Within-Host Viral Growth and Immune Response Rates Predict Foot-and-Mouth Disease Virus Transmission Dynamics for African Buffalo.

AbstractInfectious disease dynamics operate across biological scales: pathogens replicate within hosts but transmit among populations. Functional changes in the pathogen-host interaction thus generate cascading effects across organizational scales. We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. We combined data on viral dynamics and host immune responses with mathematical models to ask the following questions: How do viral and immune dynamics vary among strains? Which viral and immune parameters determine viral fitness within hosts? And how do within-host dynamics relate to virus transmission? Our data reveal contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus's relative basic reproductive number (ℛ0), suggesting that viral invasion potential may be predictable from within-host dynamics.

Foot-and-mouth disease virus infection in the domestic dog (Canis lupus familiaris), Iran.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly infectious viral disease, recognised to affect animals in the order Artiodactyla. The disease is rarely fatal in adult animals, however high mortality is associated with neonatal and juvenile infection. CASE PRESENTATION: Five puppies died after being fed lamb carcases, the lambs having died during an outbreak of FMD in Iran. Following a post-mortem examination, cardiac tissue from one of the dead puppies was subjected to virus isolation, antigen ELISA, real-time RT-PCR, sequencing and confocal microscopy to assess the presence and characteristics of any FMD virus. The virological and microscopic examination of the cardiac tissue provided evidence of FMD virus replication in the canine heart. CONCLUSIONS: The data generated in this study demonstrate for the first time that FMD virus can internalise and replicate in dogs and may represent an epidemiologically significant event in FMD transmission, highlighting the dangers of feeding diseased animal carcases to other species. The reporting of this finding may also focus attention on similar disease presentations in dogs in FMD endemic countries allowing a better understanding of the prevalence of such events.

Network analyses to quantify effects of host movement in multilevel disease transmission models using foot and mouth disease in Cameroon as a case study.

The dynamics of infectious diseases are greatly influenced by the movement of both susceptible and infected hosts. To accurately represent disease dynamics among a mobile host population, detailed movement models have been coupled with disease transmission models. However, a number of different host movement models have been proposed, each with their own set of assumptions and results that differ from the other models. Here, we compare two movement models coupled to the same disease transmission model using network analyses. This application of network analysis allows us to evaluate the fit and accuracy of the movement model in a multilevel modeling framework with more detail than established statistical modeling fitting methods. We used data that detailed mobile pastoralists' movements as input for 100 stochastic simulations of a Spatio-Temporal Movement (STM) model and 100 stochastic simulations of an Individual Movement Model (IMM). Both models represent dynamic movement and subsequent contacts. We generated networks in which nodes represent camps and edges represent the distance between camps. We simulated pathogen transmission over these networks and tested five network metrics-strength, betweenness centrality, three-step reach, density, and transitivity-to determine which could predict disease simulation outcomes and thereby be used to correlate model simulation results with disease transmission simulations. We found that strength, network density, and three-step reach of movement model results correlated with the final epidemic size of outbreak simulations. Betweenness centrality only weakly correlated for the IMM model. Transitivity only weakly correlated for the STM model and time-varying IMM model metrics. We conclude that movement models coupled with disease transmission models can affect disease transmission results and should be carefully considered and vetted when modeling pathogen spread in mobile host populations. Strength, network density, and three-step reach can be used to evaluate movement models before disease simulations to predict final outbreak sizes. These findings can contribute to the analysis of multilevel models across systems.

Risk factors for the incursion, spread and persistence of the foot and mouth disease virus in Eastern Rwanda.

