Cases Of Tuberculosis Meningitis Research Articles

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

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. 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. 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. 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.

Comparative diagnostic utility of metagenomic next-generation sequencing, GeneXpert, modified Ziehl-Neelsen staining, and culture using cerebrospinal fluid for tuberculous meningitis: Amulti-center, retrospective study in China.

BackgroundEarly diagnosis of tuberculosis meningitis (TBM) remains a great challenge during clinical practice. The diagnostic efficacies of cerebrospinal fluid (CSF)‐based mycobacterial growth indicator tube (MGIT) culture, modified Ziehl–Neelsen (ZN) staining, Xpert MTB/RIF, and metagenomic next‐generation sequencing (mNGS) for TBM remained elusive.MethodsA total of 216 adult patients with suspicious TBM were retrospectively enrolled in this multi‐cohort study. The diagnostic performances for MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS using CSF samples were evaluated.ResultsUniform clinical case definition classified 88 (40.7%) out of 216 patients as the definite TBM, 5 (2.3%) patients as probable TBM cases, and 24 (11.1%) patients as possible TBM cases. The sensitivities of MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite TBM were 25.0%, 76.1%, 73.9%, and 84.1%, respectively. Negative predictive values (NPVs) were 66.0%, 85.9%, 84.8%, and 90.1%, respectively. The sensitivities of MGIT, modified ZN staining, Xpert MTB/RIF, and mNGS for TBM diagnosis against consensus uniform case definition for definite, probable, and possible TBM were 18.8%, 57.3%, 55.5%, and 63.2%, respectively. Negative predictive values (NPVs) were 51.0%, 66.4%, 65.6%, and 69.7%, respectively. mNGS combined with modified ZN stain and Xpert could cover TBM cases against a composite microbiological reference standard, yielding 100% specificity and 100% NPV.ConclusionMetagenomic next‐generation sequencing detected TBM with higher sensitivity than Xpert, ZN staining and MGIT culture, but mNGS cannot be used as a rule‐out test. mNGS combined with Xpert or modified ZN staining could enhance the sensitivity of diagnostic tests for TBM.

NEUROLOGICAL COMPLICATIONS AND BACILLE CALMETTE-GUERIN VACCINATION STATUS OF CHILDREN WITH TUBERCULOUS MENINGITIS: A TERTIARY CARE HOSPITAL EXPERIENCE

OBJECTIVE: To assess for the neurological complications and Bacille Calmette-Guerin (BCG) vaccination status of children with tuberculosis meningitis (TBM). METHODS: This retrospective study was conducted in Ayub Teaching Hospital, Abbottabad, Pakistan. Data of diagnosed case of TBM who received anti-tuberculous therapy from 2017 to 2020 was retrieved from records. Records of children, aged 6 months to 10 years of either gender were included and vaccination status was documented along with CT scan findings. Neurological complications in hospital and outcome were recorded as discharge, expiry and transfer to other hospital. RESULTS: Out of 40 patients, 17 (42.5%) were males and 23 (57.5%) females. Age ranged from 6 months to 8 years with mean age of 2.81±2.29 years. Weight ranged from 5 to 24 kg and mean weight was 10.36±4.96 kg. About 72.5% patients were <5 years of age. About 47.5% (n=19/40) patients were not vaccinated for BCG. Primary source of tuberculosis in close contacts was identified in 35% (n=14/40) patients. Common findings on CT scan were hydrocephalus (35.0%; n=14/40) & cerebral infarct (15.0%; n=6/40). The common complication observed were hydrocephalus (35%; n=14/40), acute stroke (20%; n=8/40), cranial nerve palsies (12.5%; n=5/40), seizure disorder (12.5%; n=5/40). Mortality rate was 2.5% (n=1/40). Only 35.7% (5/14) of patients with hydrocephalus and no patient with stroke or seizures were fully vaccinated. CONCLUSION: Hydrocephalus & stroke are the most common complication in children with TBM. Neurological complications were observed more commonly in children who were either not vaccinated or partially vaccinated for BCG.

