Risk of Foot-and-Mouth Disease spread due to sole occupancy authorities and linked cattle holdings

Livestock movements in Great Britain are well recorded, have been extensively analysed with respect to their role in disease spread, and have been used in real time to advise governments on the control of infectious diseases. Typically, livestock holdings are treated as distinct entities that must observe movement standstills upon receipt of livestock, and must report livestock movements. However, there are currently two dispensations that can exempt holdings from either observing standstills or reporting movements, namely the Sole Occupancy Authority (SOA) and Cattle Tracing System (CTS) Links, respectively. In this report we have used a combination of data analyses and computational modelling to investigate the usage and potential impact of such linked holdings on the size of a Foot-and-Mouth Disease (FMD) epidemic. Our analyses show that although SOAs are abundant, their dynamics appear relatively stagnant. The number of CTS Links is also abundant, and increasing rapidly. Although most linked holdings are only involved in a single CTS Link, some holdings are involved in numerous links that can be amalgamated to form "CTS Chains" which can be both large and geographically dispersed. Our model predicts that under a worst case scenario of "one infected - all infected", SOAs do pose a risk of increasing the size (in terms of number of infected holdings) of a FMD epidemic, but this increase is mainly due to intra-SOA infection spread events. Furthermore, although SOAs do increase the geographic spread of an epidemic, this increase is predominantly local. Whereas, CTS Chains pose a risk of increasing both the size and the geographical spread of the disease substantially, under a worse case scenario. Our results highlight the need for further investigations into whether CTS Chains are transmission chains, and also investigations into intra-SOA movements and livestock distributions due to the lack of current data.     

Disease contact tracing in random and clustered networks

The efficacy of contact tracing, be it between individuals (e.g. sexually transmitted diseases or severe acute respiratory syndrome) or between groups of individuals (e.g. foot-and-mouth disease; FMD), is difficult to evaluate without precise knowledge of the underlying contact structure; i.e. who is connected to whom? Motivated by the 2001 FMD epidemic in the UK, we determine, using stochastic simulations and deterministic 'moment closure' models of disease transmission on networks of premises (nodes), network and disease properties that are important for contact tracing efficiency. For random networks with a high average number of connections per node, little clustering of connections and short latency periods, contact tracing is typically ineffective. In this case, isolation of infected nodes is the dominant factor in determining disease epidemic size and duration. If the latency period is longer and the average number of connections per node small, or if the network is spatially clustered, then the contact tracing performs better and an overall reduction in the proportion of nodes that are removed during an epidemic is observed.     

Demographic structure and pathogen dynamics on the network of livestock movements in Great Britain

Using a novel interpretation of dynamic networks, we analyse the network of livestock movements in Great Britain in order to determine the risk of a large epidemic of foot-and-mouth disease (FMD). This network is exceptionally well characterized, as there are legal requirements that the date, source, destination and number of animals be recorded and held on central databases. We identify a percolation threshold in the structure of the livestock network, indicating that, while there is little possibility of a national epidemic of FMD in winter when the catastrophic 2001 epidemic began, there remains a risk in late summer or early autumn. These predictions are corroborated by a non-parametric simulation in which the movements of livestock in 2003 and 2004 are replayed as they occurred. Despite the risk, we show that the network displays small-world properties which can be exploited to target surveillance and control and drastically reduce this risk.     

Transmission parameters of the 2001 foot and mouth epidemic in Great Britain

Despite intensive ongoing research, key aspects of the spatial-temporal evolution of the 2001 foot and mouth disease (FMD) epidemic in Great Britain (GB) remain unexplained. Here we develop a Markov Chain Monte Carlo (MCMC) method for estimating epidemiological parameters of the 2001 outbreak for a range of simple transmission models. We make the simplifying assumption that infectious farms were completely observed in 2001, equivalent to assuming that farms that were proactively culled but not diagnosed with FMD were not infectious, even if some were infected. We estimate how transmission parameters varied through time, highlighting the impact of the control measures on the progression of the epidemic. We demonstrate statistically significant evidence for assortative contact patterns between animals of the same species. Predictive risk maps of the transmission potential in different geographic areas of GB are presented for the fitted models.     

Seroprevalence and risk factors of Q fever in goats on commercial dairy goat farms in the Netherlands, 2009-2010

Background

Highly pathogenic avian influenza (HPAI) viruses have had devastating effects on poultry industries worldwide, and there is concern about the potential for HPAI outbreaks in the poultry industry in Great Britain (GB). Critical to the potential for HPAI to spread between poultry premises are the connections made between farms by movements related to human activity. Movement records of catching teams and slaughterhouse vehicles were obtained from a large catching company, and these data were used in a simulation model of HPAI spread between farms serviced by the catching company, and surrounding (geographic) areas. The spread of HPAI through real-time movements was modelled, with the addition of spread via company personnel and local transmission.

