Tuberculous meningitis: more questions, still too few answers Guy E Thwaites, Ronald van Toorn, Johan Schoeman Tuberculous meningitis is especially common in young children and people with untreated HIV infection, and it kills or disables roughly half of everyone aff ected. Com… Clinical meningitis with the following observations: Sub-acute or chronic fever with features of meningeal irritation such as headache, neck stiffness, and vomiting with or without other features of CNS involvement, CSF findings showing increased proteins, decreased glucose (CSF:blood glucose ratio <0.5), and/or pleocytosis with lymphocytic predominance, Presence of the 30-kD protein band in CSF on SDS-PAGE analysis, Good clinical response to antituberculous drugs. The cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12) specificity for the differential diagnosis of TBM from PTPM. Hatim F Daginawala. However, the sensitivity of the test overcomes this drawback since it the only reported method that can discriminate TBM from PTPM. The patients were classified as tuberculous meningitis when: (1) M. tuberculosis was isolated from the cerebrospinal fluid (that is, acid-fast bacilli was observed in the CSF, the M. tuberculosis is cultured from the CSF, or the CSF commercial nucleic acid amplification test was positive), or (2) clinical meningitis with negative gram and India ink stains, plus sterile bacterial … Neurol India. Previously, we standardized cell ELISA methodology in our laboratory using standard culture filtrate protein of M. tuberculosis (H37Rv strain) received from Colorado State University, Fort Collins USA (data not shown). CSF samples obtained from confirmed and suspected TBM cases were subjected to SDS-PAGE. Aim: To use molecular methods for the improvement of aetiological diagnosis of acute pyogenic meningitis … Further, the basal enzymatic activity in all these eight cases that died washigher as compared to those who survived. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10 IU/L and was significantly elevated as compared to viral encephalitis and enteric encephalopathy cases; but difference was insignificant in comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral malaria. doi: 10.1128/JCM.42.3.996-1002.2004. 1990;4:769–787. In bacterial meningitis it is typically lower; the CSF glucose level is therefore divided by the blood glucose (CSF glucose to serum glucose ratio). Following separation of proteins from CSF of confirmed TBM patients (AFB-positive) by SDS-PAGE, the 30-kD protein band was sliced out of the gel and pre-equilibrated in elution buffer (0.15 M phosphate-buffered saline [PBS], pH 7.4) and then electro-eluted in a whole gel eluter system (Biotech, India) for 90 min at 30 volts (11). Part of Patients were divided into the following groups. Molecular weight marker is shown in lane A. Patients with pyogenic meningitis had higher levels of IL-8 and MCP-1 than those with TBM (P<0.0001). Conclusion: Article  Google Scholar. Archives of Disease in Childhood, 1999. We previously used SDS-PAGE to demonstrate the presence of a 30-kD protein antigen in the CSF of TBM patients that is specific to M. tuberculosis and may be considered to be a diagnostic marker for TBM. Cookies policy. CSF was then subjected to routine biochemical analysis and pathological analysis including Gram staining, India ink staining, and AFB staining and culturing. CSF examination included total and differential cell count, biochemistry, and microscopic evaluation after Gram, India ink, and AFB staining. CSF TLC, DLC (total and differential leukocyte count), protein, and glucose estimation are helpful parameters for establishing a TBM diagnosis and for differentiating other infectious and non-infectious neurological disorders, but these tests are non-specific and often cannot differentiate TBM from PTPM in patients in whom organisms are not observed. However, when challenged with the 30-kD protein antigen, the cells obtained from PTPM patients and healthy volunteers gave a delayed response since they are not sensitized against this antigen. Please enable it to take advantage of the complete set of features! CAS  volume 4, Article number: 16 (2004) IgG antibody production (expressed as ELISA absorbance value) ranged from 0.7 to 2.0 for cells derived from CSF of TBM patients, with the exception of case no. The presence of a miliary pattern on chest roentgenogram and inappropriate secretion of antidiuretic hormone were nonspecific but helpful signs supporting a diagnosis of tuberculous meningitis; the presence of cryptococcal antigen was both a specific … To rule out CSF pyogenic meningitis, we performed Gram staining and culture by inoculation on chocolate and blood agars incubated at 37°C. However, these tests are time consuming and seldom positive.2 Recognising this problem of diagnosis, many newer tests have been developed to diagnose tuberculous meningitis and differentiate it from pyogenic meningitis—for example, enzyme linked immunosorbent assay, bromide partition test, tuberculostearic acid in CSF, adenosine deaminase in CSF, polymerase … However, the titer in PTPM patients was much lower than that observed in TBM patients. The cut-off value (OD at 450 nm) for positivity to the 30-kD protein antigen IgG in the control CSF is 0.6. 