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.

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

Simulation models can offer valuable insights into the effectiveness of different control strategies and act as important decision support tools when comparing and evaluating outbreak scenarios and control strategies. An international modelling study was performed to compare a range of vaccination strategies in the control of foot-and-mouth disease (FMD). Modelling groups from five countries (Australia, New Zealand, USA, UK, The Netherlands) participated in the study. Vaccination is increasingly being recognized as a potentially important tool in the control of FMD, although there is considerable uncertainty as to how and when it should be used. We sought to compare model outputs and assess the effectiveness of different vaccination strategies in the control of FMD. Using a standardized outbreak scenario based on data from an FMD exercise in the UK in 2010, the study showed general agreement between respective models in terms of the effectiveness of vaccination. Under the scenario assumptions, all models demonstrated that vaccination with 'stamping-out' of infected premises led to a significant reduction in predicted epidemic size and duration compared to the 'stamping-out' strategy alone. For all models there were advantages in vaccinating cattle-only rather than all species, using 3-km vaccination rings immediately around infected premises, and starting vaccination earlier in the control programme. This study has shown that certain vaccination strategies are robust even to substantial differences in model configurations. This result should increase end-user confidence in conclusions drawn from model outputs. These results can be used to support and develop effective policies for FMD control.

FMD vaccine allocation and surveillance resourcing options for a potential Australian incursion.

Australian Animal Disease Spread (AADIS) epidemiological simulation modelling of potential foot-and-mouth disease outbreaks in the state of Victoria, Australia examined the targeted use of limited vaccine supplies in combination with varying surveillance resources. Updated, detailed estimates of government response costs were prepared based on state level data inputs of required and available resources. Measures of outbreak spread such as duration and numbers of animals removed through depopulation of infected and vaccinated herds from the epidemiological modelling were compared to summed government response costs. This comparison illustrated the trade-offs between targeted control strategies combining vaccination-to-remove and varying surveillance capacities and their corresponding costs. For this intensive cattle and sheep producing region: (1) Targeting vaccination toward intensive production areas or toward specialized cattle operations had outbreak control and response cost advantages similar to vaccination of all species. The median duration was reduced by 27% and response costs by 11%. (2) Adding to the pool of outbreak surveillance resources available further decreased outbreak duration and outbreak response costs. The median duration was reduced by an additional 13% and response costs declined by an additional 8%. (3) Pooling of vaccine resources overcame the very early binding constraints under proportional allocation of vaccines to individual states with similar reductions in outbreak duration to those with additional surveillance resources. However, government costs rose substantially by over 40% and introduced additional risk of a negative consumer response. Increased knowledge of the outbreak situation obtained from more surveillance led to better-informed vaccination deployment decisions in the short timeframe they needed to be made.

Economic benefits of implementing trading zones for Australian livestock disease outbreaks of limited duration.

OBJECTIVE: The objective is to estimate the economic benefits of trading zones as part of foot-and-mouth disease (FMD) control measures for limited duration outbreaks. DESIGN: The proposed trading zones for FMD at the state level are determined using multiple tools. Eleven individual incursion scenarios in six Australian states are simulated within the Australian Animal Disease Spread epidemiological model to identify the potential geographic extent of outbreaks, as well as the number of animals infected and the duration of outbreaks. The disease spread information is used to identify the boundaries of trading zones. The outbreak duration data are combined with historical export data to estimate the share of Australian exports that could be embargoed. The market impacts of the potential export embargoes including changes in equilibrium quantities, prices and revenue are simulated within the Australian Bureau of Agricultural and Resource Economics and Sciences' AgEmissions partial equilibrium model of Australian agriculture. RESULTS: Results emphasize the importance of jurisdictional and outbreak characteristics in determining trading zones. Should Australia effectively implement trading zones at the state level in response to small FMD outbreaks, the potential reductions of embargoed exports lead to a reduction in estimated producer revenue losses compared with losses under a national embargo. Producer revenue losses are reduced between $3 billion and $9 billion estimated in present value terms over 10 years at a 7% discount rate. CONCLUSION: Economic analysis of the implications of trading zones identifies additional investments that would be of value to livestock industries.

