The dubious value of cerebrospinal fluid adenosine deaminase measurement for the diagnosis of tuberculous meningitis

BACKGROUND: The diagnosis of tuberculous meningitis (TBM) can be extremely difficult in the absence of culture confirmation. Cerebrospinal fluid (CSF) adenosine deaminase (ADA) can potentially assist in this regard, although its current value remains unclear. The literature on the usefulness of CSF ADA in TBM diagnosis is inconsistent, especially from an analytical point of view. METHODS: A retrospective analysis of clinical and laboratory data relating to all CSF ADA requests during 2009 and 2010 in a South African quaternary healthcare setting was performed. A CSF ADA cut-off for TBM diagnosis was calculated using receiver operating characteristic curve analysis. The performance of CSF ADA in different infective and non-infective categories was assessed. RESULTS: In total, 3548 CSF ADA requests were considered over the 2-year period. Of these, 1490 were for patients for whom both a CSF ADA and a mycobacterial culture were requested. The optimal cut-off was calculated at 2.0 U/L (AUC = 0.86; 95% CI = 0.82 – 0.89; p-value < 0.01; sensitivity of 85.9% (95% CI of 77.0 – 92.3) and specificity of 77.7% (95% CI of 75.4 – 79.8%); positive likelihood ratio = 3.85 and negative likelihood ratio = 0.18). At this cut-off 13 TBM cases were missed. CONCLUSION: An optimal cut-off for routine use could not be established as too many TBM cases were missed. Specimen integrity, lack of ADA assay standardisation and overlap in performance of the assay in different diagnostic categories affect interpretation.