BACKGROUND: Identification of risk factors is crucial in Foot-and-mouth disease (FMD) control especially in endemic countries. In Rwanda, almost all outbreaks of Foot-and-Mouth Disease Virus (FMDV) have started in Eastern Rwanda. Identifying the risk factors in this area will support government control efforts. This study was carried out to identify and map different risk factors for the incursion, spread and persistence of FMDV in Eastern Rwanda. Questionnaires were administered during farm visits to establish risk factors for FMD outbreaks. Descriptive statistical measures were determined and odds ratios were calculated to determine the effects of risk factors on the occurrence of FMD. Quantum Geographic Information System (QGIS) was used to produce thematic maps on the proportion of putative risk factors for FMD per village. RESULTS: Based on farmers' perceptions, 85.31% (with p < 0.01) experienced more outbreaks during the major dry season, a finding consistent with other reports in other parts of the world. Univariate analysis revealed that mixed farming (OR = 1.501, p = 0.163, CI = 95%), and natural breeding method (OR = 1.626; p = 0.21, CI = 95%) were associated with the occurrence of FMD indicating that the two risk factors could be responsible for FMD outbreaks in the farms. The occurrence of FMD in the farms was found to be significantly associated with lack of vaccination of calves younger than 12 months in herds (OR = 0.707; p = 0.046, CI = 95%). CONCLUSIONS: This is the first study to describe risk factors for persistence of FMDV in livestock systems in Rwanda. However, further studies are required to understand the role of transboundary animal movements and genotypic profiles of circulating FMDV in farming systems in Rwanda.

Phylogeographical and cross-species transmission dynamics of SAT1 and SAT2 foot-and-mouth disease virus in Eastern Africa.

Understanding the dynamics of foot-and-mouth disease virus (FMDV), an endemic and economically constraining disease, is critical in designing control programmes in Africa. This study investigates the evolutionary epidemiology of SAT1 and SAT2 FMDV in Eastern Africa, as well as between cattle and wild African buffalo. Bayesian phylodynamic models were used to analyse SAT1 and SAT2 VP1 gene segments collected between 1975 and 2016, focusing on the SAT1 and SAT2 viruses currently circulating in Eastern Africa. The root state posterior probabilities inferred from our analyses suggest Zimbabwe as the ancestral location for SAT1 currently circulating in Eastern Africa (p = 0.67). For the SAT2 clade, Kenya is inferred to be the ancestral location for introduction of the virus into other countries in Eastern Africa (p = 0.72). Salient (Bayes factor >10) viral dispersal routes were inferred from Tanzania to Kenya, and from Kenya to Uganda for SAT1 and SAT2, respectively. Results suggest that cattle are the source of the SAT1 and SAT2 clades currently circulating in Eastern Africa. In addition, our results suggest that the majority of SAT1 and SAT2 in livestock come from other livestock rather than wildlife, with limited evidence that buffalo serve as reservoirs for cattle. Insights from the present study highlight the role of cattle movements and anthropogenic activities in shaping the evolutionary history of SAT1 and SAT2 in Eastern Africa. While the results may be affected by inherent limitations of imperfect surveillance, our analysis elucidates the dynamics between host species in this region, which is key to guiding disease intervention activities.

Assessing the spread of foot and mouth disease in mainland China by dynamical switching model.

In mainland China, there are three prevalent serotypes of foot and mouth disease virus (FMDV) and they circulate in different susceptible animals, which respond to viral infection in various ways and present different prevalent features. Although powerful control measures are carried on regularly, the epidemic are still prevalent in livestock. Therefore it is essential to assess the disease trends of foot and mouth disease (FMD) in domestic animals in mainland China. The participation of contaminated environment in the transmission dynamics has been confirmed in laboratory research and it can alter the conditions for FMDV invasion and persistence. So environment transmission plays a key role in disease spreading process. In this paper, we establish a dynamical switching model with environment transmission to investigate the relevant internal force mechanism with respect to the threshold switching, effect of saturation of the quantity of FMDV in environment, and prevalent characteristics of the disease in mainland China. Through the dynamical analysis of the model, we understand that under different conditions, there may appear coexistence of one, two, three or even four steady states, and bistability might occur, showing that the development trend of epidemic not only depends on the model parameters, but also is associated with the initial condition. We further study the influence of key parameters on the dynamical behavior and classify the parameter space into several regions with different composition patterns. Applying the model to assess the development trend of FMD in livestock in mainland China, we find that under certain conditions, some of the serotypes persists and some may disappear, thus we can provide some suggestions for disease control of prevailing serotype.

Need for speed: An optimized gridding approach for spatially explicit disease simulations.

