Cerebrospinal Fluid Adenosine Deaminase Activity Research Articles

Study of cerebrospinal fluid adenosine deaminase activity for differential diagnosis of tuberculous and non-tuberculous meningitis

Background: Diagnosing a case of tuberculous meningitis (TBM) has always been challenging. Numerous previous studies have demonstrated that cerebrospinal fluid-Adenosine deaminase (CSF-ADA) estimation is useful in the diagnosis of TBM and can differentiate TBM from other types of meningitis. Aims and Objectives: The current study aims to look for a simple, rapid, cost-effective, and specific test to differentiate tubercular etiology from other causes of meningitis. Materials and Methods: A total of 80 patients admitted to the hospital with signs and symptoms of meningitis were selected and divided into two groups: Group 1 (Cases): 40 patients of TBM, Group 2 (Control): 40 patients of pyogenic and viral meningitis. The CSF ADA was estimated by enzymatic method, CSF Protein by turbidimetric method, and CSF Glucose by Glucose oxidase (GOD) and Peroxidase (POD) method. Results: CSF ADA levels (mean ± SD) in the TBM and non-TBM groups were 10.874+7.72 IU/L and 2.44+1.757 IU/L, respectively (highly significant, P<0.001). With the CSF ADA cut off as >6 IU/L, the sensitivity of the test was 95%, and the specificity of 92.5%. On comparison of the values of CSF ADA in the two groups, the t value is −6.75, and the difference in these two values was found to be highly significant (P<0.01). Conclusion: ADA estimation in CSF is a simple, inexpensive, rapid, and specific method for making a diagnosis of tuberculous etiology in TBM. As a screening test, the determination of ADA activity in CSF can help the physician diagnose TBM early and reduce irreversible brain damage and neurologic sequelae by early administration of anti-tuberculous medications.

Determination of cerebrospinal fluid adenosine deaminase activity cut-off for the diagnosis of tuberculous meningitis in Hong Kong

AimsTuberculous meningitis (TBM) is a severe infection which may lead to serious complication and mortality. Prompt diagnosis and treatment are essential. There is a need for a simple and fast...

Study of adenosine deaminase levels in Tb meningitis and its comparision with other types of meningitis

Tubercular meningitis is a type of septic meningitis and is a significant cause of morbidity and mortality in developing countries like India due to lack of early and timely diagnosis and so the case of fatality remains higher. Cerebrospinal fluid (CSF) evaluation is single most important aspect of lab diagnosis in meningitis. Aims: 1. To evaluate the diagnostic significance of CSF adenosine deaminase (ADA) activity in tuberculous meningitis. 2. To compare the values of CSF ADA in different types of meningitis and with that of controls. Materials and Methods: It was clinical cross-sectional study of 25 cases of tuberculosis, 25 cases of pyogenic meningitis, and 25 cases of aseptic meningitis. Twenty five controls with age and sex matched individuals without evidence of any neurological diseases served as control for CSF ADA. Results: In this study of 100 patients, 25 (100%) patients of the tubercular group had CSF ADA levels of more than 10 IU/dL with a mean of 13.68 IU/dL with 80% of the patients having ADA levels between 11 and 15 IU/dL. Mean ADA levels of aseptic meningitis was 8.00 IU/dL, pyogenic was 5.76 IU/dL, and control group had mean ADA of 2.12 IU/dL. Conclusion: All patients with tuberculous meningitis had elevated CSF ADA activity. CSF ADA activity in tuberculous meningitis was significantly higher when compared with pyogenic meningitis, aseptic meningitis, and controls.

Role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in children

Background: Early and correct treatment is essential for successful outcome in patients of tuberculous men-ingitis. Adenosine deaminase activity in the cerebrospinal fluid has been found to be a simple and useful investigation in the diagnosis of tuberculous meningitis in children.Methods: It is a cross sectional observational hospital based study conducted at the Department of Paediatrics, Deccan College of Medical Sciences, Kanchanbagh, Hyderabad, India. Children aged 2 months to 12 years were included in the study during April 2016 to October 2016.Results: The mean value of adenosine deaminase activity in the cerebrospinal fluid of tuberculous meningitis cases was 13.3±14.49. The mean cerebrospinal fluid adenosine deaminase levels in tuberculous meningitis patients was significantly higher than non-tuberculous meningitis patients with P <0.01.Conclusions: The mean cerebrospinal fluid adenosine deaminase level was significantly raised in tuberculous meningitis patients.

