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

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-γ-inducible-10kDa 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 antigendetection
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 forM. tuberculosisor 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 ~20% of TB cases and mis-diagnosed ~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 antigendetection
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.