Michael J. Tildesley

Optimal reactive vaccination strategies for a foot-and-mouth outbreak in the UK

Foot-and-mouth disease (FMD) in the UK provides an ideal opportunity to explore optimal control measures for an infectious disease. The presence of fine-scale spatio-temporal data for the 2001 epidemic has allowed the development of epidemiological models that are more accurate than those generally created for other epidemics and provide the opportunity to explore a variety of alternative control measures. Vaccination was not used during the 2001 epidemic; however, the recent DEFRA (Department for Environment Food and Rural Affairs) contingency plan details how reactive vaccination would be considered in future. Here, using the data from the 2001 epidemic, we consider the optimal deployment of limited vaccination capacity in a complex heterogeneous environment. We use a model of FMD spread to investigate the optimal deployment of reactive ring vaccination of cattle constrained by logistical resources. The predicted optimal ring size is highly dependent upon logistical constraints but is more robust to epidemiological parameters. Other ways of targeting reactive vaccination can significantly reduce the epidemic size; in particular, ignoring the order in which infections are reported and vaccinating those farms closest to any previously reported case can substantially reduce the epidemic. This strategy has the advantage that it rapidly targets new foci of infection and that determining an optimal ring size is unnecessary.

Accuracy of models for the 2001 foot-and-mouth epidemic

Since 2001 models of the spread of foot-and-mouth disease, supported by the data from the UK epidemic, have been expounded as some of the best examples of problem-driven epidemic models. These claims are generally based on a comparison between model results and epidemic data at fairly coarse spatio-temporal resolution. Here, we focus on a comparison between model and data at the individual farm level, assessing the potential of the model to predict the infectious status of farms in both the short and long terms. Although the accuracy with which the model predicts farms reporting infection is between 5 and 15%, these low levels are attributable to the expected level of variation between epidemics, and are comparable to the agreement between two independent model simulations. By contrast, while the accuracy of predicting culls is higher (20–30%), this is lower than expected from the comparison between model epidemics. These results generally support the contention that the type of the model used in 2001 was a reliable representation of the epidemic process, but highlight the difficulties of predicting the complex human response, in terms of control strategies to the perceived epidemic risk.

The role of pre-emptive culling in the control of foot-and-mouth disease

The 2001 foot-and-mouth disease epidemic was controlled by culling of infectious premises and pre-emptive culling intended to limit the spread of disease. Of the control strategies adopted, routine culling of farms that were contiguous to infected premises caused the most controversy. Here we perform a retrospective analysis of the culling of contiguous premises as performed in 2001 and a simulation study of the effects of this policy on reducing the number of farms affected by disease. Our simulation results support previous studies and show that a national policy of contiguous premises (CPs) culling leads to fewer farms losing livestock. The optimal national policy for controlling the 2001 epidemic is found to be the targeting of all contiguous premises, whereas for localized outbreaks in high animal density regions, more extensive fixed radius ring culling is optimal. Analysis of the 2001 data suggests that the lowest-risk CPs were generally prioritized for culling, however, even in this case, the policy is predicted to be effective. A sensitivity analysis and the development of a spatially heterogeneous policy show that the optimal culling level depends upon the basic reproductive ratio of the infection and the width of the dispersal kernel. These analyses highlight an important and probably quite general result: optimal control is highly dependent upon the distance over which the pathogen can be transmitted, the transmission rate of infection and local demography where the disease is introduced.

Impact of spatial clustering on disease transmission and optimal control

Spatial heterogeneities and spatial separation of hosts are often seen as key factors when developing accurate predictive models of the spread of pathogens. The question we address in this paper is how coarse the resolution of the spatial data can be for a model to be a useful tool for informing control policies. We examine this problem using the specific case of foot-and-mouth disease spreading between farms using the formulation developed during the 2001 epidemic in the United Kingdom. We show that, if our model is carefully parameterized to match epidemic behavior, then using aggregate county-scale data from the United States is sufficient to closely determine optimal control measures (specifically ring culling). This result also holds when the approach is extended to theoretical distributions of farms where the spatial clustering can be manipulated to extremes. We have therefore shown that, although spatial structure can be critically important in allowing us to predict the emergent population-scale behavior from a knowledge of the individual-level dynamics, for this specific applied question, such structure is mostly subsumed in the parameterization allowing us to make policy predictions in the absence of high-quality spatial information. We believe that this approach will be of considerable benefit across a range of disciplines where data are only available at intermediate spatial scales.

