![]() However, for nonlinear dose–response relationships, the total probability of spillover differs between scenarios. If the dose–response relationship is linear (green line), these two excretion scenarios generate the same total probability of spillover over the time interval shown. Bottom panel: the likelihood that this dose will translate into infection depends on the functional form of the dose–response relationship. In both scenarios, the mean dose over the time interval is the same. In scenario 2 (solid light blue line), the pathogen is excreted in regular but short high-intensity pulses over time. In scenario 1 (dashed light blue line), the pathogen is excreted consistently from infected reservoir hosts. c | Top panel: hypothetical dose available over time for a given pathogen. For other pathogens, protracted survival in the environment (for example, Bacillus anthracis spores 109), or wide dissemination (for example, the spread of aerosolized Coxiella burnetii by wind 35), may stagger the alignment of barriers to spillover. Spillover of some pathogens requires that gaps (depicted as holes) in all of the barriers align within a narrow window in space and time (indicated by the blue arrow, see Supplementary information S2 (movie)). ![]() If any of these barriers is impenetrable, spillover cannot occur. b | A pathogen must overcome a series of barriers to transmit from one species to another. Consequently, zoonotic spillover is a relatively rare event, and although humans are continually exposed to many potentially infectious pathogens that are derived from other species, most of these microorganisms cannot infect or cause disease in humans 7, 8, 9, 10.īarriers to spillover and dose–response relationships.Ī | Determinants of spillover are being studied by researchers in many disciplines. Spillover requires the pathogen to pass every barrier and thus can only occur when gaps align in each successive barrier within an appropriate window in space and time ( Fig. A series of within-host barriers then determine host susceptibility, and, therefore, the probability and severity of infection for a given pathogen dose.Įach phase presents multiple barriers to the flow of a pathogen from a reservoir host to a recipient host. Pathogen pressure then interacts with the behaviour of the recipient host (and vector for vector-borne pathogens) to determine the likelihood, dose and route of exposure. The distribution and intensity of infection in reservoir hosts, followed by pathogen release, movement, survival and possible development to infectious stage, determine the pathogen pressure, which is defined as the amount of pathogen available to the recipient host at a given point in space and time. The risk of spillover is determined by a series of processes that link the ecological dynamics of infection in reservoir hosts, the microbiological and vector determinants of survival and dissemination outside of reservoir hosts, the epidemiological and behavioural determinants of exposure, and the within-host biological factors that shape the susceptibility of recipient hosts. Third, genetic, physiological and immunological attributes of the recipient human host, together with the dose and route of exposure, affect the probability and severity of infection. ![]() Second, human and vector behaviour determine pathogen exposure specifically, the likelihood, route and dose of exposure. In the first phase, the amount of pathogen available to the human host at a given point in space and time, known as the pathogen pressure, is determined by interactions among reservoir host distribution, pathogen prevalence and pathogen release from the reservoir host, followed by pathogen survival, development and dissemination outside of the reservoir hosts. These factors can be partitioned into three functional phases that describe all major routes of transmission ( Fig. The probability of zoonotic spillover is determined by interactions among several factors, including disease dynamics in the reservoir host, pathogen exposure and the within-human factors that affect susceptibility to infections. Spillover transmission is promoted by successive processes that enable an animal pathogen to establish infection in a human. The public health burden that is presented by zoonoses includes outbreaks of pathogens such as Ebola virus, influenza A virus (H1N1)pdm09 and Middle East respiratory syndrome coronavirus (MERS-CoV), as well as the ongoing transmission of endemic pathogens, such as Salmonella spp., Leptospira spp., Trypanosoma spp., Mycobacterium spp. The phenomenon of cross-species spillover is the defining characteristic of pathogens that transmit from vertebrate animals to humans (zoonoses).
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