Comparative analysis of cerebrospinal fluid adenosine deaminase levels in infective meningitis of different aetiologies

Background: Meningitis can be caused by bacteria, viruses, parasites, and fungi as well as by non-infectious conditions including inflammatory disorders (e.g., systemic lupus erythematosis or Kawasaki disease) and neoplasia (e.g., leukemic meningitis). The objective of this study were to study cerebrospinal fluid (CSF) adenosine deaminase (ADA) levels in infective meningitis of different aetiologies. And to assess the role of cerebrospinal fluids (CSF) adenosine deaminase (ADA) levels in differentiating tubercular from non-tubercular meningitis.Methods: The study was conducted on 70 patients of meningitis at Postgraduate Department of Paediatrics, in G. B. Pant Hospital, an associated hospital of Government Medical College Srinagar. Out of 70 patients included in the study 27 cases were Aseptic Meningitis (AM), 14 cases partially treated pyogenic -meningitis (PTM), 19 cases pyogenic meningitis (PM), and 10 cases were tubercular meningitis (TBM). ADA activity of CSF was quantified by colorimetry.Results: In our study we observed a significant high level of ADA 30.0±3.2U/L (20.0, 54.0) among the tubercular meningitis (TBM) patients and its respective level among Aseptic Meningitis (AM), was 8.1±0.3U/L (4.0, 11.5), partially treated pyo -meningitis (PTM) was 7.6±0.4U/L (5.0, 11.0), pyogenic meningitis (PM) was 11.6±0.5U/L (8.0, 14.5). In total Non-TBM ADA level was 9.1±0.3U/L (4.0, 14.5) units/liter. At cut off of > or equal to 10U/L sensitivity was 100% specificity66.67% positive predictive value33.33% negative predictive value of 100% diagnostic accuracy 71.43%. At a higher cut off of > or equal to 12U/L sensitivity was 100% and specificity increased to 81.67% positive predictive value 47.62% negative predictive value100% diagnostic accuracy was 84.29%.Conclusions: The sensitivity and specificity of CSF ADA activity is markedly high in differentiating TBM from non-TBM. Hence CSF ADA activity may be used as a simple, cost-effective and reliable test for early diagnosis of TBM.

Clinical characteristics and cerebrospinal fluid adenosine deaminase activity in patients with meningitis caused by Varicella-Zoster virus

Clinical characteristics and cerebrospinal fluid adenosine deaminase activity in patients with meningitis caused by Varicella-Zoster virus

The validity of cerebrospinal fluid parameters for the diagnosis of tuberculous meningitis

To assess the diagnostic validity of laboratory cerebrospinal fluid (CSF) parameters for discriminating between tuberculous meningitis (TBM) and other causes of meningeal syndrome in high tuberculosis incidence settings. From November 2009 to November 2011, we included patients with a clinical suspicion of meningitis attending two hospitals in Lima, Peru. Using a composite reference standard, we classified them as definite TBM, probable TBM, and non-TBM cases. We assessed the validity of four CSF parameters, in isolation and in different combinations, for diagnosing TBM: adenosine deaminase activity (ADA), protein level, glucose level, and lymphocytic pleocytosis. One hundred and fifty-seven patients were included; 59 had a final diagnosis of TBM (18 confirmed and 41 probable). ADA was the best performing parameter. It attained a specificity of 95%, a positive likelihood ratio of 10.7, and an area under the receiver operating characteristics curve of 82.1%, but had a low sensitivity (55%). None of the combinations of CSF parameters achieved a fair performance for 'ruling out' TBM. Finding CSF ADA greater than 6 U/l in patients with a meningeal syndrome strongly supports a diagnosis of TBM and permits the commencement of anti-tuberculous treatment.

