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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
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.
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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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