Numerical models for simulating outbreaks of infectious diseases are powerful tools for informing surveillance and control strategy decisions. However, large-scale spatially explicit models can be limited by the amount of computational resources they require, which poses a problem when multiple scenarios need to be explored to provide policy recommendations. We introduce an easily implemented method that can reduce computation time in a standard Susceptible-Exposed-Infectious-Removed (SEIR) model without introducing any further approximations or truncations. It is based on a hierarchical infection process that operates on entire groups of spatially related nodes (cells in a grid) in order to efficiently filter out large volumes of susceptible nodes that would otherwise have required expensive calculations. After the filtering of the cells, only a subset of the nodes that were originally at risk are then evaluated for actual infection. The increase in efficiency is sensitive to the exact configuration of the grid, and we describe a simple method to find an estimate of the optimal configuration of a given landscape as well as a method to partition the landscape into a grid configuration. To investigate its efficiency, we compare the introduced methods to other algorithms and evaluate computation time, focusing on simulated outbreaks of foot-and-mouth disease (FMD) on the farm population of the USA, the UK and Sweden, as well as on three randomly generated populations with varying degree of clustering. The introduced method provided up to 500 times faster calculations than pairwise computation, and consistently performed as well or better than other available methods. This enables large scale, spatially explicit simulations such as for the entire continental USA without sacrificing realism or predictive power.

Real-time decision-making during emergency disease outbreaks.

In the event of a new infectious disease outbreak, mathematical and simulation models are commonly used to inform policy by evaluating which control strategies will minimize the impact of the epidemic. In the early stages of such outbreaks, substantial parameter uncertainty may limit the ability of models to provide accurate predictions, and policymakers do not have the luxury of waiting for data to alleviate this state of uncertainty. For policymakers, however, it is the selection of the optimal control intervention in the face of uncertainty, rather than accuracy of model predictions, that is the measure of success that counts. We simulate the process of real-time decision-making by fitting an epidemic model to observed, spatially-explicit, infection data at weekly intervals throughout two historical outbreaks of foot-and-mouth disease, UK in 2001 and Miyazaki, Japan in 2010, and compare forward simulations of the impact of switching to an alternative control intervention at the time point in question. These are compared to policy recommendations generated in hindsight using data from the entire outbreak, thereby comparing the best we could have done at the time with the best we could have done in retrospect. Our results show that the control policy that would have been chosen using all the data is also identified from an early stage in an outbreak using only the available data, despite high variability in projections of epidemic size. Critically, we find that it is an improved understanding of the locations of infected farms, rather than improved estimates of transmission parameters, that drives improved prediction of the relative performance of control interventions. However, the ability to estimate undetected infectious premises is a function of uncertainty in the transmission parameters. Here, we demonstrate the need for both real-time model fitting and generating projections to evaluate alternative control interventions throughout an outbreak. Our results highlight the use of using models at outbreak onset to inform policy and the importance of state-dependent interventions that adapt in response to additional information throughout an outbreak.

Transmission dynamics of foot and mouth disease in selected outbreak areas of northwest Ethiopia.

Foot and mouth disease (FMD) is a highly contagious and economically important disease of cloven-hoofed animals, which is endemic in Ethiopia. An outbreak follow-up study was undertaken to quantify the transmission parameters of FMD in the crop-livestock mixed (CLM) system and commercial dairy farms in selected areas of northwest Ethiopia. The transmission parameters were quantified using a generalised linear model (GLM) based on a susceptible-infectious-recovered (SIR) epidemic model. The per day average transmission rate between animals was 0.26 (95% CI 0.22-0.32) and 0.33 (95% CI 0.21-0.57) in the CLM system and in the commercial dairy farms, respectively. The average basic reproduction ratio of FMD was 1.68 (95% CI 1.42-2.07) in the CLM system and 1.98 (95% CI 1.26-3.42) in the commercial dairy farms. The medium per day transmission rate and moderate basic reproduction ratio observed in this study indicated that a vaccination coverage needed to stop transmission of the disease in these populations might not be very high.

Molecular investigation of foot-and-mouth disease virus circulating in Pakistan during 2014-17.