RARE FINDING OF TB MENINGITIS FOLLOWING INITIATION OF METHOTREXATE

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Mycobacterium tuberculosis (TB) is the leading infectious cause of death in adults worldwide (3). Only 1% of patients with TB infection have CNS involvement and it is exceptionally rare in North America (1,2). Typical manifestations of CNS infection include meningitis, tuberculoma, or abscess (2). The most common presenting symptoms are fever, vomiting, headache, and altered consciousness (1,2). CNS infection can have devastating consequences such as hydrocephalus, brain tissue damage, and cerebral vasculitis (2). This is a case of TB meningitis in North America with both brain and iliopsoas TB abscess formation following initiation of methotrexate. CASE PRESENTATION: 75-year-old female presented to outside ER with weakness, fatigue, and vomiting. She was discharged home and instructed to stop methotrexate as her symptoms were an adverse reaction. Methotrexate was started four days earlier for polymyalgia rheumatica. Two days later she became difficult to arouse and minimally responsive. CT abdomen and pelvis showed rim-enhancing collection in the right iliacus with brain MRI showing scattered punctate lesions. Empiric antibiotics, pan culturing including CSF, and iliopsoas abscess drainage and culture was performed. CSF showed low glucose and high protein indicating bacterial infection. However, all cultures showed no growth. Patient continued to be non-responsive with increasing oxygen requirements. Bronchoscopy was performed as well as PET scan which showed increased uptake in left supraclavicular and mediastinal nodes. Lymph node biopsy showed caseating granulomatous inflammation. With these findings, spinal fluid from prior lumbar puncture was sent for mycobacterial culture and PCR. Family reported the patient’s husband had active tuberculosis 2 years prior and the patient was treated prophylactically with 4 months of rifampin. Ultimately, PCR of spinal fluid and bronchoalveolar lavage returned positive for TB. Mycobacterial cultures of CSF fluid and iliopsoas abscess fluid also grew TB. DISCUSSION: Tuberculosis meningitis is the most common CNS manifestation of tuberculosis infection (1,5). Prompt initiation of anti-tuberculosis drugs and corticosteroids is critical as these patients often have irreversible CNS damage (4,5). The unknown exposure history was a key factor in directing the diagnosis and initiation of treatment in this case. Our patient responded well to dexamethasone, rifampin, pyrazinamide, levofloxacin and ethambutol. However, her mentation never returned to baseline, showing the severity and devastation CNS TB. CONCLUSIONS: Ultimately the patient’s latent TB was likely activated by the immunosuppression from methotrexate. This is something to contemplate in any patient before starting an immune altering drug. TB should be considered in altered mental status with CSF signs of bacterial meningitis without growth on cultures. Reference #1: 1.Chin JH. Tuberculous meningitis: Diagnostic and therapeutic challenges. Neurol Clin Pract. 2014;4(3):199–205. doi:10.1212/CPJ.0000000000000023 Reference #2: 2.Hamid Changal, K. (2014). Central Nervous System Manifestations of Tuberculosis: A Review Article. Mycobacterial Diseases, 04(02). Reference #3: 3.WHO. Treatment of tuberculosis: guidelines: 4th ed. Available at: http://www.who.int/tb/publications/2010/9789241547833/en/index.html. Accessed May 12, 2019 4.Tuberculous meningitis. Garg RK. Acta Neurol Scand. 2010;122:75–90. DISCLOSURES: No relevant relationships by Muhammad Ahmed, source=Admin input No relevant relationships by Alyson Bundy, source=Web Response No relevant relationships by Simon Meredith, source=Web Response No relevant relationships by karan Singh, source=Web Response No relevant relationships by Rodney Steff, source=Web Response

Trends of tuberculosis meningitis and associated mortality in Texas, 2010-2017, a large population-based analysis.

