Cargando…

Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results

BACKGROUND: The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert MTB Host Response [MTB-HR] prototype), which gene...

Descripción completa

Detalles Bibliográficos
Autores principales: Sutherland, Jayne S, van der Spuy, Gian, Gindeh, Awa, Thuong, Nguyen Thuy Thuong, Namuganga, AnnRitah, Owolabi, Olumuyiwa, Mayanja-Kizza, Harriet, Nsereko, Mary, Thwaites, Guy, Winter, Jill, Dockrell, Hazel M, Scriba, Thomas J, Geluk, Annemieke, Corstjens, Paul, Stanley, Kim, Richardson, Tracy, Shaw, Jane A, Smith, Bronwyn, Malherbe, Stephanus T, Walzl, Gerhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258935/
https://www.ncbi.nlm.nih.gov/pubmed/34550342
http://dx.doi.org/10.1093/cid/ciab839
_version_ 1784741661372317696
author Sutherland, Jayne S
van der Spuy, Gian
Gindeh, Awa
Thuong, Nguyen Thuy Thuong
Namuganga, AnnRitah
Owolabi, Olumuyiwa
Mayanja-Kizza, Harriet
Nsereko, Mary
Thwaites, Guy
Winter, Jill
Dockrell, Hazel M
Scriba, Thomas J
Geluk, Annemieke
Corstjens, Paul
Stanley, Kim
Richardson, Tracy
Shaw, Jane A
Smith, Bronwyn
Malherbe, Stephanus T
Walzl, Gerhard
author_facet Sutherland, Jayne S
van der Spuy, Gian
Gindeh, Awa
Thuong, Nguyen Thuy Thuong
Namuganga, AnnRitah
Owolabi, Olumuyiwa
Mayanja-Kizza, Harriet
Nsereko, Mary
Thwaites, Guy
Winter, Jill
Dockrell, Hazel M
Scriba, Thomas J
Geluk, Annemieke
Corstjens, Paul
Stanley, Kim
Richardson, Tracy
Shaw, Jane A
Smith, Bronwyn
Malherbe, Stephanus T
Walzl, Gerhard
author_sort Sutherland, Jayne S
collection PubMed
description BACKGROUND: The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert MTB Host Response [MTB-HR] prototype), which generates a “TB score” based on messenger RNA (mRNA) expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. METHODS: Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda, and Vietnam was analyzed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). RESULTS: When data from all sites (n = 75 TB, 120 ORD) were analyzed, the TB score discriminated between TB and ORD with an area under the curve (AUC) of 0.94 (95% confidence interval [CI], .91–.97), sensitivity of 87% (95% CI, 77–93%) and specificity of 94% (88–97%). When sensitivity was set at 90% for a triage test, specificity was 86% (95% CI, 75–97%). These results were not influenced by human immunodeficiency virus (HIV) status or geographical location. When evaluated against a composite microbiological score (n = 80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0.88 (95% CI, .83–.94), 80% sensitivity (95% CI, 76–85%) and 94% specificity (95% CI, 91–96%). CONCLUSIONS: Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status.
format Online
Article
Text
id pubmed-9258935
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-92589352022-07-07 Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results Sutherland, Jayne S van der Spuy, Gian Gindeh, Awa Thuong, Nguyen Thuy Thuong Namuganga, AnnRitah Owolabi, Olumuyiwa Mayanja-Kizza, Harriet Nsereko, Mary Thwaites, Guy Winter, Jill Dockrell, Hazel M Scriba, Thomas J Geluk, Annemieke Corstjens, Paul Stanley, Kim Richardson, Tracy Shaw, Jane A Smith, Bronwyn Malherbe, Stephanus T Walzl, Gerhard Clin Infect Dis Major Articles and Commentaries BACKGROUND: The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert MTB Host Response [MTB-HR] prototype), which generates a “TB score” based on messenger RNA (mRNA) expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. METHODS: Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda, and Vietnam was analyzed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). RESULTS: When data from all sites (n = 75 TB, 120 ORD) were analyzed, the TB score discriminated between TB and ORD with an area under the curve (AUC) of 0.94 (95% confidence interval [CI], .91–.97), sensitivity of 87% (95% CI, 77–93%) and specificity of 94% (88–97%). When sensitivity was set at 90% for a triage test, specificity was 86% (95% CI, 75–97%). These results were not influenced by human immunodeficiency virus (HIV) status or geographical location. When evaluated against a composite microbiological score (n = 80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0.88 (95% CI, .83–.94), 80% sensitivity (95% CI, 76–85%) and 94% specificity (95% CI, 91–96%). CONCLUSIONS: Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status. Oxford University Press 2021-09-22 /pmc/articles/PMC9258935/ /pubmed/34550342 http://dx.doi.org/10.1093/cid/ciab839 Text en © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Articles and Commentaries
Sutherland, Jayne S
van der Spuy, Gian
Gindeh, Awa
Thuong, Nguyen Thuy Thuong
Namuganga, AnnRitah
Owolabi, Olumuyiwa
Mayanja-Kizza, Harriet
Nsereko, Mary
Thwaites, Guy
Winter, Jill
Dockrell, Hazel M
Scriba, Thomas J
Geluk, Annemieke
Corstjens, Paul
Stanley, Kim
Richardson, Tracy
Shaw, Jane A
Smith, Bronwyn
Malherbe, Stephanus T
Walzl, Gerhard
Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
title Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
title_full Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
title_fullStr Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
title_full_unstemmed Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
title_short Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results
title_sort diagnostic accuracy of the cepheid 3-gene host response fingerstick blood test in a prospective, multi-site study: interim results
topic Major Articles and Commentaries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9258935/
https://www.ncbi.nlm.nih.gov/pubmed/34550342
http://dx.doi.org/10.1093/cid/ciab839
work_keys_str_mv AT sutherlandjaynes diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT vanderspuygian diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT gindehawa diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT thuongnguyenthuythuong diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT namugangaannritah diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT owolabiolumuyiwa diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT mayanjakizzaharriet diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT nserekomary diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT thwaitesguy diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT winterjill diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT dockrellhazelm diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT scribathomasj diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT gelukannemieke diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT corstjenspaul diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT stanleykim diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT richardsontracy diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT shawjanea diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT smithbronwyn diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT malherbestephanust diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT walzlgerhard diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults
AT diagnosticaccuracyofthecepheid3genehostresponsefingerstickbloodtestinaprospectivemultisitestudyinterimresults