This study reports the molecular characterization of foot-and-mouth disease virus (FMDV) in the provinces of Punjab and Sindh, Pakistan during 2014-17. FMDV genome was detected in 42 and 41 out of 46 samples (epithelial tissue and saliva) by reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and reverse transcriptase polymerase chain reaction (RT-PCR), respectively. Sequences of the complete VP1 coding region of the samples (n = 33) was achieved showing that 10, 4 and 19 samples belonged to serotype O, A and Asia1 respectively. Phylogenetic analysis of serotype O revealed that at least one novel sublineage within the ME-SA topotype is circulating in the region, named here as PAK-14. This sublineage showed similarity with the viruses circulating in Turkey and Pakistan during 2010 indicating that viruses circulating in these countries have common origin. Analysis of serotype A viruses revealed a new lineage is circulating in the region, reported here as A-PAK14 showing close identity with the strain prevalent in Pakistan during 2007. Circulation of these new linages in the region shows continuous evolution of the viruses. Two of the undisclosed serotype A sublineages within the Iran-05 lineage were also found circulating in the region. In addition, molecular investigation of the VP1 coding region sequences of serotype Asia1 strains revealed that they belong to Group-VII (Sindh-08). Interestingly some of the serotype Asia1 isolates (n = 6) showed 99.9% similarity (among themselves) although they were collected from different districts more than 100 Km apart from one another. This unusual conservation among serotype Asia1 over long distances can be explored by studying the role of wild animals, slaughter houses and milk collection centres in the spread the disease.

Evaluating vaccination strategies to control foot-and-mouth disease: a country comparison study.

Vaccination is increasingly being recognised as a potential tool to supplement 'stamping out' for controlling foot-and-mouth disease (FMD) outbreaks in non-endemic countries. Infectious disease simulation models provide the opportunity to determine how vaccination might be used in the face of an FMD outbreak. Previously, consistent relative benefits of specific vaccination strategies across different FMD simulation modelling platforms have been demonstrated, using a UK FMD outbreak scenario. We extended this work to assess the relative effectiveness of selected vaccination strategies in five countries: Australia, New Zealand, the USA, the UK and Canada. A comparable, but not identical, FMD outbreak scenario was developed for each country with initial seeding of Pan Asia type O FMD virus into an area with a relatively high density of livestock farms. A series of vaccination strategies (in addition to stamping out (SO)) were selected to evaluate key areas of interest from a disease response perspective, including timing of vaccination, species considerations (e.g. vaccination of only those farms with cattle), risk area vaccination and resources available for vaccination. The study found that vaccination used with SO was effective in reducing epidemic size and duration in a severe outbreak situation. Early vaccination and unconstrained resources for vaccination consistently outperformed other strategies. Vaccination of only those farms with cattle produced comparable results, with some countries demonstrating that this could be as effective as all species vaccination. Restriction of vaccination to higher risk areas was less effective than other strategies. This study demonstrates consistency in the relative effectiveness of selected vaccination strategies under different outbreak start up conditions conditional on the assumption that each of the simulation models provide a realistic estimation of FMD virus spread. Preferred outbreak management approaches must however balance the principles identified in this study, working to clearly defined outbreak management objectives, while having a good understanding of logistic requirements and the socio-economic implications of different control measures.

Evidence of subclinical foot-and-mouth disease virus infection in young calves born from clinically recovered cow under natural condition.

Foot-and-mouth disease (FMD) is a highly contagious and economically important, transboundary viral disease of cloven-hoofed animals. It is known that an asymptomatic, persistent FMD virus (FMDV) infection may occur subsequent to acute or subclinical FMDV infection in adult ruminants. However, virus persistence in young calves has not been studied. In the current investigation, FMDV infection parameters were examined for calves born to FMD-clinically recovered cows (CRC), asymptomatic cows from infected herds (ASC) and cows from with no history of FMD (NHF). The study was conducted in natural condition after FMD outbreaks in two dairy herds in India. No calves described herein had any clinical signs of FMD. Six out of 12 calves born to CRC had detectable FMDV RNA in oesophageal-pharyngeal fluid consistent with asymptomatic FMDV infection. Three of the 12 calves of CRC group had seroreactivity against FMDV non-structural proteins. One calf had detectable FMDV RNA at two consecutive samplings at 2 months apart. However, infectious FMDV was not isolated from any calf in the study. None of the calves in the ASC or NHF groups had any evidence of FMDV infection. Overall, these data are consistent with earlier report on calves having been infected in utero. Further investigation of FMDV persistence in calves under controlled conditions may lead to greater understanding of the viral pathogenesis.

Predicting the Ability of Preclinical Diagnosis To Improve Control of Farm-to-Farm Foot-and-Mouth Disease Transmission in Cattle.

