title: Adenosine deaminase and tuberculous meningitis--a systematic review with meta-analysis.
abstract: Tuberculous meningitis (TBM) is a severe infection of the central nervous system, particularly in developing countries. Prompt diagnosis and treatment are necessary to decrease the high rates of disability and death associated with TBM. The diagnosis is often time and labour intensive; thus, a simple, accurate and rapid diagnostic test is needed. The adenosine deaminase (ADA) activity test is a rapid test that has been used for the diagnosis of the pleural, peritoneal and pericardial forms of tuberculosis. However, the usefulness of ADA in TBM is uncertain. The aim of this study was to evaluate ADA as a diagnostic test for TBM in a systematic review. A systematic search was performed of the medical literature (MEDLINE, LILACS, Web of Science and EMBASE). The ADA values from TBM cases and controls (diagnosed with other types of meningitis) were necessary to calculate the sensitivity and specificity. Out of a total of 522 studies, 13 were included in the meta-analysis (380 patients with TBM). The sensitivity, specificity and diagnostic odds ratios (DOR) were calculated based on arbitrary ADA cut-off values from 1 to 10 U/l. ADA values from 1 to 4 U/l (sensitivity >93% and specificity <80%) helped to exclude TBM; values between 4 and 8 U/l were insufficient to confirm or exclude the diagnosis of TBM (p = 0.07), and values >8 U/l (sensitivity <59% and specificity >96%) improved the diagnosis of TBM (p < 0.001). None of the cut-off values could be used to discriminate between TBM and bacterial meningitis. In conclusion, ADA cannot distinguish between bacterial meningitis and TBM, but using ranges of ADA values could be important to improve TBM diagnosis, particularly after bacterial meningitis has been ruled out. The different methods used to measure ADA and the heterogeneity of data do not allow standardization of this test as a routine.
authors.affiliation: Department of Infectious and Parasitic Diseases, Hospital das Clinicas, School of Medicine, University of Sao Paulo, SP, Brazil.
authors.forename: Felipe Francisco
authors.initials: FF
authors.lastname: Tuon
authors.forename: Hermes Ryoiti
authors.initials: HR
authors.lastname: Higashino
authors.forename: Max Igor Banks Ferreira
authors.initials: MI
authors.lastname: Lopes
authors.forename: Marcelo Nóbrega
authors.initials: MN
authors.lastname: Litvoc
authors.forename: Angela Naomi
authors.initials: AN
authors.lastname: Atomiya
authors.forename: Leila
authors.initials: L
authors.lastname: Antonangelo
authors.forename: Olavo Munhoz
authors.initials: OM
authors.lastname: Leite
mesh_terms: D000243:Adenosine Deaminase / Q000134:cerebrospinal fluid*; D006801:Humans; D012680:Sensitivity and Specificity; D014390:Tuberculosis, Meningeal / Q000175:diagnosis*
chemical_list: D000243:Adenosine Deaminase