The diagnostic potential of urine in paediatric patients undergoing initial treatment for tuberculous meningitis.

Tuberculous meningitis (TBM)-the extrapulmonary form of tuberculosis, is the most severe complication associated with tuberculosis, particularly in infants and children. The gold standard for the diagnosis of TBM requires cerebrospinal fluid (CSF) through lumbar puncture-an invasive sample collection method, and currently available CSF assays are often not sufficient for a definitive TBM diagnosis. Urine is metabolite-rich and relatively unexplored in terms of its potential to diagnose neuroinfectious diseases. We used an untargeted proton magnetic resonance (1H-NMR) metabolomics approach to compare the urine from 32 patients with TBM (stratified into stages 1, 2 and 3) against that from 39 controls in a South African paediatric cohort. Significant spectral bins had to satisfy three of our four strict cut-off quantitative statistical criteria. Five significant biological metabolites were identified-1-methylnicotinamide, 3-hydroxyisovaleric acid, 5-aminolevulinic acid, N-acetylglutamine and methanol-which had no correlation with medication metabolites. ROC analysis revealed that methanol lacked diagnostic sensitivity, but the other four metabolites showed good diagnostic potential. Furthermore, we compared mild (stage 1) TBM and severe (stages 2 and 3) TBM, and our multivariate metabolic model could successfully classify severe but not mild TBM. Our results show that urine can potentially be used to diagnose severe TBM.

Predictors of Resolution of Meningitis Symptoms in Tuberculous Meningitis: A Clinical, Magnetic Resonance Imaging, and Biomarker Study.

In tuberculous meningitis (TBM), the meningeal symptoms and their resolution after treatment may be dependent on clinical-radiological severity, cerebrospinal fluid (CSF), and proinflammatory cytokines, and these findings may be associated with outcome. There is a paucity of studies on the resolution of meningitis symptoms in TBM. We report on associations of clinical, magnetic resonance imaging (MRI), laboratory, and proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin 6 (IL-6)] findings with the resolution of meningitis symptoms (RMS), and the impact of RMS duration on the outcome in TBM. Seventy-one patients with TBM were included, and their clinical, laboratory, and MRI findings at baseline were recorded. mRNA profiling of TNF-α and IL-6 was done by reverse transcriptase polymerase chain reaction. The day of RMS (fever, headache, and vomiting) after treatment was noted. Predictors of long duration of RMS (>3 weeks) were evaluated by univariate followed by multivariate analysis. The impact of RMS on 6-month mortality and outcome was analyzed. Patients' median age was 25 years, and 45 (63.4%) were males. After antitubercular treatment, meningeal symptoms resolved in 35 (50.70%) by 21 days and in 90% of patients by 49 days. Longer time of RMS was associated with TBM stage, pretreatment duration, seizure, and hydrocephalus but not with TNF-α and IL-6. Seven (9.8%) patients died at 6 months, and duration of RMS predicted death (hazard ratio = 25.55, 95% CI: 1.108-589.40; P = 0.04).

Clinical, Laboratory and Radiological Correlates of Xpert MTB/RIF Assay Study in Cerebrospinal Fluid in CNS Tuberculosis.

BACKGROUND: Cerebrospinal fluid (CSF) Xpert MTB/RIF assay is an initial test for the diagnosis of tuberculous meningitis (TBM). Nevertheless, it is not very clear which of the factors govern CSF-Gene Xpert/MTB positivity. OBJECTIVE: Hence, we aimed to assess the relationship, if any, between the clinical, laboratory and radiological parameters of the central nervous system (CNS) tuberculosis patients and the Gene Xpert study in CSF in such patients. METHODS AND MATERIAL: First, we studied 200 patients with CNS tuberculosis according to the case definition, and subsequently, we performed a Gene Xpert study on the CSF of these patients. Then, we correlated the clinical, radiological, and CSF criteria with the Gene Xpert positivity using the univariate binary logistic regression method via SPSS 20 (P-value <0.05). RESULTS: Seventy-five (37.5%) patients (57.3% females) of median 24 years of age, were CSF-Gene Xpert/MTB-positive and 125 (62.5%) patients were negative. The mean duration of illness (P = 0.017), weight loss or failure to thrive (P < 0.001), loss of consciousness or seizure (P = 0.001), signs of meningeal irritation (P = 0.027), stage III of TBM (P < 0.001), evidence of dissemination (P = 0.003), basal exudates (P = 0.004), hydrocephalus (P = 0.018), CSF lymphocytic predominance (P < 0.001), and reduced CSF glucose (P = 0.011) correlated significantly with positive the Gene Xpert/MTB results. Also, Gene Xpert had a sensitivity of 80% and a specificity of 74.84% against culture Xpert. CONCLUSIONS: Xpert MTB/RIF might be more useful in the later stages of the disease and those with more severe disease.