BackgroundAs the most severe form of tuberculosis (TB), TB meningitis (TBM) is still associated with high mortality even in developed countries. In certain areas of the United States (U.S.), more than 50% of the TBM patients die with TB or have neurological sequelae and complications despite the availability of advanced health care. This population-based analysis aimed to determine the risk factors and trends associated with TBM morbidity and mortality using state-wide surveillance data.MethodsDe-identified surveillance data of all confirmed TB patients from the state of Texas between 01/2010 and 12/2017 reported to the National TB Surveillance System was analyzed. Spatial distribution of TBM cases was presented by Stata's Geographic Information Systems mapping. Univariate and multiple generalized linear modeling were used to identify risk factors associated with meningitis morbidity and mortality. Non-parametric testing was used to analyze morbidity and mortality trends.ResultsAmong 10,103 TB patients reported in Texas between 2010 and 2017, 192 (1.9%) had TBM. During this 8-year period, the TBM proportion fluctuated between 1.5% and 2.7% with peaks in 2011 (2.7%) and 2016 (2.1%) and an overall non-significant trend (z = -1.32, p = 0.19). TBM had a higher mortality at diagnosis (8.9%), during treatment (14.1%) and overall (22.9%) compared to non-TBM (1.9%, 5.3%, and 7.2%, respectively, p<0.001). While mortality during treatment was unchanged over time in non-TBM patients (z = 0.5, p = 0.62), it consistently increased in TBM patients after 2013 (z = 3.09, p = 0.002). TBM patients had nearly five times the risk for overall death in multivariate analysis [aRR 4.91 (95% CI 3.71, 6.51), p<0.001]. TBM patients were younger, and more likely to present with miliary TB or HIV (+). Age ≥45 years, resident of a long-term care facility, IDU, diabetes, chronic kidney disease, abnormal chest radiography, positive AFB smear or culture and HIV (+) were independently associated with higher mortality.ConclusionTBM remains challenging in Texas with significantly high mortality. Risk factors determined by multivariate modeling will inform health professionals and lay a foundation for the development of more effective strategies for TBM prevention and management.

778. Trend of Tuberculosis Meningitis and Associated Mortality in Texas, 2010–2017, A Large Population-Based Analysis

BackgroundAs the most severe form of tuberculosis (TB), TB meningitis (TBM) is still associated with high mortality even in developed countries. In certain US states more than 50% of the TBM patients eventually die or have neurological complications despite having advanced healthcare settings. This population-based analysis aimed to determine the risk factors and trends associated with TBM morbidity and mortality using state-wide surveillance data.MethodsDe-identified surveillance data of all confirmed TB patients from the state of Texas reported between January 2010 and December 2017 to the National TB Surveillance System was analyzed. Spatial distribution of TBM cases was presented by Stata’s Geographic Information Systems mapping. Univariate and multiple logistic regression were used to identify risk factors associated with meningitis morbidity and mortality. Non-parametric trend testing was used for the morbidity and mortality trends.ResultsAmong 10,103 TB patients reported from Texas between 2010 and 2017, 192 (1.9%) had TBM. Over the 8-year period, TBM proportion fluctuated between 1.5% and 2.7% with peaks in 2011 (2.7%) and 2016 (2.1%) and an overall trend z = −1.32, P = 0.19. TBM had higher mortality at diagnosis (8.9%), during treatment (20.3%) and overall (22.9%) than non-TBM (1.9%, 6.8%, and 7.2%, respectively, P < 0.001). While the mortality during treatment was unchanged overtime in non-TBM patients (z=0.5, P = 0.62), it has consistently increased in TBM patients since 2013 (z=3.09, P = 0.002). TBM patients had more than 7 times the odds for overall death in multivariate analysis [OR 7.25 (95% CI 4.64, 11.33), P < 0.001]. TBM patients were younger, more likely to present with miliary TB or HIV(+). Age ≥45 years, resident of a long-term care facility, IDU, diabetes, chronic kidney disease, abnormal chest radiograph, positive AFB smear or culture, culture not converted from positive to negative, and HIV(+) were independently associated with a higher mortality.ConclusionTBM remains a challenge in Texas with significantly higher mortality. Risk factors determined by multivariate modeling will inform health professionals and lay a foundation for the development of more effective strategies for TBM prevention and management. Disclosures All authors: No reported disclosures.

Tuberculous meningitis with pulmonary military tuberculosis: case report

Introduction: central nervous system (CNS) Tuberculosis (TB) is the most dangerous form of extra-pulmonary TB. It occurs in approximately 1% of all patients with active tuberculosis (1). It includes meningitis, intracranial tuberculomas and abscesses. The diagnosis and treatment of Tuberculosis Meningitis (TBM) is still a clinical challenge. We report a case of TBM with pulmonary military tuberculosis.