Evaluation of Cerebrospinal fluid adenosine deaminase activity as a complimentary tool in the early diagnosis of tuberculous meningitis in children

The diagnosis of tuberculous meningitis cannot be made or excluded on the basis of clinical findings. Definite laboratory diagnosis is cumbersome and time consuming. Delay in diagnosis and institution of proper treatment is directly related to poor outcome and sequalae. Adenosine deaminase activity (ADA) was estimated in cerebrospinal fluid (CSF) in addition to routine CSF analysis of 32 patients of tuberculous meningitis (TBM) and 7 patients of partially treated pyomeningitis (PTM), 10 patients aseptic meningitis (AM) and 13 patients pyogenic meningitis (PM). Mean ADA levels in CSF of TBM patients were higher (15.42 U/L) as compared to 7.21 U/L, 6.41 U/L and 7.50 U/L in PTM, AM and PM respectively. This difference of ADA values in CSF between TBM and other types of meningitis was statistically significant (p<0.01). ADA values were also compared with other biochemical and cytological parameters of CSF & a positive correlation was found with CSF protein level. Sensitivity and specificity of ADA levels in CSF of children to diagnose tuberculous meningitis was 75% and 90% respectively at 10 U/L cut off of ADA levels in CSF. Journal of College of Medical Sciences-Nepal,2012,Vol-8,No-2, 17-23 DOI: http://dx.doi.org/10.3126/jcmsn.v8i2.6833

Evaluation of Cerebrospinal Fluid Adenosine Deaminase Activity for the Differential Diagnosis of Tuberculous and Nontuberculous Meningitis

IntroductionThe diagnosis value of adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of tuberculous meningitis (TBM) has been well documented. However, the cutoff point of CSF ADA has not been fully assessed. In the current study, the authors set to calculate the cutoff points of ADA and monitor the changes of CSF ADA activities in patients with TBM after antitubercular therapy. MethodsCSF ADA activity in patients with different types of meningitis was measured by Trinder enzyme-coupled assay. ResultsThe mean CSF ADA values in the patients with TBM, bacterial meningitis, viral meningitis, cryptococcal meningitis and noninfectious neurologic disorders were 14.1 ± 5.4, 9.6 ± 5.5, 4.3 ± 2.5, 7.8 ± 3.4 and 2.6 ± 1.3 U/L, respectively. CSF ADA activity was significantly higher in TBM compared with patients with non-TBM (P < 0.05). Moreover, the best cutoff point for differentiating between TBM and non-TBM was 9.5 U/L. In addition, CSF ADA activity was decreased in patients with TBM after antitubercular therapy in a time-dependent manner. ConclusionsThe determination of ADA with a cutoff value of 9.5 U/L in CSF is a useful aid for the differential diagnosis of TBM and non-TBM. Moreover, dynamic monitoring of CSF ADA activity may be an indicator for evaluating antitubercular therapy in TBM.

Comparative analysis of cerebrospinal fluid adenosine deaminase activity in meningitis

The purpose is to determine the cut-off value of adenosine deaminase (ADA) activity in cerebrospinal fluid (CSF) of patients with tuberculous and non-tuberculous meningitis, and to assess its value in differential diagnosis. This study was conducted in 91 patients with meningitis in two university hospitals in Turkey. 24 patients had tuberculous meningitis (TBM), 25 purulent meningitis (PM), 25 aseptic meningitis (AM) and 17 neurobrucellosis (BM). ADA activity of CSF was quantified by colorimetry. In our study, mean ADA values in CSF were 28.34 ± 14.83 IU/L in TB cases, 8.71 ± 5.83 IU/L in BM, 6.18 ± 2.54 IU/L in PM and 3.43 ± 3.48 U/L in AM cases. If we accept for CSF ADA an activity cut-off value of 12.5 IU/L for differential diagnosis of TBM and BM, its sensitivity was 92% and specificity was 88%. If we accept 12.35 IU/L for differential diagnosis of TBM and PM, its sensitivity was 92% and specificity was 100%. If we accept 6.45 IU/L for differential diagnosis of TBM and AM, its sensitivity was 100% and specificity was 92%. Additionally, we examined the cases after dividing them into two groups, viz. TB and non-TB. If we accept an ADA activity cut-off level of 11 IU/L for differential diagnosis of TB and non-TB by applying ROC analysis, its sensitivity was 92% and specificity was 90%. The sensitivity and specificity for CSF ADA activity are markedly high in differential diagnosis of TB from non-TB. Hence CSF ADA activity may be used as a simple, cost-effective and reliable test for early differential diagnosis of TB.