Using cerebrospinal fluid nanopore sequencing assay to diagnose tuberculous meningitis: a retrospective cohort study in China.

OBJECTIVE: This study aimed to evaluate the efficiency of nanopore sequencing for the early diagnosis of tuberculous meningitis (TBM) using cerebrospinal fluid and compared it with acid-fast bacilli (AFB) smear, mycobacterial growth indicator tube culture and Xpert Mycobacterium tuberculosis (MTB)/rifampicin (RIF). DESIGN: Single-centre retrospective study. SETTING: The Tuberculosis Diagnosis and Treatment Center of Zhejiang Chinese and Western Medicine Integrated Hospital. PARTICIPANTS: We enrolled 64 adult patients with presumptive TBM admitted to our hospital from August 2021 to August 2023. METHODS: We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AFB smear, culture, Xpert MTB/RIF and nanopore sequencing to evaluate their diagnostic efficacy compared with a composite reference standard for TBM. RESULTS: Among these 64 patients, all tested negative for TBM by AFB smear. The sensitivity, specificity, PPV and NPV were 11.11%, 100%, 100% and 32.2% for culture, 13.33%, 100%, 100% and 2.76% for Xpert MTB/RIF, and 77.78%, 100%, 100% and 65.52% for nanopore sequencing, respectively. CONCLUSION: The diagnostic accuracy of the nanopore sequencing test was significantly higher than that of conventional testing methods used to detect TBM.

A comparison of clinical features between neurobrucellosis and tuberculous meningitis.

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

Chronic meningitis in adults: a comparison between neurotuberculosis and neurobrucellosis.

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

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

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

The application value of cerebrospinal fluid immunoglobulin in tuberculous meningitis.

This article aims to study the value of cerebrospinal fluid (CSF) immunoglobulin in differential diagnosis, prediction, and prognosis of tuberculous meningitis (TBM). The clinical data of 65 patients with TBM in our hospital were collected, and 65 patients with cryptococcal meningitis (CM) were enrolled in 1:1 matching. Relevant data were collected for comparison. CSFs IgG [331.51 (164.85, 645.00) vs 129.00 (55.05, 251.00) ng/mL], IgM [22.38 (8.52, 40.18) vs 6.08 (2.19, 23.30) ng/mL], and IgA [64.11 (21.44, 115.48) vs 16.55 (4.76, 30.36) ng/mL] in the TBM group were higher than those in the CM group (P < 0.001). In the TBM group, after 24 weeks of treatment, the CSFs IgG, IgM, and IgA were significantly decreased, and the difference was statistically significant (P < 0.05). The predictive results of CSF immunoglobulin for TBM showed that IgG, IgM, and IgA all had some predictive value for TBM, and the combined predictive value of the three was the highest, with an area under the curve of 0.831 (95% CI: 0.774-0.881). Logistic regression analysis of CSF immunoglobulins and TBM prognosis showed that IgG [odds ratio (OR) = 4.796, 95% confidence interval (CI): 2.575-8.864], IgM (OR = 3.456, 95% CI: 2.757-5.754), and IgA (OR = 4.371, 95% CI: 2.731-5.856) were TBM risk factors for poor prognosis in patients. The levels of IgG, IgM, and IgA in CSF were positively correlated with the severity of cranial magnetic resonance imaging (MRI) in TBM patients (R2 = 0.542, F = 65.392, P < 0.05). CSFs IgG, IgM, and IgA can be used as a routine monitoring index for TBM patients, which has a certain reference value in differential diagnosis and efficacy evaluation. IMPORTANCE: In clinical practice, physicians can determine the physical conditions of patients based on the levels of cerebrospinal fluids (CSFs) IgG, IgM, and IgA. Higher levels of CSFs IgG, IgM, and IgA suggest more possibility of tuberculous meningitis and worse prognosis and magnetic resonance imaging manifestations.

