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.     

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.     

Epidemiological consequences of an incursion of highly pathogenic H5N1 avian influenza into the British poultry flock

Highly pathogenic avian influenza and in particular the H5N1 strain has resulted in the culling of millions of birds and continues to pose a threat to poultry industries worldwide. The recent outbreak of H5N1 in the UK highlights the need for detailed assessment of the consequences of an incursion and of the efficacy of control strategies. Here, we present results from a model of H5N1 propagation within the British poultry industry. We find that although the majority of randomly seeded incursions do not spread beyond the initial infected premises, there is significant potential for widespread infection. The efficacy of the European Union strategy for disease control is evaluated and our simulations emphasize the pivotal role of duck farms in spreading H5N1.     

Contact structures in the poultry industry in Great Britain: Exploring transmission routes for a potential avian influenza virus epidemic

Background  

The commercial poultry industry in United Kingdom (UK) is worth an estimated ￡3.4 billion at retail value, producing over 174 million birds for consumption per year. An epidemic of any poultry disease with high mortality or which is zoonotic, such as avian influenza virus (AIV), would result in the culling of significant numbers of birds, as seen in the Netherlands in 2003 and Italy in 2000. Such an epidemic would cost the UK government millions of pounds in compensation costs, with further economic losses through reduction of international and UK consumption of British poultry. In order to better inform policy advisers and makers on the potential for a large epidemic in GB, we investigate the role that interactions amongst premises within the British commercial poultry industry could play in promoting an AIV epidemic, given an introduction of the virus in a specific part of poultry industry in Great Britain (GB).     

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

Optimal intervention for disease outbreaks is often impeded by severe scientific uncertainty. Adaptive management (AM), long-used in natural resource management, is a structured decision-making approach to solving dynamic problems that accounts for the value of resolving uncertainty via real-time evaluation of alternative models. We propose an AM approach to design and evaluate intervention strategies in epidemiology, using real-time surveillance to resolve model uncertainty as management proceeds, with foot-and-mouth disease (FMD) culling and measles vaccination as case studies. We use simulations of alternative intervention strategies under competing models to quantify the effect of model uncertainty on decision making, in terms of the value of information, and quantify the benefit of adaptive versus static intervention strategies. Culling decisions during the 2001 UK FMD outbreak were contentious due to uncertainty about the spatial scale of transmission. The expected benefit of resolving this uncertainty prior to a new outbreak on a UK-like landscape would be £45–£60 million relative to the strategy that minimizes livestock losses averaged over alternate transmission models. AM during the outbreak would be expected to recover up to £20.1 million of this expected benefit. AM would also recommend a more conservative initial approach (culling of infected premises and dangerous contact farms) than would a fixed strategy (which would additionally require culling of contiguous premises). For optimal targeting of measles vaccination, based on an outbreak in Malawi in 2010, AM allows better distribution of resources across the affected region; its utility depends on uncertainty about both the at-risk population and logistical capacity. When daily vaccination rates are highly constrained, the optimal initial strategy is to conduct a small, quick campaign; a reduction in expected burden of approximately 10,000 cases could result if campaign targets can be updated on the basis of the true susceptible population. Formal incorporation of a policy to update future management actions in response to information gained in the course of an outbreak can change the optimal initial response and result in significant cost savings. AM provides a framework for using multiple models to facilitate public-health decision making and an objective basis for updating management actions in response to improved scientific understanding.     

