Dose–response and transmission: the nexus between reservoir hosts, environment and recipient hosts

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Lunn, Tamika J
Restif, Olivier
Peel, Alison J
Munster, Vincent J
de Wit, Emmie
Sokolow, Sanna
van Doremalen, Neeltje
Hudson, Peter
McCallum, Hamish
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Dose is the nexus between exposure and all upstream processes that determine pathogen pressure, and is thereby an important element underlying disease dynamics. Understanding the relationship between dose and disease is particularly important in the context of spillover, where nonlinearities in the dose–response could determine the likelihood of transmission. There is a need to explore dose–response models for directly transmitted and zoonotic pathogens, and how these interactions integrate within-host factors to consider, for example, heterogeneity in host susceptibility and dose-dependent antagonism. Here, we review the dose–response literature and discuss the unique role dose–response models have to play in understanding and predicting spillover events. We present a re-analysis of dose–response experiments for two important zoonotic pathogens (Middle East respiratory syndrome coronavirus and Nipah virus), to exemplify potential difficulties in differentiating between appropriate models with small exposure experiment datasets. We also discuss the data requirements needed for robust selection between dose–response models. We then suggest how these processes could be modelled to gain more realistic predictions of zoonotic transmission outcomes and highlight the exciting opportunities that could arise with increased collaboration between the virology and epidemiology disciplines.

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Philosophical Transactions of the Royal Society B: Biological Sciences
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© 2019 Royal Society. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
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Biological sciences
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Lunn, TJ; Restif, O; Peel, AJ; Munster, VJ; de Wit, E; Sokolow, S; van Doremalen, N; Hudson, P; McCallum, H, Dose–response and transmission: the nexus between reservoir hosts, environment and recipient hosts, Philosophical Transactions of the Royal Society B: Biological Sciences, 2019, 374 (1782), pp. 20190016-20190016