Principles of epidemiological modelling.

Epidemiological modelling can be a powerful tool to assist animal health policy development and disease prevention and control. Models can vary from simple deterministic mathematical models through to complex spatially-explicit stochastic simulations and decision support systems. The approach used will vary depending on the purpose of the study, how well the epidemiology of a disease is understood, the amount and quality of data available, and the background and experience of the modellers. Epidemiological models can be classified into various categories depending on their treatment of variability, chance and uncertainty (deterministic or stochastic), time (continuous or discrete intervals), space (non-spatial or spatial) and the structure of the population (homogenous or heterogeneous mixing). The increasing sophistication of computers, together with greater recognition of the importance of spatial elements in the spread and control of disease, mean that models which incorporate spatial components are becoming more important in epidemiological studies. Multidisciplinary approaches using a range of new technologies make it possible to build more sophisticated models of animal disease. New generation epidemiological models enable disease to be studied in the context of physical, economic, technological, health, media and political infrastructures. To be useful in policy development, models must be fit for purpose and appropriately verified and validated. This involves ensuring that the model is an adequate representation of the system under study and that its outputs are sufficiently accurate and precise for the intended purpose. Finally, models are just one tool for providing technical advice, and should not be considered in isolation from data from experimental and field studies.

Foot and mouth disease model verification and 'relative validation' through a formal model comparison.

Researchers from Australia, New Zealand, Canada and the United States collaborated to validate their foot and mouth disease models--AusSpread, InterSpread Plus and the North American Animal Disease Spread Model--in an effort to build confidence in their use as decision-support tools. The final stage of this project involved using the three models to simulate a number of disease outbreak scenarios, with data from the Republic of Ireland. The scenarios included an uncontrolled epidemic, and epidemics managed by combinations of stamping out and vaccination. The predicted numbers of infected premises, the duration of each epidemic, and the size of predicted outbreak areas were compared. Relative within-model between-scenario changes resulting from different control strategies or resource constraints in different scenarios were quantified and compared. Although there were differences between the models in absolute outcomes, between-scenario comparisons within each model were similar. In all three models, early use of ring vaccination resulted in the largest drop in number of infected premises compared with the standard stamping-out regimen. This consistency implies that the assumptions made by each of the three modelling teams were appropriate, which in turn serves to increase end-user confidence in predictions made by these models.

A serological and virological survey for evidence of infection with Newcastle disease virus in Australian chicken farms.

OBJECTIVE: To determine the prevalence and distribution of antibodies to Newcastle disease virus on Australian chicken farms and to determine the pathotype and relationships of the Newcastle disease viruses present on those farms. DESIGN: A cross-sectional survey of 753 commercial chicken farms. PROCEDURE: The survey comprised a detailed questionnaire and collection of venous blood samples. The titre of antibodies to Newcastle disease virus was determined by haemagglutination inhibition. Virus isolation was conducted from cloacal and tracheal swabs taken from chickens in serologically positive flocks. Virus isolates were pathotyped on the basis of the deduced Fusion protein cleavage site determined by nucleotide sequencing of a 265 bp region of the genome in the region of the cleavage site. RESULTS: Antibody evidence of Newcastle disease virus infection was found on 300 of the 753 surveyed farms throughout all 11 geographic regions of the survey. The highest prevalence occurred in the Sydney basin, New South Wales and Victoria east regions. Antibody titres were also highest in the regions where serologically positive flocks were most prevalent. The 259 virus isolates revealed nine different RNA sequences. Of the nine virus groups isolated, the most common group W was identical in sequence to the V4 vaccine strain. Five of the other groups had novel RNA sequences in the region of the F protein cleavage site. CONCLUSIONS: Antibodies to Newcastle disease virus are highly prevalent in the Australian chicken flock but all identified strains were avirulent in nature.

