Darton, T.C. orcid.org/0000-0003-2209-9956, Baker, S., Randall, A. et al. (18 more authors) (2017) Identification of novel serodiagnostic signatures of typhoid fever using a Salmonella proteome array. Frontiers in Microbiology, 8. 1794. ISSN 1664-302X
Abstract
Current diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. We aimed to identify serodiagnostic signatures of typhoid fever by assessing microarray signals to 4,445 S. Typhi antigens in sera from 41 participants challenged with oral S. Typhi. We found broad, heterogeneous antibody responses with increasing IgM/IgA signals at diagnosis. In down-selected 250-antigen arrays we validated responses in a second challenge cohort (n = 30), and selected diagnostic signatures using machine learning and multivariable modeling. In four models containing responses to antigens including flagellin, OmpA, HlyE, sipC, and LPS, multi-antigen signatures discriminated typhoid (n = 100) from other febrile bacteremia (n = 52) in Nepal. These models contained combinatorial IgM, IgA, and IgG responses to 5 antigens (ROC AUC, 0.67 and 0.71) or 3 antigens (0.87), although IgA responses to LPS also performed well (0.88). Using a novel systematic approach we have identified and validated optimal serological diagnostic signatures of typhoid fever.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Darton, Baker, Randall, Dongol, Karkey, Voysey, Carter, Jones, Trappl, Pablo, Hung, Teng, Shandling, Le, Walker, Molina, Andrews, Arjyal, Basnyat, Pollard and Blohmke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection, Immunity and Cardiovascular Disease The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 06 Oct 2017 14:48 |
Last Modified: | 06 Oct 2017 14:48 |
Published Version: | https://doi.org/10.3389/fmicb.2017.01794 |
Status: | Published |
Publisher: | Frontiers Media |
Refereed: | Yes |
Identification Number: | 10.3389/fmicb.2017.01794 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:122154 |