Results

The model predicted that although large outbreaks are rare, they may occur, with long distances between infected premises. Final outbreak size was most sensitive to the probability of spread via slaughterhouse-linked movements whereas the probability of onward spread beyond an index premises was most sensitive to the frequency of company personnel movements.

Conclusions

Results obtained from this study show that, whilst there is the possibility that HPAI virus will jump from one cluster of farms to another, movements made by catching teams connected fewer poultry premises in an outbreak situation than slaughterhouses and company personnel. The potential connection of a large number of infected farms, however, highlights the importance of retaining up-to-date data on poultry premises so that control measures can be effectively prioritised in an outbreak situation.     

Transmission pathways of foot-and-mouth disease virus in the United Kingdom in 2007

Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contaminated persons, objects, and aerosols). Here, we show that the outbreaks of FMD in the United Kingdom in August 2007 were caused by a derivative of FMDV O(1) BFS 1860, a virus strain handled at two FMD laboratories located on a single site at Pirbright in Surrey. Genetic analysis of complete viral genomes generated in real-time reveals a probable chain of transmission events, predicting undisclosed infected premises, and connecting the second cluster of outbreaks in September to those in August. Complete genome sequence analysis of FMD viruses conducted in real-time have identified the initial and intermediate sources of these outbreaks and demonstrate the value of such techniques in providing information useful to contemporary disease control programmes.     

The number of links to and from the starting node as a predictor of epidemic size in small-size directed networks

Much recent modelling is focusing on epidemics in large-scale complex networks. Whether or not findings of these investigations also apply to networks of small size is still an open question. This is an important gap for many biological applications, including the spread of the oomycete pathogen Phytophthora ramorum in networks of plant nurseries. We use numerical simulations of disease spread and establishment in directed networks of 100 individual nodes at four levels of connectivity. Factors governing epidemic spread are network structure (local, small-world, random, scale-free) and the probabilities of infection persistence in a node and of infection transmission between connected nodes. Epidemic final size at equilibrium varies widely depending on the starting node of infection, although the latter does not affect the threshold condition for spread. The number of links from (out-degree) but not the number of links to (in-degree) the starting node of the epidemic explains a substantial amount of variation in final epidemic size at equilibrium irrespective of the structure of the network. The proportion of variance in epidemic size explained by the out-degree of the starting node increases with the level of connectivity. Targeting highly connected nodes is thus likely to make disease control more effective also in case of small-size populations, a result of relevance not just for the horticultural trade, but for epidemiology in general.     

Seasonality and heterogeneity of live fish movements in Scottish fish farms

Movement of live animals is a key contributor to disease spread. Farmed Atlantic salmon Salmo salar, rainbow trout Onchorynchus mykiss and brown/sea trout Salmo trutta are initially raised in freshwater (FW) farms; all the salmon and some of the trout are subsequently moved to seawater (SW) farms. Frequently, fish are moved between farms during their FW stage and sometimes during their SW stage. Seasonality and differences in contact patterns across production phases have been shown to influence the course of an epidemic in livestock; however, these parameters have not been included in previous network models studying disease transmission in salmonids. In Scotland, farmers are required to register fish movements onto and off their farms; these records were used in the present study to investigate seasonality and heterogeneity of movements for each production phase separately for farmed salmon, rainbow trout and brown/sea trout. Salmon FW-FW and FW-SW movements showed a higher degree of heterogeneity in number of contacts and different seasonal patterns compared with SW-SW movements. FW-FW movements peaked from May to July and FW-SW movements peaked from March to April and from October to November. Salmon SW-SW movements occurred more consistently over the year and showed fewer connections and number of repeated connections between farms. Therefore, the salmon SW-SW network might be treated as homogeneous regarding the number of connections between farms and without seasonality. However, seasonality and production phase should be included in simulation models concerning FW-FW and FW-SW movements specifically. The number of rainbow trout FW-FW and brown/sea trout FW-FW movements were different from random. However, movements from other production phases were too low to discern a seasonal pattern or differences in contact pattern.     

