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Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis

The World Health Organization (WHO) emphasizes that tuberculosis (TB) in children and adolescents is often overlooked by healthcare providers and difficult to diagnose. As childhood TB cases rise, finding a diagnostic high in sensitivity and specificity is critical. In this study 91 urine samples fr...

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Autores principales: Amin, Anita G., De, Prithwiraj, Graham, Barbara, Jensen, Brooke L., Moreau, Emmanuel, Chatterjee, Delphi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9553055/
https://www.ncbi.nlm.nih.gov/pubmed/36219600
http://dx.doi.org/10.1371/journal.pone.0275838
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author Amin, Anita G.
De, Prithwiraj
Graham, Barbara
Jensen, Brooke L.
Moreau, Emmanuel
Chatterjee, Delphi
author_facet Amin, Anita G.
De, Prithwiraj
Graham, Barbara
Jensen, Brooke L.
Moreau, Emmanuel
Chatterjee, Delphi
author_sort Amin, Anita G.
collection PubMed
description The World Health Organization (WHO) emphasizes that tuberculosis (TB) in children and adolescents is often overlooked by healthcare providers and difficult to diagnose. As childhood TB cases rise, finding a diagnostic high in sensitivity and specificity is critical. In this study 91 urine samples from children aged 1–10 years were analyzed for tuberculostearic acid (TBSA) by gas chromatography/mass spectrometry (GC/MS) and capture ELISA (C-ELISA). In C-ELISA the CS35/A194-01 antibody performed very poorly with both curve-based and model-based cutoffs. The area under the ROC curve (AUC) of the CS35 OD(450) values was only 0.60. Replacing the capture antibody with BJ76 gave a better performance in both sensitivity and specificity (AUC = 0.95). When these samples were analyzed by GC/MS, 41 classified as ‘probable/possible’ for TB were distinctly TBSA positive with ten samples having <3 ng/mL LAM. However, from the 50 samples with ‘unlikely’ TB classification, 36 were negative but 7 had >3 ng/mL and were designated as LAM positive. This experimental assay assessment study signifies that i) the antibody pair CS35/A194-01 that has been successful for adult active TB diagnosis is not adequate when LAM level is low as in pediatric TB; ii) no one mAb appears to recognize all TB-specific LAM epitopes.
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spelling pubmed-95530552022-10-12 Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis Amin, Anita G. De, Prithwiraj Graham, Barbara Jensen, Brooke L. Moreau, Emmanuel Chatterjee, Delphi PLoS One Research Article The World Health Organization (WHO) emphasizes that tuberculosis (TB) in children and adolescents is often overlooked by healthcare providers and difficult to diagnose. As childhood TB cases rise, finding a diagnostic high in sensitivity and specificity is critical. In this study 91 urine samples from children aged 1–10 years were analyzed for tuberculostearic acid (TBSA) by gas chromatography/mass spectrometry (GC/MS) and capture ELISA (C-ELISA). In C-ELISA the CS35/A194-01 antibody performed very poorly with both curve-based and model-based cutoffs. The area under the ROC curve (AUC) of the CS35 OD(450) values was only 0.60. Replacing the capture antibody with BJ76 gave a better performance in both sensitivity and specificity (AUC = 0.95). When these samples were analyzed by GC/MS, 41 classified as ‘probable/possible’ for TB were distinctly TBSA positive with ten samples having <3 ng/mL LAM. However, from the 50 samples with ‘unlikely’ TB classification, 36 were negative but 7 had >3 ng/mL and were designated as LAM positive. This experimental assay assessment study signifies that i) the antibody pair CS35/A194-01 that has been successful for adult active TB diagnosis is not adequate when LAM level is low as in pediatric TB; ii) no one mAb appears to recognize all TB-specific LAM epitopes. Public Library of Science 2022-10-11 /pmc/articles/PMC9553055/ /pubmed/36219600 http://dx.doi.org/10.1371/journal.pone.0275838 Text en © 2022 Amin et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Amin, Anita G.
De, Prithwiraj
Graham, Barbara
Jensen, Brooke L.
Moreau, Emmanuel
Chatterjee, Delphi
Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis
title Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis
title_full Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis
title_fullStr Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis
title_full_unstemmed Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis
title_short Overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis
title_sort overcome low levels of detection limit and choice of antibody affects detection of lipoarabinomannan in pediatric tuberculosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9553055/
https://www.ncbi.nlm.nih.gov/pubmed/36219600
http://dx.doi.org/10.1371/journal.pone.0275838
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