Specificity Of Adenosine Deaminase Research Articles

Validity of Adenosine Deaminase (ADA) Level in Pleural Fluid for the Diagnosis of Tuberculosis

Introduction: The pleural fluid LDH/ADA ratio, which can be determined from routine biochemical analysis, is highly predictive of TPE at a cut-off level of 16.20. Measurement of this parameter may be helpful for clinicians in distinguishing between TPE and PPE. Despite wide variations in the reported sensitivity and specificity of pleural fluid ADA level, it can be used as a surrogate for pleural biopsy when the latter is not feasible. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. Objectives: To determine the diagnostic accuracy of ADA level in pleural fluid for the diagnosis of TB as compared to other conventional methods available like gene expert. Materials & Methods: The design of this study was a cross sectional study design. This study was conducted in Medicine Unit III, S.P.H. Quetta and the duration of this study was from 23rd October 2019 to 22nd April 2020. A total of 423 patients with pulmonary TB between the ages of 25 years to 45 years, having developed pleural effusion were included. Patients with pleural effusion due to causes other than TB, having extra pulmonary TB and those with other respiratory infections were excluded. Tests done specifically for TB in our setup include sputum AFB, CXR, and genexpert. These patients’ pleural fluid ADA were then sent. Results: Adenosine deaminase (ADA) found that 217 were True Positive and 13 were False Positive. Among 193, adenosine deaminase (ADA) negative patients, 12 (False Negative) had TB on gene expert whereas 181 (True Negative) had no TB on gene expert (p=0.0001). Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of ADA level in pleural fluid for the diagnosis of TB as compared to other conventional methods available like gene expert was 94.76%, 93.30%, 94.35%, 93.78% and 94.09% respectively. Practical Implication: This study was conducted to determine the validity of ADA levels for the diagnosis of TB and the results of this study if favorable will decrease the need for other laboratory tests usually done which take longer time, thus helping to decrease the need for multiple tests, early availability of report and timely management of the disease. This will further help to reduce the contact rate of TB and the risk of developing MDR TB by starting early treatment. Conclusion: This study concluded that diagnostic accuracy of ADA level in pleural fluid for the diagnosis of TB is quite high. Keywords: Pulmonary Tuberculosis, Pleural Fluid, Adenosine Deaminase, Biochemical, Mycobacterium .

Diagnostic Value of Pleural Fluid Adenosine Deaminase In Patients With Pleural Tuberculosis

Background and Objectives Extra-pulmonary tuberculosis occurs in about 10-20% of patients with tuberculosis. It most commonly manifests as tuberculous lymphadenitis or pleural effusion. Pleural fluid Adenosine deaminase (ADA) activity considered as a useful biomarker for detecting pleural tuberculosis. The purpose of this study was to evaluate the diagnostic accuracy of pleural fluid adenosine deaminase level in patients with pleural tuberculosis. Methods In this study, 113 patients with exudative pleural effusion with unknown underlying diagnosis, were enrolled. Physical examination, chest CT, ADA level of pleural fluid, direct thoracoscopic examination, and biopsy of pleura were obtained for all individuals. ADA level and thoracoscipoc appearance of the lesions was then compaierd among the patients with regard to the pleural biopsy report as the diagnostic goldstandard. Results The diagnosis of tuberculous pleurisy was established in 40 individuals based on the pathology reports. The mean ADA level of the TB and the non-TB group was 39.90±22.93 IU/L and 30.74±38.27 IU/L, respectively (P-value=0.167). Sensitivity, specificity, positive predictive value, and negative predictive value of ADA test were 35%, 86.30%, 58.33%, and 70.79%, respectively. Conclusion Based insuffiecient sensitivity and specificity of ADA, in patients with unexplained exudative pleural effusion especially in those with a high suspicion of tuberculous pleurisy, despite the low level of ADA, direct thoracoscopic pleural evaluation with obtaining multiple biopsies of pleura is highly recommended.

Diagnostic performance of adenosine deaminase for abdominal tuberculosis: A systematic review and meta-analysis.

