Adenosine deaminase and tuberculous meningitis—A systematic review with meta-analysis (original) (raw)
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Adenosine deaminase, an aid in the diagnosis of tubercular meningitis – hospital based study
IP innovative publication pvt. ltd, 2019
Introduction: Tubercular meningitis (TBM) is the most prevalent and most grave form of extrapulmonary tuberculosis. It is associated with high mortality rate. The confounding factor for this is the delay in diagnosing the disease and initiation of treatment. The present study aims to look for the diagnostic utility of ADA estimations in Tubercular meningitis patients. Materials and Methods: For this study the patients with the signs and symptoms of meningitis and attending our hospital within a st ipulated period of one year approximately, were taken as subjects. As per the accepted criteria, the patients were segregated into two broad groups: tubercular meningitis cases and nontubercular meningitis cases. CSF specimens were collected and ADA levels were estimated on semiautoanalyser in the laboratory. Results: Out of 31 patients of tubercular meningitis, 27 showed ADA levels above 10 U/L while 2 showed lower values. On the other hand 32 cases of non- tubercular meningitis showed ADA levels below 10 U/L and 4 showed higher values, thereby supporting the fact that ADA evaluation in CSF is of substantial value in diagnosing TBM. It also illustrious that if CSF ADA value of 10 U/L is taken as bench mark then the sensitivity for diagnosing TBM is 93.10% and specificity is 88.87% which is fairly good. Conclusion: Therefore, just by evaluating CSF ADA levels we can diagnose the TBM cases with respectably good sensitivity and high specificity and consuming least time and resources. Therefore, ADA estimation is a valuable adjunct to routine investigations in diagnosis of TBM.
Cureus, 2023
Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find relevant articles from January 1980 to June 2022. The random-effect model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval was adopted to derive the diagnostic efficacy of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for the diagnosis of tuberculous meningitis (TBM) in adult patients. A total of 22 studies (20 prospective and two retrospective data) have been included in this meta-analysis, having 1927 participants. We perceived acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROCs), and diagnostic odds ratio (DOR) of 0.85 (95% CI: 0.77-0.90), 0.90 (95% CI: 0.85-0.93), 0.94 (95% CI: 0.91-0.96) and 48 (95% CI: 26-86), respectively, for CSF-ADA for differentiating TBM from non-TBM in adult patients. To ascertain the certainty of evidence for CSF-ADA as a diagnostic marker for TBM, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis was used. CSF-ADA is an auspicious diagnostic test with a high degree of specificity and acceptable sensitivity for the diagnosis of tuberculous meningitis, however, with very low certainty of evidence.
2006
Background: Tuberculous meningitis (TBM) is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB). The diagnosis of TBM is often difficult. A reliable, costeffective and rapid diagnostic test, which can be performed in any standard pathology laboratory, could be of help in the diagnosis of TBM. In the present study we measured the adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of TBM and non-TBM patients. Method: ADA activity in CSF was determined according to a method based on the Berthlot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically. Results: The CSF ADA activity from TBM patients was compared with CSF ADA from non-TBM infectious meningitis patients, and from patients with non-infectious neurological disorders. The mean CSF ADA activity was found to be significantly higher in CSF of TBM patients, 14.31 ± 3.87 (2.99-26.94), mean ± SD with range, than in the CSF from non-TBM infectious meningitis, 9.25 ± 2.14 (4.99-13.96) and from the non-infectious neurological disorders group, 2.71 ± 1.96 (0.00-7.68), P < 0.0001 for both comparisons. A cutoff value of 11.39 U/L/min for the TBM patients was calculated from the mean + SD of the non-TBM patients. The ADA test gave a sensitivity of 82% and a specificity of 83% for infectious TBM when this cutoff value was used. Conclusion: This study demonstrated that ADA activity in the CSF of TBM patients, using a cutoff value 11.39 U/L/min, can be useful for the early differential diagnosis of TBM. This test can be performed in any pathology laboratory where more sophisticated methods are not available.
Journal of Infection, 2017
Introduction: The measurement of adenosine deaminase (ADA) level in CSF has generated as a suitable test for TBM diagnosis. The main objective in the present metaanalysis focused on analyzing the ADA test accuracy in order to diagnose TBM. Methods: We searched several databases including Medline, Embase and Cochrane databases to identify studies addressing the diagnosis of TBM. The quality of included reports were assessed by RevMan5 software (via QUADS2 checklist). Accuracy measures of ADA test (sensitivity, specificity and others) pooled with random effects models. In addition, the data was elicited by using midas and metan packages in stata (version 12). Result: conceptually twenty studies were eligible for inclusion within the meta-analysis. The pooled sensitivity and specificity for TBM diagnosis hallmarks were 89 % (95% CI: 0.84-0.92) and 91 % (95% CI: 0.87-0.93), respectively. The positive likelihood ratio was 9.4 (95% CI: 7-12.8), negative likelihood ratio was 0.12 (95% CI: 0.09-0.17), and diagnostic odds ratio was 77 (95% CI: 45-132). Indeed, the area under the SROC was 0.96. Conclusion: It was magnificently attained that ADA test hade a relatively high accuracy for TBM diagnosis. .
