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A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations

Limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics could address these challenges. However, using 4,200 samples across 69 blood transcriptome datasets from 20 countries from patients with bacterial or viral in...

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Autores principales: Rao, Aditya M., Popper, Stephen J., Gupta, Sanjana, Davong, Viengmon, Vaidya, Krista, Chanthongthip, Anisone, Dittrich, Sabine, Robinson, Matthew T., Vongsouvath, Manivanh, Mayxay, Mayfong, Nawtaisong, Pruksa, Karmacharya, Biraj, Thair, Simone A., Bogoch, Isaac, Sweeney, Timothy E., Newton, Paul N., Andrews, Jason R., Relman, David A., Khatri, Purvesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797950/
https://www.ncbi.nlm.nih.gov/pubmed/36543117
http://dx.doi.org/10.1016/j.xcrm.2022.100842
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author Rao, Aditya M.
Popper, Stephen J.
Gupta, Sanjana
Davong, Viengmon
Vaidya, Krista
Chanthongthip, Anisone
Dittrich, Sabine
Robinson, Matthew T.
Vongsouvath, Manivanh
Mayxay, Mayfong
Nawtaisong, Pruksa
Karmacharya, Biraj
Thair, Simone A.
Bogoch, Isaac
Sweeney, Timothy E.
Newton, Paul N.
Andrews, Jason R.
Relman, David A.
Khatri, Purvesh
author_facet Rao, Aditya M.
Popper, Stephen J.
Gupta, Sanjana
Davong, Viengmon
Vaidya, Krista
Chanthongthip, Anisone
Dittrich, Sabine
Robinson, Matthew T.
Vongsouvath, Manivanh
Mayxay, Mayfong
Nawtaisong, Pruksa
Karmacharya, Biraj
Thair, Simone A.
Bogoch, Isaac
Sweeney, Timothy E.
Newton, Paul N.
Andrews, Jason R.
Relman, David A.
Khatri, Purvesh
author_sort Rao, Aditya M.
collection PubMed
description Limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics could address these challenges. However, using 4,200 samples across 69 blood transcriptome datasets from 20 countries from patients with bacterial or viral infections representing a broad spectrum of biological, clinical, and technical heterogeneity, we show current host-response-based gene signatures have lower accuracy to distinguish intracellular bacterial infections from viral infections than extracellular bacterial infections. Using these 69 datasets, we identify an 8-gene signature to distinguish intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC) > 0.91 (85.9% specificity and 90.2% sensitivity). In prospective cohorts from Nepal and Laos, the 8-gene classifier distinguished bacterial infections from viral infections with an AUROC of 0.94 (87.9% specificity and 91% sensitivity). The 8-gene signature meets the target product profile proposed by the World Health Organization and others for distinguishing bacterial and viral infections.
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spelling pubmed-97979502022-12-30 A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations Rao, Aditya M. Popper, Stephen J. Gupta, Sanjana Davong, Viengmon Vaidya, Krista Chanthongthip, Anisone Dittrich, Sabine Robinson, Matthew T. Vongsouvath, Manivanh Mayxay, Mayfong Nawtaisong, Pruksa Karmacharya, Biraj Thair, Simone A. Bogoch, Isaac Sweeney, Timothy E. Newton, Paul N. Andrews, Jason R. Relman, David A. Khatri, Purvesh Cell Rep Med Article Limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics could address these challenges. However, using 4,200 samples across 69 blood transcriptome datasets from 20 countries from patients with bacterial or viral infections representing a broad spectrum of biological, clinical, and technical heterogeneity, we show current host-response-based gene signatures have lower accuracy to distinguish intracellular bacterial infections from viral infections than extracellular bacterial infections. Using these 69 datasets, we identify an 8-gene signature to distinguish intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC) > 0.91 (85.9% specificity and 90.2% sensitivity). In prospective cohorts from Nepal and Laos, the 8-gene classifier distinguished bacterial infections from viral infections with an AUROC of 0.94 (87.9% specificity and 91% sensitivity). The 8-gene signature meets the target product profile proposed by the World Health Organization and others for distinguishing bacterial and viral infections. Elsevier 2022-12-20 /pmc/articles/PMC9797950/ /pubmed/36543117 http://dx.doi.org/10.1016/j.xcrm.2022.100842 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rao, Aditya M.
Popper, Stephen J.
Gupta, Sanjana
Davong, Viengmon
Vaidya, Krista
Chanthongthip, Anisone
Dittrich, Sabine
Robinson, Matthew T.
Vongsouvath, Manivanh
Mayxay, Mayfong
Nawtaisong, Pruksa
Karmacharya, Biraj
Thair, Simone A.
Bogoch, Isaac
Sweeney, Timothy E.
Newton, Paul N.
Andrews, Jason R.
Relman, David A.
Khatri, Purvesh
A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations
title A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations
title_full A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations
title_fullStr A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations
title_full_unstemmed A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations
title_short A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations
title_sort robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9797950/
https://www.ncbi.nlm.nih.gov/pubmed/36543117
http://dx.doi.org/10.1016/j.xcrm.2022.100842
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