Estimating Resource Requirements to Staff a Response to a Medium to Large Outbreak of Foot and Mouth Disease in Australia.

A recent report to the Australian Government identified concerns relating to Australia's capacity to respond to a medium to large outbreak of FMD. To assess the resources required, the AusSpread disease simulation model was used to develop a plausible outbreak scenario that included 62 infected premises in five different states at the time of detection, 28 days after the disease entered the first property in Victoria. Movements of infected animals and/or contaminated product/equipment led to smaller outbreaks in NSW, Queensland, South Australia and Tasmania. With unlimited staff resources, the outbreak was eradicated in 63 days with 54 infected premises and a 98% chance of eradication within 3 months. This unconstrained response was estimated to involve 2724 personnel. Unlimited personnel was considered unrealistic, and therefore, the course of the outbreak was modelled using three levels of staffing and the probability of achieving eradication within 3 or 6 months of introduction determined. Under the baseline staffing level, there was only a 16% probability that the outbreak would be eradicated within 3 months, and a 60% probability of eradication in 6 months. Deployment of an additional 60 personnel in the first 3 weeks of the response increased the likelihood of eradication in 3 months to 68%, and 100% in 6 months. Deployment of further personnel incrementally increased the likelihood of timely eradication and decreased the duration and size of the outbreak. Targeted use of vaccination in high-risk areas coupled with the baseline personnel resources increased the probability of eradication in 3 months to 74% and to 100% in 6 months. This required 25 vaccination teams commencing 12 days into the control program increasing to 50 vaccination teams 3 weeks later. Deploying an equal number of additional personnel to surveillance and infected premises operations was equally effective in reducing the outbreak size and duration.

Comparison of alternatives to passive surveillance to detect foot and mouth disease incursions in Victoria, Australia.

This study aimed to evaluate strategies to enhance the early detection of foot and mouth disease incursions in Australia. Two strategies were considered. First, improving the performance of the current passive surveillance system. Second, supplementing the current passive system with active surveillance strategies based on testing animals at saleyards or through bulk milk testing of dairy herds. Simulation modelling estimated the impact of producer education and awareness by either increasing the daily probability that a farmer will report the presence of diseased animals or by reducing the proportion of the herd showing clinical signs required to trigger a disease report. Both increasing the probability of reporting and reducing the proportion of animals showing clinical signs resulted in incremental decreases in the time to detection, the size and the duration of the outbreak. A gold standard system in which all producers reported the presence of disease once 10% of the herd showed clinical signs reduced the median time to detection of the outbreak from 20 to 15days, the duration of the subsequent outbreak from 53 to 42days and the number of infected farms from 46 to 32. Bulk milk testing reduced the median time to detection by two days and the number of infected farms by six but had no impact on the duration of the outbreak. Screening of animals at saleyards provided no improvement over the current passive surveillance system alone while having significant resource issues. It is concluded that the most effective way to achieve early detection of incursions of foot and mouth disease into Victoria, Australia is to invest in improving producer reporting.

Assessing the delay to detection and the size of the outbreak at the time of detection of incursions of foot and mouth disease in Australia.

The time delay to detection of an outbreak of an emergency animal disease directly affects the size of the outbreak at detection and the likelihood that the disease can be eradicated. This time delay is a direct function of the efficacy of the surveillance system in the country involved. Australia has recently completed a comprehensive review of its general surveillance system examining regional variation in both the behaviour of modelled outbreaks of foot and mouth disease and the likelihood that each outbreak will be detected and reported to government veterinary services. The size of the outbreak and the time delay from introduction to the point where 95% confidence of detection was reached showed significant (p < 0.05) regional variation with the more remote northern areas experiencing smaller outbreaks that are less likely to spread and less likely to be reported to government services than outbreaks in the more developed southern areas of Australia. Outbreaks in the more densely populated areas may take up to 43 days until a 95% confidence of detection is achieved and at that time, the outbreak may involve up to 53 farms.

Modelling the spread of foot-and-mouth disease in Australia.