Epithelial expression of mRNA and protein for IL-6, IL-10 and TNF-α in endobronchial biopsies in horses with recurrent airway obstruction

Background  

Models of Foot and Mouth Disease (FMD) transmission have assumed a homogeneous landscape across which Euclidean distance is a suitable measure of the spatial dependency of transmission. This paper investigated features of the landscape and their impact on transmission during the period of predominantly local spread which followed the implementation of the national movement ban during the 2001 UK FMD epidemic. In this study 113 farms diagnosed with FMD which had a known source of infection within 3 km (cases) were matched to 188 control farms which were either uninfected or infected at a later timepoint. Cases were matched to controls by Euclidean distance to the source of infection and farm size. Intervening geographical features and connectivity between the source of infection and case and controls were compared.     

An analysis of the possible effects of the 2001 foot and mouth disease epidemic on grass pollen concentrations in the Midlands, UK

The 2001 grass pollen season in the United Kingdom was notably severe. An epidemic of foot and mouth disease (FMD) occurred in the UK during February and spread through the country during the summer. The media claimed that the control measures of culling infected animals and the restricted movement of stock, led to reduced grazing allowing pastures to flower more than in previous years. This study aimed to examine whether the severity was due only to weather factors or if the control measures also contributed. Three pollen sites from the FMD-affected Midlands region were investigated and compared with two sites from regions unaffected for differences in pollen catches, culling levels and weather. The June pollen catch in the Midlands was particularly high but this pattern also features in areas such as Cambridge in the East that were minimally affected by the epidemic. In most of the catchment areas affected by FMD the quantity of animals culled was less than 10% of the total livestock. In areas where culling was concentrated we can assume that there would have been some localized affect on the pollen levels. The results show that the main influencing variable on the 2001 grass pollen counts in the Midlands was the weather and that culling due to the foot and mouth epidemic did not exert an important influence at the regional level.     

An analysis of the possible effects of the 2001 foot and mouth disease epidemic on grass pollen concentrations in the Midlands, UK

The 2001 grass pollen season in the United Kingdom was notably severe. An epidemic of foot and mouth disease (FMD) occurred in the UK during February and spread through the country during the summer. The media claimed that the control measures of culling infected animals and the restricted movement of stock, led to reduced grazing allowing pastures to flower more than in previous years. This study aimed to examine whether the severity was due only to weather factors or if the control measures also contributed. Three pollen sites from the FMD-affected Midlands region were investigated and compared with two sites from regions unaffected for differences in pollen catches, culling levels and weather. The June pollen catch in the Midlands was particularly high but this pattern also features in areas such as Cambridge in the East that were minimally affected by the epidemic. In most of the catchment areas affected by FMD the quantity of animals culled was less than 10% of the total livestock. In areas where culling was concentrated we can assume that there would have been some localized affect on the pollen levels. The results show that the main influencing variable on the 2001 grass pollen counts in the Midlands was the weather and that culling due to the foot and mouth epidemic did not exert an important influence at the regional level.     

An analysis of the possible effects of the 2001 foot and mouth disease epidemic on grass pollen concentrations in the Midlands,UK

The 2001 grass pollen season in the United Kingdom was notably severe. An epidemic of foot and mouth disease (FMD) occurred in the UK during February and spread through the country during the summer. The media claimed that the control measures of culling infected animals and the restricted movement of stock, led to reduced grazing allowing pastures to flower more than in previous years. This study aimed to examine whether the severity was due only to weather factors or if the control measures also contributed. Three pollen sites from the FMD-affected Midlands region were investigated and compared with two sites from regions unaffected for differences in pollen catches, culling levels and weather. The June pollen catch in the Midlands was particularly high but this pattern also features in areas such as Cambridge in the East that were minimally affected by the epidemic. In most of the catchment areas affected by FMD the quantity of animals culled was less than 10% of the total livestock. In areas where culling was concentrated we can assume that there would have been some localized affect on the pollen levels. The results show that the main influencing variable on the 2001 grass pollen counts in the Midlands was the weather and that culling due to the foot and mouth epidemic did not exert an important influence at the regional level.     

The impact of local heterogeneity on alternative control strategies for foot-and-mouth disease

The 2001 epidemic of foot-and-mouth disease (FMD) in the UK resulted in the death of nearly 10 million livestock at a cost that was estimated to be up to 8 billion pounds. Owing to the controversy surrounding the epidemic, the question of whether or not alternative policies would have resulted in significantly better control of the epidemic remains of great interest. A hexagonal lattice simulation of FMD in Cumbria is used to address the central question of whether or not better use could have been made of expert knowledge of FMD transmission to target pre-emptive culling, by assuming that the premises at greatest risk of becoming infected can be targeted for culling. The 2000 UK census and the epidemiological database collected during the epidemic are used to describe key characteristics of disease transmission, and the model is fit to the epidemic time-series. Under the assumptions of the model, the parameters that best fit the epidemic in Cumbria indicate that a policy based on expert knowledge would have exacerbated the epidemic compared with the policy as implemented. However, targeting more distant, high-risk farms could be more valuable under different epidemic conditions, notably, if risk factors of sufficient magnitude could be identified to aid in prioritizing vaccination or culling of farms at high risk of becoming infected.     