Emergency rabies control in a community of two high-density hosts

ABSTRACT: BACKGROUND: Rabies is a fatal viral disease that potentially can affect all mammals. Terrestrial rabies is not present in the United Kingdom and has been eliminated from Western Europe. Nevertheless the possibility remains that rabies could be introduced to England, where it would find two potentially suitable hosts, red foxes and badgers. With the aim to analyse the spread and emergency control of rabies in this two species host community, a simulation model was constructed. Different control strategies involving anti-rabies vaccination and population culling were developed, considering control application rates, spatial extent and timing. These strategies were evaluated for efficacy and feasibility to control rabies in hypothetical rural areas in the South of England immediately after a disease outbreak. RESULTS: The model confirmed that both fox and badger populations, separately, were competent hosts for the spread of rabies. Realistic vaccination levels were not sufficient to control rabies in high-density badger populations. The combined species community was a very strong rabies host. However, disease spread within species appeared to be more important than cross-species infection. Thus, the drivers of epidemiology depend on the potential of separate host species to sustain the disease. To control a rabies outbreak in the two species, both species had to be targeted. Realistic and robust control strategies involved vaccination of foxes and badgers, but also required badger culling. Although fox and badger populations in the UK are exceptionally dense, an outbreak of rabies can be controlled with a higher than 90% chance, if control response is quick and follows a strict regime. This requires surveillance and forceful and repeated control campaigns. In contrast, an uncontrolled rabies outbreak in the South of England would quickly develop into a strong epizootic involving tens of thousands of rabid foxes and badgers. CONCLUSIONS: If populations of both host species are sufficiently large, epizootics are driven by within-species transmission, while cross-species-infection appears to be of minor importance. Thus, the disease control strategy has to target both host populations.     

Modeling control of rabies outbreaks in red fox populations to evaluate culling,vaccination, and vaccination combined with fertility control

A predictive model of spread and control of rabies in red fox (Vulpes vulpes) populations was used to evaluate efficacy of culling, oral vaccination, and oral vaccination and fertility control (V + FC) as rabies control strategies. In addition, effects of season, fox population density, and a delay in starting control were modeled. At fox densities of 0.5 fox families/km2 or greater, a single oral vaccination campaign with bait uptake rates of less than 50% resulted in ineffective rabies control. An uptake rate of at least 80% was required to give a better than 80% chance of eliminating rabies. Vaccination was least effective at controlling rabies if applied 1 or 2 mo before the foxes gave birth. Seasonal timing of poison or V + FC had little effect on efficacy, which was always more successful than the oral vaccination alone. The longer the delay between the simulated start of the rabies infection and the application of a single vaccination campaign, the less successful was the control, particularly at the higher fox densities tested. At a fox density of 0.25 families/km2, all the strategies were equally successful at eliminating rabies. At higher fox densities V + FC was slightly less successful than culling, whereas vaccination-only was considerably less successful. The sole use of vaccination is not considered a viable control method for areas with high fox densities. The model suggests that an area of culling centered on the disease focus, plus an outer ring of vaccine or V + FC, could be the best strategy to control a point-source wildlife rabies outbreak.     

Effects of behavioral changes in a smallpox attack model

The impact of individual and community behavioral changes in response to an outbreak of a disease with high mortality is often not appreciated. Response strategies to a smallpox bioterrorist attack have focused on interventions such as isolation of infectives, contact tracing, quarantine of contacts, ring vaccination, and mass vaccination. We formulate and analyze a mathematical model in which some individuals lower their daily contact activity rates once an epidemic has been identified in a community. Transmission parameters are estimated from data and an expression is derived for the effective reproduction number. We use computer simulations to analyze the effects of behavior change alone and in combination with other control measures. We demonstrate that the spread of the disease is highly sensitive to how rapidly people reduce their contact activity rates and to the precautions that the population takes to reduce the transmission of the disease. Even gradual and mild behavioral changes can have a dramatic impact in slowing an epidemic. When behavioral changes are combined with other interventions, the epidemic is shortened and the number of smallpox cases is reduced. We conclude that for simulations of a smallpox outbreak to be useful, they must consider the impact of behavioral changes. This is especially true if the model predictions are being used to guide public health policy.     

A Bayesian Approach to Quantifying the Effects of Mass Poultry Vaccination upon the Spatial and Temporal Dynamics of H5N1 in Northern Vietnam

