Pathways to zoonotic spillover

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Zoonotic spillover, which is the transmission of a pathogen from a vertebrate animal to a human, presents a global public health burden but is a poorly understood phenomenon. Zoonotic spillover requires several factors to align, including the ecological, epidemiological and behavioural determinants of pathogen exposure, and the within-human factors that affect susceptibility to infection. In this Opinion article, we propose a synthetic framework for animal-to-human transmission that integrates the relevant mechanisms. This framework reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans. Understanding how these barriers are functionally and quantitatively linked, and how they interact in space and time, will substantially improve our ability to predict or prevent spillover events. This work provides a foundation for transdisciplinary investigation of spillover and synthetic theory on zoonotic transmission.

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Figure 1: Pathways to spillover.
Figure 2: Barriers to spillover and dose–response relationships.
Figure 3: Bottlenecks to spillover.


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The authors thank J. Wood and E. Fleishman for helpful comments and conversations. R.K.P. and H.M. are supported by the Commonwealth of Australia, the State of New South Wales and the State of Queensland under the National Hendra Virus Research Program, awarded through the Rural Industries Research and Development Corporation. R.K.P. is supported by the US National Institutes of General Medical Sciences IDeA Program (grants P20GM103474 and P30GM110732), P. Thye, the Morris Animal Foundation, Montana University System Research Initiative (grant 51040-MUSRI2015-03), a Defense Advanced Research Projects Agency (DARPA) Young Faculty Award and the US Department of Defense Strategic Environmental Research and Development Program (SERDP; grant RC-2633). J.O.L.-S. is supported by the US National Science Foundation (NSF; grants OCE-1335657 and DEB-1557022) and the US Department of Defense SERDP (grant RC-2635). J.O.L.-S., A.L.G. and P.J.H. are supported by the RAPIDD program of the Science & Technology Directorate of the Department of Homeland Security, the Fogarty International Center (part of the US National Institutes of Health), and by IDEAS (Infectious Disease Evolution Across Scales), which is a Research Coordination Network (DEB-1354890) funded by the US National Science Foundation.

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Correspondence to Raina K. Plowright.

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A mathematical representation of spillover (PDF 110 kb)

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Spatiotemporal dynamics of spillover. Gaps in barriers to spillover may be highly dynamic in time and space meaning that the alignment of gaps in all barriers may be rare and brief. (GIF 2542 kb)

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Plowright, R., Parrish, C., McCallum, H. et al. Pathways to zoonotic spillover. Nat Rev Microbiol 15, 502–510 (2017) doi:10.1038/nrmicro.2017.45

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