Background and aimAbdominal tuberculosis (TB) is a common type of extrapulmonary TB with an insidious onset and non-specific symptoms. Adenosine deaminase (ADA) levels increase rapidly in the early stages of abdominal TB. However, it remains unclear whether ADA serves as a diagnostic marker for abdominal TB.MethodsWe performed a systematic literature search for relevant articles published in PubMed, Web of Science, Cochrane Library, and Embase up to April 2022. First, we used the Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2), to evaluate the quality of the included articles. Bivariate and hierarchical summary receiver operating characteristic (HSROC) models were then utilized to analyze pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC). In addition, we explored a subgroup analysis for potential heterogeneity and publication bias among the included literature.ResultsTwenty-four articles (3,044 participants, 3,044 samples) which met the eligibility criteria were included in this study. The pooled sensitivity and specificity of ADA for abdominal TB detection were 93% [95% confidence interval (CI): 0.89–0.95] and 95% (95% CI: 0.93–0.96), respectively. PLR and NLR were 18.6 (95% CI: 14.0–24.6) and 0.08 (95% CI: 0.05–0.12), respectively. DOR and AUROC were 236 (95% CI: 134–415) and 0.98 (95% CI: 0.96–0.99), respectively. Furthermore, no heterogeneity or publication bias was found.ConclusionsOur meta-analysis found ADA to be of excellent diagnostic value for abdominal TB and could be used as an auxiliary diagnostic tool.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42022297931.

Factors Predictive of Varicella Zoster Virus Encephalitis/Meningitis: A Single-Center, Retrospective Study.

BackgroundThe outcomes of varicella zoster virus (VZV) encephalitis/meningitis vary from complete recovery to severe complications. This study aimed to investigate the predictive factors of encephalitis and meningitis caused by VZV reactivation.Material/MethodsVZV encephalitis/meningitis patients (n=39) who were treated between January 2019 and December 2021 were included. Patients were followed up for 3 months after discharge and divided into a favorable outcome group (FO, n=18; 46.2%) and an unfavorable outcome group (UO, n=21; 53.8%) according to whether it affects quality of life. The clinical data were retrospectively analyzed and compared between groups.ResultsAs compared to the FO group, patients in the UO group were more likely to have higher body temperature (>38°C) at admission, longer interval from onset of CNS symptoms to initial of antiviral therapy, higher white blood cells (WBC) and adenosine deaminase (ADA) in the cerebrospinal fluid (CSF) and higher CRP in the blood (P<0.05 or P<0.01). Univariate logistic regression analysis showed CSF ADA (OR=1.279, 95% CI: 0.996~1.642) and interval from onset of CNS symptoms to initial of antiviral therapy (OR=1.299, 95% CI: 1.011~1.669) were independent risk factors for unfavorable outcomes (P<0.05). The sensitivity and specificity of combined CSF ADA and time interval from onset of CNS symptoms to initial of antiviral therapy were 78.8% and 95.2%, respectively, in predicting outcomes.ConclusionsHigher CSF ADA and longer interval from onset of CNS symptoms to initial of antiviral therapy predict an unfavorable outcome, and the combination of both factors can achieve better performance.

To study the diagnostic yield of pleural fluid adenosine deaminase (ADA) combined with Lymphocytic/Neutrophil (L/N) ratio in tubercular pleural effusion at a tertiary care center

Introduction: Tuberculosis is one of the leading causes of death worldwide and tubercular pleural effusion is the second most common form of extrapulmonary tuberculosis after lymph node tuberculosis. The most commonly used method to diagnose exudative pleural effusion is by the help of Light’s Criteria. The goal of our study was to search for another diagnostic tool that may have a better diagnostic yield for diagnosing pleural effusion than the present methods. Material and Methods: A prospective observational study was conducted in the pulmonary medicine department of a tertiary care center over a period of 18 months, where patients with pleural effusion were enrolled in the study after proper informed consent. These effusion cases were differentiated among tubercular and non-tubercular groups by recognized methods. Among these cases, the non-tubercular patients were taken as controls. Results: A total of 45 cases were taken after considering the inclusion and exclusion criteria, with 30 tubercular effusion cases and 15 controls. The sensitivity and specificity of combined ADA &amp; LNR were calculated to be 94.4% with a test accuracy of 89.29%. Conclusion: Our study concludes, that tubercular pleural effusion contributes substantially to the burden of disease in the world including in India.

