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Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Perceived risk and personality traits explaining heterogeneity in Dutch dairy farmers’ beliefs about vaccination against Bluetongue
    Sok, J. ; Hogeveen, H. ; Elbers, A.R.W. ; Oude Lansink, A.G.J.M. - \ 2018
    Journal of Risk Research 21 (2018)5. - ISSN 1366-9877 - p. 562 - 578.
    beliefs - Bluetongue - perceived risk - personality traits - reasoned action approach - vaccination

    When designing effective voluntary vaccination strategies against animal disease epidemics, policy-makers need to take into account that different groups of farmers base their participation decisions on different considerations. Using the past Bluetongue virus serotype 8 epidemic of 2006–2009 in Europe as an example, this paper uses the Reasoned Action Approach to identify a set of attitudinal beliefs being the major drivers behind the intended decision to participate in voluntary vaccination. The results show that there is heterogeneity among farmers in these beliefs. In particular, perceived risk, which was captured by a risk attitude and a risk perception of the farmer, and personality traits are associated with variability in beliefs about vaccination against Bluetongue. The patterns found between perceived risk, personality traits and other farm and farmer characteristics were discussed in relation to the governance of animal health.

    Rabies in Ethiopia: modelling the burden and the effectiveness of control
    Beyene, Tariku Jibat - \ 2017
    Wageningen University. Promotor(en): H. Hogeveen, co-promotor(en): M.C.M. Mourits. - Wageningen : Wageningen University - ISBN 9789463432177 - 194
    cattle - dogs - rabies - farmers - cattle farming - vaccination - business economics - cost effectiveness analysis - ethiopia - east africa - rundvee - honden - hondsdolheid - boeren - rundveeteelt - vaccinatie - bedrijfseconomie - cost effective analysis - ethiopië - oost-afrika

    Rabies claims the lives of more than 24,000 people in Africa annually, but efforts to control the disease are still lacking, particularly in sub-Saharan Africa such as Ethiopia. The overall objective of this study was to support the design of an appropriate cost-effective rabies control policy in Ethiopia by providing insights in the health burden of the disease and its economic impacts, as well as an understanding of the relationship between intervention levels, implementation costs and potential returns.

    As most human rabies cases result from the bite of domestic dogs, the disease can be eliminated by mass canine rabies vaccination. An extensive literature review on mass canine vaccination programs in Africa indicated that most dogs in Africa are owned and therefore accessible for vaccination, but vaccination coverages strongly depend on the implemented cost schemes. Canine vaccination in Ethiopia is voluntarily based, i.e. “owner-charged”, resulting in one of the lowest coverages in the world.

    To assess the current burden of rabies in Ethiopia a retrospective study was conducted by collecting data on human rabies exposure over the period of one year through extensive bite case searching in three representative districts of Ethiopia. Extrapolation of the results to national level indicated an annual average of 3,000 human deaths and 97,000 rabies-exposed persons treated at an average costs of 21 USD per case, causing 2 million USD on treatment costs per year and a health loss of about 93,000 DALYs. About 77% of the exposure cases visited a health centre, while only 57% received sufficient doses of post exposure treatment. Important factors that influenced victim’s medical treatment seeking behaviour were ownership status of the biting dog, severity of the bite, body part bitten, monthly spending and distance to the nearest health centre whereas the likelihood of receiving sufficient doses of treatment were determined by monthly spending and distance to health centre. The district in which victims lived appeared to have a relevant influence on the likelihood of seeking medical treatment but not on the likelihood of treatment compliance. By means of a structured questionnaire administered to cattle-owning households the economic impact of rabies in livestock was assessed. Herd-level incidence rates appeared higher in the mixed crop-livestock system (21%) than in the pastoral system (11%). Average economic losses per herd due to rabies were estimated at 49 USD per year for the mixed-crop livestock system, and at 52 USD per year for the pastoral system.