8600 Rockville Pike -, Katti MK. Of all the enzymes, CSF GGTP levels correlated best with theclinical picture. We have also demonstrated that antibody production against the 30-kD protein antigen is higher in cells derived from CSF of TBM patients compared to PTPM patients. We attempt to identify simple parameters for early diagnosis. 4 (ELISA absorbance value, 0.79). PubMed  Various methods have been developed in our laboratory that yield a high specificity and sensitivity for diagnosis of TBM, but a small number of false positive results have been observed in pyogenic meningitis cases, particularly PTPM cases [17, 18]. Kinnman J, Fryden S, Eriksson S, Moller E, Link H: Tuberculous meningitis :immune reactions within central nervous system. Methods We analyzed 306 patients with central nervous system (CNS) … Tuberculous meningitis. Indian J Pediatr. CAS  Molecular weight marker is shown in lane A. Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). In addition to the patients described in Table 1, we also tested an additional 700 CSF samples, including 150 from TBM patients. Tuberculous meningitis. All these eight cases died. Comparison of Conventional Bacteriology with Nucleic Acid Amplification (Amplified Mycobacterium Direct Test) for Diagnosis of Tuberculous Meningitis before and after Inception of Antituberculosis Chemotherapy. Background: The cytokine and MMP levels did not correlate … In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. 20 patients treated for tuberculous meningitis were excluded because they did not meet the study criteria for the diagnosis of tuberculous meningitis, and all died shortly after the start of antituberculosis chemotherapy. Figure 1 shows the presence of the 30-kD protein band in the CSF of suspected TBM cases. Immunodiagnosis of tuberculous meningitis: rapid detection of Mycobacterial antigens on cerebrospinal fluid by reverse passive hemagglutination assay and their characterization by Western blotting. To establish a diagnosis of meningitis, 2–5 ml CSF was withdrawn from patients using a lumbar puncture. Springer Nature. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM. Band size (i.e., molecular weight) was estimated using molecular weight markers (Genei, Bangalore, India) in a parallel lane. 10.1016/0962-8479(94)90045-0. Neurol India. 1981, 13 (3): 289-96. Objectives. CSF cell counting and smear examination of a centrifuged CSF sample were carried out after conventional Ziehl-Neelsen staining. BMC Neurology The ELISA test had a sensitivity of 97.72% and a specificity of 95.35% using MSE antigen. Leonard JM, Des Prez RM: Tuberculous meningitis. 2002, 8: MT95-98. SDS-PAGE was performed with a vertical slab gel electrophoresis system (Broviga, India) using the standard Laemmali method (10). The arrow indicates the 30-kD band, which represents the 30-kD protein antigen, B Cell response (IgG reactivity) to the 30-kD protein antigen in CSF cells derived from tuberculous meningitis (TBM) and partially-treated pyogenic meningitis (PTPM) patients and peripheral blood cells from control subjects. There was no significant difference seen between HIV seropositive and seronegative tuberculous meningitis, except for the IL-1β level, which was significantly lower in the HIV-infected patients. Manage cookies/Do not sell my data we use in the preference centre. doi: 10.1016/S0928-8244(01)00241-3. Kennedy DH, Fallon RJ: Tuberculous meningitis. These patients were already on broad-spectrum antibiotics, such as third-generation cephalosporins and aminoglycosides. California Privacy Statement, The sensitivity and specificity of IgG antibody in differential diagnosis of TBM from PTPM using the 30-kD protein antigen by cell ELISA was found to be 92% (11/12). Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity of 44% and specificity of 75% was observed. Clipboard, Search History, and several other advanced features are temporarily unavailable. FEMS Immunol Med Microbial. Google Scholar. Diagnosis of TBM was based on the clinical … Bethesda, MD 20894, Copyright Differential diagnosis of tuberculous meningitis from partially-treated pyogenic meningitis by cell ELISA. Childhood disease can be prevented by vaccination and by giving prophylactic isoniazid to children … (i) Tuberculous meningitis. Google Scholar. Cellular immune function is characterized by the existence of various types of lymphoid cells. Out of the 12 PTPM patients, two cases harbored microorganisms, which were cultured (gram-positive cocci in one case and gram-negative bacilli in the other case). 