Utility of ADA (Adenosine Deaminase) enzyme assay in diagnosis of tuberculous meningitis
IP Innovative Publication Pvt. Ltd., 2017
Introduction: Tuberculous meningitis (TBM) remains one of the leading causes of morbidity and mortality worldwide, including India. Treatment and prevention of TBM is depended on early and quality assured diagnosis. Earlier studies have showed that there is wide delay in diagnosing TBM. ADA is essential for proliferation and differentiation of lymphoid cells, especially T cells. ADA activity increases during activation of the cell, for energy demand to detoxify the toxic metabolites generated. This enzyme increases in TB patients because of delayed hypersensitivity reaction to mycobacterial antigen. Objective: To evaluate the diagnostic utility of the ADA assay for the diagnosis of tuberculous meningitis and to compare ADA results with results of Ziehl Neelsen stain, routine biochemical tests and cytology. Materials and Method: Total 86 Cerebrospinal fluid (17 cases of TBM and 69 cases of non-TBM) were studied for ADA levels, ZN stain, routine biochemical tests and cytological evaluation. Results: Mean level of ADA in TBM is 11.81 U/L and in non-TBM 1.65 U/L. Comparison between different tests for TBM shows: ZN stain is having high specificity of 100% but its sensitivity is 5.88%. Sensitivity of cytological analysis is 88.83% and specificity is 26.87%. Specificity of sugar test is only 34%. Protein estimation is also very less specific, 61%. ADA test is having both sensitivity (64.70%) and specificity (97%) higher than other tests. Conclusion: As an alternative to subjecting CSF of suspected tuberculous meningitis to various tests (cytology, protein and sugar estimation and ZN stain), subjecting sample for single test, ADA test(very easy, sensitive, specific, cheap and less time consuming: one and half hour) is better option with good results.
Cerebrospinal Fluid Adenosine Deaminase Activity: A Valid Ancillary Test for Tubercular Meningitis
Innovative publication, 2016
Background: Tuberculosis affects 1.80 million persons every year with 3.70 lakh annual deaths, ~ 10% of which are of meningeal involvement. Diagnosis of Tubercular meningitis is difficult with often under or over diagnosis. Delay in diagnosis and initiation of treatment results in poor prognosis and sequel in up to 25% of cases. Cerebrospinal fluid (CSF) Adenosine deaminase (ADA) is a simple, reliable, cost effective and rapid diagnostic test that can even be done in small clinical laboratory set up. We evaluated CSF-ADA as an ancillary test for tubercular meningitis (TBM). Materials and Methods: Total 118 CSF samples were analyzed in this study under four different groups viz. TBM (n= 30), pyogenic meningitis (PM, n=24), aseptic meningitis (AM, n=20) and Controls (no meningeal involvement, n=44). Diagnosis of meningitis was done by clinicians on the basis of presence of signs of meningeal irritation and cytological and biochemical examination of CSF. CSF-ADA was estimated by method based on Berthelot reaction, which is the formation of a colored indophenol complex from ammonia liberated from adenosine, and quantified colorimetrically. Kruskal-Wallis test with Dunnett's multiple comparison post-test was done to compare CSF-ADA activity in different groups. ROC curve analysis was done for CSF-ADA cutoff value. Result: Mean CSF-ADA (U/L) value in TBM patients were significantly higher (24.37±10.73) than in PM (14.28±5.979), AM (10.32±5.554) and Controls (6.520±4.801), p-value <0.0001 in TBM vs AM and TBM vs Controls. A cutoff value of 13.3 U/L gave a sensitivity of 91% and specificity of 90% when used to diagnose TBM. Conclusion: CSF-ADA is not only simple, cost effective and rapid but also fairly sensitive and specific in diagnosis of TBM, especially in dilemma of differentiating the tuberculous etiology from non-infectious one. For these reasons CSF-ADA is a well performer as an ancillary test of TBM.
Diagnostic Role of Adenosine Deaminase (ADA) among Tuberculous Meningitis Patients
Bangladesh Journal of Neuroscience, 2013
Background: In the developing countries where TB is endemic; an ideal test for tuberculous meningitis should be economic, minimally invasive, of high accuracy and quick to perform.In many countries, also in India, several studies were conducted to establish the ADA activity as a sensitive and specific test of tuberculous meningitis.So it is very much needed to evaluate the diagnostic role of CSF ADA in tuberculous meningitis in Bangladesh. Aim: This study aimed to find out CSF ADA as a sensitive and specific test for early diagnosis of tuberculous meningitis. Methods: This case control study was carried out in the Department of Neurology, SSMC and Mitford Hospital, Dhaka from June 2011 to July 2012, to evaluate ADA activity in CSF for diagnosis of tuberculous meninigitis. Results: In the present study, sixty meningitis patients were enrolled. Of which, 30(50%) were tuberculous meningitis (TBM) taken as cases and rest 30(50%) were non-tuberculous meningitis (NTBM) taken as control.Th...
Adenosine Deaminase Levels in CSF of Tuberculous Meningitis Patients
Background: Tuberculosis kills five lakh patients in India every year, out of which 7-12 % are with meningeal involvement. Delay in its diagnosis and in initiation of treatment results in poor prognosis and sequlae in up to 25% of cases. The aim of the present study is to look for a simple, rapid, cost effective, non-invasive and fairly specific test in differentiating tubercular etiology from other causes.
BMC infectious diseases, 2017
The diagnosis of tuberculous meningitis (TBM) can be extremely difficult in the absence of culture confirmation. Cerebrospinal fluid (CSF) adenosine deaminase (ADA) can potentially assist in this regard, although its current value remains unclear. The literature on the usefulness of CSF ADA in TBM diagnosis is inconsistent, especially from an analytical point of view. A retrospective analysis of clinical and laboratory data relating to all CSF ADA requests during 2009 and 2010 in a South African quaternary healthcare setting was performed. A CSF ADA cut-off for TBM diagnosis was calculated using receiver operating characteristic curve analysis. The performance of CSF ADA in different infective and non-infective categories was assessed. In total, 3548 CSF ADA requests were considered over the 2-year period. Of these, 1490 were for patients for whom both a CSF ADA and a mycobacterial culture were requested. The optimal cut-off was calculated at 2.0 U/L (AUC = 0.86; 95% CI = 0.82 - 0.8...