Foot-and-mouth disease (FMD) can cause large disruptive epidemics in livestock. Current eradication measures rely on the rapid clinical detection and removal of infected herds. Here, we evaluated the potential for preclinical diagnosis during reactive surveillance to reduce the risk of between-farm transmission. We used data from transmission experiments in cattle where both samples from individual animals, such as blood, probang samples, and saliva and nasal swabs, and herd-level samples, such as air samples, were taken daily during the course of infection. The sensitivity of each of these sample types for the detection of infected cattle during different phases of the early infection period was quantified. The results were incorporated into a mathematical model for FMD, in a cattle herd, to evaluate the impact of the early detection and culling of an infected herd on the infectious output. The latter was expressed as the between-herd reproduction ratio, Rh , where an effective surveillance approach would lead to a reduction in the Rh value to <1. Applying weekly surveillance, clinical inspection alone was found to be ineffective at blocking transmission. This was in contrast to the impact of weekly random sampling (i.e., using saliva swabs) of at least 10 animals per farm or daily air sampling (housed cattle), both of which were shown to reduce the Rh to <1. In conclusion, preclinical detection during outbreaks has the potential to allow earlier culling of infected herds and thereby reduce transmission and aid the control of epidemics.

The Foot-and-Mouth Disease Carrier State Divergence in Cattle.

UNLABELLED: The pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naive or had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDV persistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle having been protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergence between FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattle and by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restricted to the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemically disseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subset of animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated and nonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsal soft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed by laser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gamma interferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast, during the transitional phase of infection, the level of expression of IFN-λ mRNA was higher in follicle-associated epithelium of animals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistence and contributes to further understanding of this critical aspect of FMDV pathogenesis. IMPORTANCE: The existence of a prolonged, asymptomatic carrier state is a political impediment for control and potential eradication of foot-and-mouth disease (FMD). When FMD outbreaks occur, they are often extinguished by massive depopulation of livestock due to the fear that some animals may have undiagnosed subclinical infection, despite uncertainty over the biological relevance of FMD virus (FMDV) persistence. The work described here elucidates aspects of the FMDV carrier state in cattle which may facilitate identification and/or abrogation of asymptomatic FMDV infection. The divergence between animals that clear infection and those that develop persistent infection was demonstrated to occur earlier than previously established. The host antiviral response in tissues maintaining persistent FMDV was downregulated, whereas upregulation of IFN-λ mRNA was found in the epithelium of cattle that had recently cleared the infection. This suggests that the clearing of FMDV infection is associated with an enhanced mucosal antiviral response, whereas FMDV persistence is associated with suppression of the host antiviral response.

Differential Persistence of Foot-and-Mouth Disease Virus in African Buffalo Is Related to Virus Virulence.

UNLABELLED: Foot-and-mouth disease (FMD) virus (FMDV) circulates as multiple serotypes and strains in many regions of endemicity. In particular, the three Southern African Territories (SAT) serotypes are maintained effectively in their wildlife reservoir, the African buffalo, and individuals may harbor multiple SAT serotypes for extended periods in the pharyngeal region. However, the exact site and mechanism for persistence remain unclear. FMD in buffaloes offers a unique opportunity to study FMDV persistence, as transmission from carrier ruminants has convincingly been demonstrated for only this species. Following coinfection of naive African buffaloes with isolates of three SAT serotypes from field buffaloes, palatine tonsil swabs were the sample of choice for recovering infectious FMDV up to 400 days postinfection (dpi). Postmortem examination identified infectious virus for up to 185 dpi and viral genomes for up to 400 dpi in lymphoid tissues of the head and neck, focused mainly in germinal centers. Interestingly, viral persistence in vivo was not homogenous, and the SAT-1 isolate persisted longer than the SAT-2 and SAT-3 isolates. Coinfection and passage of these SAT isolates in goat and buffalo cell lines demonstrated a direct correlation between persistence and cell-killing capacity. These data suggest that FMDV persistence occurs in the germinal centers of lymphoid tissue but that the duration of persistence is related to virus replication and cell-killing capacity. IMPORTANCE: Foot-and-mouth disease virus (FMDV) causes a highly contagious acute vesicular disease in domestic livestock and wildlife species. African buffaloes (Syncerus caffer) are the primary carrier hosts of FMDV in African savannah ecosystems, where the disease is endemic. We have shown that the virus persists for up to 400 days in buffaloes and that there is competition between viruses during mixed infections. There was similar competition in cell culture: viruses that killed cells quickly persisted more efficiently in passaged cell cultures. These results may provide a mechanism for the dominance of particular viruses in an ecosystem.