Adenosine deaminase as a marker for the severity of infectious mononucleosis secondary to EBV in children

BackgroundInfectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed to determine whether adenosine deaminase is a marker of severity in children with infectious mononucleosis, especially those with elevated alanine transaminase levels.MethodsThis case-control study was conducted at the Children’s Hospital of Soochow University. A total of 104 children with infectious mononucleosis and 50 controls with other acute infections and fever, tonsillitis, or lymphadenitis, were enrolled in the study. Among the 104 children with infectious mononucleosis, 54 had normal alanine transaminase levels and 50 had elevated alanine transaminase levels. The children’s clinical and laboratory data were analyzed to assess the diagnostic value of adenosine deaminase in the three groups.ResultsThe adenosine deaminase level in the infectious mononucleosis group was significantly higher than that in the control group (P < 0.001). The adenosine deaminase levels were highly correlated with lymphocyte count, CD3+CD8+ T cells (%), CD4+/CD8+ ratio, and CD3−CD19+ (%) (r > 0.7, P < 0.01). The sensitivity and specificity of adenosine deaminase in predicting children with infectious mononucleosis were 97.1% and 94.0%, respectively. Furthermore, multivariate regression analysis revealed that adenosine deaminase level was a risk factor for elevated alanine transaminase in children with infectious mononucleosis.ConclusionsAdenosine deaminase may be a marker of the severity of infectious mononucleosis in children, and a predictor of elevated alanine transaminase in children with infectious mononucleosis.

The Applicability of ADA, AFU, and LAC in the Early Diagnosis and Disease Risk Assessment of Hepatitis B-Associated Liver Cirrhosis and Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the applicability of adenosine deaminase (ADA), α-l-fucosidase (AFU), lactic acid (LAC), and their combined detection in the early diagnosis of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC).Methods: A retrospective analysis of hepatitis B-positive liver disease patients admitted between 2015 and 2020 was conducted. The receiver operating characteristic (ROC) curve was used to determine the diagnostic value of each indicator in LC and HCC, and binary logistic regression analysis was performed to determine the factors and risks related to the occurrence of the two conditions.Results: The levels of ADA, AFU, and LAC were significantly increased in patients with CHB, LC, and HCC (p < 0.05). The ROC curve showed that the sensitivity and specificity of ADA, AFU, LAC, and their combined detection in the CHB and LC groups as well as in the LC and HCC groups reflected different degrees of clinical value. In the CHB and LC groups, the adjusted odds ratio (OR) values of ADA, AFU, and LAC among patients in the high-level group were 3.218, 1.859, and 11.474, respectively, when the median was considered the cutoff point. When quartiles were considered the cutoff point, the OR risk values of the adjusted levels of ADA, AFU, and LAC were higher than those of the lowest-level group (Q1) (p < 0.05). In the LC and HCC groups, the adjusted OR values of ADA, AFU, and LAC among patients in the high-level group were 0.967, 2.365, and 38.368, respectively. When quartiles were considered the cutoff point, the OR risk values of AFU and LAC levels were higher than those of the lowest-level group (Q1) (p < 0.05).Conclusion: ADA, AFU, and LAC demonstrated good value in the early diagnosis of LC and HCC. The combined detection of ADA+AFU+LAC is more effective than single detection for the early diagnosis of the two conditions. ADA, AFU, and LAC can serve as risk predictors of LC, while AFU and LAC can be considered early risk predictors of HCC.

Adenosine deaminase for diagnosis of tuberculous pleural effusion: A systematic review and meta-analysis.

