Role of cerebrospinal fluid adenosine deaminase measurement in the diagnosis of tuberculous meningitis: an updated systematic review and meta-analysis

Abstract

Abstract Introduction: Tuberculous meningitis (TBM) can be difficult to diagnose. Elevated cerebrospinal fluid (CSF) adenosine deaminase (ADA) is often seen in TBM, but its reliability has been questioned. A previous meta-analysis in 2017 had demonstrated the diagnostic utility of CSF ADA in TBM versus non-TBM. We sought to update this meta-analysis with more recent studies, to determine whether CSF ADA could be used to aid in the early recognition of TBM. Methods: Electronic searches were performed in PubMed and Scopus on studies published from 2016 to 2022. Ten additional studies were identified and added to 20 studies (from 2000 to 2016) from a previous meta-analysis. Meta-analysis was conducted using the random effects method, estimating the pooled diagnostic odds ratio (DOR) for elevated CSF ADA in the diagnosis of TBM. Results: Of the 30 studies included, 16/30 (53.3%) used the Giusti method for measuring ADA. Fourteen (46.7%) studies used an ADA cut-off of 10 IU/L, and 11 (36.7%) studies used an even lower cut-off. The pooled DOR for elevated CSF ADA in the diagnosis of TBM was 45.40 (95% confidence interval [CI] 31.96–64.47, I 2 = 44%). When only studies using the Giusti method were considered, DOR was 44.21 (95% CI 28.37–68.91, I 2 = 40%). Among the studies that used a cut-off of 10 IU/L, DOR was 58.09 (95% CI 33.76–99.94, I 2 = 41%). Conclusion: Studies remain heterogeneous but demonstrate that CSF ADA can differentiate TBM from non-TBM. In line with most studies, CSF ADA >10 IU/L supports the diagnosis of TBM in a patient with compatible symptoms and high-risk epidemiology.