    In light of policy support for rabies control, an evaluation of the cost-effectiveness of control strategies was performed by the use of a dynamic epidemiological model coupled with an economic analysis to predict the human health impact and economic benefit (reducing human treatment costs and livestock rabies-related losses) across a range of vaccination scenarios. Human exposures, human deaths, and rabies-related livestock losses decreased monotonically with increasing vaccination coverage. In the evaluated urban and rural districts, 50% coverage was identified as most likely scenario to provide the greatest net health benefits at the WHO-recommended willingness-to-pay threshold over a time frame of 10 years. The additional economic benefit from rabies control in livestock justified the additional costs of vaccination campaigns with higher coverages than would have been efficient from a strict human health perspective, highlighting the importance of applying a broad perspective with regard to the evaluation of vaccination benefits.

    Farmers’ willingness to invest in livestock disease control: the case of voluntary vaccination against bluetongue
    Sok, Jaap - \ 2017
    Wageningen University. Promotor(en): A.G.J.M. Oude Lansink; H. Hogeveen, co-promotor(en): A.R.W. Elbers. - Wageningen : Wageningen University - ISBN 9789463437059 - 214
    business economics - farmers - livestock - vaccination - bluetongue virus - animal diseases - animal disease prevention - netherlands - bedrijfseconomie - boeren - vee - vaccinatie - bluetonguevirus - dierziekten - dierziektepreventie - nederland

    Animal health authorities in the European Union nowadays consider voluntary approaches based on a neoliberal model of cost and responsibility sharing as a tool for controlling livestock diseases. Policy makers aim for policies that are soft and optional, and use insights from behavioural economics and social psychology. Voluntary approaches are flexible in terms of legislation and can be effective at lower costs, provided that farmers are willing to participate. In 2008, the Dutch animal health authorities used a voluntary vaccination approach to control an emerging bluetongue epidemic that started end of 2006. Nearly 60,000 holdings with ruminants were already affected by the end of 2007 and experts indicated that transmission could only be stopped through mass vaccination. Farmers were motivated to participate by informational and financial, incentive-based policy instruments.

    Economic theory predicts that farmers underinvest in private disease control measures in the presence of externalities. These studies, however, assume farmers only consider the private economic motives and that they only can be extrinsically motivated via (monetary) incentives. If the willingness to invest in livestock disease control is also driven by intrinsic and social motives, this could imply that not only financial compensation, but a mix of policy instruments is needed to make voluntary approaches work.

    The overarching research objective of this thesis was to assess the key determinants of farmers’ willingness to vaccinate against bluetongue and study the impact of different policy designs on the effectiveness of voluntary vaccination approaches to bluetongue disease control.

    A three-stage research approach was conducted. Two models of decision making, one from economics and one from social psychology, were first applied to the case study to obtain a solid understanding of important perceptions and motivations that farmers have to invest in livestock disease control. These motivations (sometimes incentives) and perceptions were then related to different attributes of a vaccination scheme to have a better understanding of how a higher uptake can be obtained. In the third stage, the effect of the interplay between farmers’ collective behaviour and disease epidemiology on disease rate and vaccination uptake was studied.

    Expected utility theory was used in combination with decision analysis and Monte Carlo simulation in chapter 2. The economic risk and monetary outcomes of the vaccination decision were considered, intrinsic or social motives ignored. The theoretical expectation from the analysis is that with high probabilities of herd exposure and disease effects at the start of the outbreak the farmer decides to vaccinate. Re-vaccination is uncertain during the course of the epidemic due to a lower probability of herd exposure and enduring protection against infection from previous vaccination. Factors that make re-vaccination more likely to happen are risk-averse behaviour and farm management aimed at the export of heifers. The decision moment – before or during an epidemic – and the characteristics of the disease – endemic, epidemic or emerging – are important factors in perceptions of disease risk.