ObjectivePleural fluid adenosine deaminase (ADA) is a useful diagnostic test for tuberculous pleural effusion (TPE), but its exact threshold and accuracy in clinical decision-making is unclear. We aimed to assess diagnostic performance of ADA in TPE and to clarify its optimal diagnostic threshold.MethodsWe searched PubMed, Embase, and Cochrane Library databases for articles indexed up to October 2018. We included English language studies that provided both sensitivity and specificity of ADA in TPE diagnosis. Summary estimates for sensitivity and specificity were obtained through bivariate random effects model, both overall and at prespecified threshold ranges of <36, 40±4, 45–65 and >65 IU/L.ResultsWe retrieved 2162 citations, and included 174 publications with 27009 patients. All studies showed high risk of bias. Summary sensitivity, specificity and diagnostic odds ratio estimates were 0.92 (95% CI 0.90–0.93), 0.90 (95% CI 0.88–0.91) and 97.42 (95% CI 74.90–126.72) respectively. 65 studies with ADA threshold of 40±4 IU/L showed summary sensitivity and specificity of 0.93 (95% CI 0.90–0.95) and 0.90 (95% CI 0.87–0.91) respectively. Four studies with ADA threshold >65 IU/L showed summary sensitivity and specificity of 0.86 (95% CI 0.61–0.96) and 0.94 (95% CI 0.80–0.99) respectively.ConclusionADA levels in pleural fluid show good diagnostic accuracy in diagnosis of TPE; however, all included studies showed high risk of bias. It was not possible to derive any firm inference on relative clinical utility of different diagnostic thresholds.

Meta-analysis of Indian studies evaluating adenosine deaminase for diagnosing tuberculous pleural effusion.

To determine the diagnostic accuracy of pleural fluid adenosine deaminase (ADA) in diagnosing tuberculous pleural effusion (TPE) among Indian patients using systematic review and meta-analysis. The PubMed, Embase, IndMED and Cochrane databases and other relevant publications were searched to identify Indian studies evaluating the sensitivity and specificity of ADA in diagnosing TPE. Pooled diagnostic accuracy measures and 95% confidence intervals (95%CI) were generated using a bivariate random-effects model, and examined using forest plots and hierarchical summary receiver operating characteristic (HSROC) curves. Forty publications with 3524 patients were studied. Pooled sensitivity, specificity and diagnostic odds ratio estimates were high (0.94, 95%CI 0.89-0.96; 0.89, 95%CI 0.83-0.93; and 119.85, 95%CI 48.35-297.08, respectively). The area under the HSROC curve was 0.966. The most common ADA threshold was 40 international units (IU)/l in 18 studies. Pooled positive and negative likelihood ratios for thresholds between 38 and 42 IU/l were respectively 6.80 (95%CI 4.18-11.07) and 0.06 (95%CI 0.03-0.11). There was no clear change in diagnostic performance with increasing ADA thresholds. Multivariate meta-regression did not reveal any factor that significantly influenced the substantial heterogeneity between studies. Pleural fluid ADA has good diagnostic accuracy for TPE in Indian patients, and appears more useful at excluding TPE at a threshold value of around 40 IU/l.

A study of Cerebrospinal Fluid Adenosine deaminase and C-reactive protein in Bacterial, Tubercular and Viral meningitis.

Cerebrospinal Fluid Adenosine deaminase (ADA) activity and C-reactive protein (CRP) measurement were done in 30 patients of tubercular meningitis (TBM), 36 patients of bacterial meningitis (BM) and 34 patients of Viral meningitis (VM), to evaluate, whether CSF CRP and ADA levels could be used to differentiate the bacterial, tubercular & viral meningitis. The mean CSF ADA activity was significantly raised in TBM as compared to BM and VM. (p< 0.001) while mean CSF CRP activity was significantly raised in BM as compared to TBM and VM. (p< 0.001). At cut of level 10 IU/L, the sensitivity and specificity of ADA for TBM was 90% and 97.14% respectively while at cut of level 15 mg/L, the sensitivity and specificity of the CRP for BM was 86.11% and 98.43% respectively. Since both the tests are simple and take lesser time to perform, they can be used to differentiate BM, TBM and VM.

Utility of adenosine deaminase (ADA), PCR & thoracoscopy in differentiating tuberculous & non-tuberculous pleural effusion complicating chronic kidney disease.

