Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle
Gesham Magombedze1,2,3, Tinevimbo Shiri4, Shigetoshi Eda3,5
1Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, TX, USA.
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.
Insights
New diagnostic markers are needed for Mycobacterium avium subsp. paratuberculosis (MAP) infection. A simulated macrophage-based assay shows promise for detecting persistent MAP infections and predicting disease stages.
Area of Science:
- Veterinary immunology
- Infectious disease diagnostics
- Mathematical modeling in biology
Background:
- Current diagnostic assays for Mycobacterium avium subsp. paratuberculosis (MAP) exhibit low sensitivity, failing to detect early infection stages.
- There is a critical need for novel diagnostic markers to identify early MAP infections and track disease progression.
Purpose of the Study:
- To evaluate existing diagnostic assays for MAP infection.
- To infer biological mechanisms influencing biomarker dynamics during MAP infection.
- To predict disease stages in naturally MAP-infected animals.
Main Methods:
- Analysis of longitudinal IFN-γ, ELISA-antibody, and fecal shedding data.
- Application of statistical methods and dynamic mathematical modeling.
- Evaluation of assay performance for MAP infection detection and disease staging.
Main Results:
- Fecal shedding tests are the most effective markers for monitoring MAP disease progression.
- IFN-γ and ELISA antibody assays are valuable for initial infection detection but less reliable for predicting persistent infections.
- A simulated macrophage-based assay demonstrated potential as a diagnostic marker for persistent MAP infections and disease staging.
Conclusions:
- Existing diagnostic tools for MAP have limitations in early detection and predicting persistent infections.
- A macrophage-based assay warrants further investigation as a superior diagnostic tool for MAP.
- Further experimental validation is recommended for the proposed macrophage-based assay in MAP diagnosis.
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