A model for the assessment of bluetongue virus serotype 1 persistence in Spain.

Bluetongue virus (BTV) is an arbovirus of ruminants that has been circulating in Europe continuously for more than two decades and has become endemic in some countries such as Spain. Spain is ideal for BTV epidemiological studies since BTV outbreaks from different sources and serotypes have occurred continuously there since 2000; BTV-1 has been reported there from 2007 to 2017. Here we develop a model for BTV-1 endemic scenario to estimate the risk of an area becoming endemic, as well as to identify the most influential factors for BTV-1 persistence. We created abundance maps at 1-km2 spatial resolution for the main vectors in Spain, Culicoides imicola and Obsoletus and Pulicaris complexes, by combining environmental satellite data with occurrence models and a random forest machine learning algorithm. The endemic model included vector abundance and host-related variables (farm density). The three most relevant variables in the endemic model were the abundance of C. imicola and Obsoletus complex and density of goat farms (AUC 0.86); this model suggests that BTV-1 is more likely to become endemic in central and southwestern regions of Spain. It only requires host- and vector-related variables to identify areas at greater risk of becoming endemic for bluetongue. Our results highlight the importance of suitable Culicoides spp. prediction maps for bluetongue epidemiological studies and decision-making about control and eradication measures.

Effectiveness and cost-benefit study to encourage herd owners in a cost sharing vaccination programme against bluetongue serotype-8 in Belgium.

Bluetongue (BT) is a ruminant viral infectious disease transmitted by Culicoides spp. midges. In 2006, when bluetongue virus serotype 8 (BTV-8) appeared for the first time in Northern Europe, it rapidly spread and infected a large proportion of animals. BThas a significant economic impact due to a direct effect on animal health and to an indirect effect in disrupting international trade of animals and animal products. In spring 2008, a compulsory subsidized vaccination programme in Europe resulted in a drastic decrease in the number of reported cases. However, due to the turn-over of the population, without a continuous vaccination programme, the animal population was becoming progressively susceptible. Vaccination would enable Belgium to maintain its status of freedom from infection of BTV-8 that could possibly be re-introduced. Subsidizing it could be an incentive to convince more farmers to vaccinate. To finance this programme, both decision-makers and stakeholders need to be persuaded by the effectiveness and the cost-benefit of vaccination. The study evaluated the effectiveness of vaccination against BTV-8 in Belgium. The change in serology which has shown the effectiveness of the vaccine to induce antibody production has been significantly associated with the time between the first injection and the sampling date and the number of injections of the primo-vaccination. This study also clearly confirms the benefit of vaccination by reducing economic impact of treatment and production losses, especially in dairy cattle. Based on a participating epidemiological approach, a national voluntary and subsidized vaccination was accepted, and permitted Belgium to vaccinate more than 9,000 herds in 1 month. Because this mass vaccination occurred before the vector season, it probably helped Belgium remain free from BTV-8.

Assessment of cross-protection induced by a bluetongue virus (BTV) serotype 8 vaccine towards other BTV serotypes in experimental conditions.

Bluetongue disease is caused by bluetongue virus (BTV) and BTV serotype 8 (BTV8) caused great economic damage in Europe during the last decade. From 1998 to 2007, in addition to BTV8, Europe had to face the emergence of BTV1, 2, 4, 9, and 16, spreading in countries where the virus has never been detected before. These unprecedented outbreaks trigger the need to evaluate and compare the clinical, virological and serological features of the European BTV serotypes in the local epidemiological context. In this study groups of calves were infected with one of the following European BTV serotypes, namely BTV1, 2, 4, 9 and 16. For each tested serotype, two groups of three male Holstein calves were used: one group vaccinated against BTV8, the other non-vaccinated. Clinical signs were quantified, viral RNA was detected in blood and organs and serological relationship was assessed. Calves were euthanized 35 days post-infection and necropsied. Most of the infected animals showed mild clinical signs. A partial serological cross reactivity has been reported between BTV8 and BTV4, and between BTV1 and BTV8. BTV2 and BTV4 viral RNA only reached low levels in blood, when compared to other serotypes, whereas in vitro growth assays could not highlight significant differences. Altogether the results of this study support the hypothesis of higher adaptation of some BTV strains to specific hosts, in this case calves. Furthermore, cross-protection resulting from a prior vaccination with BTV8 was highlighted based on cross-neutralization. However, the development of neutralizing antibodies is probably not totally explaining the mild protection induced by the heterologous vaccination.