    Chapters 3 to 5 used data from a survey that was based on the reasoned action approach. Data were analysed with a variety of statistical, mostly multivariate, techniques. The relative importance of the social-psychological constructs in predicting the intention to participate in a hypothetical reactive vaccination scheme against bluetongue was assessed in chapter 3. It was found that intended vaccination behaviour was mainly explained by farmers’ attitude, but also by social pressures from injunctive and descriptive norms. Perceived behavioural control was the least important predictor of intention.

    The most influential beliefs underlying the social-psychological constructs were assessed in chapter 4. Results suggested that instrumental beliefs (e.g. risk reduction) as well as experiential beliefs (e.g. animal welfare) were important drivers of the attitude towards vaccination against bluetongue. This indicates that in addition to monetary outcomes of the decision, at least a group of farmers also consider the non-monetary (or non-pecuniary) outcomes. The results further showed that the most influencing referents for the farmer are the veterinarian, his or her family members and colleague dairy farmers (peers). Two influencing control beliefs were associated with the provision of information and perceived trust and confidence in the vaccine safety, effectiveness and government approach to control the disease.

    The aim of chapter 5 was to explore factors that could explain heterogeneity in farmers’ attitudinal beliefs. In particular, perceived risk, measured by a relative risk attitude and risk perception, and the Big Five personality traits were associated with variability in these beliefs. Conscientiousness discriminated farmers into a group of ‘vaccination intenders’ and non-intenders although it remained somewhat unclear how it relates to the decision problem, as it can be a sense of duty, achievement striving or both. The perceived risk measures were related to the milk production intensity and also discriminated intenders from non-intenders. These differences in perceived risk indicated that farmers might not be commonly risk averse, however, it is important to account for the domain specificity of risk taking behaviour.

    A survey-based discrete choice experiment was used in chapter 6 to study more deeply farmers’ choices for different voluntary bluetongue vaccination scheme designs. A generalised random utility model of farmers’ behaviour allowed for heterogeneity in motives to invest in bluetongue disease control. Results showed that farmers have private economic motives (incentives) to participate in a vaccination scheme, such as to insure the production risk from disease infection and to maintain the export of heifers.

    Interaction effects found between social-psychological constructs and specific designs of policy instruments highlighted the importance of perceived trust and confidence in the vaccine safety and effectiveness and in the disease control strategy chosen by animal health authorities. Attitude interacted positively with government communication (information) provided via veterinarians. Descriptive norm interacted positively with a lower perceived probability of adverse effects. This suggests that farmers are more likely to vaccinate if they perceive that others in their social network perform vaccination without experiencing adverse effects. Injunctive norm interacted negatively with a higher level of government subsidy. This suggested a crowding-out mechanism through which subsidization adversely affect farmer’s motivation to comply with the vaccination policy.

    The interplay between farmers’ collective behaviour and bluetongue disease epidemiology was studied in chapter 7 with an agent-based model. The utility model specification from chapter 6 was used to describe the decision-making process of farmers. Other components that added to the dynamic nature of the model were a social network structure of the diffusion process of sharing information about vaccination status and a susceptible-latent-infectious-recovered model of disease spread. The effectiveness of different bluetongue vaccinations scheme designs was studied as measured by disease rate and vaccination uptake.

    Results of chapter 7 showed that vaccination schemes that focus more on motivating farmers via informational instruments were somewhat more effective than predicted from the comparative static analysis in chapter 6. Motivation via financial incentives resulted in a somewhat lower effectiveness than was predicted from that same model. This might be explained as an emergent effect that evolves under specific vaccination scheme designs from the interactions between farmers themselves and with the environment from which they observe the progress of the disease. These schemes focus more on serving the information needs of farmers and raising the perceived trust and confidence in the disease control approach rather than on incentivising with higher levels of subsidy.

