Learning and strategic imitation in modelling farmers' dynamic decisions on bovine viral diarrhoea vaccination.

Considering human decision-making is essential for understanding the mechanisms underlying the propagation of real-life diseases. We present an extension of a model for pathogen spread that considers farmers' dynamic decision-making regarding the adoption of a control measure in their own herd. Farmers can take into account the decisions and observed costs of their trade partners or of their geographic neighbours. The model and construction of such costs are adapted to the case of bovine viral diarrhoea, for which an individual-based stochastic model is considered. Simulation results suggest that obtaining information from geographic neighbours might lead to a better control of bovine viral diarrhoea than considering information from trade partners. In particular, using information from all geographic neighbours at each decision time seems to be more beneficial than considering only the information from one geographic neighbour or trade partner at each time. This study highlights the central role that social dynamics among farmers can take in the spread and control of bovine viral diarrhoea, providing insights into how public policy efforts could be targeted in order to increase voluntary vaccination uptake against this disease in endemic areas.

The African swine fever modelling challenge: Model comparison and lessons learnt.

Robust epidemiological knowledge and predictive modelling tools are needed to address challenging objectives, such as: understanding epidemic drivers; forecasting epidemics; and prioritising control measures. Often, multiple modelling approaches can be used during an epidemic to support effective decision making in a timely manner. Modelling challenges contribute to understanding the pros and cons of different approaches and to fostering technical dialogue between modellers. In this paper, we present the results of the first modelling challenge in animal health - the ASF Challenge - which focused on a synthetic epidemic of African swine fever (ASF) on an island. The modelling approaches proposed by five independent international teams were compared. We assessed their ability to predict temporal and spatial epidemic expansion at the interface between domestic pigs and wild boar, and to prioritise a limited number of alternative interventions. We also compared their qualitative and quantitative spatio-temporal predictions over the first two one-month projection phases of the challenge. Top-performing models in predicting the ASF epidemic differed according to the challenge phase, host species, and in predicting spatial or temporal dynamics. Ensemble models built using all team-predictions outperformed any individual model in at least one phase. The ASF Challenge demonstrated that accounting for the interface between livestock and wildlife is key to increasing our effectiveness in controlling emerging animal diseases, and contributed to improving the readiness of the scientific community to face future ASF epidemics. Finally, we discuss the lessons learnt from model comparison to guide decision making.

SCoVMod - a spatially explicit mobility and deprivation adjusted model of first wave COVID-19 transmission dynamics.

Background: Mobility restrictions prevent the spread of infections to disease-free areas, and early in the coronavirus disease 2019 (COVID-19) pandemic, most countries imposed severe restrictions on mobility as soon as it was clear that containment of local outbreaks was insufficient to control spread. These restrictions have adverse impacts on the economy and other aspects of human health, and it is important to quantify their impact for evaluating their future value. Methods: Here we develop Scotland Coronavirus transmission Model (SCoVMod), a model for COVID-19 in Scotland, which presents unusual challenges because of its diverse geography and population conditions. Our fitted model captures spatio-temporal patterns of mortality in the first phase of the epidemic to a fine geographical scale. Results: We find that lockdown restrictions reduced transmission rates down to an estimated 12\% of its pre-lockdown rate. We show that, while the timing of COVID-19 restrictions influences the role of the transmission rate on the number of COVID-related deaths, early reduction in long distance movements does not. However, poor health associated with deprivation has a considerable association with mortality; the Council Area (CA) with the greatest health-related deprivation was found to have a mortality rate 2.45 times greater than the CA with the lowest health-related deprivation considering all deaths occurring outside of carehomes. Conclusions: We find that in even an early epidemic with poor case ascertainment, a useful spatially explicit model can be fit with meaningful parameters based on the spatio-temporal distribution of death counts. Our simple approach is useful to strategically examine trade-offs between travel related restrictions and physical distancing, and the effect of deprivation-related factors on outcomes.

Research perspectives on animal health in the era of artificial intelligence.