Cost distribution of bluetongue surveillance and vaccination programmes in Austria and Switzerland (2007-2016).

Bluetongue virus (BTV) is an emerging transboundary disease in Europe, which can cause significant production losses among ruminants. The analysis presented here assessed the costs of BTV surveillance and vaccination programmes in Austria and Switzerland between 2007 and 2016. Costs were compared with respect to time, type of programme, geographical area and who was responsible for payment. The total costs of the BTV vaccination and surveillance programmes in Austria amounted to €23.6 million, whereas total costs in Switzerland were €18.3 million. Our analysis demonstrates that the costs differed between years and geographical areas, both within and between the two countries. Average surveillance costs per animal amounted to approximately €3.20 in Austria compared with €1.30 in Switzerland, whereas the average vaccination costs per animal were €6.20 in Austria and €7.40 in Switzerland. The comparability of the surveillance costs is somewhat limited, however, due to differences in each nation's surveillance (and sampling) strategy. Given the importance of the export market for cattle production, investments in such programmes are more justified for Austria than for Switzerland. The aim of the retrospective assessment presented here is to assist veterinary authorities in planning and implementing cost-effective and efficient control strategies for emerging livestock diseases.

Assessment of biosecurity and control measures to prevent incursion and to limit spread of emerging transboundary animal diseases in Europe: An expert survey.

Decision-makers and risk managers are often called upon to prioritise on and recommend suitable measures to prevent the risk of introduction and spread of pathogens. The main objective of this study was to assess the perceptions of experts in Italy, Switzerland and the United Kingdom concerning the importance, effectiveness, feasibility, costs and acceptability of selected biosecurity measures to prevent the introduction and limit the spread of rabies, blue tongue (BT) and classical swine fever (CSF). After identifying the most relevant measures by the project team, an expert knowledge elicitation was implemented through a questionnaire. After preliminary descriptive analyses, a number of statistical calculations were performed such as weighted medians, Spearman rank correlation tests, Wilcoxon comparison tests and ranking of measures. Three experts from each country completed the questionnaires, one expert for each disease. The mean answer rates for CSF, BT and rabies were 73%, 100% and 99% respectively. "Tracing system for live animal trade" was highlighted as very relevant in all diseases. The implementation of a "restriction zone after a suspicion or confirmation" was also rated as a relevant measure, especially for CSF. We identified generally a small correlation between costs and the other criteria. Among the rabies experts, measures related to "zoonotic risk" were rated highly, supporting the idea of a One Health approach. Disagreement among experts concerned 43 measures for the three pathogens: the debated measures were "control of the wildlife CSF status", "arthropod-vector control" and "rabies vaccination for domestic animals". Facing budget restriction, decision-makers need to prioritise their actions and make efficient prevention choices. With this study, we aimed to provide elements for reflection and to inform priority setting. The results can be applied through the implementation of similar surveys or directly from the knowledge already gathered in this study.

Economic analysis of animal disease outbreaks--BSE and Bluetongue disease as examples.

Although there is a long tradition of research on animal disease control, economic evaluation of control measures is rather limited in veterinary medicine. This may, on the one hand, be due to the different types of costs and refunds and the different people and organizations bearing them, such as animal holders, county, region, state or European Union, but it may also be due to the fact that economic analyses are both complex and time consuming. Only recently attention has turned towards economic analysis in animal disease control. Examples include situations, when decisions between different control measures must be taken, especially if alternatives to culling or compulsory vaccination are under discussion. To determine an optimal combination of control measures (strategy), a cost-benefit analysis should be performed. It is not necessary to take decisions only based on the financial impact, but it becomes possible to take economic aspects into account. To this end, the costs caused by the animal disease and the adopted control measures must be assessed. This article presents a brief overview of the methodological approaches used to retrospectively analyse the economic impact of two particular relevant diseases in Germany in the last few years: Blue-tongue disease (BT) and Bovine Spongiform Encephalopathy (BSE).