Preparedness for an incursion of an exotic animal disease is of key importance to government, industry, producers and the Australian community. An important aspect of Australia's preparedness for a possible incursion of foot-and-mouth disease is investigation into the likely effectiveness and cost-efficiency of eradication strategies when applied to different regional outbreak scenarios. Disease modelling is a tool that can be used to study diseases such as foot-and-mouth disease to better understand potential disease spread and control under different conditions. The Australian Government Department of Agriculture, Fisheries and Forestry has been involved with epidemiologic simulation modelling for more than 10 years, and has developed a sophisticated spatial model for foot-and-mouth disease (AusSpread) that operates within a geographic information system framework. The model accommodates real farm boundary or point-location data, as well as synthesised data based on agricultural census and land use information. The model also allows for interactions between herds or flocks of different animal species and production type, and considers the role that such interactions are likely to play in the epidemiology of a regional outbreak of foot-and-mouth disease. The user can choose mitigations and eradication strategies from those that are currently described in Australia's veterinary emergency plan. The model also allows the user to evaluate the impact of constraints on the availability of resources for mitigations or eradication measures. Outputs include a range of maps and tabulated outbreak statistics describing the geographic extent of the outbreak and its duration, the numbers of affected, slaughtered, and, as relevant, vaccinated herds or flocks, and the cost of control and eradication. Cost-related outputs are based on budgets of the value of stock and the cost of mitigations, each of which can be varied by the user. These outputs are a valuable resource to assist with policy development and disease management.

Modelling foot-and-mouth disease transmission in a wild pig-domestic cattle ecosystem.

OBJECTIVE: To use simulation modelling to predict the potential spread and to explore control options for a foot-and-mouth disease (FMD) incursion in a mixed wild pig-domestic cattle ecosystem in northern Australia. DESIGN: Based on aerial surveys, expert opinion and published data, the wild pig and grazing cattle distributions were simulated. A susceptible-infected-resistant disease-spread model was coded and parameterised according to published literature and expert opinion. METHODS: A baseline scenario was simulated in which infection was introduced via wild pigs, with transmission from pigs to cattle and no disease control. Assumptions regarding disease transmission were investigated via sensitivity analyses. Predicted size and length of outbreaks were compared for different control strategies based on movement standstill, surveillance and depopulation. RESULTS: In most of the simulations, FMD outbreaks were predicted to be ongoing after 6 months, with more cattle herds infected than wild pig herds (median 907 vs. 22, respectively). Assuming only pig-to-pig transmission, the infection routinely died out. In contrast, assuming cattle-to-cattle, cattle-to-pig or pig-to-cattle transmission resulted in FMD establishing and spreading in more than 75% of simulations. A control strategy targeting wild pigs only was not predicted to be successful. Control based on cattle only was successful in eradicating the disease. However, control targeting both pigs and cattle resulted in smaller outbreaks. CONCLUSIONS: If FMD is controlled in cattle in the modelled ecosystem, it is likely to be self-limiting in wild pigs. However, to eradicate disease as quickly as possible, both wild pigs and cattle should be targeted for control.

Assessing the efficacy of general surveillance for detection of incursions of livestock diseases in Australia.