Frequency of Hydrocephalus in Cases of TBM

Tuberculosis meningitis (TBM) is a serious public health problem in developing countries as it leads to significant mortality and residual neurological squeal. The estimated mortality due to TBM in Asia is 1.5 per 100,000 populations. Objectives: To determine the frequency of hydrocephalus in cases of TBM. Methodology: This was a cross sectional study conducted during July 2016 to December 2016 conducted at Department of Medicine Services Hospital, Lahore. The detailed demographic data was collected. Cases fulfilling the criteria of TBM underwent CT scan of brain (with IV contrast) for confirmation of TBM at the Department of Radiology, Sheikh Zayed hospital Rahim Yar Khan. Results: In this study there were 93 cases, out of which 54 were males and 39 females with mean of 34.13±9.45 years. Hydrocephalus was seen in 61 (65.59%) out of 93 cases of TBM. It was seen significantly higher in male group where it caused it in 40 out of 54 males (74.1%) with p value of 0.04 (table 1). In context of age groups with respect to hydrocephalus it was seen maximum in patients with age group of 31 to 40 years affecting 12 (80%) out of 15 of its respective group. It was followed by 41 to 50 years affecting 28 (68.3%) of 41 cases, though this difference was not found statistically significant with p value of 0.24. Hydrocephalus was observed maximum in stage I of TBM where it affected 4 out of 5 cases followed by stage II with 36 of 52 cases and then stage III with 21 of 36 patients. This difference was also not significant with p= 0.44. Conclusion: Hydrocephalus is an important and deadly complication of tuberculous meningitis and is noted in every 2 (65.59%) out of 3 cases. There is significant association of male gender with hydrocephalus.

Frequency of Hydrocephalus in Cases of TBM

Tuberculosis meningitis (TBM) is a serious public health problem in developing countries as it leads to significant mortality and residual neurological squeal. The estimated mortality due to TBM in Asia is 1.5 per 100,000 populations. Objectives: To determine the frequency of hydrocephalus in cases of TBM. Methodology: This was a cross sectional study conducted during July 2016 to December 2016 conducted at Department of Medicine Services Hospital, Lahore. The detailed demographic data was collected. Cases fulfilling the criteria of TBM underwent CT scan of brain (with IV contrast) for confirmation of TBM at the Department of Radiology, Sheikh Zayed hospital Rahim Yar Khan. Results: In this study there were 93 cases, out of which 54 were males and 39 females with mean of 34.13±9.45 years. Hydrocephalus was seen in 61 (65.59%) out of 93 cases of TBM. It was seen significantly higher in male group where it caused it in 40 out of 54 males (74.1%) with p value of 0.04 (table 1). In context of age groups with respect to hydrocephalus it was seen maximum in patients with age group of 31 to 40 years affecting 12 (80%) out of 15 of its respective group. It was followed by 41 to 50 years affecting 28 (68.3%) of 41 cases, though this difference was not found statistically significant with p value of 0.24. Hydrocephalus was observed maximum in stage I of TBM where it affected 4 out of 5 cases followed by stage II with 36 of 52 cases and then stage III with 21 of 36 patients. This difference was also not significant with p= 0.44. Conclusion: Hydrocephalus is an important and deadly complication of tuberculous meningitis and is noted in every 2 (65.59%) out of 3 cases. There is significant association of male gender with hydrocephalus.

TUBERCULOSIS MENINGITIS IN CHILDREN: MODERN REQUIREMENTS TO DIAGNOSTICS

Тhe aim: to analyze reasons of late diagnostics and course specifics of tuberculosis meningitis (TBM) in children in Saint Petersburg, Russia. Materials and methods: Data was obtained from the Russian official statistics on the frequency of childhood tuberculosis meningitis in 2000-2016. We also analyzed the frequency, the course and the diagnostic specifics of tuberculosis meningitis in children in 2005–2016 in Saint Petersburg. Results and discussion: In the Russian Federation the number of children diagnosed with tuberculosis meningitis per year was reduced from 51 in 2000 to 13 in 2016. In Saint Petersburg over the period of 2005 to 2016 there were seven registered cases of childhood tuberculosis meningitis. Unfortunately only three children out of seven in Saint Petersburg tuberculosis meningitis cases survived. The main factors associated with tuberculosis meningitis in children were young age, children three years old and younger (5 out of 7 children), the presence of a TB patient in the family (6 out of 7 children), lack of BCG vaccination (5 out of 7 children), and poor socio-economic situation (5 out of 7 children). Three out of seven children developed tuberculosis meningitis after becoming HIV positive. The following methods of tuberculosis meningitis diagnostics exist in Russia: Diaskintest, PCR, and Bactec culture tests for Mycobacterium tuberculosis. QuantiFERON-TB Gold and T-SPOT.TB are available but too expensive for most patients. However, a low prevalence of tuberculosis meningitis cases resulted in insufficient attention to TBM, late diagnostics and fatal cases. Three clinical cases were analyzed. Conclusion: To improve tuberculosis meningitis treatment outcomes it is necessary to raise awareness of TB infection among treatment providers, especially when evaluating high risk children population. It is critical to determine presence of latent Mycobacterium tuberculosis, use all etiological diagnostic methods, including PCR and Bactec, when analyzing cerebrospinal fluid and other specimen, and initiate anti-TB treatment immediately when tuberculosis meningitis is suspected.

