The transmission of zoonotic diseases between animals and humans poses an increasing threat. Rabies is a prominent example with various instances globally. The abundance of anthropogenic resources leads to dense populations meso-predators close to human establishments. These facultative synanthropic species such as golden jackals (Canis aureus, hereafter jackals) facilitate the spread of rabies. To mitigate rabies outbreaks and prevent human infections, the Israeli authorities target the jackal, which is the main rabies vector in many regions, through a wide spread dissemination of oral vaccines, as well as opportunistic dilution to reduce population density in known jackals’ activity centers. Because dilution is not selective towards sick or un-vaccinated individuals, these two complementary epizootic intervention policies (EIPs, vaccination and dilution) can interfere with each other but their interactive effectiveness remains understudied, limiting their simultaneous application. In this study, we aim to address this knowledge gap by modeling the combined effect of these EIPs on rabies epizootic spread dynamics. Towards this end, we introduce a novel spatio-temporal extended-SIR (susceptible–infected–recovered) model with a graph-based spatial framework. After formulating the model, we implement it in the case study of the jackal population in northern Israel, by using spatial and movement tracking data (bio-telemetry). Realizing the model as an agent-based simulation approach allows us to explore various biologically-realistic scenarios, and assess the impact of different EIPs configurations. Our model suggests that under biologically-realistic underlying assumptions and scenarios, the effectiveness of both EIPs is not influenced much by the jackal population size but is sensitive to their dispersal between adjacent activity centers. Furthermore, we show both theoretically and empirically, that interference between the two EIPs can lead to mal-practice. Counter intuitively, there are cases in which the practice of both EIPs together actually leads to an increas in the spread of the epizootic (or endemic), due to elevated vector movement and removal of vaccinated individuals. Our findings emphasize the importance of accurately capturing the local jackal movement dynamics to obtain and predict the desired outcome from an applied EIP configuration, and the value of extended-SIR models in predicting the efficiency of realistic EIP scenarios
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