Australia, as a relatively isolated country with a high level of agricultural production, depends on, and has the opportunity to maintain, freedom from a range of important diseases of livestock. Occasional incursions of such diseases are generally detected by 'passive', general surveillance (GS). In current surveillance planning, a risk-based approach has been taken to optimising allocation of resources to surveillance needs, and having mapped the relative risk of introduction and establishment of diseases of concern, a means of mapping the efficacy of GS for their detection was required, as was a means of assessing the likely efficacy of options for improving GS efficacy if needed. This paper presents the structure and application of a tool for estimating the efficacy of Australia's GS, using the example of foot and mouth disease (FMD). The GS assessment tool (GSAT) is a stochastic spreadsheet model of the detection, diagnosis and reporting of disease on a single infected farm. It utilises the output of an intraherd disease spread model to determine the duration and prevalence of infection on different types of farm. It was applied separately to each of twelve regions of Australia, demarcated by dominant livestock production practices. Each region supplied estimates of probabilities relevant to the detection of FMD, for each of fourteen farm types and all species susceptible to the disease. Outputs of the GSAT were the average probability that FMD on the farm would be detected (single farm sensitivity), the average time elapsed from incursion of the disease to the chief veterinary officer (CVO) being notified (time to detection), and the number of average properties that would need to be infected before the CVO could be 95% confident of detecting at least one. The median single farm sensitivity for FMD varied among regions from 0.23 to 0.52, the median time to detection from 20 to 33 days, and the number of properties infected for 95% confidence of detecting at least one from 4 to 12. The GSAT has proved a valuable tool in planning surveillance for detection of exotic livestock disease in Australia, and it provides a practical example of the use of probabilistic modelling to answer important questions in the face of imperfect information.

Effect of angiotensin II on baroreceptor reflex control of heart rate in conscious baboons.

Studies of the baroreceptor-heart rate reflex were performed in four conscious, unrestrained male baboons to determine whether changes in circulating angiotensin II within the physiological range are associated with alterations in baroreceptor reflex sensitivity. With the animals on a high sodium intake, studies were performed before and during graded angiotensin II infusion (10 and 20 ng/kg/min). To separate effects on baroreceptor reflex function mediated by angiotensin II-induced increases in arterial pressure, these studies were repeated on a different day with simultaneous glyceryl trinitrate infusion to prevent increases in pressure during angiotensin II infusion. With the animals on a low sodium intake, studies were performed before and after angiotensin converting enzyme inhibition with captopril (1 and 5 mg/kg). These studies were also repeated on a separate day during simultaneous phenylephrine infusion to prevent a decrease in pressure with captopril. Reduction in sodium intake had no significant effect on arterial pressure, heart rate, or plasma volume, although arterial plasma angiotensin II concentration and renin activity were significantly increased (p less than 0.01). Infusion of angiotensin II produced a significant reduction in baroreceptor reflex sensitivity (p less than 0.01), and converting enzyme inhibition produced a significant increase (p less than 0.05). These effects accompanied significant increases and decreases in arterial angiotensin II concentration, respectively (p less than 0.01), but were independent of angiotensin II-related changes in arterial pressure. The data indicate that physiological variations in circulating angiotensin II have a direct effect on sensitivity of the baroreceptor-heart rate reflex.

Circulatory adaptation to pregnancy--serial studies of haemodynamics, blood volume, renin and aldosterone in the baboon (Papio hamadryas).

To test the hypothesis that haemodynamic changes in pregnancy precede any significant increase in circulating blood volume, serial haemodynamic studies were performed in eight baboon pregnancies using Swan-Ganz catheterization and arterial cannulation. Simultaneous measurements were made of red cell and plasma volumes, and of plasma renin activity and aldosterone concentration. Haemodynamic changes identified by 4 weeks gestation included significant (P less than 0.01) reductions in right atrial pressure, systemic and pulmonary arterial pressures, and systemic and pulmonary vascular resistance. Stroke volume increased in early pregnancy (P less than 0.01), with a consequent increase in cardiac output. Plasma renin activity and aldosterone concentration were elevated by 4 weeks (P less than 0.01), but plasma volume did not expand until 12 weeks. At no stage in middle or late pregnancy was cardiac filling pressure increased. These results provide the first haemodynamic evidence that pregnancy is a state of reduced effective blood volume associated with vasodilatation from the early weeks.

Nonocclusive chronic vascular catheterization of conscious unrestrained baboons.

A surgical technique is described for chronic arterial and venous catheterization of unrestrained adult baboons. Vascular access was achieved through a small (5 cm) abdominal incision and an extraperitoneal approach to the iliac vessels, which minimizes postoperative morbidity, discomfort, and restriction of movement. The method permits secure but nonocclusive catheterization, confirmed by angiography. Catheters were removed without further surgery, leaving the baboons intact for reuse. Catheters placed in the distal common or proximal external iliac vessels were all patent when removed at 46-61 days. The results demonstrate arterial pressure, pulse rates, drug administration, blood sampling, and plasma volume measurement as examples of the technique's application in conscious unrestrained baboons.