Pleural effusion is a common occurrence in patients with late-stage chronic kidney disease (CKD). In developing countries, many effusions remain undiagnosed after pleural fluid analysis (PFA) and patients are empirically treated with antitubercular therapy. The aim of this study was to evaluate the role of adenosine deaminase (ADA), nucleic acid amplification tests (NAAT) and medical thoracoscopy in distinguishing tubercular and non-tubercular aetiologies in exudative pleural effusions complicating CKD. Consecutive stage 4 and 5 CKD patients with pleural effusions underwent PFA including ADA and PCR [65 kDa gene; multiplex (IS6110, protein antigen b, MPB64)]. Patients with exudative pleural effusion undiagnosed after PFA underwent medical thoracoscopy. All 107 patients underwent thoracocentesis with 45 and 62 patients diagnosed as transudative and exudative pleural effusions, respectively. Twenty six of the 62 patients underwent medical thoracoscopy. Tuberculous pleurisy was diagnosed in six while uraemic pleuritis was diagnosed in 20 subjects. The sensitivity and specificity of pleural fluid ADA, 65 kDa gene PCR, and multiplex PCR were 66.7 and 90 per cent, 100 and 50 per cent, and 100 and 100 per cent, respectively. Thoracoscopy was associated with five complications in three patients. Uraemia remains the most common cause of pleural effusion in CKD even in high TB prevalence country. Multiplex PCR and thoracoscopy are useful investigations in the diagnostic work-up of pleural effusions complicating CKD while the sensitivity and/or specificity of ADA and 65 kDa gene PCR is poor.

Adenosine Deaminase Assay in Different Body Fluids for the Diagnosis of Tubercular Infection

Diagnosis of tuberculosis from different body fluids remains challenging due to various limitations of the conventional and molecular methods. We studied the role of adenosine deaminase (ADA) assay to diagnose tubercular infection in cerebrospinal fluid, peritoneal fluid and pleural fluid. Fifty three patients with tubercular meningitis, peritonitis and pleuritis were enrolled in this study on the basis of clinical, radiological, cytological, biochemical and somewhere bacteriological evidences. Cases positive by AFB smear, culture or PCR were considered as confirmed TB and other as probable TB cases. Another 28 non-TB cases were included as control. In 53 suspected TB cases ADA was found positive in highest 42 (79.2%) cases, whereas smear and/ culture in 10 (18.7%) and PCR in 18 (33.9%) cases. ADA assay revealed 100% positivity in confirmed TB cases and 14.3% in non TB cases. The sensitivity and specificity of ADA was found 79% and 86% respectively when the cut off value was used ≥ 10 IU/L for CSF and ≥ 40 IU/L for pleural or peritoneal fluid. Mean ADA values of confirmed and probable TB cases were found significantly higher than that of non TB cases (< 0.05). Significance of difference was determined by ANOVA and Kruskal-Wallis test. Thus, adenosine deaminase assay in body fluids has proved to be efficient, reliable and simple method to diagnose tubercular meningitis, peritonitis and pleuritis.

Pleural Fluid Adenosine Deaminase (ADA) Level in Tuberculous Pleurisy

Adenosine Deaminase (ADA) is used as a well established biological marker for diagnosis of tuberculous pleuritis. The aim of this study was to assess the sensitivity and specificity of ADA in patients with pleural effusion admitted in the medical ward. This was an cross sectional study. The information was gathered only from those patients whose pleural fluid sample was sent for ADA in clinical biochemistry laboratory of KIST Medical College and Teaching hospital. The data was acquired from the medical records of patients attending medical ward. The patients were considered as TB positive if they were clini­cally diagnosed so and taken as negative otherwise. Fifty six pleuritis patients were evaluated. Using the cut off value of 30 U/L, the overall sensitivity and specificity was 93.3% and 57.1% respectively. The association between ADA findings and the clinical findings were statistically significant (p &lt;0.001). The positive predictive value (PVP) and the negative predictive value (PVN) were 82.3% and 80% respectively. ADA is an inexpensive, rapid and simple test for analysis of tuberculous pleuritis. Though, it is a sensitive test for tuberculosis, due to its low specificity, sometimes negative cases can be considered as positive. DOI: http://dx.doi.org/10.3126/jcmc.v3i3.8634Journal of Chitwan Medical College 2013; 3(3): 26-27