    Three themes for livestock disease control emerged from the synthesis of the results in chapter 8, which were subsequently discussed in relation to the wider economic and (social) psychological literature. These themes coincide with shortcoming of the standard economic model of rational choice to describe and predict behaviour. The first theme was about understanding how farmers cope with risk in the context of livestock diseases. The second theme focused on the usefulness of financial compensation as a policy instrument. The third theme discussed the role of trust and social norms. After discussing the implications for policy making, main scientific contributions and suggestions for future research, the chapter concluded that:

    Dutch dairy farmers who operate large-scale and intensive farms or keep heifers for export are likely to have private economic motives to vaccinate against bluetongue (Chapter 2, 4, 5 and 6).Farmers’ willingness to vaccinate against bluetongue is mostly driven by attitude, followed by perceived social pressures from injunctive norms and descriptive norms. This implies farmers can be motivated intrinsically, extrinsically, or both (Chapter 3).Dutch dairy farmers have intrinsic motives to vaccinate against bluetongue. They do not want to be confronted with animal suffering but want to keep job satisfaction high from working with healthy animals (Chapter 4).Dutch dairy farmers have social motives to vaccinate against bluetongue. They consider what important referents, such as the veterinarian or family members, think they should do and take into account the perceived behaviour of peers (Chapter 3 and 4).

    Perceived risk, personality traits and past behaviour are important behavioural variables for explaining the heterogeneity in beliefs to vaccinate against bluetongue (Chapter 5).

    The efficacy of financial, incentive based instruments to motivate to vaccinate against bluetongue is heterogeneous and not necessarily positive for each farmer. They are not effective if farmers already expect a positive net benefit from vaccination or if they crowd-out the motivation to comply with the vaccination policy (Chapter 2, 4, 6, 7).

    The efficacy of informational policy instruments to motivate farmers to vaccinate against bluetongue is positively affected by farmers’ attitude towards vaccination and in case farmers perceive the communication channels used as credible and trustworthy (Chapter 3, 4, 6).

    The efficacy of social interaction mechanisms in policy making, such as the perceived social pressuretovaccinateagainstbluetongue,ispositivelyaffectedbyfarmers’trustandconfidence in the government approach to control the disease (Chapter 4, 6, 7).

    On the role of vaccine dose and antigenic distance in the transmission dynamics of Highly Pathogenic Avian Influenza (HPAI) H5N1 virus and its selected mutants in vaccinated animals
    Sitaras, Ioannis - \ 2017
    Wageningen University. Promotor(en): M.C.M. Jong, co-promotor(en): B. Peeters. - Wageningen : Wageningen University - ISBN 9789463438063 - 209
    avian influenza viruses - avian influenza - disease transmission - vaccines - vaccination - dosage - antigenic variation - mutants - mutations - immunity - vaccine development - virology - epidemiology - aviaire influenzavirussen - aviaire influenza - ziekteoverdracht - vaccins - vaccinatie - dosering - antigene variatie - mutanten - mutaties - immuniteit - vaccinontwikkeling - virologie - epidemiologie

    Influenza virus infections can cause high morbidity and mortality rates among animals and humans, and result in staggering direct and indirect financial losses amounting to billions of US dollars. Ever since it emerged in 1996 in Guangdong province, People’s Republic of China, one particular highly pathogenic avian influenza (HPAI) H5N1 virus has spread globally, and is responsible for massive losses of poultry, as well as human infections. For these reasons, HPAI H5N1 is considered as one of the viruses possible to cause a future influenza pandemic.

    One of the main reasons why influenza is a recurring problem is its ability to constantly evolve through the selection of mutants that are able to avoid immunity (be it natural or acquired). Due to the accumulation of mutations during genome replication, diverse/variant influenza genome sequences co-exist in a virus pool (quasispecies). These sequences can contain mutations that are able to confer selective advantages to the influenza virus given the opportunity. As a consequence, whenever a situation arises that places the virus under any type of pressure that the dominant virus sequence cannot cope with (i.e. immune pressure, selective receptor binding, etc.), the virus with the genome sequence that allows it to better adapt to that particular pressure becomes selected and takes over.