The Role of Community Mixing Styles in Shaping Epidemic Behaviors in Weighted Networks

The dynamics of infectious diseases that are spread through direct contact have been proven to depend on the strength of community structure or modularity within the underlying network. It has been recently shown that weighted networks with similar modularity values may exhibit different mixing styles regarding the number of connections among communities and their respective weights. However, the effect of mixing style on epidemic behavior was still unclear. In this paper, we simulate the spread of disease within networks with different mixing styles: a dense-weak style (i.e., many edges among the communities with small weights) and a sparse-strong style (i.e., a few edges among the communities with large weights). Simulation results show that, with the same modularity: 1) the mixing style significantly influences the epidemic size, speed, pattern and immunization strategy; 2) the increase of the number of communities amplifies the effect of the mixing style; 3) when the mixing style changes from sparse-strong to dense-weak, there is a ‘saturation point’, after which the epidemic size and pattern become stable. We also provide a mean-field solution of the epidemic threshold and size on weighted community networks with arbitrary external and internal degree distribution. The solution explains the effect of the second moment of the degree distribution, and a symmetric effect of internal and external connections (incl. degree distribution and weight). Our study has both potential significance for designing more accurate metrics for the community structure and exploring diffusion dynamics on metapopulation networks.     

Animal disease and human trauma: the psychosocial implications of the 2001 UK foot and mouth disease disaster

The 2001 UK foot and mouth disease (FMD) crisis is commonly understood to have been a nonhuman animal problem, an economic industrial crisis that was resolved after eradication. By using a different lens, a longitudinal ethnographic study of the health and social consequences of the epidemic, the research reported here indicates that 2001 was a human tragedy as well as an animal one. In a diary-based study, it can be seen that life after the FMD crisis was accompanied by distress, feelings of bereavement, fear of a new disaster, loss of trust in authority and systems of control, and the undermining of the value of local knowledge. Diverse groups experienced distress well beyond the farming community. Such distress remained largely invisible to the range of “official” inquiries into the disaster. That an FMD epidemic of the scale of 2001 could happen again in a developed country is a deeply worrying prospect, but it is to be hoped that contingency plans are evolving along with enhanced understanding of the human, animal, and financial cost.     

Modelling disease spread and control in networks: implications for plant sciences

Networks are ubiquitous in natural, technological and social systems. They are of increasing relevance for improved understanding and control of infectious diseases of plants, animals and humans, given the interconnectedness of today's world. Recent modelling work on disease development in complex networks shows: the relative rapidity of pathogen spread in scale-free compared with random networks, unless there is high local clustering; the theoretical absence of an epidemic threshold in scale-free networks of infinite size, which implies that diseases with low infection rates can spread in them, but the emergence of a threshold when realistic features are added to networks (e.g. finite size, household structure or deactivation of links); and the influence on epidemic dynamics of asymmetrical interactions. Models suggest that control of pathogens spreading in scale-free networks should focus on highly connected individuals rather than on mass random immunization. A growing number of empirical applications of network theory in human medicine and animal disease ecology confirm the potential of the approach, and suggest that network thinking could also benefit plant epidemiology and forest pathology, particularly in human-modified pathosystems linked by commercial transport of plant and disease propagules. Potential consequences for the study and management of plant and tree diseases are discussed.     

Epidemic threshold and network structure: The interplay of probability of transmission and of persistence in small-size directed networks

A growing number of studies are investigating the effect of contact structure on the dynamics of epidemics in large-scale complex networks. Whether findings thus obtained apply also to networks of small size, and thus to many real-world biological applications, is still an open question. We use numerical simulations of disease spread in directed networks of 100 individual nodes with a constant number of links. We show that, no matter the type of network structure (local, small-world, random and scale-free), there is a linear threshold determined by the probability of infection transmission between connected nodes and the probability of infection persistence in an infected node. The threshold is significantly lower for scale-free networks compared to local, random and small-world ones only if super-connected nodes have a higher number of links both to and from other nodes. The starting point, the node at which the epidemic starts, does not affect the threshold conditions, but has a marked influence on the final size of the epidemic in all kinds of network. There is evidence that contact structure has an influence on the average final size of an epidemic across all starting nodes, with significantly lower values in scale-free networks at equilibrium. Simulations in scale-free networks show a distinctive time-series pattern, which, if found in a real epidemic, can be used to infer the underlying network structure. The findings have relevance also for meta-population ecology and species conservation.     