Molecular Infectious Disease Epidemiology: Survival Analysis and Algorithms Linking Phylogenies to Transmission Trees.

Recent work has attempted to use whole-genome sequence data from pathogens to reconstruct the transmission trees linking infectors and infectees in outbreaks. However, transmission trees from one outbreak do not generalize to future outbreaks. Reconstruction of transmission trees is most useful to public health if it leads to generalizable scientific insights about disease transmission. In a survival analysis framework, estimation of transmission parameters is based on sums or averages over the possible transmission trees. A phylogeny can increase the precision of these estimates by providing partial information about who infected whom. The leaves of the phylogeny represent sampled pathogens, which have known hosts. The interior nodes represent common ancestors of sampled pathogens, which have unknown hosts. Starting from assumptions about disease biology and epidemiologic study design, we prove that there is a one-to-one correspondence between the possible assignments of interior node hosts and the transmission trees simultaneously consistent with the phylogeny and the epidemiologic data on person, place, and time. We develop algorithms to enumerate these transmission trees and show these can be used to calculate likelihoods that incorporate both epidemiologic data and a phylogeny. A simulation study confirms that this leads to more efficient estimates of hazard ratios for infectiousness and baseline hazards of infectious contact, and we use these methods to analyze data from a foot-and-mouth disease virus outbreak in the United Kingdom in 2001. These results demonstrate the importance of data on individuals who escape infection, which is often overlooked. The combination of survival analysis and algorithms linking phylogenies to transmission trees is a rigorous but flexible statistical foundation for molecular infectious disease epidemiology.

U.K. Foot and Mouth Disease: A Systemic Risk Assessment of Existing Controls.

This article details a systemic analysis of the controls in place and possible interventions available to further reduce the risk of a foot and mouth disease (FMD) outbreak in the United Kingdom. Using a research-based network analysis tool, we identify vulnerabilities within the multibarrier control system and their corresponding critical control points (CCPs). CCPs represent opportunities for active intervention that produce the greatest improvement to United Kingdom's resilience to future FMD outbreaks. Using an adapted 'features, events, and processes' (FEPs) methodology and network analysis, our results suggest that movements of animals and goods associated with legal activities significantly influence the system's behavior due to their higher frequency and ability to combine and create scenarios of exposure similar in origin to the U.K. FMD outbreaks of 1967/8 and 2001. The systemic risk assessment highlights areas outside of disease control that are relevant to disease spread. Further, it proves to be a powerful tool for demonstrating the need for implementing disease controls that have not previously been part of the system.

Quantitative Assessment of the Risk of Release of Foot-and-Mouth Disease Virus via Export of Bull Semen from Israel.

Various foot-and-mouth disease (FMD) virus strains circulate in the Middle East, causing frequent episodes of FMD outbreaks among Israeli livestock. Since the virus is highly resistant in semen, artificial insemination with contaminated bull semen may lead to the infection of the receiver cow. As a non-FMD-free country with vaccination, Israel is currently engaged in trading bull semen only with countries of the same status. The purpose of this study was to assess the risk of release of FMD virus through export of bull semen in order to estimate the risk for FMD-free countries considering purchasing Israeli bull semen. A stochastic risk assessment model was used to estimate this risk, defined as the annual likelihood of exporting at least one ejaculate of bull semen contaminated with viable FMD virus. A total of 45 scenarios were assessed to account for uncertainty and variability around specific parameter estimates and to evaluate the effect of various mitigation measures, such as performing a preexport test on semen ejaculates. Under the most plausible scenario, the annual likelihood of exporting bull semen contaminated with FMD virus had a median of 1.3 * 10-7 for an export of 100 ejaculates per year. This corresponds to one infected ejaculate exported every 7 million years. Under the worst-case scenario, the median of the risk rose to 7.9 * 10-5 , which is equivalent to the export of one infected ejaculate every 12,000 years. Sensitivity analysis indicated that the most influential parameter is the probability of viral excretion in infected bulls.

Foot and mouth disease: the risks of the international trade in live animals.