    Because of the influenza virus’s high rate of mutations, a global surveillance network is in place to monitor changes in circulating strains among humans that would warrant an update of the vaccines used. For human influenza strains, vaccines are updated frequently (every one or two years) and a similar situation holds true for racehorse vaccination. For avian influenza vaccination, however, the situation is different. In most countries, vaccination against avian influenza is not used, and in the countries where vaccines are used (either as routine or emergency measures), they are not updated as frequently as human vaccines are. In addition, in many instances vaccination against avian influenza viruses has met with some spectacular failures, since it failed to produce a level of immunity that would protect against circulating field strains. These vaccination failures have often been attributed to the fact that without constant vaccine updating (as is done for human influenza), the vaccines used are not able to keep up with continuously evolving antigenic variants selected in the field, and thus to protect poultry against them. In addition, since it is known that immune pressure resulting from vaccination can be a driving force in the evolution of influenza viruses and the selection of immune-escape mutants, there is a school of thought that posits that vaccination against avian influenza is not only a very expensive affair (especially if vaccines need to be frequently updated), but can also lead to selection of mutants that are able to avoid vaccination-induced immunity.

    The research reported in this thesis started with addressing the gaps in the knowledge regarding the role of vaccination-induced immunity in the selection of immune-escape mutants of HPAI H5N1, and if there is a way for vaccines to still be able to protect against antigenically-distant variants of the vaccine seed strain, without the need for frequent vaccine updates.

    Our first step in studying influenza virus evolution and selection of immune-escape mutants was to investigate how antigenic pressure may drive the selection of such mutants, and what the effect of the selected mutations on the pathogenicity and transmissibility of the mutants may be. Although there exist a variety of methods to select for influenza virus mutations (i.e. monoclonal antibodies, site-directed mutagenesis, reverse genetics, etc.), none of them is representative of selection as it happens in a vaccinated animal. In Chapter 2, we discuss in detail a laboratory-based system we have developed, in which immune-escape mutants are selected using homologous polyclonal chicken sera, similar to how they are selected in the field due to vaccination- induced immune pressure. We find that selection takes place early on, and additional mutations are selected when immune pressure is increased. Antigenic distances between the selected mutants and their parent strains are also increased throughout the selection process, but not in a linear fashion. Our selection system proved to be robust and replicable, and to be representative of selection in the field, since the mutations we selected for are also found in naturally-selected field isolates, and the antigenic distances between our selected mutants and their parent strains are similar to antigenic distances between vaccine strains and field isolates.

    We continued our research by addressing the roles played by vaccine dose (and resulting immunity) and antigenic distance between vaccine and challenge strains, in the transmission of HPAI H5N1 viruses, by employing transmission experiments using vaccinated chickens (Chapter 3). To our surprise, we found that the effect of antigenic distances between vaccine and challenge strains on transmission is very small compared to the effect of vaccine dose. We then quantified, for the first time, the minimum level of immunity and minimum percentage of the vaccinated population exhibiting said immunity, in order for vaccines to be able to protect against transmission even of strains that are antigenically distant to the vaccine seed strain. Transmission of such strains in well-vaccinated populations would allow for a scenario where vaccination- induced immunity may drive the selection of immune-escape mutants. Our results show that in order for vaccines to prevent transmission of antigenically distant strains (such as the ones resulting from selection due to immune pressure), the threshold level of immunity against these strains should be ≥23 haemagglutination inhibition units (HIU), in at least 86.5% of the vaccinated population. This level of immunity can be estimated by knowing the antigenic distance between the vaccine and challenge (field) strain, and the HI titre against the vaccine strain, which would then allow the approximate level of immunity against the field strain to be deduced. For example, assuming the HI titre against a vaccine strain is 210 HIU, and the distance with the challenge (field) strain is 24 HIU, according to our results the vaccine should be able to protect against the challenge strain, because the difference in HI titres should be around 26 HIU (i.e. above 23 HIU). These results, taken together with our previous work on selection of mutants, where we showed that the antigenic distances between our mutants and their parent strains are representative of distances found in the field, point to the fact that it is unlikely that vaccination-induced immunity can lead to selection of mutants able to escape it, given that a threshold level of immunity in a minimum percentage of the vaccinated population is achieved. As a consequence, we believe that constant vaccine updating may not be necessary for avian influenza viruses, as long as a threshold level of immunity is maintained. This makes vaccination a more attractive control measure, both from a health perspective and a financial one, than just applying biosecurity measures.