Cost analysis of bluetongue virus serotype 8 surveillance and vaccination programmes in Austria from 2005 to 2013.

This study was designed to evaluate the costs between 2005 and 2013 of the national bluetongue virus (BTV) surveillance and vaccination programmes before, during and after the BTV serotype 8 (BTV-8) outbreak in Austria commencing in 2008. In addition to an assessment of the temporal development of costs, a spatial cost analysis was performed. Within the context of this study, the term 'costs' refers to actual financial expenditure and imputed monetary costs for contributions in-kind. Costs were financed directly by the private-public sectors, by the European Commission (EC), and (in-kind) by responsible national institutions and individuals (e.g. blood sampling by veterinarians). The total net cost of the BTV-8 surveillance and vaccination programmes arising from the outbreak amounted to €22.8 million (0.86% of the national agricultural Gross Value Added), of which 32% was allocated to surveillance and 68% to the vaccination programme. Of the total programme costs, the EC supplied €4.9 million, while the remaining costs (€18 million) were directly financed from national resources. Of the latter, €14.5 million was classed as public costs, including €2 million contributions in-kind, and €3.4 million as private costs. The assessment of the costs revealed heterogeneous temporal and spatial distributions. The methodology of this analysis might assist decision makers in calculating costs for other surveillance and intervention programmes. The assessment of contributions in-kind is of importance to public authorities as it increases visibility of the available resources and shows how they have been employed. This study also demonstrates the importance of tracking changing costs per payer over time.

Economic comparison of the monitoring programmes for bluetongue vectors in Austria and Switzerland.

With the bluetongue virus serotype 8 (BTV-8) outbreak in 2006, vector monitoring programmes (according to EU regulation 1266/2007) were implemented by European countries to obtain information on the spatial distribution of vectors and the vector-free period. This study investigates the vector monitoring programmes in Austria and Switzerland by performing a retrospective cost analysis for the period 2006-2010. Two types of costs were distinguished: costs financed directly via the national bluetongue programmes and costs contributed in-kind by the responsible institutions and agricultural holdings. The total net costs of the monitoring programme in Austria amounted to €1,415,000, whereby in Switzerland the costs were valued at €94,000. Both countries followed the legislation complying with requirements, but differed in regard to sampling frequency, number of trap sites and sampling strategy. Furthermore, the surface area of Austria is twice the area of Switzerland although the number of ruminants is almost the same in both countries. Thus, for comparison, the costs were normalised with regard to the sampling frequency and the number of trap sites. Resulting costs per trap sample comprised €164 for Austria and €48 for Switzerland. In both countries, around 50 per cent of the total costs can be attributed to payments in-kind. The benefit of this study is twofold: first, veterinary authorities may use the results to improve the economic efficiency of future vector monitoring programmes. Second, the analysis of the payment in-kind contribution is of great importance to public authorities as it makes the available resources visible and demonstrates how they have been used.

Cost assessment of the movement restriction policy in France during the 2006 bluetongue virus episode (BTV-8).

This study aims at evaluating the costs of the movement restriction policy (MRP) during the 2006 BTV-8 epidemic in France for the producers of 6-9 month old Charolais beef weaned calves (BWC), an important sector that was severely affected by the restrictions imposed. This study estimates the change in the number of BWC sold that was due to the movement restrictions, and evaluates the economic effect of the MRP. The change in BWC sold by producers located inside the restriction zone (RZ) was analyzed for 2006 by using a multivariate matching approach to control for any internal validity threat. The economic evaluation of the MRP was based on several scenarios that describe farms' capacity constraints, feeding prices, and the animal's selling price. Results show that the average farmer experienced a 21% decrease in animals sold due to the MRP. The economic evaluation of the MRP shows a potential gain during the movement standstill period in the case of no capacity constraint faced by the farm and food self-sufficiency. This gain remains limited and close to zero in case of a low selling price and when animals are held until they no longer fit the BWC market so that they cannot be sold as an intermediate product. Capacity constraints represent a tremendous challenge to farmers facing movement restrictions and the fattening profit becomes negative under such conditions. The timing and length of the movement standstill period significantly affect the profitability of the strategy employed by the farmer: for a 5.5 month-long standstill period with 3.5 months of cold weather, farmers with capacity constraints have stronger incentives to leave their animals outside during the whole period and face higher mortality and morbidity rates than paying for a boarding facility for the cold months. This is not necessarily true for a shorter standstill period. Strategies are also sensitive to the feed costs and to the food self-sufficiency of the farm. Altogether, the present work shows the farmer's vulnerability to animal movement restrictions and quantifies the costs of the standstill. These results should assist decision-makers who seek to calculate adequate subsidies/aid or to efficiently allocate resources to prevent future outbreaks.