Targeted sequencing from cerebrospinal fluid for rapid identification of drug-resistant tuberculous meningitis.

Mortality from tuberculous meningitis (TBM) remains around 30%, with most deaths occurring within 2 months of starting treatment. Mortality from drug-resistant strains is higher still, making early detection of drug resistance (DR) essential. Targeted next-generation sequencing (tNGS) produces high read depths, allowing the detection of DR-associated alleles with low frequencies. We applied Deeplex Myc-TB-a tNGS assay-to cerebrospinal fluid (CSF) samples from 72 adults with microbiologically confirmed TBM and compared its genomic drug susceptibility predictions to a composite reference standard of phenotypic susceptibility testing (pDST) and whole genome sequencing, as well as to clinical outcomes. Deeplex detected Mycobacterium tuberculosis complex DNA in 24/72 (33.3%) CSF samples and generated full DR reports for 22/24 (91.7%). The read depth generated by Deeplex correlated with semi-quantitative results from MTB/RIF Xpert. Alleles with <20% frequency were seen at canonical loci associated with first-line DR. Disregarding these low-frequency alleles, Deeplex had 100% concordance with the composite reference standard for all drugs except pyrazinamide and streptomycin. Three patients had positive CSF cultures after 30 days of treatment; reference tests and Deeplex identified isoniazid resistance in two, and Deeplex alone identified low-frequency rifampin resistance alleles in one. Five patients died, of whom one had pDST-identified pyrazinamide resistance. tNGS on CSF can rapidly and accurately detect drug-resistant TBM, but its application is limited to those with higher bacterial loads. In those with lower bacterial burdens, alternative approaches need to be developed for both diagnosis and resistance detection.

Utilization of Truenat chips in defining XDR, pre-XDR and MDR in tuberculous meningitis.

SETTING AND OBJECTIVE: To develop and evaluate newer molecular tests that identify drug resistance according to contemporary definitions in Tuberculous meningitis (TBM), the most severe form of EPTB. DESIGN: 93 cerebrospinal fluid (CSF) specimens [41 culture-positive and 52 culture-negative], were subjected to Truenat MTB Plus assay along with chips for rifampicin, isoniazid, fluoroquinolones and bedaquiline resistance. The performance was compared against phenotypic drug susceptibility testing (pDST), Line probe assay (LPA) and gene sequencing. RESULTS: Against pDST, Truenat chips had a sensitivity and specificity of 100%; 94.47%, 100%; 94.47%, 100%; 97.14% and 100%; 100%, respectively for rifampicin, isoniazid, fluoroquinolones and bedaquiline. Against LPA, all Truenat chips detected resistant isolates with 100% sensitivity; but 2 cases each of false-rifampicin and false-isoniazid resistance and 1 case of false-fluoroquinolone resistance was reported. Truenat drug chips gave indeterminate results in ∼25% cases, which were excluded. All cases reported indeterminate were found to be susceptible by pDST/LPA. CONCLUSION: The strategic drug resistance chips of Truenat Plus assay can contribute greatly to TB elimination by providing rapid and reliable detection of drug resistance pattern in TBM. Cases reported indeterminate require confirmation by other phenotypic and genotypic methods.