Development of novel strategies to control foot-and-mouth disease: Marker vaccines and antivirals

Foot-and-mouth disease (FMD) is economically the most important viral-induced livestock disease worldwide. The disease is highly contagious and FMD virus (FMDV) replicates and spreads extremely rapidly. Outbreaks in previously FMD-free countries, including Taiwan, the United Kingdom, and Uruguay, and the potential use of FMDV by terrorist groups have demonstrated the vulnerability of countries and the need to develop control strategies that can rapidly inhibit or limit disease spread. The current vaccine, an inactivated whole virus preparation, has a number of limitations for use in outbreaks in disease-free countries. We have developed an alternative approach using a genetically engineered FMD subunit vaccine that only contains the portions of the viral genome required for virus capsid assembly and lacks the coding region for most of the viral nonstructural (NS) proteins including the highly immunogenic 3D protein. Thus, animals inoculated with this marker vaccine can readily be differentiated from infected animals using diagnostic assays employing the NS proteins not present in the vaccine and production of this vaccine, which does not contain infectious FMDV, does not require expensive high-containment manufacturing facilities. One inoculation of this subunit vaccine delivered in a replication-defective human adenovirus vector can induce rapid, within 7 days, and relatively long-lasting protection in swine. Similarly cattle inoculated with one dose of this recombinant vector are rapidly protected from direct and contact exposure to virulent virus. Furthermore, cattle given two doses of this vaccine developed high levels of FMDV-specific neutralizing antibodies, but did not develop antibodies against viral NS proteins demonstrating the ability of FMD subunit vaccinated animals to be differentiated from infected animals. To stimulate early protection prior to the vaccine-induced adaptive immune response we inoculated swine with the antiviral agent, type I interferon, and induced complete protection within 1 day. Protection can last for 3-5 days. The combination of the FMD marker vaccine and type I interferon can induce immediate, within 1 day, and long-lasting protection against FMD. Thus, this combination approach successfully addresses a number of concerns of FMD-free countries with the current disease control plan. By rapidly limiting virus replication and spread this strategy may reduce the number of animals that need to be slaughtered during an outbreak.     

Estimates for local and movement-based transmission of bovine tuberculosis in British cattle

Both badgers and livestock movements have been implicated in contributing to the ongoing epidemic of bovine tuberculosis (BTB) in British cattle. However, the relative contributions of these and other causes are not well quantified. We used cattle movement data to construct an individual (premises)-based model of BTB spread within Great Britain, accounting for spread due to recorded cattle movements and other causes. Outbreak data for 2004 were best explained by a model attributing 16% of herd infections directly to cattle movements, and a further 9% unexplained, potentially including spread from unrecorded movements. The best-fit model assumed low levels of cattle-to-cattle transmission. The remaining 75% of infection was attributed to local effects within specific high-risk areas. Annual and biennial testing is mandatory for herds deemed at high risk of infection, as is pre-movement testing from such herds. The herds identified as high risk in 2004 by our model are in broad agreement with those officially designated as such at that time. However, border areas at the edges of high-risk regions are different, suggesting possible areas that should be targeted to prevent further geographical spread of disease. With these areas expanding rapidly over the last decade, their close surveillance is important to both identify infected herds qucikly, and limit their further growth.     

Geographic and topographic determinants of local FMD transmission applied to the 2001 UK FMD epidemic

Background

Models of Foot and Mouth Disease (FMD) transmission have assumed a homogeneous landscape across which Euclidean distance is a suitable measure of the spatial dependency of transmission. This paper investigated features of the landscape and their impact on transmission during the period of predominantly local spread which followed the implementation of the national movement ban during the 2001 UK FMD epidemic. In this study 113 farms diagnosed with FMD which had a known source of infection within 3 km (cases) were matched to 188 control farms which were either uninfected or infected at a later timepoint. Cases were matched to controls by Euclidean distance to the source of infection and farm size. Intervening geographical features and connectivity between the source of infection and case and controls were compared.

Results

Road distance between holdings, access to holdings, presence of forest, elevation change between holdings and the presence of intervening roads had no impact on the risk of local FMD transmission (p > 0.2). However the presence of linear features in the form of rivers and railways acted as barriers to FMD transmission (odds ratio = 0.507, 95% CIs = 0.297,0.887, p = 0.018).

Conclusion

This paper demonstrated that although FMD spread can generally be modelled using Euclidean distance and numbers of animals on susceptible holdings, the presence of rivers and railways has an additional protective effect reducing the probability of transmission between holdings.