The growth in world trade has generated significant benefits to humankind, but it has also generated costs. Among these is an increase in the dispersal of pests and pathogens across the globe. International trade has been implicated in outbreaks of several re-occurring livestock diseases. This paper is focused on the risk of foot and mouth disease (FMD) associated with the international trade in live animals. A model was used to estimate FMD risk as a function of the international trade in live animals, controlling for the biosecurity measures undertaken by importing and exporting countries, and for the presence of endemic FMD reservoirs. It was found that the indirect risks associated with exports may be as great as the direct risks associated with imports. For countries where livestock production occurs in disease-free zones (with or without vaccination), the trade risks vary with both species and trading partner. These findings may assist the targeting of disease risk mitigation activities.

La croissance du commerce international a apporté des bénéfices significatifs à l'humanité tout en générant certains coûts. Parmi ceux-ci figure la propagation accrue de parasites et d'agents pathogènes à l'échelle planétaire. Les échanges internationaux sont responsables de la résurgence de nombreuses maladies affectant le bétail. Les auteurs examinent en particulier le cas des risques de fièvre aphteuse associés aux échanges internationaux d'animaux vivants. Ils ont fait appel à un modèle pour estimer le risque de fièvre aphteuse en relation avec les échanges internationaux d'animaux vivants, le contrôle des mesures de biosécurité appliquées par les pays importateurs et exportateurs et la surveillance des réservoirs endémiques du virus. Il ressort de cette étude que les risques indirects associés aux exportations paraissent aussi importants que les risques directs associés aux importations. Dans les pays où l'élevage se déploie dans des zones indemnes de fièvre aphteuse (avec ou sans vaccination), les risques liés aux échanges varient en fonction de l'espèce et du partenaire commercial. Ces résultats peuvent contribuer à cibler les actions d'atténuation du risque de maladie.

El crecimiento del comercio mundial ha traído consigo importantes beneficios para la humanidad, pero también ha generado costos, entre ellos una mayor dispersión de plagas y patógenos por todo el planeta. El comercio internacional ha tenido cierto papel en la aparición de brotes recurrentes de varias enfermedades del ganado. Los autores se centran en el riesgo de fiebre aftosa ligado al comercio internacional de animales vivos. Con el empleo de un modelo para estimar el riesgo de fiebre aftosa como una función del comercio internacional de animales vivos, teniendo en cuenta las medidas de seguridad biológica implantadas por los países importadores y exportadores y la presencia de reservorios endémicos de fiebre aftosa, los autores descubrieron que los riesgos indirectos vinculados a las exportaciones pueden ser de igual magnitud que los riesgos directos ligados a las importaciones. En aquellos países donde la producción ganadera se sitúa en zonas libres de la enfermedad (con o sin vacunación), los riesgos ligados al comercio difieren en función de la especie y de cuál sea la contraparte comercial. Estas conclusiones pueden ayudar a seleccionar con más precisión las actividades de reducción del riesgo zoosanitario.

The impact of importation of live ruminants on the epizootiology of foot and mouth disease in Saudi Arabia.

Approximately five million live ruminants are imported annually into Saudi Arabia. The majority of these animals are imported shortly before the pilgrimage season from Sudan and the Horn of Africa, where foot and mouth disease (FMD) is known to be enzootic. This study was designed to investigate the impact of the importation of these live ruminants on the epizootiology of FMD in Saudi Arabia. The authors carried out antibody testing on a total of 480 sheep and 233 cattle from the sacrificial livestock yards of the Saudi Project for Utilization of Hajj Meat, which performs ritual slaughter on behalf of pilgrims in the Holy City of Makkah. The results revealed that 136 (28.3%) of the 480 sheep tested were serologically positive for FMD, using an indirect enzymelinked immunosorbent assay (ELISA) (3ABC FMD ELISA). This included 17.7% of Sawakani sheep (imported from Sudan) and 40.9% of Barbari sheep (imported from the Horn of Africa). Among the cattle, 120 (51.5%) of 233 animals tested positive for FMD virus (FMDV) antibodies. The 120 seropositive cattle included all clinically suspected cattle and 62 (35.4%) symptom-free, in-contact cattle. The findings highlight the risks associated with the annual importation of live ruminants from FMD-enzootic areas. The risks include the possible introduction of new exotic FMDV serotypes, particularly when potential carriers or subclinically infected animals are considered. An understanding of the epidemiology of different strains and the ability to track their movement between geographical regions is essential for the development of efficient control strategies for the disease. Therefore, genotyping of FMDV strains isolated from imported and local animals is recommended.