    To examine the effect the mutations in the haemagglutinin protein of our selected mutants may have in their transmission among chickens vaccinated with the parent strain, we used reverse genetics techniques to insert the HA gene of our most antigenically distant mutant into the parent strain backbone (Chapter 4). We vaccinated animals with a sub-optimal dose of vaccine, and we concluded that the mutations we selected for did not allow the mutant to avoid even low levels of immunity, such as the ones resulting from a sub-optimal vaccine dose (which resembles a poor field vaccination scenario). At the same time, the HA mutations we selected for did not appear to have a negative effect either on the pathogenicity of the mutant, or its ability to transmit to unvaccinated animals, since both parameters were comparable to the parent strain.

    Finally, we studied the role inter-animal variation in immunity – as measured by HI titres – has in the accuracy of antigenic cartography calculations (Chapter 5). We found that using sera from more than one animal significantly increased the accuracy of antigenic distance calculations, since it takes into account individual differences in immune responses to vaccination, an inevitable phenomenon documented in both humans and animals. In addition, we increased the accuracy of antigenic maps by avoiding the use of dimension-reducing algorithms as is currently done. By not reducing the dimensionality of virus positioning in space, our maps retain the original geometry between strains or sera, leading to more accurate positioning (Chapters 2 and 5). We hope that improving the accuracy of antigenic cartography can lead to a more precise surveillance of influenza evolution and better informed decisions regarding the need to update vaccines.

    Taken collectively, our results can improve field vaccination outcomes, since they provide guidelines on how to increase vaccination efficiency in stopping transmission of even antigenically-distant strains. In addition, our method for selecting for immune- escape mutants can be a valuable addition to research on influenza virus evolution. Moreover, policy making decisions regarding vaccination against any type of influenza can also benefit from our improvement on antigenic cartography accuracy, saving unnecessary costs in vaccine updating, and reducing morbidity and mortality of both animals and humans.

    Socio-economic modelling of rabies control in Flores Island, Indonesia
    Wera, Ewaldus - \ 2017
    Wageningen University. Promotor(en): Henk Hogeveen, co-promotor(en): Monique Mourits. - Wageningen : Wageningen University - ISBN 9789463430586 - 182
    rabies - rabies virus - control programmes - control methods - dogs - indonesia - decision making - vaccination - hondsdolheid - hondsdolheidvirus - bestrijdingsprogramma's - bestrijdingsmethoden - honden - indonesië - besluitvorming - vaccinatie

    Rabies is a zoonotic viral disease that can cause encephalomyelitis both in animals and humans. Since its introduction in Flores Island, Indonesia in 1997, it has been a serious public health threat with significant economic consequences. To control the disease, annual dog vaccination campaigns have been implemented to vaccinate all dogs free of any charge. Nevertheless, the campaigns have not been successful in eliminating rabies from the island.

    The main objective of this dissertation was to support future decisions on the control of rabies in Flores Island by providing insight into the role of socio-demographic and psychological factors of dog owners in the uptake of rabies control measures and by analyzing the cost-effectiveness of alternative mass dog vaccination strategies.

    By means of a cost accounting model, the costs of the currently applied rabies control measures in Flores Island were estimated at US$1.12 million (range: US$0.60–1.47 million) per year. The costs of culling roaming dogs resulted in the highest cost portion (39%), followed by the costs of post-exposure treatment (35%) and mass vaccination (24%).