Topographic determinants of foot and mouth disease transmission in the UK 2001 epidemic

BackgroundA key challenge for modelling infectious disease dynamics is to understand the spatial spread of infection in real landscapes. This ideally requires a parallel record of spatial epidemic spread and a detailed map of susceptible host density along with relevant transport links and geographical features.ResultsHere we analyse the most detailed such data to date arising from the UK 2001 foot and mouth epidemic. We show that Euclidean distance between infectious and susceptible premises is a better predictor of transmission risk than shortest and quickest routes via road, except where major geographical features intervene.ConclusionThus, a simple spatial transmission kernel based on Euclidean distance suffices in most regions, probably reflecting the multiplicity of transmission routes during the epidemic.

Adaptive Management and the Value of Information: Learning Via Intervention in Epidemiology

This Research Article explores the benefits of applying Adaptive Management approaches to disease outbreaks, finding that formally integrating science and policy allows one to reduce uncertainty and improve disease management outcomes.

The impact of movements and animal density on continental scale cattle disease outbreaks in the United States.

Globalization has increased the potential for the introduction and spread of novel pathogens over large spatial scales necessitating continental-scale disease models to guide emergency preparedness. Livestock disease spread models, such as those for the 2001 foot-and-mouth disease (FMD) epidemic in the United Kingdom, represent some of the best case studies of large-scale disease spread. However, generalization of these models to explore disease outcomes in other systems, such as the United States’s cattle industry, has been hampered by differences in system size and complexity and the absence of suitable livestock movement data. Here, a unique database of US cattle shipments allows estimation of synthetic movement networks that inform a near-continental scale disease model of a potential FMD-like (i.e., rapidly spreading) epidemic in US cattle. The largest epidemics may affect over one-third of the US and 120,000 cattle premises, but cattle movement restrictions from infected counties, as opposed to national movement moratoriums, are found to effectively contain outbreaks. Slow detection or weak compliance may necessitate more severe state-level bans for similar control. Such results highlight the role of large-scale disease models in emergency preparedness, particularly for systems lacking comprehensive movement and outbreak data, and the need to rapidly implement multi-scale contingency plans during a potential US outbreak.

Modelling foot-and-mouth disease: a comparison between the UK and Denmark.

Whilst the UK 2001 FMD (foot-and-mouth disease) outbreak provides an extremely rich source of spatio-temporal epidemic data, it is not clear how the models and parameters from the UK can be translated to other scenarios. Here we consider how the model framework used to capture the UK epidemic can be applied to a hypothetical FMD outbreak in Denmark. Whilst pigs played a relatively minor role in the UK epidemic (being the infected animal on just 18 farms), they dominate the Danish livestock landscape. In addition, it is not clear whether transmission parameters from the UK will transfer to Denmark where farming practices may be significantly different. We therefore explore a large volume of high-dimensional parameter space, but seek to relate final epidemic size, risk of spread to Danish islands and potential success of control measures, to early indicators of epidemic dynamics. The results of this extensive modelling exercise therefore allow us to provide timely advice on control options based on the observed behaviours of the first few generations.

Is R0 a good predictor of final epidemic size: Foot-and-mouth disease in the UK

One of the main uses of an epidemic model is to predict the scale of an outbreak from the first few cases. In a homogeneous and non-spatial model there is a straightforward relationship between the basic reproductive ratio, R(0), and the final epidemic size; however when there is a significant spatial component to disease spread and the population is heterogeneous predicting how the epidemic size varies with the initial source of infection is far more complex. Here we use a well-developed spatio-temporal model of the spread of foot-and-mouth disease, parameterized to match the 2001 UK outbreak, to address the relationship between the scale of the epidemic and the nature of the initially infected farm. We show that there is considerable heterogeneity in both the likelihood of a epidemic and the epidemic impact (total number of farms losing livestock to either infection or control) and that these two elements are best captured by measurements at different spatial scales. The likelihood of an epidemic can be predicted from a knowledge of the reproduction ratio of the initial farm (R(i)), whereas the epidemic impact conditional on an epidemic occurring is best predicted by averaging the second-generation reproduction ratio (R(i)((2))) in a 58 km ring around the infected farm. Combining these two predictions provides a good assessment of both the local and larger-scale heterogeneities present in this complex system.

Effect of data quality on estimates of farm infectiousness trends in the UK 2001 foot-and-mouth disease epidemic

Most of the mathematical models that were developed to study the UK 2001 foot-and-mouth disease epidemic assumed that the infectiousness of infected premises was constant over their infectious periods. However, there is some controversy over whether this assumption is appropriate. Uncertainty about which farm infected which in 2001 means that the only method to determine if there were trends in farm infectiousness is the fitting of mechanistic mathematical models to the epidemic data. The parameter values that are estimated using this technique, however, may be influenced by missing and inaccurate data. In particular to the UK 2001 epidemic, this includes unreported infectives, inaccurate farm infection dates and unknown farm latent periods. Here, we show that such data degradation prevents successful determination of trends in farm infectiousness.