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Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data

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Magombedze, Gesham, Shiri, Tinevimbo, Eda, Shigetoshi and Stabel, Judy R. (2017) Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data. Scientific Reports, 7 . 44765. doi:10.1038/srep44765

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Official URL: http://www.nature.com/articles/srep44765

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Abstract

Available diagnostic assays for Mycobacterium avium subsp. paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN-γ, ELISA-antibody and fecal shedding experimental sensitivity scores for MAP infection detection and disease progression. We used both statistical methods and dynamic mathematical models to (i) evaluate the empirical assays (ii) infer and explain biological mechanisms that affect the time evolution of the biomarkers, and (iii) predict disease stages of 57 animals that were naturally infected with MAP. This analysis confirms that the fecal test is the best marker for disease progression and illustrates that Th1/Th2 (IFN-γ/ELISA antibodies) assays are important for infection detection, but cannot reliably predict persistent infections. Our results show that the theoretical simulated macrophage-based assay is a potential good diagnostic marker for MAP persistent infections and predictor of disease specific stages. We therefore recommend specifically designed experiments to test the use of a based assay in the diagnosis of MAP infections.

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Q Science > QR Microbiology > QR180 Immunology
S Agriculture > SF Animal culture
Divisions: Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit
Faculty of Medicine > Warwick Medical School > Health Sciences
Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Mycobacterium avium paratuberculosis, Bacterial diseases, Systems theory, Ruminants -- Diseases
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group
ISSN: 2045-2322
Official Date: 20 March 2017
Dates:
DateEvent
20 March 2017Published
9 February 2017Accepted
22 September 2016Submitted
Volume: 7
Article Number: 44765
DOI: 10.1038/srep44765
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
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