Prospective Analysis of 55 Cases of Tuberculosis Meningitis (TBM) in North India.

To assess the clinical profile, laboratory and neuroimaging data of adult tuberculous meningitis (TBM) patients and to determine the predictors of mortality. A total of 55 TBM patients and 60 controls were enrolled in this prospective study. Detailed clinical, radiological, biochemical and microbiological evaluation was performed. Done using SPSS 15.0 for Windows. P value of <0.05 was considered to be significant. 61.8% were males and majority of the study subjects belonged to age group of 21-40 years. Duration of symptoms in all cases was >14 days and commonly included fever, headache, neck rigidity, altered sensorium and vomiting. Biochemical features of cerebrospinal fluid (CSF) showed significant results where 94.5%, 85.45%,83.63% and 81.81% of patients showed CSF sugar levels <2/3 corresponding blood sugar, proteins>100mg%, CSF total leucocyte count of >20 cells/mm(3) and ADA >9.5IU/L respectively while neuroimaging revealed hydrocephalus, basal exudates and meningeal enhancement as significant findings. More than half of TBM patients presented in stage II of disease and overall mortality was 43.63%. A model for prediction of mortality in TBM cases was framed which included variables of age>40 years, past history of tuberculosis (TB), presence of basal exudates and hydrocephalus. TBM is a serious extrapulmonary form of TB and should arise suspicion in mind of clinician based on clinical, laboratory and radiologic results. Further, a model for prediction of mortality in such patients may be helpful for early intervention and better prognosis.

A hypothetical astrocyte-microglia lactate shuttle derived from a 1H NMR metabolomics analysis of cerebrospinal fluid from a cohort of South African children with tuberculous meningitis.

Tuberculosis meningitis (TBM) is the most severe form of extra-pulmonary tuberculosis and is particularly intense in small children; there is no universally accepted algorithm for the diagnosis and substantiation of TB infection, which can lead to delayed intervention, a high risk factor for morbidity and mortality. In this study a proton magnetic resonance (1H NMR)-based metabolomics analysis and several chemometric methods were applied to data generated from lumber cerebrospinal fluid (CSF) samples from three experimental groups: (1) South African infants and children with confirmed TBM, (2) non-meningitis South African infants and children as controls, and (3) neurological controls from the Netherlands. A total of 16 NMR-derived CSF metabolites were identified, which clearly differentiated between the controls and TBM cases under investigation. The defining metabolites were the combination of perturbed glucose and highly elevated lactate, common to some other neurological disorders. The remaining 14 metabolites of the host’s response to TBM were likewise mainly energy-associated indicators. We subsequently generated a hypothesis expressed as an “astrocyte–microglia lactate shuttle” (AMLS) based on the host’s response, which emerged from the NMR-metabolomics information. Activation of microglia, as implied by the AMLS hypothesis, does not, however, present a uniform process and involves intricate interactions and feedback loops between the microglia, astrocytes and neurons that hamper attempts to construct basic and linear cascades of cause and effect; TBM involves a complex integration of the responses from the various cell types present within the CNS, with microglia and the astrocytes as main players.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-014-0741-z) contains supplementary material, which is available to authorized users.