Diagnostic Evaluation of Adenosine Deaminase (ADA) Test in the Early Diagnosis of Tuberculous Meningitis

Objective: Tuberculous meningitis (TB M) is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB). The diagnosis of TBM is often difficult. A reliable, cost effective and rapid diagnostic test, which can be performed in any routine 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 modified Berthlot reaction, which is the formation of a colour indophenol complex from ammonia liberated from adenosine, and quantified spectrophotometrically. Results: ADA activity was studied in CSF of 45 cases of tuberculous meningitis, 20 cases of pyogenic meningitis and 20 controls (patients without any neurological disorders who were given spinal anaesthesia). The mean ADA activity was 13.43 ± 4.76, 8.23 ± 2.91 and 2.64 ± 1.57 IU/L in tuberculous meningitis, pyogenic meningitis and controls respectively. The higher level of ADA in tuberculous meningitis was statistically significant (p < 0.0001). The sensitivity and specificity of ADA test in CSF at cut-off 10 U/L was 100% and 93.75% respectively. Conclusion: This study demonstrated that adenosine deaminase activity in CSF, a relatively inexpensive and easy procedure, can be of great value in the diagnosis of tuberculous meningitis. This test can be performed in any routine laboratory where more sophisticated methods are not available.

Evaluation of cerebrospinal fluid adenosine deaminase activity in HIV-seropositive subjects and its association with lactate dehydrogenase and protein levels

The purpose of this study was to investigate the role of ADA as additional marker of HIV infection as well as its association with other biochemical markers. This study included 55 patients, 26 being diagnosed as HIV positive and 29 patients diagnosed as HIV negative. Glucose, total protein, lactate dehydrogenase, and adenosine deaminase (ADA) activity were measured on cerebrospinal fluid (CSF). ADA activity on CSF was statistically different in HIV-seropositive subjects compared with HIV-negative subjects. The sensitivity and specificity of ADA activity on CSF was 50 and 82.76%, respectively. ADA activity was positively correlated with lactate dehydrogenase and protein in patients with HIV positive and it was negatively correlated with glucose levels. ADA determination in CSF could add information about inflammatory processes in patients with HIV infection.

Cerebrospinal fluid adenosine deaminase activity: a complimentary tool in the early diagnosis of tuberculous meningitis.

BackgroundTuberculous meningitis (TBM) is the commonest form of neurotuberculosis caused by Mycobacterium tuberculosis bacilli (MTB). The diagnosis of TBM is often difficult. A reliable, cost-effective 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.MethodADA 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.ResultsThe 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 cut-off 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 cut-off value was used.ConclusionThis study demonstrated that ADA activity in the CSF of TBM patients, using a cut-off 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.

Adenosine deaminase activity in cerebrospinal fluid of HIV-infected patients: limited value for diagnosis of tuberculous meningitis

Adenosine deaminase activity (ADA) determination in cerebrospinal fluid (CSF) is considered a specific test for the diagnosis of tuberculous meningitis. In order to study the variability of this marker in patients with different neurological disorders associated with HIV infection, and its utility for the diagnosis of tuberculous meningitis in these patients, the ADA levels in 417 CSF samples from HIV-infected patients with neurological symptoms were reviewed. HIV infection, HIV-associated neurological disorders, and progressive multifocal leukoencephalopathy were not associated with elevated ADA in CSF. Among patients with meningitis, receiver operating characteristic curve analysis gave an optimal ADA cut-off point of 8.5 IU/l for the diagnosis of tuberculous meningitis, with 57% sensitivity, 87% specificity, and an area under the curve of 0.747 (similar to that for CSF glucose concentration). False-positive results were found in patients with neurological CMV disease and cryptococcal, lymphomatous, and probable candidal meningitis. The results of this study indicate that ADA determination in CSF has limited utility for the diagnosis of tuberculous meningitis in HIV-infected patients.

