Frontiers in Microbiology (Sep 2017)
Identification of Novel Serodiagnostic Signatures of Typhoid Fever Using a Salmonella Proteome Array
- Thomas C. Darton,
- Thomas C. Darton,
- Thomas C. Darton,
- Stephen Baker,
- Arlo Randall,
- Sabina Dongol,
- Abhilasha Karkey,
- Merryn Voysey,
- Merryn Voysey,
- Michael J. Carter,
- Claire Jones,
- Krista Trappl,
- Jozelyn Pablo,
- Chris Hung,
- Andy Teng,
- Adam Shandling,
- Tim Le,
- Cassidy Walker,
- Douglas Molina,
- Jason Andrews,
- Amit Arjyal,
- Buddha Basnyat,
- Andrew J. Pollard,
- Christoph J. Blohmke
Affiliations
- Thomas C. Darton
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, and the Oxford National Institutes for Health Research Biomedical Research Centre, University of OxfordOxford, United Kingdom
- Thomas C. Darton
- The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research UnitHo Chi Minh City, Vietnam
- Thomas C. Darton
- Department of Infection, Immunity and Cardiovascular Disease, The University of SheffieldSheffield, United Kingdom
- Stephen Baker
- The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research UnitHo Chi Minh City, Vietnam
- Arlo Randall
- Antigen Discovery Incorporated, IrvineCA, United States
- Sabina Dongol
- Oxford University Clinical Research Unit, Patan Academy of Health SciencesKathmandu, Nepal
- Abhilasha Karkey
- Oxford University Clinical Research Unit, Patan Academy of Health SciencesKathmandu, Nepal
- Merryn Voysey
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, and the Oxford National Institutes for Health Research Biomedical Research Centre, University of OxfordOxford, United Kingdom
- Merryn Voysey
- Nuffield Department of Primary Care Health Sciences, University of OxfordOxford, United Kingdom
- Michael J. Carter
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, and the Oxford National Institutes for Health Research Biomedical Research Centre, University of OxfordOxford, United Kingdom
- Claire Jones
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, and the Oxford National Institutes for Health Research Biomedical Research Centre, University of OxfordOxford, United Kingdom
- Krista Trappl
- Antigen Discovery Incorporated, IrvineCA, United States
- Jozelyn Pablo
- Antigen Discovery Incorporated, IrvineCA, United States
- Chris Hung
- Antigen Discovery Incorporated, IrvineCA, United States
- Andy Teng
- Antigen Discovery Incorporated, IrvineCA, United States
- Adam Shandling
- Antigen Discovery Incorporated, IrvineCA, United States
- Tim Le
- Antigen Discovery Incorporated, IrvineCA, United States
- Cassidy Walker
- Antigen Discovery Incorporated, IrvineCA, United States
- Douglas Molina
- Antigen Discovery Incorporated, IrvineCA, United States
- Jason Andrews
- Division of Infectious Diseases and Geographic Medicine, Stanford University, StanfordCA, United States
- Amit Arjyal
- Nuffield Department of Primary Care Health Sciences, University of OxfordOxford, United Kingdom
- Buddha Basnyat
- Nuffield Department of Primary Care Health Sciences, University of OxfordOxford, United Kingdom
- Andrew J. Pollard
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, and the Oxford National Institutes for Health Research Biomedical Research Centre, University of OxfordOxford, United Kingdom
- Christoph J. Blohmke
- Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, and the Oxford National Institutes for Health Research Biomedical Research Centre, University of OxfordOxford, United Kingdom
- DOI
- https://doi.org/10.3389/fmicb.2017.01794
- Journal volume & issue
-
Vol. 8
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.
Keywords