Evaluation of seegene anyplex MTB/NTM real-time detection assay for diagnosis of tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is a common central nervous system infectious disease. Polymerase chain reaction (PCR) assay is a useful method for the rapid diagnosis of TBM. The Seegene Anyplex MTB/NTM real-time detection assay has good sensitivity and specificity for detection of tuberculosis in respiratory specimens, though, data regarding other specimens are lacking. This study aims to define the diagnostic role of Seegene Anyplex MTB/NTM real-time detection assay in TBM in adults. METHODS: This was a retrospective study of 367 adults with symptomatic community acquired meningitis between December 2013 and December 2019. Cerebrospinal fluid (CSF) had been sent for conventional diagnosis, including culture to identify Mycobacterium tuberculosis, and Seegene Anyplex MTB/NTM real-time detection assay. Other diagnostic examinations were performed as necessary. RESULTS: Of the 367 patients in the study, 37 were diagnosed with TBM (14 with definite TBM and 23 with probable TBM). Between the total TBM cases (n = 37) and non-TBM cases (n = 330), clinical sensitivity was 32.4% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 93.0%. Between the definite TBM cases (n = 14) and non-TBM cases (n = 330), clinical sensitivity was 50.0% and specificity was 100%, the positive predictive value was 100%, and the negative predictive value was 97.9%. CONCLUSION: Due to lack of sensitivity, we suggest Seegeen Anyplex MTB/NTM real-time detection assay should not be used to rule out TBM but is useful for definite diagnosis.

Rifampicin and protein concentrations in paired spinal versus ventricular cerebrospinal fluid samples of children with tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal form of TB. To study the disease, drug concentrations in samples obtained from the spinal CSF are usually used to reflect brain concentrations. Emerging data suggest that transport of substances across capillaries in the brain (ventricular CSF) and spinal cord may differ. METHODS: We examined paired, time-linked samples of ventricular CSF (VCSF) and lumbar CSF (LCSF) of 28 patients with TBM and analysed these for rifampicin and total protein concentrations. Clinically indicated samples from procedures to determine the level of CSF block were collected from children being treated for TBM and hydrocephalus. Total protein concentrations were determined using the bicinchoninic acid (BCA) or turbidimetry assay, and rifampicin concentrations were determined using a validated LC coupled with tandem MS method. A paired Wilcoxon signed-rank test was used to determine significance. RESULTS: TBM was confirmed in 19 cases (68%) using TB culture or GeneXpert Mtb/Rifampicin assay. All other cases were classified as probable. The median total protein concentration in LCSF was 6.0 g/L and in VCSF was 1.3 g/L. The median rifampicin concentration in LCSF was 299 ng/mL and 133 ng/mL in VCSF. The median ratio of LCSF/VSCF for protein was 4.23 and 1.57 for rifampicin. CONCLUSIONS: Total protein and rifampicin concentrations differed significantly between the two compartments, both being higher in LCSF than in VCSF samples (P < 0.0001 for total protein and P = 0.0046 for rifampicin). Further studies are required to explore the causative reasons for the observed differences.

Development and validation of a new model for the early diagnosis of tuberculous meningitis in adults based on simple clinical and laboratory parameters.

BACKGROUND: The differential diagnosis between tuberculous meningitis (TBM) and viral meningitis (VM) or bacterial meningitis (BM) remains challenging in clinical practice, particularly in resource-limited settings. This study aimed to establish a diagnostic model that can accurately and early distinguish TBM from both VM and BM in adults based on simple clinical and laboratory parameters. METHODS: Patients diagnosed with TBM or non-TBM (VM or BM) between January 2012 and October 2021 were retrospectively enrolled from the General Hospital (derivation cohort) and Branch Hospital (validation cohort) of Ningxia Medical University. Demographic characteristics, clinical symptoms, concomitant diseases, and cerebrospinal fluid (CSF) parameters were collated. Univariable logistic analysis was performed in the derivation cohort to identify significant variables (P < 0.05). A multivariable logistic regression model was constructed using these variables. We verified the performance including discrimination, calibration, and applicability of the model in both derivation and validation cohorts. RESULTS: A total of 222 patients (70 TBM and 152 non-TBM [75 BM and 77 VM]) and 100 patients (32 TBM and 68 non-TBM [31 BM and 37 VM]) were enrolled as derivation and validation cohorts, respectively. The multivariable logistic regression model showed that disturbance of consciousness for > 5 days, weight loss > 5% of the original weight within 6 months, CSF lymphocyte ratio > 50%, CSF glucose concentration < 2.2 mmol/L, and secondary cerebral infarction were independently correlated with the diagnosis of TBM (P < 0.05). The nomogram model showed excellent discrimination (area under the curve 0.959 vs. 0.962) and great calibration (P-value in the Hosmer-Lemeshow test 0.128 vs. 0.863) in both derivation and validation cohorts. Clinical decision curve analysis showed that the model had good applicability in clinical practice and may benefit the entire population. CONCLUSIONS: This multivariable diagnostic model may help clinicians in the early discrimination of TBM from VM and BM in adults based on simple clinical and laboratory parameters.