Outbreaks of H5N1 in poultry in Vietnam continue to threaten the livelihoods of those reliant on poultry production whilst simultaneously posing a severe public health risk given the high mortality associated with human infection. Authorities have invested significant resources in order to control these outbreaks. Of particular interest is the decision, following a second wave of outbreaks, to move from a “stamping out” approach to the implementation of a nationwide mass vaccination campaign. Outbreaks which occurred around this shift in policy provide a unique opportunity to evaluate the relative effectiveness of these approaches and to help other countries make informed judgements when developing control strategies. Here we use Bayesian Markov Chain Monte Carlo (MCMC) data augmentation techniques to derive the first quantitative estimates of the impact of the vaccination campaign on the spread of outbreaks of H5N1 in northern Vietnam. We find a substantial decrease in the transmissibility of infection between communes following vaccination. This was coupled with a significant increase in the time from infection to detection of the outbreak. Using a cladistic approach we estimated that, according to the posterior mean effect of pruning the reconstructed epidemic tree, two thirds of the outbreaks in 2007 could be attributed to this decrease in the rate of reporting. The net impact of these two effects was a less intense but longer-lasting wave and, whilst not sufficient to prevent the sustained spread of outbreaks, an overall reduction in the likelihood of the transmission of infection between communes. These findings highlight the need for more effectively targeted surveillance in order to help ensure that the effective coverage achieved by mass vaccination is converted into a reduction in the likelihood of outbreaks occurring which is sufficient to control the spread of H5N1 in Vietnam.     

Spatial expansions and travelling waves of rabies in vampire bats

A major obstacle to anticipating the cross-species transmission of zoonotic diseases and developing novel strategies for their control is the scarcity of data informing how these pathogens circulate within natural reservoir populations. Vampire bats are the primary reservoir of rabies in Latin America, where the disease remains among the most important viral zoonoses affecting humans and livestock. Unpredictable spatiotemporal dynamics of rabies within bat populations have precluded anticipation of outbreaks and undermined widespread bat culling programs. By analysing 1146 vampire bat-transmitted rabies (VBR) outbreaks in livestock across 12 years in Peru, we demonstrate that viral expansions into historically uninfected zones have doubled the recent burden of VBR. Viral expansions are geographically widespread, but severely constrained by high elevation peaks in the Andes mountains. Within Andean valleys, invasions form wavefronts that are advancing towards large, unvaccinated livestock populations that are heavily bitten by bats, which together will fuel high transmission and mortality. Using spatial models, we forecast the pathways of ongoing VBR epizootics across heterogeneous landscapes. These results directly inform vaccination strategies to mitigate impending viral emergence, reveal VBR as an emerging rather than an enzootic disease and create opportunities to test novel interventions to manage viruses in bat reservoirs.     

Sterilization as an alternative strategy to control wildlife diseases: bovine tuberculosis in European badgers as a case study

Sterilization has rarely been considered as an alternative to culling or vaccination to control wildlife diseases. Disease control by sterilization, as by culling, has most promise when the host'ss ability for compensatory growth following the removal of density-dependent inhibitions is limited, and when moderate reductions in population density cause disproportionately large reductions in disease prevalence, or even eliminate the disease. For many host/disease examples this will not be the case and vaccination may have overwhelming advantages or may be the only practical option. The impact of sterilization on host density and disease prevalence will develop relatively slowly because sterilization can prevent the recruitment of only one age-cohort at a time. Moreover, unless there is vertical transmission, this age-cohort will consist only of susceptibles. Culling, on the contrary, removes infected as well as susceptible animals. However, for certain disease/host examples, the r elative effectiveness of the different control strategies may be altered considerably if their variable effects on the probability of disease transmission are taken into account. Social perturbation or stress could render certain culling strategies ineffective or even counter-productive. Depending on how disease dynamics are influenced by the host'ss age-structure and reproductive investment, fertility control could offer epidemiological advantages that have been ignored by most disease/host models. We illustrate some of these principles by investigating the theoretical and practical feasibility of an hypothetical sterilization campaign to control bovine tuberculosis in badgers (and hence cattle) in Britain.     

H5N1 avian influenza in China

H5N1 highly pathogenic avian influenza virus was first detected in a goose in Guangdong Province of China in 1996. Multiple genotypes of H5N1 viruses have been identified from apparently healthy waterfowl since 1999. In the years 2004–2008, over 100 outbreaks in domestic poultry occurred in 23 provinces and caused severe economic damage to the poultry industry in China. Beginning from 2004, a culling plus vaccination strategy has been implemented for the control of epidemics. Since then, over 35420000 poultry have been depopulated, and over 55 billion doses of the different vaccines have been used to control the outbreaks. Although it is logistically impossible to vaccinate every single bird in China due to the large poultry population and the complicated rearing styles, there is no doubt that the increased vaccination coverage has resulted in decreased disease epidemic and environmental virus loading. The experience in China suggests that vaccination has played an important role in the protection of poultry from H5N1 virus infection, the reduction of virus load in the environment, and the prevention of H5N1 virus transmission from poultry to humans. Supported by the Key Animal Infectious Disease Control Program of the Ministry of Agriculture, the Chinese National S&T Plan(Grant No. 2004BA519A-57), National Key Basic Research and Development Program of China (Grant Nos: 2005CB523005, 2005CB523200).     

