Abstract
BackgroundCurrent 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.MethodsWe 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 FindingsOf 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 antigen-detection was not diagnostically useful.ConclusionAlthough 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.
Highlights
Over half a million pleural effusions are diagnosed world-wide and it is one of the commonest forms of extra-pulmonary tuberculosis (TB; [1])
In this study we prospectively evaluated the comparative diagnostic utility of established, more recent and newer technologies (IP-10 levels and a standardized LAM mycobacterial antigen-detection assay) for the evaluation of pleural effusions in 78 South African tuberculosis suspects
The mean (SD) pleural fluid protein levels were significantly higher in the TB vs non-TB group [58.9(15.7) vs 43.4(18.5), respectively; p = 0.003]
Summary
Over half a million pleural effusions are diagnosed world-wide and it is one of the commonest forms of extra-pulmonary tuberculosis (TB; [1]). The diagnosis of TB pleural effusion is challenging. Other rapid diagnostic tools such as nucleic acid amplification tests (NAAT) have poor sensitivity in pleural fluid (,50%; [3]), though the performance outcomes of a standardized NAAT has not previously been evaluated in a high HIV sero-prevalence setting [3]. Given the drawbacks of existing tools investigators have pursued the detection of measurable biomarkers, including IFN-c levels [4] and adenosine-deaminase (ADA), as diagnostic adjuncts [2]. Measuring IFN-c is relatively expensive in high burden settings [5] and ADA is not widely available in clinical laboratories, and is non-specific even in high burden settings [2,6]. Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Detection of LAM antigen has not previously been evaluated in pleural fluid
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
