1. Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting.
- Author
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Dheda K, Van-Zyl Smit RN, Sechi LA, Badri M, Meldau R, Symons G, Khalfey H, Carr I, Maredza A, Dawson R, Wainright H, Whitelaw A, Bateman ED, and Zumla A
- Subjects
- Adenosine Deaminase analysis, Biomarkers, Biopsy, Diagnosis, Differential, Endemic Diseases, Mycobacterium tuberculosis immunology, Mycobacterium tuberculosis isolation & purification, Nucleic Acid Amplification Techniques, Pleural Effusion immunology, Pleural Effusion microbiology, Pleural Effusion, Malignant diagnosis, Prospective Studies, Sensitivity and Specificity, South Africa epidemiology, Tuberculosis, Pleural epidemiology, Tuberculosis, Pleural immunology, Tuberculosis, Pleural microbiology, Tuberculosis, Pleural pathology, Antigens, Bacterial analysis, Chemokine CXCL10 analysis, Lipopolysaccharides analysis, Pleural Effusion diagnosis, Tuberculosis, Pleural diagnosis
- Abstract
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.
- Published
- 2009
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