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Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients
Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312950/ https://www.ncbi.nlm.nih.gov/pubmed/34310609 http://dx.doi.org/10.1371/journal.pone.0254156 |
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author | Connelly, John T. Andama, Alfred Grant, Benjamin D. Ball, Alexey Mwebe, Sandra Asege, Lucy Nakaye, Martha Lopez, Brianda Barrios Hsieh, Helen V. Katumba, David Mukwatamundu, Job Nalubega, Mayimuna Hunt, Victoria M. Burkot, Stephen Ramachandraiah, Harisha Choudhary, Alok Ignatowicz, Lech Weigl, Bernhard H. Bachman, Christine Mulondo, Jerry Semitala, Fred Worodria, William Pinter, Abraham Hamasur, Beston Bell, David Cattamanchi, Adithya Somoskovi, Akos |
author_facet | Connelly, John T. Andama, Alfred Grant, Benjamin D. Ball, Alexey Mwebe, Sandra Asege, Lucy Nakaye, Martha Lopez, Brianda Barrios Hsieh, Helen V. Katumba, David Mukwatamundu, Job Nalubega, Mayimuna Hunt, Victoria M. Burkot, Stephen Ramachandraiah, Harisha Choudhary, Alok Ignatowicz, Lech Weigl, Bernhard H. Bachman, Christine Mulondo, Jerry Semitala, Fred Worodria, William Pinter, Abraham Hamasur, Beston Bell, David Cattamanchi, Adithya Somoskovi, Akos |
author_sort | Connelly, John T. |
collection | PubMed |
description | Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51–69%) and specificity of 80% (95%CI 73–85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p<0.0001) and HIV-positive patients with CD4+ T-cell counts >200cells/μL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity. |
format | Online Article Text |
id | pubmed-8312950 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83129502021-07-31 Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients Connelly, John T. Andama, Alfred Grant, Benjamin D. Ball, Alexey Mwebe, Sandra Asege, Lucy Nakaye, Martha Lopez, Brianda Barrios Hsieh, Helen V. Katumba, David Mukwatamundu, Job Nalubega, Mayimuna Hunt, Victoria M. Burkot, Stephen Ramachandraiah, Harisha Choudhary, Alok Ignatowicz, Lech Weigl, Bernhard H. Bachman, Christine Mulondo, Jerry Semitala, Fred Worodria, William Pinter, Abraham Hamasur, Beston Bell, David Cattamanchi, Adithya Somoskovi, Akos PLoS One Research Article Detection of tuberculosis at the point-of-care (POC) is limited by the low sensitivity of current commercially available tests. We describe a diagnostic accuracy field evaluation of a prototype urine Tuberculosis Lipoarabinomannan Lateral Flow Assay (TB-LAM LFA) in both HIV-positive and HIV-negative patients using fresh samples with sensitivity and specificity as the measures of accuracy. This prototype combines a proprietary concentration system with a sensitive LFA. In a prospective study of 292 patients with suspected pulmonary tuberculosis in Uganda, the clinical sensitivity and specificity was compared against a microbiological reference standard including sputum Xpert MTB/RIF Ultra and solid and liquid culture. TB-LAM LFA had an overall sensitivity of 60% (95%CI 51–69%) and specificity of 80% (95%CI 73–85%). When comparing HIV-positive (N = 86) and HIV-negative (N = 206) patients, there was no significant difference in sensitivity (sensitivity difference 8%, 95%CI -11% to +24%, p = 0.4351) or specificity (specificity difference -9%, 95%CI -24% to +4%, p = 0.2051). Compared to the commercially available Alere Determine TB-LAM Ag test, the TB-LAM LFA prototype had improved sensitivity in both HIV-negative (difference 49%, 95%CI 37% to 59%, p<0.0001) and HIV-positive patients with CD4+ T-cell counts >200cells/μL (difference 59%, 95%CI 32% to 75%, p = 0.0009). This report is the first to show improved performance of a urine TB LAM test for HIV-negative patients in a high TB burden setting. We also offer potential assay refinement solutions that may further improve sensitivity and specificity. Public Library of Science 2021-07-26 /pmc/articles/PMC8312950/ /pubmed/34310609 http://dx.doi.org/10.1371/journal.pone.0254156 Text en © 2021 Connelly 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 Connelly, John T. Andama, Alfred Grant, Benjamin D. Ball, Alexey Mwebe, Sandra Asege, Lucy Nakaye, Martha Lopez, Brianda Barrios Hsieh, Helen V. Katumba, David Mukwatamundu, Job Nalubega, Mayimuna Hunt, Victoria M. Burkot, Stephen Ramachandraiah, Harisha Choudhary, Alok Ignatowicz, Lech Weigl, Bernhard H. Bachman, Christine Mulondo, Jerry Semitala, Fred Worodria, William Pinter, Abraham Hamasur, Beston Bell, David Cattamanchi, Adithya Somoskovi, Akos Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients |
title | Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients |
title_full | Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients |
title_fullStr | Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients |
title_full_unstemmed | Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients |
title_short | Field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on HIV-positive and HIV-negative patients |
title_sort | field evaluation of a prototype tuberculosis lipoarabinomannan lateral flow assay on hiv-positive and hiv-negative patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312950/ https://www.ncbi.nlm.nih.gov/pubmed/34310609 http://dx.doi.org/10.1371/journal.pone.0254156 |
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