Diagnostic Accuracy of Adenosine Deaminase and Lymphocyte Proportion in Pleural Fluid for Tuberculous Pleurisy in Different Prevalence Scenarios

BackgroundTuberculous pleural effusion (TPE) is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. We analyse the diagnostic usefulness of ADA alone and the combination of ADA ≥40 U/l (ADA40) and LP≥50% (LP50) in three different prevalence scenarios over 11 years in our area.Materials and MethodsBiochemistry, cytology and microbiology studies from 472 consecutive pleural fluid samples were retrospectively analyzed. ADA and differential cell count were determined in all samples. We established three different prevalence periods, based on percentage of pleural effusion cases diagnosed as tuberculosis: 1998–2000 (31.3%), 2001–2004 (11.8%), and 2005–2008 (7.4%). ROC curves, dispersion diagrams and pre/post-test probability graphs were produced. TPE accounted for 73 episodes (mean prevalence: 15.5%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ADA40 were 89%, 92.7%, 69.2% and 97.9%, respectively. For ADA40+LP50 the specificity and PPV increased (98.3% and 90%) with hardly any decrease in the sensitivity or NPV (86.3% and 97.5%). No relevant differences were observed between the three study periods.Conclusions/SignificanceADA remains useful for the diagnosis of TPE even in low-to-intermediate prevalence scenarios when combined with the lymphocyte proportion.

Diagnostic efficacy of adenosine deaminase levels in cerebrospinal fluid in patients of tubercular meningitis: A comparison with PCR for Mycobacterium Tuberculosis.

The rapid diagnosis of Tubercular meningitis (TBM) is fundamental to clinical outcome. The key to diagnosis lies in Cerebrospinal fluid (CSF) analysis and radiological investigations. There are numerous lacunae in the confirmation of diagnosis of TBM from CSF. The aim of present study was to compare the efficacy of CSF adenosine deaminase (ADA) level assays and Polymerase chain reaction (PCR) for Mycobacterium tuberculosis (M. tuberculosis) in the diagnosis of TBM. Fifty four adult patients with suspected TBM and 37 controls were included in the study and CSF analyzed for ADA and PCR for M. tuberculosis. The cases were subdivided into definite (5), highly probable (22), probable (22) and possible TBM (5) as per previously validated criteria. The first two were grouped as "most likely" TBM (27) and last two as "unconfirmed" TBM (27). The mean ADA of the "most likely" TBM was 29±24, "unconfirmed" TBM was 21 ± 15 and controls were 4.8±2.2 U/L. The ADA levels correlated with CSF proteins, absolute lymphocyte count and the staging of the disease. Using a cut off level of >L10 U/L, CSF ADA had a sensitivity of 92.5% and specificity of 97%. PCR for M. 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. PCR for M. tuberculosis had a sensitivity of 44.5% and specificity of 92% in the "most likely" TBM cases. ADA is a rapid, inexpensive and sensitive test in the diagnosis of TBM. It is more sensitive than AFB smear and culture. PCR is another rapid test in the diagnosis of TBM with a good specificity, even in those patients already on presumptive anti-tuberculous treatment. However, despite the sensitivity and specificity of CSF ADA, it should be corroborated with AFB smear and CSF PCR.

Structural and Metabolic Specificity of Methylthiocoformycin for Malarial Adenosine Deaminases