A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge

Abstract The prognosis of tuberculous meningitis, a rare form of extrapulmonary tuberculosis, depends on the stage of treatment initiation. We report a fatal case of tuberculous meningitis. The patient had received successive tumor necrosis factor (TNF) antagonists and abatacept to treat juvenile idiopathic arthritis, with negative results for polymerase chain reaction and acid-fast bacilli on smear, had normal cerebrospinal fluid (CSF) adenosine deaminase and glucose levels. Six weeks post-admission, the CSF culture demonstrated Mycobacterium tuberculosis. The altered immunological responses caused by anti-TNF treatment made the diagnosis challenging. Clinicians should bear this in mind and, if suspected, treatment should be initiated immediately.

Comparación de adenosina deaminasa y detección de anticuerpos anti-antígeno A60 para el diagnóstico de meningitis tuberculosa / A comparative study for adenosine deaminase and anti-antigen A-60 antibodies detection for the diagnosis of tuberculous meningitis

Background: Diagnosis of tuberculous meningitis (TBM) is hampered by the lack of rapid and accurate diagnostic tools. We evaluated the immunological response to Mycobacterium tuberculosis anti-A60 antibodies in cerebrospinal fluid (CSF) in comparison to adenosine deaminase (ADA) determination, for the diagnosis of TBM. Methods: A total of 63 CSF samples were analyzed by indirect ELISA for the detection of anti- A60 IgG, IgM and IgA. These include samples from 17 patients with confirmed TBM and 46 control patients with other infections. Results: The mean individual anti-A60 IgM, IgG and IgA CSF antibody titers were significantly higher in TBM in comparison with control groups (p < 0.01). The best discriminatory CSF antibody for confirming TBM diagnosis was IgM, with an area under the receiver operating characteristic curve of 0.928 (95%CI 0.834-0.978), compared to 0.863 (95% CI: 0.752-0.936) for ADA testing (p = NS). The sensitivity of anti- A60 IgM CSF antibody titers (cutoff > 0.06 U/ml) was 94.1% compared to 88.2% for ADA (cutoff > 6.2 U/ml), p = NS. Both anti A60 IgM and ADA showed the same moderate specificity (80.4%). Two cases of TBM were correctly identified by anti-A60 IgM but missed by ADA. Conclusion: The ELISA test for anti-antigen A60 antibodies (IgM) is a rapid and sensitive tool for the rapid diagnosis of TBM that can be a complement to ALDA determination. The specificity of both tests is still a limitation in TBM diagnosis.

Antecedentes: El diagnóstico de meningitis tuberculosa (MTBC) se ve limitado por la ausencia de técnicas diagnósticas rápidas y precisas en líquido cefalorraquídeo (LCR). En este estudio evaluamos la respuesta inmunoló-gica de anticuerpos anti-antígeno A60 de Mycobacterium tuberculosis en LCR en comparación a la determinación de adenosina deaminasa (ADA). Métodos: Un total de 63 muestras de LCR fueron estudiadas mediante ELISA indirecto para detección de IgG, IgM e IgA anti-A60. Estas muestras incluyeron 17 casos de MTBC confirmada y 46 controles con otras infecciones. Resultados: Los títulos de IgG, IgM e IgA anti A-60 resultaron significativamente superiores en casos de MTBC versus controles (p > 0,01). El anticuerpo con mej or poder discriminatorio resultó IgM, con un área bajo la curva ROC de 0,928 (95%IC 0,8340,978), comparado a 0,863 (95% IC: 0,752-0,936) para ADA (p = NS). La sensibilidad de IgM anti-A60 (nivel de corte > 0,06 U/ml) fue de 94,1% versus 88,2% para ADA (nivel de corte > 6,2 U/ml), p = NS. Ambos IgM anti-A60 y ADA presentaron la misma especificidad baja-moderada (80,4%). Dos casos de MMTBC fueron correctamente identificados por IgM anti-A60 pero no por ALDA. Conclusión: La detección de anticuerpos anti-A60 (IgM) puede ser de ayuda en el diagnostico de MTBC en forma complementaria a la determinación de ALDA. La baja especificidad de ambos tests constituye su principal limitante.