Environ 5 millions de ruminants vivants sont importés chaque année par l'Arabie saoudite. La plupart de ces importations ont lieu peu avant la saison du pèlerinage (hajj) et proviennent du Soudan et de la Corne de l'Afrique, où la fièvre aphteuse est réputée endémique. Les auteurs ont élaboré une étude visant à déterminer l'impact de ces importations de ruminants vivants sur l'épizootiologie de la fièvre aphteuse en Arabie saoudite. Pour ce faire, ils ont testé 480 moutons et 233 bovins appartenant au cheptel d'animaux destinés à l'abattage du Projet saoudien d'utilisation de la viande sacrificielle, qui effectue l'abattage rituel pour le compte des pèlerins de la ville sainte de La Mecque. Le test sérologique utilisé était une épreuve immuno-enzymatique de détection d'anticorps dirigés contre la protéine 3ABC (3ABC FMD ELISA). Sur les 480 moutons testés, 136 (28,3 %) ont donné des résultats positifs. Les moutons trouvés positifs étaient pour 17,7 % d'entre eux, de race sawakani (importés du Soudan) et pour 40,9 % de race barabarine (importés de la Corne de l'Afrique). Concernant les bovins, 120 (51,5 %) des 233 bovins testés possédaient des anticorps dirigés contre la fièvre aphteuse. Parmi ces 120 bovins séropositifs figuraient tous les cas cliniquement suspects, mais aussi 62 bovins (35,4 %) qui ne présentaient aucun signe clinique et qui avaient été exposés naturellement à l'infection. Ces résultats mettent en exergue l'existence des risques associés aux importations annuelles de ruminants vivants en provenance de régions où la fièvre aphteuse est enzootique. Ce risque comprend celui d'une introduction de sérotypes exotiques nouveaux du fait de la présence de porteurs potentiels ou d'animaux infectés asymptomatiques. Pour mettre en place des stratégies de lutte efficaces contre la fièvre aphteuse, il est nécessaire de bien comprendre l'épidémiologie des différentes souches et d'être en mesure de les suivre à mesure qu'elles se propagent d'une région à l'autre. Il est donc recommandé de procéder à la caractérisation des génotypes des souches du virus de la fièvre aphteuse isolées chez les animaux importés et autochtones.

Cada año Arabia Saudí importa aproximadamente 5 millones de rumiantes vivos. En su gran mayoría esos animales son importados, poco antes de la temporada de peregrinajes, desde el Sudán y el Cuerno de África, regiones donde la fiebre aftosa, según se sabe, es enzoótica. Los autores refieren un estudio encaminado a analizar los efectos de la importación de esos rumiantes vivos sobre la epizootiología de la fiebre aftosa en Arabia Saudí. Utilizando un ensayo inmunoenzimático (ELISA) indirecto (detección de anticuerpos contra la poliproteína 3ABC del virus), se practicaron pruebas de detección de anticuerpos a un total de 480 ovejas y 233 vacunos procedentes de los establos de sacrificio del proyecto saudí para la utilización de carne «halal¼, donde se practican sacrificios rituales en nombre de los peregrinos que llegan a la ciudad santa de La Meca. Los resultados revelaron que 136 (un 28,3%) de las 480 ovejas eran seropositivas para la fiebre aftosa, de las cuales un 17,7% eran ovejas sawakani (importadas del Sudán) y un 40,9% ovejas barbarinas (importadas del Cuerno de África). Por lo que respecta a los vacunos, resultaron positivos a los anticuerpos contra el virus de la fiebre aftosa 120 (un 51,5%) de los 233 animales. Entre esos 120 seropositivos estaban todos los ejemplares clínicamente sospechosos y 62 (un 35,4%) asintomáticos, que eran contactos naturales. Los resultados ponen de manifiesto los riesgos ligados a la importación anual de rumiantes vivos desde zonas donde la fiebre aftosa es enzoótica. Entre ellos figura el riesgo de introducir nuevos serotipos exóticos del virus, sobre todo si se tiene en cuenta la existencia de posibles portadores o animales con infección asintomática. Para concebir e instituir estrategias eficaces de lucha contra la enfermedad es fundamental entender la epidemiología de las diferentes cepas y poder seguir sus movimientos entre regiones geográficas. Es recomendable, por lo tanto, determinar el genotipo de las cepas víricas que se aíslen en animales importados y locales.