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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting
PLoS ONE, Volume 4, No. 3, Article e4689, Year 2009
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Description
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 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 ∼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. 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. Copyright: © 2009 Dheda et al.
Authors & Co-Authors
Dheda, Keertan U.J.
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Ucl Medical School
South Africa, Observatory
Groote Schuur Hospital
van Zyl-Smit, Richard N.
South Africa, Cape Town
University of Cape Town
Sechi, Leonardo Antonio
Italy, Sassari
Università Degli Studi Di Sassari
Badri, Motasim A.
South Africa, Cape Town
University of Cape Town
Meldau, Richard
South Africa, Cape Town
University of Cape Town
Symons, Greg J.
South Africa, Cape Town
University of Cape Town
Khalfey, Hoosain
South Africa, Cape Town
University of Cape Town
Carr, Igshaan
South Africa, Cape Town
University of Cape Town
Maredza, Alice
South Africa, Cape Town
University of Cape Town
Dawson, Rodney
South Africa, Cape Town
University of Cape Town
Wainright, Helen
South Africa, Cape Town
University of Cape Town
Whitelaw, Andrew C.
South Africa, Johannesburg
National Health Laboratory Service
South Africa, Cape Town
University of Cape Town
Bateman, E. D.
South Africa, Cape Town
University of Cape Town
Zumla, A. I.
United Kingdom, London
Ucl Medical School
Statistics
Citations: 86
Authors: 14
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pone.0004689
e-ISSN:
19326203
Research Areas
Infectious Diseases
Study Design
Case-Control Study