: computed tomography; E: ethambutol; GeneXpert MTB/RIF: GeneXpert Mycobacterium tuberculosis and rifampicin resistance; H: isoniazid; IVF-ET: in-vitro fertilization-embryo transfer; Lzd: linezolid; Mfx: moxifloxacin; MTB: Mycobacterium tuberculosis; mNGS: next generation sequencing; MTB-DNA: Mycobacterium tuberculosis-deoxyribonucleic acid; Pto: protionamide; R: rifampicin; TB: tuberculosis; T-SPOT.TB: spot test of mycobacterium TB infection T-lymphocytes; Z: pyrazinamide.

A study of risk factors for tuberculous meningitis among patients with tuberculosis in China: An analysis of data between 2012 and 2019.

Purpose: The present study aimed to explore the risk factors for tuberculous meningitis (TBM) among patients with tuberculosis (TB). Methods: This retrospective study was conducted on patients with TB who were hospitalized in Beijing Chest Hospital between January 2012 and December 2019. Demographic and clinical data of patients with TB were extracted from electronic medical records using a standardized data collection system. Logistic regression was used to analyze the risk factors associated with TBM. Results: Of the total number of 22,988 cases enrolled, 3.1% were cases of TBM, which included 127 definite and 581 probable TBM, respectively. Multivariate analysis showed that definite TBM was significantly associated with patients aged < 30 years [adjusted odds ratio (aOR) = 3.015, 95% confidence interval (CI): (1.451-6.266)], who were farmers [aOR = 1.490, 95%CI: (1.020-2.177)], with miliary pulmonary TB [aOR = 105.842, 95%CI: (71.704-156.235)], and with malnutrition [aOR = 2.466, 95%CI: (1.110-5.479)]. Additionally, probable TBM was significantly associated with patients aged < 30 years [aOR = 2.174, 95% CI: (1.450-3.261)], aged 30-59 years [aOR = 1.670, 95% CI: (1.222-2.282)], who were farmers [aOR = 1.482, 95%CI: (1.203-1.825)], with miliary pulmonary TB [aOR = 108.696, 95%CI: (87.122-135.613)], and with a digestive system TB [aOR = 2.906, 95%CI: (1.762-4.793)]. Conclusion: An age of < 30 years, being a farmer, and having miliary pulmonary TB were risk factors for TBM among patients with TB. Further screening of patients with TB with aforementioned characteristics could facilitate clinicians to identify patients with TBM at an early stage.

Prevalence of primary immunodeficiency syndromes in tuberculous meningitis: A case-control study.

BACKGROUND: Only a proportion of patients with tuberculosis develop tuberculous meningitis. We hypothesize that inherent abnormalities in the host's innate or adaptive immune system may affect the outcome in tuberculous meningitis. In this study, we evaluated the proportion of underlying primary immunodeficiency in patients with tuberculous meningitis and its impact on the outcome. METHODS: Newly-diagnosed cases with tuberculous meningitis and healthy controls were included. Patients with HIV disease were excluded. Blood specimen were subjected to immunological assessment to detect primary immunodeficiency syndrome/s. We estimated serum levels of IgG, IgA, IgM, IgE and IgD along with complement C3, C4, and C5 assay. Absolute lymphocyte count was obtained from an automated three-part cell counter. Flow cytometry was used to enumerate the following lymphocyte subsets: T Cell (CD3, CD4, CD8), B cell (CD19/CD20), and Natural killer cells (CD16 and CD56). Cases were followed for 6 months. Modified Barthel Index was used as a measure of disability. RESULTS: We included 55 cases with tuberculous meningitis and 30 healthy controls. We notedthat among immune parameters, absolute lymphocyte count and CD4 T-cell count in the tuberculous meningitis group was lower; higher serum IgG levels were noted in the poor outcome group. On multivariate regression analysis, none of the immunological, clinical or radiological features were found to predict a poor outcome. CONCLUSION: Host's immune factors contribute to the pathogenesis of tuberculous meningitis. Absolute lymphocyte count and CD4+ T-cell count were lower in tuberculous meningitis cases. Higher serum IgG levels may be associated with a poor outcome. A study with a larger sample size is needed to confirm our findings.

Epidemiology of concurrent extrapulmonary tuberculosis in inpatients with extrapulmonary tuberculosis lesions in China: a large-scale observational multi-centre investigation.

AIMS: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China. METHODS: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm. RESULTS: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%). CONCLUSIONS: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease.

Tuberculous meningitis during infancy: 26 cases in South Turkey among 20 years.

