Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis

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dc.contributor.authorKerkhoff, Andrew Den_ZA
dc.contributor.authorWood, Robinen_ZA
dc.contributor.authorVogt, Monicaen_ZA
dc.contributor.authorLawn, Stephen Den_ZA
dc.date.accessioned2015-11-23T12:28:34Z
dc.date.available2015-11-23T12:28:34Z
dc.date.issued2014en_ZA
dc.description.abstractBACKGROUND: Detection of the mycobacterial cell wall antigen lipoarabinomannan (LAM) in urine can be used to diagnose HIV-associated tuberculosis (TB) using a qualitative (positive/negative) read-out. However, it is not known whether the quantity of LAM present in urine provides additional prognostic information. Methods/FINDINGS: Consecutively recruited adult outpatients initiating antiretroviral therapy (ART) in South Africa were investigated for TB regardless of clinical symptoms using sputum smear microscopy and liquid culture (reference standard). Urine samples were tested using the Clearview TB-ELISA for LAM and the Xpert MTB/RIF assay. The ELISA optical densities (OD) were used as a quantitative assessment of urine LAM. Among 514 patients with complete sputum and urine LAM OD results, culture-confirmed TB was diagnosed in 84 patients. Twenty-three (27.3%) were LAM-positive with a median LAM OD of 0.68 (IQR 0.16-2.43; range, 0.10-3.29) and 61 (72.6%) were LAM negative (LAM OD <0.1 above background). Higher LAM ODs were associated with a range of prognostic indices, including lower CD4 cell counts, lower haemoglobin levels, higher blood neutrophil counts and higher mycobacterial load as assessed using both sputum and urine samples. The median LAM OD among patients who died was more than 6.8-fold higher than that of patients who remained alive at 3 months (P<0.001). The small number of deaths, however, precluded adequate assessment of mortality risk stratified according to urine LAM OD. CONCLUSIONS: In patients with HIV-associated TB, concentrations of LAM in urine were strongly associated with a range of poor prognostic characteristics known to be associated with mortality risk. Urine LAM assays with a semi-quantitative (negative vs. low-positive vs. high-positive) read-out may have improved clinical utility over assays with a simple binary result.en_ZA
dc.identifier.apacitationKerkhoff, A. D., Wood, R., Vogt, M., & Lawn, S. D. (2014). Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis. <i>PLoS One</i>, http://hdl.handle.net/11427/15294en_ZA
dc.identifier.chicagocitationKerkhoff, Andrew D, Robin Wood, Monica Vogt, and Stephen D Lawn "Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/15294en_ZA
dc.identifier.citationKerkhoff, A. D., Wood, R., Vogt, M., & Lawn, S. D. (2014). Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis. PloS one, 9(7), e103285. doi:10.1371/journal.pone.0103285en_ZA
dc.identifier.ris TY - Journal Article AU - Kerkhoff, Andrew D AU - Wood, Robin AU - Vogt, Monica AU - Lawn, Stephen D AB - BACKGROUND: Detection of the mycobacterial cell wall antigen lipoarabinomannan (LAM) in urine can be used to diagnose HIV-associated tuberculosis (TB) using a qualitative (positive/negative) read-out. However, it is not known whether the quantity of LAM present in urine provides additional prognostic information. Methods/FINDINGS: Consecutively recruited adult outpatients initiating antiretroviral therapy (ART) in South Africa were investigated for TB regardless of clinical symptoms using sputum smear microscopy and liquid culture (reference standard). Urine samples were tested using the Clearview TB-ELISA for LAM and the Xpert MTB/RIF assay. The ELISA optical densities (OD) were used as a quantitative assessment of urine LAM. Among 514 patients with complete sputum and urine LAM OD results, culture-confirmed TB was diagnosed in 84 patients. Twenty-three (27.3%) were LAM-positive with a median LAM OD of 0.68 (IQR 0.16-2.43; range, 0.10-3.29) and 61 (72.6%) were LAM negative (LAM OD <0.1 above background). Higher LAM ODs were associated with a range of prognostic indices, including lower CD4 cell counts, lower haemoglobin levels, higher blood neutrophil counts and higher mycobacterial load as assessed using both sputum and urine samples. The median LAM OD among patients who died was more than 6.8-fold higher than that of patients who remained alive at 3 months (P<0.001). The small number of deaths, however, precluded adequate assessment of mortality risk stratified according to urine LAM OD. CONCLUSIONS: In patients with HIV-associated TB, concentrations of LAM in urine were strongly associated with a range of poor prognostic characteristics known to be associated with mortality risk. Urine LAM assays with a semi-quantitative (negative vs. low-positive vs. high-positive) read-out may have improved clinical utility over assays with a simple binary result. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0103285 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis TI - Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis UR - http://hdl.handle.net/11427/15294 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15294
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0103285
dc.identifier.vancouvercitationKerkhoff AD, Wood R, Vogt M, Lawn SD. Prognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosis. PLoS One. 2014; http://hdl.handle.net/11427/15294.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDesmond Tutu HIV Centreen_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© 2014 Kerkhoff 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.otherUrineen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherSputumen_ZA
dc.subject.otherHIVen_ZA
dc.subject.otherTuberculosis diagnosis and managementen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherBlood countsen_ZA
dc.titlePrognostic value of a quantitative analysis of lipoarabinomannan in urine from patients with HIV-associated tuberculosisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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