Disease Prevention versus Data Privacy: Using Landcover Maps to Inform Spatial Epidemic Models

The availability of epidemiological data in the early stages of an outbreak of an infectious disease is vital for modelers to make accurate predictions regarding the likely spread of disease and preferred intervention strategies. However, in some countries, the necessary demographic data are only available at an aggregate scale. We investigated the ability of models of livestock infectious diseases to predict epidemic spread and obtain optimal control policies in the event of imperfect, aggregated data. Taking a geographic information approach, we used land cover data to predict UK farm locations and investigated the influence of using these synthetic location data sets upon epidemiological predictions in the event of an outbreak of foot-and-mouth disease. When broadly classified land cover data were used to create synthetic farm locations, model predictions deviated significantly from those simulated on true data. However, when more resolved subclass land use data were used, moderate to highly accurate predictions of epidemic size, duration and optimal vaccination and ring culling strategies were obtained. This suggests that a geographic information approach may be useful where individual farm-level data are not available, to allow predictive analyses to be carried out regarding the likely spread of disease. This method can also be used for contingency planning in collaboration with policy makers to determine preferred control strategies in the event of a future outbreak of infectious disease in livestock.     

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.     

人感染H7亚型禽流感事件

本研究综述了自1959年以来国内外发生的人感染H7亚型禽流感事件。大多数是在家禽爆发禽流感期间,农场工人在处置感染鸡群过程中被暴露而感染;也有曾接触活禽或曾到过活禽市场而感染;有经禽流感病毒致病的哺乳动物（海豹）感染于人或实验室感染（事故）所致。引起人感染的H7亚型中已知有H7N2、H7N3、H7N7以及2013年在中国发现的新的致病亚型H7N9。H7N2、H7N3、H7N7感染以结膜炎为主,大多为轻症;而H7N9感染以严重的呼吸道感染为特征,表现为重症肺炎,呼吸窘迫综合症,病死率高达33.6%。     

Wildlife disease elimination and density dependence

Disease control by managers is a crucial response to emerging wildlife epidemics, yet the means of control may be limited by the method of disease transmission. In particular, it is widely held that population reduction, while effective for controlling diseases that are subject to density-dependent (DD) transmission, is ineffective for controlling diseases that are subject to frequency-dependent (FD) transmission. We investigate control for horizontally transmitted diseases with FD transmission where the control is via culling or harvest that is non-selective with respect to infection and the population can compensate through DD recruitment or survival. Using a mathematical model, we show that culling or harvesting can eradicate the disease, even when transmission dynamics are FD. Eradication can be achieved under FD transmission when DD birth or recruitment induces compensatory growth of new, healthy individuals, which has the net effect of reducing disease prevalence by dilution. We also show that if harvest is used simultaneously with vaccination, and there is high enough transmission coefficient, application of both controls may be less efficient than vaccination alone. We illustrate the effects of these control approaches on disease prevalence for chronic wasting disease in deer where the disease is transmitted directly among deer and through the environment.     

Quantifying the Risk of Localised Animal Movement Bans for Foot-and-Mouth Disease

The maintenance of disease-free status from Foot-and-Mouth Disease is of significant socio-economic importance to countries such as the UK. The imposition of bans on the movement of susceptible livestock following the discovery of an outbreak is deemed necessary to prevent the spread of what is a highly contagious disease, but has a significant economic impact on the agricultural community in itself. Here we consider the risk of applying movement restrictions only in localised zones around outbreaks in order to help evaluate how quickly nation-wide restrictions could be lifted after notification. We show, with reference to the 2001 and 2007 UK outbreaks, that it would be practical to implement such a policy provided the basic reproduction ratio of known infected premises can be estimated. It is ultimately up to policy makers and stakeholders to determine the acceptable level of risk, involving a cost benefit analysis of the potential outcomes, but quantifying the risk of spread from different sized zones is a prerequisite for this. The approach outlined is relevant to the determination of control zones and vaccination policies and has the potential to be applied to future outbreaks of other diseases.     

