Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study

Background: Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculo...

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Main Authors: Prof. Mark P Nicol, PhD, Veronica Allen, MSc, Lesley Workman, MPH, Washiefa Isaacs, MSc, Jacinta Munro, Sandra Pienaar, MSc, Faye Black, MBBCh, Layla Adonis, MSc, Widaad Zemanay, PhD, Yonas Ghebrekristos, BSc, Prof. Heather J Zar, PhD
Format: Article
Language:English
Published: Elsevier 2014-05-01
Series:The Lancet Global Health
Online Access:http://www.sciencedirect.com/science/article/pii/S2214109X14701950
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spelling doaj-98c9d216f8f54c8cb08face658c3d3e22020-11-25T01:56:45ZengElsevierThe Lancet Global Health2214-109X2014-05-0125e278e28410.1016/S2214-109X(14)70195-0Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective studyProf. Mark P Nicol, PhD0Veronica Allen, MSc1Lesley Workman, MPH2Washiefa Isaacs, MSc3Jacinta Munro4Sandra Pienaar, MSc5Faye Black, MBBCh6Layla Adonis, MSc7Widaad Zemanay, PhD8Yonas Ghebrekristos, BSc9Prof. Heather J Zar, PhD10Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South AfricaDivision of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDivision of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South AfricaDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa Background: Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children. Methods: We prospectively recruited children (aged ≤15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral flow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid. Findings: 535 children (median age 42·5 months, IQR 19·1–66·3) had urine and two induced specimens available for testing. 89 (17%) had culture-confirmed tuberculosis and 106 (20%) had HIV. The lateral flow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3% (95% CI 37·6–59·2), specificity of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3·0%, 95% CI 0·4–10·5) and children with HIV (0%, 0·0–14·3); overall specificity was 95·7% (93·4–97·4). Interpretation: Urine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population. Funding: US National Institutes of Health, the National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, and the Wellcome Trust. http://www.sciencedirect.com/science/article/pii/S2214109X14701950
collection DOAJ
language English
format Article
sources DOAJ
author Prof. Mark P Nicol, PhD
Veronica Allen, MSc
Lesley Workman, MPH
Washiefa Isaacs, MSc
Jacinta Munro
Sandra Pienaar, MSc
Faye Black, MBBCh
Layla Adonis, MSc
Widaad Zemanay, PhD
Yonas Ghebrekristos, BSc
Prof. Heather J Zar, PhD
spellingShingle Prof. Mark P Nicol, PhD
Veronica Allen, MSc
Lesley Workman, MPH
Washiefa Isaacs, MSc
Jacinta Munro
Sandra Pienaar, MSc
Faye Black, MBBCh
Layla Adonis, MSc
Widaad Zemanay, PhD
Yonas Ghebrekristos, BSc
Prof. Heather J Zar, PhD
Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study
The Lancet Global Health
author_facet Prof. Mark P Nicol, PhD
Veronica Allen, MSc
Lesley Workman, MPH
Washiefa Isaacs, MSc
Jacinta Munro
Sandra Pienaar, MSc
Faye Black, MBBCh
Layla Adonis, MSc
Widaad Zemanay, PhD
Yonas Ghebrekristos, BSc
Prof. Heather J Zar, PhD
author_sort Prof. Mark P Nicol, PhD
title Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study
title_short Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study
title_full Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study
title_fullStr Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study
title_full_unstemmed Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study
title_sort urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study
publisher Elsevier
series The Lancet Global Health
issn 2214-109X
publishDate 2014-05-01
description Background: Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children. Methods: We prospectively recruited children (aged ≤15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral flow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid. Findings: 535 children (median age 42·5 months, IQR 19·1–66·3) had urine and two induced specimens available for testing. 89 (17%) had culture-confirmed tuberculosis and 106 (20%) had HIV. The lateral flow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3% (95% CI 37·6–59·2), specificity of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3·0%, 95% CI 0·4–10·5) and children with HIV (0%, 0·0–14·3); overall specificity was 95·7% (93·4–97·4). Interpretation: Urine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population. Funding: US National Institutes of Health, the National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, and the Wellcome Trust.
url http://www.sciencedirect.com/science/article/pii/S2214109X14701950
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