Expected utility of voluntary vaccination in the middle of an emergent Bluetongue virus serotype 8 epidemic: a decision analysis parameterized for Dutch circumstances.

In order to put a halt to the Bluetongue virus serotype 8 (BTV-8) epidemic in 2008, the European Commission promoted vaccination at a transnational level as a new measure to combat BTV-8. Most European member states opted for a mandatory vaccination campaign, whereas the Netherlands, amongst others, opted for a voluntary campaign. For the latter to be effective, the farmer's willingness to vaccinate should be high enough to reach satisfactory vaccination coverage to stop the spread of the disease. This study looked at a farmer's expected utility of vaccination, which is expected to have a positive impact on the willingness to vaccinate. Decision analysis was used to structure the vaccination decision problem into decisions, events and payoffs, and to define the relationships among these elements. Two scenarios were formulated to distinguish farmers' mindsets, based on differences in dairy heifer management. For each of the scenarios, a decision tree was run for two years to study vaccination behaviour over time. The analysis was done based on the expected utility criterion. This allows to account for the effect of a farmer's risk preference on the vaccination decision. Probabilities were estimated by experts, payoffs were based on an earlier published study. According to the results of the simulation, the farmer decided initially to vaccinate against BTV-8 as the net expected utility of vaccination was positive. Re-vaccination was uncertain due to less expected costs of a continued outbreak. A risk averse farmer in this respect is more likely to re-vaccinate. When heifers were retained for export on the farm, the net expected utility of vaccination was found to be generally larger and thus was re-vaccination more likely to happen. For future animal health programmes that rely on a voluntary approach, results show that the provision of financial incentives can be adjusted to the farmers' willingness to vaccinate over time. Important in this respect are the decision moment and the characteristics of the disease. Farmers' perceptions of the disease risk and about the efficacy of available control options cannot be neglected.

Policy-driven development of cost-effective, risk-based surveillance strategies.

Animal health and residue surveillance verifies the good health status of the animal population, thereby supporting international free trade of animals and animal products. However, active surveillance is costly and time-consuming. The development of cost-effective tools for animal health and food hazard surveillance is therefore a priority for decision-makers in the field of veterinary public health. The assumption of this paper is that outcome-based formulation of standards, legislation leaving room for risk-based approaches and close collaboration and a mutual understanding and exchange between scientists and policy makers are essential for cost-effective surveillance. We illustrate this using the following examples: (i) a risk-based sample size calculation for surveys to substantiate freedom from diseases/infection, (ii) a cost-effective national surveillance system for Bluetongue using scenario tree modelling and (iii) a framework for risk-based residue monitoring. Surveys to substantiate freedom from infectious bovine rhinotracheitis and enzootic bovine leucosis between 2002 and 2009 saved over 6 million € by applying a risk-based sample size calculation approach, and by taking into account prior information from repeated surveys. An open, progressive policy making process stimulates research and science to develop risk-based and cost-efficient survey methodologies. Early involvement of policy makers in scientific developments facilitates implementation of new findings and full exploitation of benefits for producers and consumers.

Assessment of the utility of routinely collected cattle census and disposal data for syndromic surveillance.