2000, 68: 289-99. PubMed  For patients undergoing cranial surgery, analysis of CSF was performed if they were suspected of having meningitis. Tubercle Lung Dis. Accessibility Methods of identification are standard culture and other phenotypic tests in many resource poor settings. We developed a cell enzyme-linked immunosorbant assay (Cell ELISA) to quantitatively measure production of antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM patients. Journal of Clinical Microbiology. The testing for both meningitis and aseptic meningitis is mostly the … 1970, 227: 68-685. Two-hundred μl of the cell preparation derived from CSF of patients with TBM or PTPM were then added to the wells and coated. A retrospective study was performed to compare the clinical and laboratory features of cultured-confirmed, TBM (134) and other bacterial meningitis … J Clin Microbial. 10.1016/S0928-8244(01)00241-3. Therefore, an early response on this time scale is indicative of TBM. The fall in CSF glucose is probably due to bacterial metabolism and not to phagocytosis. Supportive radiological evidence of tuberculous meningitis was present in 85 of 106 adults with clinical tuberculous meningitis. Because the … 1 AI-75320, entitled "Tuberculosis Research Materials and Vaccine Testing. ", Biochemistry Research Laboratory, Central India Institute of Medical Sciences, 88/2 Bajaj Nagar, Nagpur, 440010, India, Rajpal S Kashyap, Rani P Kainthla, Ravindra M Satpute, Neha P Agarwal, Nitin H Chandak, Girdhar M Taori & Hatim F Daginawala, Environmental Modeling and Genomic division, NEERI, Nehru Marg, Nagpur, 440020, India, You can also search for this author in Objective: To compare the differences in presentation and outcome of patients with tuberculous meningitis (TBM) and cryptococcal meningitis (CCM). Additionally our results suggest that lymphocytes from CSF of TBM patients when challenged with 30 kD protein give a quick response by producing IgG antibodies when compared with that of PTPM and healthy volunteers. The TMB/H2O2 served as a substrate for HRP. The cells obtained from CSF of TBM patients gave an early response, presumably because they were already sensitized against the TBM antigen. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM. 1990, 57: 679-83. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from December 1995 to December 2005. In logistic regression, age (OR = 1.297; 95%CI 1.067, 1.576), CSF … The following day, the plates were washed with PBS and horseradish peroxidase (HRP)-conjugated rabbit anti-human IgG (1:10,000) was then added to the plates. Peripheral blood samples from six healthy volunteers were also analyzed and included as negative controls. Various researchers have shown that CSF-derived cells have a significantly higher proliferation response to purified protein derivative (PPD) in patients with TBM, which is suggestive of an intrathecal immune response [11, 19]. BACKGROUND: Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). Tuberculous meningitis (TBM) is a major clinical and public health problem, both for diagnosis and management. 2001;31:59–64. In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. PubMed Central  The CSFprotein is raised in 90% of cases. Hence, the cell ELISA should be a very useful tool for the differential diagnosis of TBM from PTPM. Newton RW: Tuberculous meningitis:. There were few distinguishing characteristics between the two infections with regard to symptoms and signs. No IgG antibodies to the 30-kD protein antigen were produced by PBMCs from six healthy individuals within 48 h of exposure to the 30-kD protein antigen. After a 15-min incubation, 100 μl stop solution (2.5 N sulphuric acid) were added and the plates were then read with an ELISA reader at 450 nm (12). The sample was then harvested from the unit and dialyzed against PBS and the protein content was measured using a Bio Lab KIT. Baig SM: Anti-purified protein derivative Cell Enzyme Linked immunosorbent assay, a Sensitive method for early diagnosis of Tuberculos meningitis. 1976, 26: 1081-1084. … Arch Dis Child. Ahuja G, Mohan K, Prasad K, Behari M: Diagnostic criteria for tuberculous meningitis and their validation. High-titer values for IgG antibody production against the 30-kD protein antigen were observed in 11 out of 12 TBM patients. Clinicians who made a diagnosis of acute bacterial meningitis on the basis of neck stiffness or CSF turbidity were likely to miss 30% (21 of 71) of proven or probable cases. Heparinized blood samples were obtained from six healthy volunteers. Estimation of CSF-LDH activity shows more sensitive (82.5%) and specificity (87.5%) to differentiate pyogenic meningitis from non bacterial meningitis. The sensitivity of the cell ELISA was 92% and the specificity was 92% for differential diagnosis of TBM from PTPM. The newer diagnostic tests and neuroimaging methods are unlikely to be available in many developing countries. When induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients respond to IgG production within 24 h while those derived from PTPM patients do not respond. Kashyap RS, Biswas SK, Agarwal N, Chandak N, Purohit H, Taori GM, Daginawala HF: Significance of 30 KD protein marker as diagnostic marker in CSF of Tuberculous meningitis.

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