Leveraging artificial intelligence (AI) approaches in animal health (AH) makes it possible to address highly complex issues such as those encountered in quantitative and predictive epidemiology, animal/human precision-based medicine, or to study host × pathogen interactions. AI may contribute (i) to diagnosis and disease case detection, (ii) to more reliable predictions and reduced errors, (iii) to representing more realistically complex biological systems and rendering computing codes more readable to non-computer scientists, (iv) to speeding-up decisions and improving accuracy in risk analyses, and (v) to better targeted interventions and anticipated negative effects. In turn, challenges in AH may stimulate AI research due to specificity of AH systems, data, constraints, and analytical objectives. Based on a literature review of scientific papers at the interface between AI and AH covering the period 2009-2019, and interviews with French researchers positioned at this interface, the present study explains the main AH areas where various AI approaches are currently mobilised, how it may contribute to renew AH research issues and remove methodological or conceptual barriers. After presenting the possible obstacles and levers, we propose several recommendations to better grasp the challenge represented by the AH/AI interface. With the development of several recent concepts promoting a global and multisectoral perspective in the field of health, AI should contribute to defract the different disciplines in AH towards more transversal and integrative research.

EMULSION: Transparent and flexible multiscale stochastic models in human, animal and plant epidemiology.

Stochastic mechanistic epidemiological models largely contribute to better understand pathogen emergence and spread, and assess control strategies at various scales (from within-host to transnational scale). However, developing realistic models which involve multi-disciplinary knowledge integration faces three major challenges in predictive epidemiology: lack of readability once translated into simulation code, low reproducibility and reusability, and long development time compared to outbreak time scale. We introduce here EMULSION, an artificial intelligence-based software intended to address those issues and help modellers focus on model design rather than programming. EMULSION defines a domain-specific language to make all components of an epidemiological model (structure, processes, parameters…) explicit as a structured text file. This file is readable by scientists from other fields (epidemiologists, biologists, economists), who can contribute to validate or revise assumptions at any stage of model development. It is then automatically processed by EMULSION generic simulation engine, preventing any discrepancy between model description and implementation. The modelling language and simulation architecture both rely on the combination of advanced artificial intelligence methods (knowledge representation and multi-level agent-based simulation), allowing several modelling paradigms (from compartment- to individual-based models) at several scales (up to metapopulation). The flexibility of EMULSION and its capability to support iterative modelling are illustrated here through examples of progressive complexity, including late revisions of core model assumptions. EMULSION is also currently used to model the spread of several diseases in real pathosystems. EMULSION provides a command-line tool for checking models, producing model diagrams, running simulations, and plotting outputs. Written in Python 3, EMULSION runs on Linux, MacOS, and Windows. It is released under Apache-2.0 license. A comprehensive documentation with installation instructions, a tutorial and many examples are available from: https://sourcesup.renater.fr/www/emulsion-public.

Modeling the Transmission of Vibrio aestuarianus in Pacific Oysters Using Experimental Infection Data.

Vibrio aestuarianus is a bacterium related to mortality outbreaks in Pacific oysters, Crassostrea gigas, in France, Ireland, and Scotland since 2011. Knowledge about its transmission dynamics is still lacking, impairing guidance to prevent and control the related disease spread. Mathematical modeling is a relevant approach to better understand the determinants of a disease and predict its dynamics in imperfectly observed pathosystems. We developed here the first marine epidemiological model to estimate the key parameters of V. aestuarianus infection at a local scale in a small and closed oyster population under controlled laboratory conditions. Using a compartmental model accounting for free-living bacteria in seawater, we predicted the infection dynamics using dedicated and model-driven collected laboratory experimental transmission data. We estimated parameters and showed that waterborne transmission of V. aestuarianus is possible under experimental conditions, with a basic reproduction number R0 of 2.88 (95% CI: 1.86; 3.35), and a generation time of 5.5 days. Our results highlighted a bacterial dose-dependent transmission of vibriosis at local scale. Global sensitivity analyses indicated that the bacteria shedding rate, the concentration of bacteria in seawater that yields a 50% chance of catching the infection, and the initial bacterial exposure dose W0 were three critical parameters explaining most of the variation in the selected model outputs related to disease spread, i.e., R0, the maximum prevalence, oyster survival curve, and bacteria concentration in seawater. Prevention and control should target the exposure of oysters to bacterial concentration in seawater. This combined laboratory-modeling approach enabled us to maximize the use of information obtained through experiments. The identified key epidemiological parameters should be better refined by further dedicated laboratory experiments. These results revealed the importance of multidisciplinary approaches to gain consistent insights into the marine epidemiology of oyster diseases.