BACKGROUND: Due to the lack of a standard case definifion and the diffuculty in estabilishing a definitive diagnsos, TB in children needs increasing attention by physicians caring for pediatric patients. Tuberculous meningitis (TBM) is the most serious form of extrapulmonary tuberculosis that is associated with significant morbidity and mortality rate in the pediatric age group, especially in infants. This descriptive study was conducted in an University hospital, at the South of Turkey, from May 1999 to May 2019. METHODS: The hospital records of 26 TBM infant that was diagnosed at our hospital were retrospectively evaluated. The epidemiological findings (age, gender, family history of TB, tuberculin skin test results, status of BCG scaring), stage of TBM at admission and clinical, laboratory and radiological features were collected. RESULTS: Of the 26 infants, 61.5% were male and mean age of the patients was 7,65±2,6 (range, 3-12 months). The history of close contact with an infected adult was encountered in 73.1% (19 infant) of the cases. Only 69.2% of the patients (18 case) had a BCG scar. The prodromal stage (period between the onset of symptoms to hospital admission) ranged from 4 days to 180 days (39±51.3). 2 cases were defined as stage I, 10 cases as stage II and 14 cases as stage III TBM. Only two patients were initially positive for PPD test. While no neurological findings were found in 2 patients (diagnosed as stage I), neurologic findings at the time of admission included increased intracranial pressure; alteration in consciousness (92.3%), seizures (88.4%), vomiting (61.5%) cranial nerve palsy (23%), irritability 19.2%, hemiplegia 15.3% and meningeal signs (7%, only 2 patients). The presence of hepatomegaly 26.9 % and/or splenomegaly 11.5 % and/or extrapulmonary lymphadenopathy 3.8 % in nearly half of the cases suggested that totally 42,2% of cases had disseminated of tuberculosis. On admission, 46.1% of the patients were noted to have hyponatremia. Microbiologic confirmation was established in eleven (42.3%) of the 26 infant. A positive CSF culture for Mtb and/or smear for AFB and/or PCR was obtained in only 5 (19.2%) patients, whereas 3 of the cases had accompaining gastric aspirate examination positivity. Pulmonary consolidation in 14 (53.8%) patients, miliary patern in 10 (41.6%) and pulmonary hilar lymphadenopathy in only 5 (20.8%) patients. 23 (88.4 %) had hydrocephalus, 15 (57.6 %) infarction, 10 (38.4 %) basilar meningitis and 9 (34.6%) tuberculomas. Empiric anti-tuberculosis treatment was instituted in all, at a median of 3 days (range 1-15 days) following admission. 8 (30.7%) died, 3 (11.5%) recovered completely, and 15 (57.6%) recovered with sequelae. 12 case (2 died) of the infants had required ventriculoperitoneal shunting. CONCLUSION: As early diagnosis and specific treatment appears to prevent serious complications and reduce mortality, a high index of suspicion among pediatricians is especially required in an infant with an atypical picture suggestive of tuberculosis infection.

Tuberculosis infantil en Chile: ¿de dónde provienen los casos? / Childhood tuberculosis in Chile: where do the cases come from?

La tuberculosis es la principal causa de muerte por un agente infeccioso a nivel mundial y se estima que un 6% de los casos nuevos corresponde a tuberculosis infantil. La presencia de tuberculosis en niños es una señal de la existencia de transmisión del agente en la comunidad. Esta investigación busca describir las características epidemiológicas de la tuberculosis infantil en Chile entre 2011 y 2020. METODOLOGÍA: estudio descriptivo de los casos de tuberculosis infantil registrados en Chile entre los años 2011 y 2020. RESULTADOS: se registraron 544 casos de tuberculosis en menores de 15 años en el período analizado, con una tasa de incidencia anual entre 1,1 y 2,2 casos por 100.000. Se observa un importante aumento de casos en los últimos tres años, especialmente en el grupo de menores de 5 años. 63,2% corresponden a tuberculosis pulmonar, y de ellos 62,3% fueron confirmados por bacteriología. La mayoría de los casos no presenta comorbilidades que impliquen inmunosupresión y la incidencia de meningitis tuberculosa en menores de 5 años es baja. La proporción de contactos es de 29% y la de extranjeros de 17%, ambas variables en aumento en los últimos años. CONCLUSIÓN: La tuberculosis en niños sigue siendo un problema de salud poco frecuente en Chile. Sin embargo, su aumento en los últimos años debe alertar sobre un incremento de la transmisión comunitaria de la enfermedad, por lo que se debe reforzar la detección oportuna de casos contagiantes, la investigación de contactos y el tratamiento preventivo.

Tuberculosis is the leading cause of death from a single infectious agent worldwide and it is estimated that 6% of new cases are children. Childhood tuberculosis reflects ongoing transmission within communities. This study aims to describe the epidemiological characteristics of childhood tuberculosis in Chile between 2011 and 2020. METHODOLOGY: descriptive study of the cases of tuberculosis under 15 years-old registered in Chile from 2011 to 2020. RESULTS: 544 cases were registered in the period analyzed, with an annual incidence rate between 1.1 and 2.2 cases per 100,000. A significant increase in cases is observed in the last three years, especially in the group under 5 years-old. 63.2% correspond to pulmonary tuberculosis, and among them 62.3% are confirmed by bacteriology. Most of the cases do not have comorbidities and the incidence of tuberculous meningitis in children under 5 years is low. Contacts are 29% of the cases and foreigners are 17%, both percentages are increasing in the last years. CONCLUSION: Childhood tuberculosis remains a low frequency health problem in Chile. However, its increase in recent years implies an increase in the community transmission. Active case finding, contact tracing and preventive treatment should be reinforced.

Tuberculosis in Children in a Pediatric Hospital in Mexico.

Tuberculosis (TB) remains a global problem and a diagnostic challenge, especially in pediatrics. The aim of this study was to describe the clinical, microbiological, radiological, and histopathological data of TB in children. A 7-year retrospective and descriptive cohort study that included 127 patients under 18 years of age with diagnosis of active TB was conducted from 2011 to 2018 in a pediatric hospital. Tuberculosis was microbiologically confirmed using Ziehl-Neelsen (ZN) staining, culture or polymerase chain reaction (PCR) in a total of 94 (74%) cases. Thirty-three cases were defined as probable TB based on tuberculin skin test result and epidemiological evaluation. The TB forms found were lymph node (39.3%), bone (15.7%), lung (13.6%), and meningeal TB (8.6%). The most common symptoms were fever (48.8%) and adenopathy (45.6%). History of contact was established in 34.6%. Positive ZN staining (sensitivity 30%) and culture (sensitivity 37%) were found in 29% and 37.7% of subjects, respectively. About 64.5% depicted abnormal chest X-ray. Xpert MTB/RIF® (PCR) was positive in 9.4% and biopsy was compatible in 52.7% of these samples. It is fundamental to have laboratory and epidemiological evaluation that support the diagnosis of the disease in children and thus, define its management; since, in most cases, early microbiologic confirmation is lacking.