Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

Abstract CD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the rea...

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Autores principales:	Hellen Hiza, Jerry Hella, Ainhoa Arbués, Beatrice Magani, Mohamed Sasamalo, Sebastien Gagneux, Klaus Reither, Damien Portevin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04efe1c3328540c29aa3a11fea40f034
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spelling	oai:doaj.org-article:04efe1c3328540c29aa3a11fea40f0342021-12-02T17:14:23ZCase–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood10.1038/s41598-021-92596-z2045-2322https://doaj.org/article/04efe1c3328540c29aa3a11fea40f0342021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92596-zhttps://doaj.org/toc/2045-2322Abstract CD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24 h turnaround time. We recruited 479 GeneXpert positive cases and 108 symptomatic but GeneXpert negative controls from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing IFN-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences of Mycobacterium tuberculosis (Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus. Significantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84–0.91). The assay performance was not significantly affected by HIV status. To conclude, we successfully implemented TAM-TB immunoassay routine testing with a 24 h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test.Hellen HizaJerry HellaAinhoa ArbuésBeatrice MaganiMohamed SasamaloSebastien GagneuxKlaus ReitherDamien PortevinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hellen Hiza Jerry Hella Ainhoa Arbués Beatrice Magani Mohamed Sasamalo Sebastien Gagneux Klaus Reither Damien Portevin Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
description	Abstract CD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24 h turnaround time. We recruited 479 GeneXpert positive cases and 108 symptomatic but GeneXpert negative controls from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing IFN-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences of Mycobacterium tuberculosis (Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus. Significantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84–0.91). The assay performance was not significantly affected by HIV status. To conclude, we successfully implemented TAM-TB immunoassay routine testing with a 24 h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test.
format	article
author	Hellen Hiza Jerry Hella Ainhoa Arbués Beatrice Magani Mohamed Sasamalo Sebastien Gagneux Klaus Reither Damien Portevin
author_facet	Hellen Hiza Jerry Hella Ainhoa Arbués Beatrice Magani Mohamed Sasamalo Sebastien Gagneux Klaus Reither Damien Portevin
author_sort	Hellen Hiza
title	Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
title_short	Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
title_full	Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
title_fullStr	Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
title_full_unstemmed	Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood
title_sort	case–control diagnostic accuracy study of a non-sputum cd38-based tam-tb test from a single milliliter of blood
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/04efe1c3328540c29aa3a11fea40f034
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Case–control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood

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