Thomas C Darton, Stephen Baker, Arlo Randall, Sabina Dongol, Abhilasha Karkey, 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
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.
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 October 2017.
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#6,930,326
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Outputs from Frontiers in Microbiology
#6,698
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#101,659
of 323,702 outputs
Outputs of similar age from Frontiers in Microbiology
#201
of 507 outputs
Altmetric has tracked 25,077,376 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 28,734 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.5. This one has done well, scoring higher than 76% of its peers.
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We're also able to compare this research output to 507 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 59% of its contemporaries.