Census and disposal data provide a multipurpose source of information on cattle mortality. The retrospective analyses we conducted on the data gathered in the National Cattle Register produced relevant information for describing and modelling the cattle mortality baseline and evaluating the impact of the 2007-2008 Blue Tongue epidemic on the French cattle population. This work was conducted retrospectively but showed that monitoring cattle mortality near real time could help detecting unexpected events. We are thus currently working on a timely and automated system to monitor cadaver disposal requests received by rendering plants, thanks to a data interchange system recently implemented between the Ministry of Agriculture and the fallen stock companies. Besides technical and methodological challenges, using these data for surveillance purposes raises epidemiological questions that still need to be answered. The question remains notably as to whether an abnormal increased mortality is a sensitive and timely signal for detecting unexpected health events. It appears also very challenging to identify the most adequate surveillance scale (time, space and population) and the most adequate anomaly detection algorithms to apply when the characteristics of the signals to be detected (shape, amplitude, etc.) are not known a priori. In Human health, similar systems have not yet proven their ability to detect unexpected events earlier than classical surveillance systems currently in place, but they have already demonstrated their value for real time assessment of identified and potentially dangerous events. Combined with traditional surveillance systems, we think that monitoring routinely collected data could improve the surveillance of the animal population health. Even if not used for detection purposes, cattle mortality monitoring could be used to rapidly produce information on the impact and evolution of identified events, what would facilitate decision-making regarding management measures and improve the communication.

A two year BTV-8 vaccination follow up: molecular diagnostics and assessment of humoral and cellular immune reactions.

The compulsory vaccination campaign against Bluetongue virus serotype eight (BTV-8) in Germany was exercised in the state of Bavaria using three commercial monovalent inactivated vaccines given provisional marketing authorisation for emergency use. In eleven Bavarian farms representing a cross sectional area of the state the immune reactions of sheep and cattle were followed over a two year period (2008-2009) using cELISA, a serum neutralisation test (SNT) and interferon gamma (IFN-γ) ELISPOT. For molecular diagnostics of BTV genome presence two recommended real time quantitative RT-PCR protocols were applied. The recommended vaccination scheme led to low or even undetectable antibody titers (ELISA) in serum samples of both cattle and sheep. A fourfold increase of the vaccine dose in cattle, however, induced higher ELISA titers and virus neutralising antibodies. Accordingly, repeated vaccination in sheep caused an increase in ELISA-antibody titers. BTV-8 neutralising antibodies occurred in most animals only after multiple vaccinations in the second year of the campaign. The secretion of interferon gamma (IFN-γ) in ELISPOT after in vitro re-stimulation of PBMC of BTV-8 vaccinated animals with BTV was evaluated in the field for the first time. Sera of BTV-8 infected or vaccinated animals neutralising BTV-8 could also neutralise an Italian BTV serotype 1 cell culture adapted strain and PBMC of such animals secreted IFN-γ when stimulated with BTV-1.

Economic evaluation of the surveillance and intervention programme for bluetongue virus serotype 8 in Switzerland.

Empirical analyses founded on sound economic principles are essential in advising policy makers on the efficiency of resource use for disease mitigation. Surveillance and intervention are resource-using activities directed at mitigation. Surveillance helps to offset negative disease effects by promoting successful intervention. Intervention is the process of implementing measures (e.g. vaccination or medication) to reduce or remove a hazard in a population. The scale and ratios in which the two are combined affect the efficiency of mitigation, its costs, benefits, and thus net effect on society's well-being. The Swiss national mitigation programme for bluetongue virus serotype 8 was used as case study to investigate the economic efficiency of mitigation. In 2008, Switzerland implemented a vaccination programme to avoid and reduce disease and infection in its ruminant population. To monitor the vaccination programme and the vector dynamics, a surveillance system consisting of serological and entomological surveillance was established. Retrospective analyses for the years 2008-2009 and prospective analyses for the years 2010-2012 were conducted to investigate if the mitigation programme was economically beneficial. In the retrospective analysis, the implemented programme (=comparative scenario) was compared to a hypothesised baseline scenario of voluntary vaccination and surveillance. In the prospective analysis, the comparative scenario assumed to continue was compared to two baseline scenarios: one of voluntary vaccination combined with surveillance and one of no vaccination combined with surveillance. For each scenario, monetary surveillance, intervention and disease costs were calculated. The comparison of baseline and comparative scenarios yielded estimates for the total benefit (=disease costs avoided), margin over intervention cost and the net value of the programme. For 2008-2009, in aggregate, the mean biannual total benefit was 17.46 m Swiss francs (CHF) (1CHF=0.66€ at the time of analysis) and the mean net benefit after subtraction of the intervention and surveillance cost was 3.95 m CHF. For the three years 2010-2012, overall net costs were estimated at 12.93 m and 8.11 m CHF, respectively, for comparison of the implemented mitigation programme with the two baseline scenarios. It was concluded that the surveillance and intervention programme implemented in 2008-2009 was economically beneficial, while its continuation in the same form in 2010-2012 would produce net costs. These costs were due to the mean intervention cost remaining constant at a level of approximately 11 m CHF per year while the mean total benefit would be gradually reduced in 2010-2012 due to the reduced occurrence of disease in a fully vaccinated population.