Association between neuromyelitis optica and tuberculosis in a Chinese population

BackgroundA number of reports have described the presence of tuberculosis (TB) in neuromyelitis optica (NMO) patients. However, a definite association between the two conditions has not been conclusively demonstrated.MethodsTo investigate the association between NMO and TB in a Chinese population, we performed a retrospective review of hospital records of NMO patients, control patients and tuberculosis meningitis (TBM) patients from January 1, 1995 to December 31, 2011.ResultsThe frequency of preceding/simultaneous active pulmonary TB (PTB) was not significantly different between NMO patients (1.1%) and control groups (2.3% in myasthenia gravis, 1.1% in polymyositis or dermatomyositis, zero in idiopathic facial palsy and viral meningitis/meningoencephalitis). NMO cases differed from TBM cases in terms of demographics, course (recurrent or monophasic), cerebrospinal fluid analysis and magnetic resonance images. Two TBM patients shared partial clinical features with NMO (one of the TBM patients had a longitudinal extensive spinal cord lesion involving the holocord, and the other had optic neuritis before anti-tuberculosis treatment). NMO antibodies were only detected in NMO patients and not in TBM patients with myelitis or optic neuritis.ConclusionsWe could not confirm previous suggestions of the association between PTB and NMO. Direct infection of the central nervous system by TB may mimic NMO in some respects, but whether NMO-like symptoms that develop during the course of TB should be considered and diagnosed as NMO is open to discussion.

Human Genetic Susceptibility to Tuberculosis: Time for a Bottom-Up Approach?

Human Genetic Susceptibility to Tuberculosis: Time for a Bottom-Up Approach?

Tuberculous meningitis mimicking acute polyradiculonevritis

Romania has the highest prevalence of tuberculosis (TB) among all the Central European countries. Involvement of the central nervous system (CNS) by the TB accounts for approximately 1% of all cases of tuberculosis. CNS TB includes two clinical categories: intracranial and spinal. We report two cases of tuberculosis meningitis with hemorrhagic CSF. Diagnosis was based on clinical signs, complementary investigations and response to early treatment with antituberculosis medication with adjunct of steroid therapy. Some mild neurological sequels persisted.

The current situation and treatment of childhood tuberculosis

We performed a retrospective analysis of 394 patients who were treated for active tuberculosis (TB) at our hospital from 1976 to 1997. The diagnosis criteria for establishing TB were history of direct contact with TB patients, tuberculin skin test reactivity, positive bacteriology and radiographic findings compatible with TB. There were 192 males and 202 females (age range 1 month to 18 years of age, mean 6.3 years of age). Fifty-four percent of the cases were under 5 years of age. Primary pulmonary TB was presented in 200, post primary pulmonary TB in 97, pleural effusion in 53, endbronchial TB in 4, TB meningitis (TBM) in 28, miliary TB in 28 and other extra-pulmonary TB in 31. A history of contact with the patients was obtained in 72.8% of cases. Two hundred and thirty (58.4%) had received BCG, 134 (34%) no BCG, 30 (7.6%) were unclear. Especially, under 5 years of age, only 29 (13.6%) had received BCG. TBM is not disappeared in Japan and there were 28 cases with TBM. Fifteen patients out of them recovered completely, 8 patients recovered with severe neurological sequelae which included mental retardation, motor weakness, seizures and hydrocephalus and 5 patients died. Twenty-six had no BCG. Particularly in 1990s, we had experienced 4 dead TBM cases, 1 multi-drug resistant (MDR) TBM case and 1 TBM case due to nosocomial infection. Children with TBM should received 12-month regimen using initial daily treatment with isoniazid, rifampin, pyrazinamide, and streptmycin, followed by isoniazid and rifampin administered daily. Pulmonary TB in children is successfully treated with 6-month standard chemotherapy using isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin daily for 4 months. In order to promote TB control and eliminate childhood TB, especially in infants, the following is necessary; 1) early detection and treatment of adult TB patients, source of infection, 2) prompt and appropriate contact examination and chemoprophylaxis, 3) BCG vaccination during early infancy, 4) protection from MDR TB are most important in Japan.