Effect of Salmonella vaccination of breeder chickens on contamination of broiler chicken carcasses in integrated poultry operations

While measures to control carcass contamination with Salmonella at the processing plant have been implemented with some success, on-farm interventions that reduce Salmonella prevalence in meat birds entering the processing plant have not translated well on a commercial scale. We determined the impact of Salmonella vaccination on commercial poultry operations by monitoring four vaccinated and four nonvaccinated breeder (parental) chicken flocks and comparing Salmonella prevalences in these flocks and their broiler, meat bird progeny. For one poultry company, their young breeders were vaccinated by using a live-attenuated Salmonella enterica serovar Typhimurium vaccine (Megan VAC-1) followed by a killed Salmonella bacterin consisting of S. enterica serovar Berta and S. enterica serovar Kentucky. The other participating poultry company did not vaccinate their breeders or broilers. The analysis revealed that vaccinated hens had a lower prevalence of Salmonella in the ceca (38.3% versus 64.2%; P < 0.001) and the reproductive tracts (14.22% versus 51.7%; P < 0.001). We also observed a lower Salmonella prevalence in broiler chicks (18.1% versus 33.5%; P < 0.001), acquired from vaccinated breeders, when placed at the broiler farms contracted with the poultry company. Broiler chicken farms populated with chicks from vaccinated breeders also tended to have fewer environmental samples containing Salmonella (14.4% versus 30.1%; P < 0.001). There was a lower Salmonella prevalence in broilers entering the processing plants (23.4% versus 33.5%; P < 0.001) for the poultry company that utilized this Salmonella vaccination program for its breeders. Investigation of other company-associated factors did not indicate that the difference between companies could be attributed to measures other than the vaccination program.     

Landscape attributes governing local transmission of an endemic zoonosis: Rabies virus in domestic dogs

Landscape heterogeneity plays an important role in disease spread and persistence, but quantifying landscape influences and their scale dependence is challenging. Studies have focused on how environmental features or global transport networks influence pathogen invasion and spread, but their influence on local transmission dynamics that underpin the persistence of endemic diseases remains unexplored. Bayesian phylogeographic frameworks that incorporate spatial heterogeneities are promising tools for analysing linked epidemiological, environmental and genetic data. Here, we extend these methodological approaches to decipher the relative contribution and scale‐dependent effects of landscape influences on the transmission of endemic rabies virus in Serengeti district, Tanzania (area ~4,900 km²). Utilizing detailed epidemiological data and 152 complete viral genomes collected between 2004 and 2013, we show that the localized presence of dogs but not their density is the most important determinant of diffusion, implying that culling will be ineffective for rabies control. Rivers and roads acted as barriers and facilitators to viral spread, respectively, and vaccination impeded diffusion despite variable annual coverage. Notably, we found that landscape effects were scale‐dependent: rivers were barriers and roads facilitators on larger scales, whereas the distribution of dogs was important for rabies dispersal across multiple scales. This nuanced understanding of the spatial processes that underpin rabies transmission can be exploited for targeted control at the scale where it will have the greatest impact. Moreover, this research demonstrates how current phylogeographic frameworks can be adapted to improve our understanding of endemic disease dynamics at different spatial scales.     

An integral equation model for the control of a smallpox outbreak

An integral equation model of a smallpox epidemic is proposed. The model structures the incidence of infection among the household, the workplace, the wider community and a health-care facility; and incorporates a finite incubation period and plausible infectivity functions. Linearisation of the model is appropriate for small epidemics, and enables analytic expressions to be derived for the basic reproduction number and the size of the epidemic. The effects of control interventions (vaccination, isolation, quarantine and public education) are explored for a smallpox epidemic following an imported case. It is found that the rapid identification and isolation of cases, the quarantine of affected households and a public education campaign to reduce contact would be capable of bringing an epidemic under control. This could be used in conjunction with the vaccination of healthcare workers and contacts. Our results suggest that prior mass vaccination would be an inefficient method of containing an outbreak.