Financial evaluation of different vaccination strategies for controlling the bluetongue virus serotype 8 epidemic in The Netherlands in 2008.

BACKGROUND: Bluetongue (BT) is a vector-borne disease of ruminants caused by bluetongue virus that is transmitted by biting midges (Culicoides spp.). In 2006, the introduction of BTV serotype 8 (BTV-8) caused a severe epidemic in Western and Central Europe. The principal effective veterinary measure in response to BT was believed to be vaccination accompanied by other measures such as movement restrictions and surveillance. As the number of vaccine doses available at the start of the vaccination campaign was rather uncertain, the Dutch Ministry of Agriculture, Nature and Food Quality and the Dutch agricultural industry wanted to evaluate several different vaccination strategies. This study aimed to rank eight vaccination strategies based on their efficiency (i.e. net costs in relation to prevented losses or benefits) for controlling the bluetongue virus serotype 8 epidemic in 2008. METHODOLOGY/PRINCIPAL FINDINGS: An economic model was developed that included the Dutch professional cattle, sheep and goat sectors together with the hobby farms. Strategies were evaluated based on the least cost - highest benefit frontier, the benefit-cost ratio and the total net returns. Strategy F, where all adult sheep at professional farms in The Netherlands would be vaccinated was very efficient at lowest costs, whereas strategy D, where additional to all adult sheep at professional farms also all adult cattle in the four Northern provinces would be vaccinated, was also very efficient but at a little higher costs. Strategy C, where all adult sheep and cattle at professional farms in the whole of The Netherlands would be vaccinated was also efficient but again at higher costs. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that a financial analysis differentiates between vaccination strategies and indicates important decision rules based on efficiency.

Quantitative assessment of the probability of bluetongue virus transmission by bovine semen and effectiveness of preventive measures.

Given that bluetongue (BT) may potentially be transmitted by semen, that the disease has significantly expanded in recent years, and that millions of doses of cattle semen are annually traded throughout the world, the transmission of bluetongue virus (BTV) by semen could have severe consequences in the cattle industry. The hypothesis that infected bulls could excrete BTV in their semen led to restrictions on international trade of ruminant semen and the establishment of measures to prevent BTV transmission by semen. However, neither the risk of BTV transmission by semen nor the effectiveness of these measures was estimated quantitatively. The objective of the study was to assess, in case of introduction of BTV into a bovine semen collection centre (SCC), both the risk of BTV transmission by bovine semen and the risk reduction achieved by some of the preventive measures, by means of a stochastic risk assessment model. The model was applied to different scenarios, depending on for example the type of diagnostic test and the interval between the controls (testing) of donor bulls, or the rate of BTV spread within the SCC. Enzyme-linked immunosorbant assay (ELISA) controls of donor bulls every 60 days seemed to be an ineffective method for reducing the risk of BTV transmission in contrast to polymerase chain reaction (PCR) tests every 28 days. An increase in the rate of spread within the SCC resulted in a reduced risk of BTV transmission by semen. The storage of semen for 30 days prior to dispatch seemed to be an efficient way of reducing the risk of transmission by semen. The sensitivity analysis identified the probability of BTV shedding in semen as a crucial parameter in the probability of BTV transmission by semen. However, there is a great degree of uncertainty associated with this parameter, with significant differences depending on the BTV serotype.

History of bluetongue research at Onderstepoort.

Research on this economically important disease of ruminants, especially sheep, which had been named bluetongue by farmers in the 19th century, has been part and parcel of the activities at Onderstepoort ever since its establishment in 1908 and therefore covers a full century of the OVI's existence. In view of Onderstepoort's centenary celebration a brief overview of this research is given in terms of the historic milestones which influenced and guided global research on this and other viral diseases of animals.