A review of Q fever in Australia 1991-1994.

Q fever continues to be an important disease in Australia. Despite the development of an effective vaccine that has been commercially available since 1989, the number of cases notified has continued to increase. This study reviewed national notifications of Q fever between 1991 and 1994, together with demographic, socioeconomic and occupational information, to investigate temporal and spatial disease patterns. Based on notification data, Q fever can be considered primarily a disease of adult males that occurs in eastern Australia: southern Queensland and northern New South Wales have the highest levels of activity. A significant association between Q fever activity of areas and the presence of livestock was found. A strong association with the meat industry was also confirmed. Q fever is conservatively estimated to cost Australia around A$1 million and more than 1700 weeks of work time annually. There is a need to increase awareness of this disease and its prevention. An extension program in rural communities and provision of vaccine to all abattoir workers would appear to be sensible public health approaches.

The expected economic impact of selected exotic diseases on the pig industry of Australia.

The authors assess the expected economic impact of three exotic diseases on the pig industry of Australia. An integrated epidemiological/economic approach was used to assess the effects of classical swine fever, Nipah virus and porcine reproductive and respiratory syndrome. Scenarios involving either an epidemic event, in which the outbreaks were confined to selected regions and were eradicated, or an endemic situation, in which the diseases became established in Australia, were studied. Based only on loss of sales and disposal costs, epidemics resulted in regional losses in income of the order of AUS$10 million-AUS$30 million (16%-37%) depending on disease and region. If any of these diseases became established, opportunity losses in gross national pig income of 5%-11% per year would occur, with classical swine fever the most serious of the three diseases. Establishment of any of the diseases would lead to rapid structural change in the pig industry, with concomitant social and economic dislocation in regional Australia.

Economic aspects of foot and mouth disease: perspectives of a free country, Australia.

Australia is a significant livestock producer and a major exporter of livestock, livestock products and livestock genetic material. An outbreak of foot and mouth disease (FMD) would have severe economic consequences on the economy. A recent study found that in an outbreak lasting six months, real gross domestic product in Australia would fall by an estimated 0.6% (AUS$3.5 billion), employment by 0.8%, and a depreciation of 3% would be recorded in the exchange rate in the first year. Much of this impact would be due to the loss of export markets. Given the significant consequences of an outbreak of FMD, Australia invests considerable resources in prevention and planning. These measures can be viewed at three levels, namely: pre-border, border and post-border. Australia recently further enhanced quarantine at the border to minimise the risk of entry of FMD. However, no matter how much is invested, there is no guarantee that FMD will not enter the country. Accordingly, it is important to ensure that comprehensive contingency plans are also in place. Recent outbreaks in previously free countries have shown that a large outbreak of FMD poses major problems for the animal health services of a country and a combined government and industry response is required.

Modelling the potential impact of exotic diseases on regional Australia.

Recent international initiatives for disease control suggest that, in the future, the consequences for trade of an exotic disease outbreak may not be as severe as estimated in the past. If zoning were to be accepted by Australia's trading partners, then the major effects may be felt at the regional rather than the national level. A study, using an integrated epidemiological/economic model, was undertaken to compare the impacts of 3 important exotic diseases (foot-and-mouth disease, classical swine fever and sheep pox) in 3 different regions of Australia. The study demonstrated that there are significant differences between the size and effect of different disease outbreaks. Regional factors influence not only the way that the disease will spread and manifest itself, but also the effects on local communities. Foot-and-mouth disease caused more economic losses than sheep pox or classical swine fever. The major determinant of differences in the effects of the diseases between regions was the nature of the regional economies. The less diversified the economy, the greater the effect of an exotic disease outbreak in relation to the size of that economy.