The possible role of cerebrospinal fluid adenosine deaminase activity in the diagnosis of tuberculous meningitis in adults

We studied an adenosine deaminase (ADA) activity in the cerebrospinal fluid (CSF) of 182 patients with meningitis. The patients were subdivided into four groups, (1) 36 cases of tuberculous meningitis; (2) 130 cases of viral or aseptic meningitis; (3) nine cases of bacterial meningitis; (4) seven cases of cryptococcal meningitis. Mean±S.D. ADA activity was 12.76±7.53 U/l in group 1; 2.58±2.37 U/l in group 2; 7.38±3.27 U/l in group 3; 7.42±4.38 U/l in group 4. Comparing the ADA activity in each group with the other groups, the difference is significant ( P<0.001), except between groups 3 and 4. The sensitivity of the test for group 1 compared with group 2 was 0.83 and the specificity was 0.95 when a cut-off value of 7 U/l was used. When group 1 was compared with groups 3 and 4, the sensitivity was 0.58 and the specificity was 0.89 and 0.71 with groups 3 and 4, respectively, when a cut-off value of 10 U/l was used. Values >15 U/l were not observed in any of the non-tuberculous meningitis patients; therefore, ADA activity >15 U/l could be a strong indication of tuberculous meningitis. We conclude that a determination of CSF ADA can aid in the early differential diagnosis of tuberculous meningitis.

Cerebrospinal Fluid Cytokines in Patients with Tuberculous Meningitis

The levels of tumor necrosis factor (TNF)-α, soluble TNF receptors p75 (sTNFR-75) and sTNFR-55, interferon (IFN)-γ, and interleukin (IL)-10 and IL-12 were measured in 59 cerebrospinal fluid (CSF) samples from 15 patients with tuberculous meningitis (TBM). TBM was associated with elevated concentrations of TNF-α, sTNFR-75, sTNFR-55, IFN-γ, and IL-10, while CSF IL-12 was undetectable in all TBM patients. A significant correlation between cytokines and CSF adenosine deaminase activity was also found. The levels of TNF-α did not decrease over time, being still detectable in the CSF 16 months after starting antibiotic therapy, whereas IFN-γ along with anti-inflammatory mediators sTNFR-75, sTNFR-55, and IL-10 remained elevated in the CSF for 4–8 months. The chronic release of cytokines in the CSF compartment was related neither to the TBM stage nor to the clinical outcome of the disease, thus suggesting the presence of a continuous activity of the inflammatory process at the site of infection.

Cerebrospinal fluid adenosine deaminase activity for the diagnosis of tuberculous meningitis in children.

Adenosine deaminase (ADA) activity was measured in the cerebrospinal fluid (CSF) of 27 subjects suffering from tuberculous meningitis (TBM), 19 from bacterial meningitis, 10 from encephalitis, and 10 control subjects. The mean CSF ADA level was significantly raised (P < 0.001) in TBM patients as compared to other study groups. A cut-off CSF ADA level of > 5 IU/1 was considered for the diagnosis of TBM, and the test had sensitivity and specificity of 89 and 92 per cent, respectively. Overall, it was found to be a better test in comparison to any other single test for the diagnosis of TBM. Confirmed TBM patients had significantly higher CSF ADA activity when compared with clinical TBM (P < 0.01) and the levels did not differ significantly among different stages of disease. The ADA level in TBM cases had significant correlation with CSF cell count (P < 0.01), lymphocyte percentage (P < 0.02) and protein concentration (P < 0.02). Thus, the CSF ADA activity assay was found to be a simple, useful and rapid diagnostic test for the early recognition of TBM in children.