Evaluation of Lionex TB kits and mycobacterial antigens for IgG and IgA detection in cerebrospinal fluid from tuberculosis meningitis patients

To evaluate commercial Lionex TB together with four antigens of Mycobacterium tuberculosis (MPT-64, MT10.3, 16 kDa and 38 kDa) for IgG and IgA cerebrospinal fluid (CSF) detection in the diagnosis of tuberculosis meningitis (TBM) with CSF negative acid-fast bacilli staining, 19 cases of TBM, 64 cases of other infectious meningoencephalitis and 73 cases of other neurological disorders were tested by enzyme linked immunosorbent assay. IgA-MPT-64 and IgG Lionex showed the highest sensitivities, specificities, positive predictive value and negative predictive value (63.2%, 47.4%; 95%, 93.7%; 40%, 98% and 28.4%, 97.1%, respectively). However, while grey zone was 12.7% and 6%, respectively, lowering sensitivity but maintains high specificity (>or= 95%). High protein concentration in CSF was associated with antibody positivity CSF/HIV+ which did not influence the sensitivity of both tests. To our knowledge, this is the first description of IgA-MPT-64 and IgG Lionex antibodies in CSF-TBM and, although there is good specificity, adjustments are needed based on antigen composition to enhance sensitivity.

To compare CSF adenosine deaminase levels and CSF-PCR for tuberculous meningitis

This study was planned to compare the adenosine deaminase (ADA) levels and polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) as a rapid method to diagnose tuberculosis meningitis (TBM). Fifty-four adult patients with suspected TBM and 37 controls were included in this study. The median ADA level was 21 U/L of most likely TBM, 14 U/L of unconfirmed TBM and 5 U/L of controls. PCR for Mycobacterium tuberculosis was positive in 12 out of 27 most likely TBM cases, 5 out of 27 unconfirmed TBM cases and 3 out of 37 controls. Using a cut off level of >10 U/L, CSF-ADA had a sensitivity of 92.5% and specificity of 97% for the diagnosis of TBM. PCR for M. tuberculosis had a sensitivity of 44.5% and specificity 92% in the most likely TBM cases. This study shows that CSF-ADA is a more sensitive indicator than PCR for the diagnosis of M. tuberculosis.

The Development and Impact of Tuberculosis Vaccines

Vaccination is expected to make a major contribution to the goal of eliminating tuberculosis worldwide by 2050. But developing a new effective vaccine will require innovation in scientific research, a proactive approach to clinical trials of new vaccine candidates, and application of vaccines as part of an integrated approach to disease control.

Profiles of biochemical parameters in central nervous system fluid during the therapeutic courses of adult Mycobacterium tuberculosis meningitis

Clinical features, cerebrospinal fluid (CSF) examination, and neuroimaging findings can yield a presumptive diagnosis of tuberculosis meningitis (TM). However, confirmed diagnosis depends on the culture of Mycobacterium tuberculosis from the CSF [1]. Generally, the decision to begin with tuberculostatic treatment cannot await the proof of the causative agent and the prognosis of the disease may be devastating even if treatment is started promptly [2]. Sometimes the clinicians are confused from the diagnostic burden whether to start therapy for TM or not. In some TM cases without microbiological confirmation, the clinical and laboratory parameters resolve very quickly after the initiation of antibiotics. There remains another controversy in this situation, i.e. whether the clinician will stop therapy or continue for 12 months. There is little knowledge on the changes of CSF biochemical parameters during antituberculosis therapy in TM patients. What happens to the biochemical profile in CSF in due course? To the authors’ knowledge there are no data in the literature on this issue. Our study, which was performed between 1 January 2000 and 31 December 2004, focuses on these CNF changes in biochemical profiles for TM patients receiving therapy. There is a chain of military hospitals over the country in Turkey. If a soldier is diagnosed as TM in 1 of the military hospitals, the patient is given antibiotics and sent home for 2 /3 months of rest following the hospitalization necessary for patient stabilization. The patient returns to hospital either in an emergency situation or following the end of the official rest period. Thus, all TM patients return to military hospitals every 2 to 3 months, but the patient does not necessarily apply to the hospital where the disease is diagnosed. Generally the patient applies to the military hospital nearest to where he lives, i.e. another institution may follow a TM case diagnosed in our hospital in the follow-up periods or we may follow a previously diagnosed case in another military hospital during the therapeutic course. In every periodical visit the patient was punctured once again either to delineate the status of infection or to present an official clue to provide the patient with an additional rest time. After the end of 12-month therapy, the surveillance of the patient is stopped. Therefore we have sparse data on TM patients which we may have encountered at any period during anti-tuberculosis therapy. All the cases were young males ranging from 20 to 28 y of age without immunosuppression. Dexamethasone was given to all patients in standard dosages