Diagnostic accuracy of adenosine deaminase and lymphocyte proportion in pleural fluid for tuberculous pleurisy in different prevalence scenarios

PLoS One. 2012;7(6):e38729. doi: 10.1371/journal.pone.0038729. Epub 2012 Jun 18.


Background: Tuberculous pleural effusion (TPE) is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. We analyse the diagnostic usefulness of ADA alone and the combination of ADA ≥ 40 U/l (ADA(40)) and LP ≥ 50% (LP(50)) in three different prevalence scenarios over 11 years in our area.

Materials and methods: Biochemistry, cytology and microbiology studies from 472 consecutive pleural fluid samples were retrospectively analyzed. ADA and differential cell count were determined in all samples. We established three different prevalence periods, based on percentage of pleural effusion cases diagnosed as tuberculosis: 1998-2000 (31.3%), 2001-2004 (11.8%), and 2005-2008 (7.4%). ROC curves, dispersion diagrams and pre/post-test probability graphs were produced. TPE accounted for 73 episodes (mean prevalence: 15.5%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ADA(40) were 89%, 92.7%, 69.2% and 97.9%, respectively. For ADA(40)+LP(50) the specificity and PPV increased (98.3% and 90%) with hardly any decrease in the sensitivity or NPV (86.3% and 97.5%). No relevant differences were observed between the three study periods.

Conclusions/significance: ADA remains useful for the diagnosis of TPE even in low-to-intermediate prevalence scenarios when combined with the lymphocyte proportion.

MeSH terms

  • Adenosine Deaminase / chemistry*
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Lymphocytes / pathology*
  • Male
  • Middle Aged
  • Pleural Effusion / diagnosis*
  • Pleural Effusion / etiology*
  • Prevalence
  • ROC Curve
  • Tuberculosis, Pleural / complications*
  • Tuberculosis, Pleural / epidemiology


  • Adenosine Deaminase