What is the sensitivity and specificity of Adenosine Deaminase (ADA) levels in cerebrospinal fluid (CSF) and pleural effusion for diagnosing tuberculous meningitis and pleurisy?

Adenosine Deaminase (ADA) Sensitivity and Specificity in CSF and Pleural Fluid for Tuberculosis Diagnosis

ADA testing is recommended for suspected tuberculous meningitis and pleural TB, with sensitivity of 79-91% and specificity of 91-93% in CSF (using 9-10 U/L cutoff) and sensitivity of 88-91% and specificity of 85-93% in pleural fluid (using 40 U/L cutoff). 1, 2

ADA in Cerebrospinal Fluid (CSF)

Diagnostic Performance

• Two meta-analyses of ADA in CSF showed:
  • First meta-analysis: 79% sensitivity and 91% specificity (using 9-10 U/L threshold) 1
  • Second meta-analysis: Threshold-dependent performance 1
    • 4 U/L threshold: >93% sensitivity, <80% specificity
    • 8 U/L threshold: <59% sensitivity, >96% specificity
• A 2010 systematic review found that ADA values from 1-4 U/L helped exclude TBM (sensitivity >93%, specificity <80%), while values >8 U/L improved diagnosis of TBM (sensitivity <59%, specificity >96%) 3
• A smaller study using 10 U/L as cutoff showed 94.73% sensitivity and 90.47% specificity with 90% positive predictive value and 95% negative predictive value 4

Clinical Application

• ADA levels provide supportive evidence and must be interpreted within the entire clinical context 1
• ADA cannot reliably distinguish between bacterial meningitis and tuberculous meningitis 3
• ADA testing is particularly valuable when there's difficulty differentiating tuberculous from non-tuberculous meningitis 4

ADA in Pleural Fluid

Diagnostic Performance

• Meta-analyses demonstrate excellent diagnostic performance for tuberculous pleural effusions:
  • Sensitivity: 88-91%
  • Specificity: 85-93% 2
• ADA levels >40 U/L are highly suggestive of tuberculous pleurisy 2
• One study showed 91% sensitivity and 93% specificity for pleural TB 5
• ADA-2 isoenzyme showed even better performance with 100% sensitivity, 96% specificity, and 97% efficiency 6

Clinical Application

• The American Thoracic Society/Infectious Diseases Society of America suggests measuring ADA levels in pleural fluid from patients with suspected pleural TB (conditional recommendation, low-quality evidence) 1, 2
• British Thoracic Society recommends pleural fluid ADA for diagnosing tuberculous pleural effusion in high prevalence populations and as an exclusion test in low prevalence populations 2
• Combining ADA with lymphocyte/neutrophil ratio ≥0.75 significantly improves specificity (88% sensitivity, 95% specificity) 2

ADA in Ascitic Fluid

Diagnostic Performance

• For tuberculous peritonitis without cirrhosis: 100% sensitivity and 96.6-100% specificity when ADA value is >32-40 U/L 1
• For tuberculous peritonitis with cirrhotic ascites:
  • 91.7% sensitivity, 92% specificity, and 91.9% accuracy using 32 U/L cutoff 1
  • 100% sensitivity and 93.3% specificity using 27 U/L cutoff 1

Limitations and Caveats

• ADA levels may be elevated in conditions other than TB:
  • Empyema and other pleural infections
  • Rheumatoid pleurisy
  • Some malignancies (especially lymphomas)
  • Nontuberculous mycobacterial infections 2
• ADA levels may not be elevated in patients with HIV and tuberculosis 2
• In cirrhotic patients, ADA assay shows lower sensitivity for tuberculous peritonitis due to low total protein in ascites fluid 1
• Different methods used to measure ADA and heterogeneity of data make standardization difficult 3

Improving Diagnostic Accuracy

• Combining ADA with other tests improves diagnostic yield:
  • Adding pleural biopsy histology and culture improves the diagnostic rate to about 90% 2
  • Interferon-gamma (IFN-γ) testing has excellent performance (sensitivity 89%, specificity 97%) 2
  • Using ADA alongside clinical context, radiographic findings, and other laboratory results enhances specificity 1

ADA testing represents a valuable, rapid, and relatively inexpensive diagnostic tool for tuberculous meningitis and pleural TB, though results must always be interpreted in the appropriate clinical context.