Tuberculous meningitis: a report of 60 adult cases / Meningitis tuberculosa: reporte de 60 casos adultos

OBJECTIVE: This was to evaluate the history, clinical and laboratory findings, outcome and prognosis of patients with tuberculous meningitis (TBM). METHOD: Between 1998 and 2009, 60 patients with TBM were evaluated, retrospectively. RESULT: Overall, 60 patients were selected, of which 33 (55%) were male. The patients' ages ranged from 14 to 62 years. In the majority of the patients, disease was in an advanced stage on admission (66% in stage III according to the British Research Council neurological criteria). The rate of complications was highest among patients in stages II and III with an overall mortality rate of 6.6% (n= 2 of stage II patients and n= 2 of stage III patients). CONCLUSIONS: Earlier admission of the patients with TBM could provide better outcomes with regard to sequelae and mortality. Fatal cases presented with rapid deterioration and were refractory to treatment.

OBJETIVO: El propósito de este trabajo fue evaluar la historia, los hallazgos clínicos y de laboratorio, la evolución, y la prognosis de pacientes con meningitis tuberculosa (MTB). MÉTODO: Entre 1998 y 2009, se evaluaron 60 pacientes con TBM, retrospectivamente. RESULTADOS: En general, se seleccionaron 60pacientes, de los cuales 33 (55%) fueron varones. La edad de los pacientes osciló de 14 a 62 años. En la mayoría de los pacientes, la enfermedad se encontraba en etapa avanzada al momento del ingreso (66% en la etapa III de acuerdo con los criterios neurológicos del Consejo Británico de Investigación). La tasa de complicaciones fue más alta entre los pacientes en las etapas IIy III con una tasa de mortalidad general de 6.6% (n = 2 en los pacientes de etapa IIy n = 2 en los pacientes de etapa III). CONCLUSIONES: El ingreso temprano de los pacientes con MTB podría proporcionar mejores resultados con respecto a las secuelas y la mortalidad. Los casos fatales se presentaron con deterioro rápido y fueron refractarios al tratamiento.

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 percent, 47.4 percent; 95 percent, 93.7 percent; 40 percent, 98 percent and 28.4 percent, 97.1 percent, respectively). However, while grey zone was 12.7 percent and 6 percent, respectively, lowering sensitivity but maintains high specificity (> 95 percent). 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.

Polymerase chain reaction as a useful and simple tool for rapid diagnosis of tuberculous meningitis in a Brazilian tertiary care hospital

Meningitis is a severe and potentially fatal form of tuberculosis. The diagnostic workup involves detection of acid-fast bacilli (AFB) in the cerebrospinal fluid (CSF) by microscopy or culture, however, the difficulty in detecting the organism poses a challenge to diagnosis. The use of the polymerase chain reaction (PCR) in the diagnostic approach to Mycobacterium tuberculosis (MTB) meningitis has been reported as a fast and accurate method, with several commercial kits available. As an alternative, some institutions have been developing inexpensive in house assays. In our institution, we use an in house PCR for tuberculosis. We analyzed the performance of our PCR for the diagnosis of MTB meningitis in 148 consecutive patients, using MTB culture as gold standard. The sensitivity and specificity of CSF PCR for the diagnosis of MTB meningitis was 50 percent and 98.6 percent respectively with a concordance with CSF mycobacterial culture of 96 percent (Kappa=0.52). In contrast to CSF cultures for MTB, our PCR test is a fast, simple and inexpensive tool to diagnose tuberculous meningitis with a performance similar to that obtained with the available commercial kits.