Neighbourhood contacts and trade movements drive the regional spread of bovine viral diarrhoea virus (BVDV).

To explore the regional spread of endemic pathogens, investigations are required both at within and between population levels. The bovine viral diarrhoea virus (BVDV) is such a pathogen, spreading among cattle herds mainly due to trade movements and neighbourhood contacts, and causing an endemic disease with economic consequences. To assess the contribution of both transmission routes on BVDV regional and local spread, we developed an original epidemiological model combining data-driven and mechanistic approaches, accounting for heterogeneous within-herd dynamics, animal movements and neighbourhood contacts. Extensive simulations were performed over 9 years in an endemic context in a French region with high cattle density. The most uncertain model parameters were calibrated on summary statistics of epidemiological data, highlighting that neighbourhood contacts and within-herd transmission should be high. We showed that neighbourhood contacts and trade movements complementarily contribute to BVDV spread on a regional scale in endemically infected and densely populated areas, leading to intense fade-out/colonization events: neighbourhood contacts generate the vast majority of outbreaks (72%) but mostly in low immunity herds and correlated to a rather short presence of persistently infected animals (P); trade movements generate fewer infections but could affect herds with higher immunity and generate a prolonged presence of P. Both movements and neighbourhood contacts should be considered when designing control or eradication strategies for densely populated region.

Which phenotypic traits of resistance should be improved in cattle to control paratuberculosis dynamics in a dairy herd: a modelling approach.

Paratuberculosis is a worldwide disease causing production losses in dairy cattle herds. Variability of cattle response to exposure to Mycobacterium avium subsp. paratuberculosis (Map) has been highlighted. Such individual variability could influence Map spread at larger scale. Cattle resistance to paratuberculosis has been shown to be heritable, suggesting genetic selection could enhance disease control. Our objective was to identify which phenotypic traits characterising the individual course of infection influence Map spread in a dairy cattle herd. We used a stochastic mechanistic model. Resistance consisted in the ability to prevent infection and the ability to cope with infection. We assessed the effect of varying (alone and combined) fourteen phenotypic traits characterising the infection course. We calculated four model outputs 25 years after Map introduction in a naïve herd: cumulative incidence, infection persistence, and prevalence of infected and affected animals. A cluster analysis identified influential phenotypes of cattle resistance. An ANOVA quantified the contribution of traits to model output variance. Four phenotypic traits strongly influenced Map spread: the decay in susceptibility with age (the most effective), the quantity of Map shed in faeces by high shedders, the incubation period duration, and the required infectious dose. Interactions contributed up to 12% of output variance, highlighting the expected added-value of improving several traits simultaneously. Combinations of the four most influential traits decreased incidence to less than one newly infected animal per year in most scenarios. Future genetic selection should aim at improving simultaneously the most influential traits to reduce Map spread in cattle populations.

Controlling bovine paratuberculosis at a regional scale: Towards a decision modelling tool.

