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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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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. |
format | Online Article Text |
id | pubmed-9553055 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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