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

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dc.contributor.authorDheda, Keertanen_ZA
dc.contributor.authorVan-Zyl Smit, Richard Nen_ZA
dc.contributor.authorSechi, Leonardo Aen_ZA
dc.contributor.authorBadri, Motasimen_ZA
dc.contributor.authorMeldau, Richarden_ZA
dc.contributor.authorSymons, Gregoryen_ZA
dc.contributor.authorKhalfey, Hooseinen_ZA
dc.contributor.authorCarr, Igshaanen_ZA
dc.contributor.authorMaredza, Aliceen_ZA
dc.contributor.authorDawson, Rodneyen_ZA
dc.date.accessioned2016-01-11T06:51:38Z
dc.date.available2016-01-11T06:51:38Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: 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.en_ZA
dc.identifier.apacitationDheda, K., Van-Zyl Smit, R. N., Sechi, L. A., Badri, M., Meldau, R., Symons, G., ... Dawson, R. (2009). Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting. <i>PLoS One</i>, http://hdl.handle.net/11427/16251en_ZA
dc.identifier.chicagocitationDheda, Keertan, Richard N Van-Zyl Smit, Leonardo A Sechi, Motasim Badri, Richard Meldau, Gregory Symons, Hoosein Khalfey, Igshaan Carr, Alice Maredza, and Rodney Dawson "Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting." <i>PLoS One</i> (2009) http://hdl.handle.net/11427/16251en_ZA
dc.identifier.citationDheda, K., Smit, R. N. V. Z., Sechi, L. A., Badri, M., Meldau, R., Symons, G., ... & Wainright, H. (2009). Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting. PLoS ONE, 4(3), e4689. doi:10.1371/journal.pone.0004689en_ZA
dc.identifier.ris TY - Journal Article AU - Dheda, Keertan AU - Van-Zyl Smit, Richard N AU - Sechi, Leonardo A AU - Badri, Motasim AU - Meldau, Richard AU - Symons, Gregory AU - Khalfey, Hoosein AU - Carr, Igshaan AU - Maredza, Alice AU - Dawson, Rodney AB - 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. DA - 2009 DB - OpenUCT DO - 10.1371/journal.pone.0004689 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting TI - Clinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden setting UR - http://hdl.handle.net/11427/16251 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16251
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0004689
dc.identifier.vancouvercitationDheda K, Van-Zyl Smit RN, Sechi LA, Badri M, Meldau R, Symons G, et al. 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; http://hdl.handle.net/11427/16251.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Pulmonologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2009 Dheda et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherTuberculosis diagnosis and managementen_ZA
dc.subject.otherPleural effusionen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherBiopsyen_ZA
dc.subject.otherHistologyen_ZA
dc.subject.otherDiagnostic medicineen_ZA
dc.subject.otherHIVen_ZA
dc.titleClinical diagnostic utility of IP-10 and LAM antigen levels for the diagnosis of tuberculous pleural effusions in a high burden settingen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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