Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting

PLoS One. 2009;4(3):e4689. doi: 10.1371/journal.pone.0004689. Epub 2009 Mar 11.


Background: Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-gamma-inducible-10 kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid.

Methods: We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis.

Principal findings: Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed approximately 20% of TB cases and mis-diagnosed approximately 20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful.

Conclusion: Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / analysis
  • Antigens, Bacterial / analysis*
  • Biomarkers
  • Biopsy
  • Chemokine CXCL10 / analysis*
  • Diagnosis, Differential
  • Endemic Diseases
  • Lipopolysaccharides / analysis*
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / isolation & purification
  • Nucleic Acid Amplification Techniques
  • Pleural Effusion / diagnosis*
  • Pleural Effusion / immunology
  • Pleural Effusion / microbiology
  • Pleural Effusion, Malignant / diagnosis
  • Prospective Studies
  • Sensitivity and Specificity
  • South Africa / epidemiology
  • Tuberculosis, Pleural / diagnosis*
  • Tuberculosis, Pleural / epidemiology
  • Tuberculosis, Pleural / immunology
  • Tuberculosis, Pleural / microbiology
  • Tuberculosis, Pleural / pathology


  • Antigens, Bacterial
  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Lipopolysaccharides
  • lipoarabinomannan
  • Adenosine Deaminase