Johne's disease (paratuberculosis), a worldwide enzootic disease of cattle caused by Mycobacterium avium subsp. paratuberculosis (Map), mainly introduced into farms by purchasing infected animals, has a large economic impact for dairy producers. Since diagnostic tests used in routine are poorly sensitive, observing Map spread in the field is hardly possible, whereas there is a need for evaluating control strategies. Our objective was to provide a modelling framework to compare the efficacy of regional control strategies combining internal biosecurity measures and testing of traded animals, against Map spread in a metapopulation of dairy cattle herds. We represented 12,857 dairy herds located in Brittany (France), based on data from 2005 to 2013, used to calibrate herd sizes and demographic rates and to define trade events in a multiscale model of Map infection dynamics. By clustering and categorical descriptive analysis of intensive simulations of this model, based on a numerical experimental design, a large panel of control measures was explored. Their efficacy was assessed on model outputs such as the prevalence and probability of extinction at the metapopulation level. In addition, we proposed a scoring for the effort required to implement control measures and prioritized control strategies based on their theoretical epidemiological efficacy. Our results clearly indicate that eradication cannot be achieved on the mid term using available control measures. However, we identified relevant combinations of measures that lead to the control of Map spread with realistic level of implementation and coverage. The study highlights the challenge of controlling paratuberculosis in an endemically infected region as related to the poor test characteristics and frequent trade movements. Our model lays the foundations for a flexible and efficient tool to help collective animal health managers in defining relevant control strategies at a regional scale, accounting for local specificities in terms of contact network and farms' characteristics.

Modelling of paratuberculosis spread between dairy cattle farms at a regional scale.

Mycobacterium avium subsp. paratuberculosis (Map) causes Johne's disease, with large economic consequences for dairy cattle producers worldwide. Map spread between farms is mainly due to animal movements. Locally, herd size and management are expected to influence infection dynamics. To provide a better understanding of Map spread between dairy cattle farms at a regional scale, we describe the first spatio-temporal model accounting simultaneously for population and infection dynamics and indirect local transmission within dairy farms, and between-farm transmission through animal trade. This model is applied to Brittany, a French region characterized by a high density of dairy cattle, based on data on animal trade, herd size and farm management (birth, death, renewal, and culling) from 2005 to 2013 for 12,857 dairy farms. In all simulated scenarios, Map infection highly persisted at the metapopulation scale. The characteristics of initially infected farms strongly impacted the regional Map spread. Network-related features of incident farms influenced their ability to contaminate disease-free farms. At the herd level, we highlighted a balanced effect of the number of animals purchased: when large, it led to a high probability of farm infection but to a low persistence. This effect was reduced when prevalence in initially infected farms increased. Implications of our findings in the current enzootic situation are that the risk of infection quickly becomes high for farms buying more than three animals per year. Even in regions with a low proportion of infected farms, Map spread will not fade out spontaneously without the use of effective control strategies.

A novel epidemiological model to better understand and predict the observed seasonal spread of Pestivirus in Pyrenean chamois populations.

Seasonal variations in individual contacts give rise to a complex interplay between host demography and pathogen transmission. This is particularly true for wild populations, which highly depend on their natural habitat. These seasonal cycles induce variations in pathogen transmission. The seasonality of these biological processes should therefore be considered to better represent and predict pathogen spread. In this study, we sought to better understand how the seasonality of both the demography and social contacts of a mountain ungulate population impacts the spread of a pestivirus within, and the dynamics of, this population. We propose a mathematical model to represent this complex biological system. The pestivirus can be transmitted both horizontally through direct contact and vertically in utero. Vertical transmission leads to abortion or to the birth of persistently infected animals with a short life expectancy. Horizontal transmission involves a complex dynamics because of seasonal variations in contact among sexes and age classes. We performed a sensitivity analysis that identified transmission rates and disease-related mortality as key parameters. We then used data from a long-term demographic and epidemiological survey of the studied population to estimate these mostly unknown epidemiological parameters. Our model adequately represents the system dynamics, observations and model predictions showing similar seasonal patterns. We show that the virus has a significant impact on population dynamics, and that persistently infected animals play a major role in the epidemic dynamics. Modeling the seasonal dynamics allowed us to obtain realistic prediction and to identify key parameters of transmission.