Abstract
Mechanistic mathematical models are often employed to understand the dynamics of infectious diseases within a population or within a host. They provide estimates that may not be otherwise available. We have developed a within-host mathematical model in order to understand how the pathophysiology of Salmonella Typhi contributes to its incubation period. The model describes the process of infection from ingestion to the onset of clinical illness using a set of ordinary differential equations. The model was parametrized using estimated values from human and mouse experimental studies and the incubation period was estimated as 9.6 days. A sensitivity analysis was also conducted to identify the parameters that most affect the derived incubation period. The migration of bacteria to the caecal lymph node was observed as a major bottle neck for infection. The sensitivity analysis indicated the growth rate of bacteria in late phase systemic infection and the net population of bacteria in the colon as parameters that most influence the incubation period. We have shown in this study how mathematical models aid in the understanding of biological processes and can be used in estimating parameters of infectious diseases.
Original language | English |
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Article number | 182143 |
Journal | Royal Society Open Science |
Volume | 6 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2019 |
Bibliographical note
Funding Information:Data accessibility. No primary data were generated. Data to inform the parameter values were derived from published literature fully referenced to the original accessible source. The code used to develop model simulations is available from the Dryad Digital Repository: https://doi.org/10.5061/dryad.p2gm5q8 [57]. Authors’ contributions. A.A.-O participated in developing the model, study design, solving the model and drafted the manuscript. A.P. participated in model parametrization values and reviewed the manuscript. N.M. helped with the study design and drafted the manuscript. I.H. helped in developing and solving the model and reviewed the manuscript. All authors have reviewed the manuscript and gave the final approval for publication. Competing interests. We declare we have no competing interests. Funding. The research was funded by the National Institute for Health Research Health Protection Research Unit in Gastrointestinal Infections at University of Liverpool in partnership with Public Health England, in collaboration with University of East Anglia, University of Oxford and the Institute of Food Research. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the National Institute for Health Research, the Department of Health or Public Health England.
Keywords
- Incubation period
- Mathematical modelling
- Salmonella Typhi