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

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, I2 = 44%). When only studies using the Giusti method were considered, DOR was 44.21 (95% CI 28.37-68.91, I2 = 40%). Among the studies that used a cut-off of 10 IU/L, DOR was 58.09 (95% CI 33.76-99.94, I2 = 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.