Plasmodium falciparum is a purine auxotroph requiring hypoxanthine as a key metabolic precursor. Erythrocyte adenine nucleotides are the source of the purine precursors, making adenosine deaminase (ADA) a key enzyme in the pathway of hypoxanthine formation. Methylthioadenosine (MTA) is a substrate for most malarial ADAs, but not for human ADA. The catalytic site specificity of malarial ADAs permits methylthiocoformycin (MT-coformycin) to act as a Plasmodium-specific transition state analogue with low affinity for human ADA [Tyler, P. C., Taylor, E. A., Frohlich, R. G. G., and Schramm, V. L. (2007) J. Am. Chem. Soc. 129, 6872-6879]. The structural basis for MTA and MT-coformycin specificity in malarial ADAs is the subject of speculation [Larson, E. T., et al. (2008) J. Mol. Biol. 381, 975-988]. Here, the crystal structure of ADA from Plasmodium vivax (PvADA) in a complex with MT-coformycin reveals an unprecedented binding geometry for 5'-methylthioribosyl groups in the malarial ADAs. Compared to malarial ADA complexes with adenosine or deoxycoformycin, 5'-methylthioribosyl groups are rotated 130 degrees . A hydrogen bonding network between Asp172 and the 3'-hydroxyl of MT-coformycin is essential for recognition of the 5'-methylthioribosyl group. Water occupies the 5'-hydroxyl binding site when MT-coformycin is bound. Mutagenesis of Asp172 destroys the substrate specificity for MTA and MT-coformycin. Kinetic, mutagenic, and structural analyses of PvADA and kinetic analysis of five other Plasmodium ADAs establish the unique structural basis for its specificity for MTA and MT-coformycin. Plasmodium gallinaceum ADA does not use MTA as a substrate, is not inhibited by MT-coformycin, and is missing Asp172. Treatment of P. falciparum cultures with coformycin or MT-coformycin in the presence of MTA is effective in inhibiting parasite growth.

Differential Diagnosis of Tuberculous and Malignant Pleural Effusions: What is the Role of Adenosine Deaminase?

The objective of this study was to evaluate the utility of invasive and noninvasive diagnostic procedures in tuberculous pleurisy (TPE) in an area with intermediate incidence of tuberculosis. The aim was to determine the cutoff value for adenosine deaminase (ADA) and the sensitivity and specificity of ADA and evaluate pleural fluid cytology and pleural biopsy in the differential diagnosis of malignant and tuberculous pleurisy. The study included 121 patients. TPE was confirmed in 54 patients and malignant effusion in 67 patients. Criteria used for TPE diagnosis were positive cultures of effusion or biopsy specimen, tuberculous granulomas, or positive sputum cultures without other explanation for pleural effusion. Malignancy was diagnosed by either cytology or biopsy. The cutoff value of ADA in TPE was 49 U/L, sensitivity was 89.2%, specificity was 70.4%, positive predictive value (PPV) was 84.4%, and negative predictive value (NPV) was 78.4%. ADA activity below 16 U/L suggests that TPE is highly unlikely with sensitivity=38.5%, specificity=100%, PPV=100%, and NPV=57.4%. ADA effusion/serum ratio reached a cutoff in TPE of 1.7 (sensitivity=84.6%, specificity=72.2%, PPV=81.4%, NPV=71.4%). Sensitivity, specificity, PPV, and NPV of cytology evaluation for TPE are 72.2%, 70.1%, 66.1%, and 75.8%, respectively. Pleuroscopy-guided pleural biopsy had sensitivity=66.7%, specificity=100%, PPV=100%, and NPV=78.8%. In 27.8% of TPE cases, pleural fluid cultures were positive. There is no doubt that pleuroscopy-guided biopsy is of great value for TPE diagnosis; however, sensitivity and specificity of noninvasive tests, especially ADA, can help to distinguish between TB and malignancy.

Evaluation of polymerase chain reaction and adenosine deaminase assay for the diagnosis of tuberculous effusions in children

Aim: To evaluate and compare the utility of polymerase chain reaction (PCR) for the diagnosis of tuberculous effusions in children. Methods: PCR, adenosine deaminase (ADA) activity and absolute lymphocyte count...

Inhibition and Substrate Specificity of Adenosine Deaminase. Interaction with 2′-, 3′- and/or 5′-Substituted Adenine Nucleoside Derivatives

Abstract A series of adenine nucleoside derivatives, most of them prepared for the first time, have been evaluated as substrates or inhibitors of adenosine deaminase. The best inhibitory results were obtained with the 3′, 5′-di-O-benzoyl esters of 9-β-D-pentofuranosyladenines.