Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting

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dc.contributor.authorPatel, Vinod Ben_ZA
dc.contributor.authorSingh, Raveshen_ZA
dc.contributor.authorConnolly, Cathyen_ZA
dc.contributor.authorKasprowicz, Victoriaen_ZA
dc.contributor.authorZumla, Allimudinen_ZA
dc.contributor.authorNdungu, Thumbien_ZA
dc.contributor.authorDheda, Keertanen_ZA
dc.date.accessioned2016-01-11T06:51:37Z
dc.date.available2016-01-11T06:51:37Z
dc.date.issued2010en_ZA
dc.description.abstractBackground/Objective: The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF). METHODS: Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM. RESULTS: Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs. >200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98). CONCLUSIONS: Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression.en_ZA
dc.identifier.apacitationPatel, V. B., Singh, R., Connolly, C., Kasprowicz, V., Zumla, A., Ndungu, T., & Dheda, K. (2010). Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting. <i>PLoS One</i>, http://hdl.handle.net/11427/16250en_ZA
dc.identifier.chicagocitationPatel, Vinod B, Ravesh Singh, Cathy Connolly, Victoria Kasprowicz, Allimudin Zumla, Thumbi Ndungu, and Keertan Dheda "Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting." <i>PLoS One</i> (2010) http://hdl.handle.net/11427/16250en_ZA
dc.identifier.citationPatel, V. B., Singh, R., Connolly, C., Kasprowicz, V., Zumla, A., Ndungu, T., & Dheda, K. (2010). Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting. PLOS ONE, 5(12), e15664. doi:10.1371/journal.pone.0015664en_ZA
dc.identifier.ris TY - Journal Article AU - Patel, Vinod B AU - Singh, Ravesh AU - Connolly, Cathy AU - Kasprowicz, Victoria AU - Zumla, Allimudin AU - Ndungu, Thumbi AU - Dheda, Keertan AB - Background/Objective: The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF). METHODS: Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM. RESULTS: Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs. >200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98). CONCLUSIONS: Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression. DA - 2010 DB - OpenUCT DO - 10.1371/journal.pone.0015664 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2010 T1 - Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting TI - Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting UR - http://hdl.handle.net/11427/16250 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16250
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0015664
dc.identifier.vancouvercitationPatel VB, Singh R, Connolly C, Kasprowicz V, Zumla A, Ndungu T, et al. Comparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence setting. PLoS One. 2010; http://hdl.handle.net/11427/16250.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© 2010 Patel 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.otherMeningitisen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherHIV diagnosis and managementen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherGram stainingen_ZA
dc.subject.otherBacterial meningitisen_ZA
dc.subject.otherCryptococcal meningitisen_ZA
dc.titleComparison of a clinical prediction rule and a LAM antigen-detection assay for the rapid diagnosis of TBM in a high HIV prevalence settingen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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