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      Diagnostic accuracy of cerebrospinal fluid adenosine deaminase in detecting Tuberculous Meningitis

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          Abstract

          Objective:

          To determine diagnostic accuracy of Cerebro Spinal Fluid (CSF) Adenosine De-Aminase (ADA) in detecting Tuberculous Meningitis (TBM) keeping CSF Polymerase Chain Reaction (PCR) for Mycobacterium Deoxy Ribonucleic Acid (DNA) as gold standard.

          Methods:

          This cross sectional validation study was conducted at Department of General Medicine of PNS Shifa Naval Hospital Karachi, Pakistan from Oct 2015 to Mar 2017 for a total duration of one and a half year. One hundred and thirty six patients were included. The diagnosis of TBM was based clinically on symptoms like fever, headache, altered mental state and signs of meningeal irritation with CSF findings of increased proteins, low glucose and lymphocytic pleocytosis. Lumbar puncture was done and approximately 4ml of CSF sample was withdrawn for analysis. Diagnosis of TBM was confirmed by doing CSF PCR test for mycobacterium tuberculosis DNA.

          Results:

          Total 136 patients were enrolled in this study. Mean age in our study was 47.09±12.80 years, whereas frequency and percentages of male and female patients was 102 (75%) and 34 (25%) respectively. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of CSF ADA level in detecting TBM was 71.32%, 84.21%, 95.45%, 98.97% and 53.85% respectively.

          Conclusion:

          The study concludes that diagnostic accuracy of CSF ADA in detecting TBM is high which is proposed as an investigation to differentiate it from other causes of meningitis in places where PCR test is not available.

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          Most cited references11

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          Tuberculous meningitis in adults: a review of a decade of developments focusing on prognostic factors for outcome.

          Tuberculous meningitis (TBM) is the most severe form of TB. Despite treatment, mortality and long-term disability remain unacceptably high. Prevention, early recognition, diagnosis and treatment are fundamental to improving outcomes. However, an effective vaccine remains elusive, initial symptoms are nonspecific, and sensitive diagnostic tests are not available. There has been progress in our understanding of the immunopathology of TBM, and several factors have been found to be associated with susceptibility to infection, disease progression and clinical outcome. However, these have not yet impacted on treatment. Early treatment initiation and uninterrupted continuation, severity on presentation, seizures, stroke, cranial nerve involvement, cerebrospinal fluid cell count and lactate levels, hyponatreamia and coinfection with HIV are all found to be important prognostic factors for outcome. Pathogen lineage (Beijing genotype) and host genetics (polymorphisms in TLR2, TIRAP and LTA4H genes) can influence susceptibility to TBM. However, these findings have not yet impacted on treatment. Progress in vaccine development, opportunities for better diagnostic tests, novel insights into pathogenesis and an increasing evidence base for improving treatment should impact the current high mortality and morbidity, if translated to global and local guidelines.
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            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. Methods Forty patients between the age of 6 - 24 months attending hospital with symptoms and signs of meningitis were selected and divided into two groups: tubercular and non-tubercular, depending upon the accepted criteria. CSF was drawn and ADA estimated. Results Out of 19 tubercular patients, 18 had CSF ADA at or above the cutoff value while one had below. Out of 21 non-tuberculous patients, two had ADA levels at or above the cutoff value while 19 had below this value. Results of our study indicate that ADA level estimation in CSF is not only of considerable value in the diagnosis of TBM, CSF ADA level 10 U/L as a cutoff value exhibited 94.73% sensitivity and 90.47% specificity in differentiating tuberculous from non-tuberculous meningitis; it also has 90.00% positive predictive value and 95.00% negative predictive value. Conclusions It can be concluded that ADA estimation in CSF is not only simple, inexpensive and rapid but also fairly specific method for making a diagnosis of tuberculous etiology in TBM, especially when there is a dilemma of differentiating the tuberculous etiology from non-tuberculous ones. For this reason ADA estimation in TBM may find a place as a routine investigation. Keywords Cerebrospinal fluid; Adenosine deaminase; Tuberculous meningitis
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              To compare CSF adenosine deaminase levels and CSF-PCR for tuberculous meningitis.

              This study was planned to compare the adenosine deaminase (ADA) levels and polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) as a rapid method to diagnose tuberculosis meningitis (TBM). Fifty-four adult patients with suspected TBM and 37 controls were included in this study. The median ADA level was 21U/L of most likely TBM, 14U/L of unconfirmed TBM and 5U/L of controls. PCR for Mycobacterium 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. Using a cut off level of >10U/L, CSF-ADA had a sensitivity of 92.5% and specificity of 97% for the diagnosis of TBM. PCR for M. tuberculosis had a sensitivity of 44.5% and specificity 92% in the most likely TBM cases. This study shows that CSF-ADA is a more sensitive indicator than PCR for the diagnosis of M. tuberculosis. Copyright 2010 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Pak J Med Sci
                Pak J Med Sci
                Pakistan Journal of Medical Sciences
                Professional Medical Publications (Pakistan )
                1682-024X
                1681-715X
                Sep-Oct 2018
                : 34
                : 5
                : 1215-1218
                Affiliations
                [1 ]Dr. Aamir Habib, MBBS. PNS Shifa Naval Hospital, Karachi, Pakistan
                [2 ]Dr. Zulfiqar Ali Amin, FCPS(Medicine), FCPS(Oncology). PNS Shifa Naval Hospital, Karachi, Pakistan
                [3 ]Dr. Syed Hassan Raza, MBBS. PNS Shifa Naval Hospital, Karachi, Pakistan
                [4 ]Dr. Sobia Aamir, MBBS. PNS Shifa Naval Hospital, Karachi, Pakistan
                Author notes
                Correspondence: Dr. Aamir Habib, MBBS. Registrar, Department of Medicine, PNS Shifa Naval Hospital, DHA Phase 2, Karachi, Pakistan. E-mail: aamirhabib@ 123456hotmail.com
                Article
                PJMS-34-1215
                10.12669/pjms.345.13585
                6191780
                30344579
                247e1394-5352-41d9-bf97-a9113936736e
                Copyright: © Pakistan Journal of Medical Sciences

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 July 2017
                : 23 December 2017
                : 07 July 2018
                : 20 July 2018
                Categories
                Original Article

                meningitis,tuberculous meningitis,adenosine deaminase,cerebrospinal fluid

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