    Risk factors associated with the uptake level of rabies control measures were analysed based upon an extensive survey among 450 dog-owners in the regencies of Sikka and Manggarai. Only 52% of these dog owners had at least one of their dogs vaccinated during the 2012 vaccination campaign. Vaccination uptake was significantly higher for dog owners who resided in Sikka, kept female dogs for breeding, had a monthly income of more than one million rupiah, and had easy access to their village.

    A study based on the Theory of Planned Behaviour demonstrated that the actual intention of dog owners to participate in a free-of-charge vaccination campaign was high (> 90%). The attitude item ‘vaccinating dogs reduces rabies cases in humans’, and the perceived behavioural control items ‘availability of time’ and ‘ability to confine dogs’ were shown to be significantly associated with this intention level. Relevant considerations to improve the participation level in future vaccination campaigns are therefore appropriate time management as well as the provision of skills to confine dogs during the vaccination.

    The cost-effectiveness of different mass dog vaccination strategies was evaluated by means of a deterministic model simulating transmission of rabies virus through the dog population of one village. Annual vaccination using a short-acting vaccine at a coverage of 50% was far from being cost-effective, suggesting that the currently applied rabies control in Flores Island is not an efficient investment in reducing human rabies burden. An increased investment in either an increase in the current coverage or in a switch from the short-acting vaccine to the long-acting vaccine type would certainly pay off.

    Intramammary immunization with ultraviolet-killed Escherichia coli shows partial protection against late gestation intramammary challenge with a homologous strain
    Pomeroy, B. ; Gurjar, A. ; Sipka, A. ; Klaessig, S. ; Salmon, S. ; Quesnell, R. ; Schukken, Y.H. - \ 2016
    Journal of Dairy Science 99 (2016)11. - ISSN 0022-0302 - p. 9014 - 9026.
    Escherichia coli - late gestation - mastitis - vaccination

    The objective of this study was to evaluate the efficacy of intramammary immunization with UV-killed Escherichia coli ECC-Z on prevention of intramammary colonization after a challenge with a dose of the homologous E. coli ECC-Z live bacteria. A total of 10 cows were included in a study to evaluate the efficacy of intramammary immunization. All 10 cows received an intramammary immunization of 100 cfu of UV-killed E. coli ECC-Z bacteria into one hind quarter at the time of dry off. Approximately 2 wk before the anticipated calving date, both hind quarters of all cows were challenged with 100 cfu of live E. coli ECC-Z bacteria. Five of the cows were vaccinated parenterally with a commercial J5 bacterin, and 5 cows served as controls with no parenteral vaccination. The cows were then followed over time and infection risk, clinical scores, somatic cell count, and milk production were observed over time. The results of these 10 cows showed partial protection of intramammary immunization on the outcome of a subsequent homologous intramammary challenge. Immunization resulted in a lower probability of infection, a lower bacteria count, lower somatic cell counts and milk conductivity, a lower clinical mastitis score, and increased milk production compared with unimmunized control quarters. Once the analysis was corrected for immunization, parenteral J5 vaccination had no significant effect on any of the measured parameters. These results provide the first evidence that intramammary immunization may improve the outcome of an intramammary E. coli infection in late gestation and onset of mastitis immediately following parturition. Unlike systemic vaccination, which generally does not reduce the intramammary infection risk, the intramammary immunization did show a 5-times reduced odds of an established intramammary infection after challenge. Cytokine profiles indicated a local return of proinflammatory response after challenge as the data showed a more pronounced increase in in IFN-γ with a subsequent negative feedback due to a spike in the level of IL-10 in immunized quarters relative to nonimmunized quarters. Although these results are preliminary and obtained on only 10 cows, the results provide insight into the biological benefits of triggering mucosal immunity in the mammary gland.

    Financial analysis of brucellosis control for small-scale goat farming in the Bajio Region, Mexico
    Oseguera Montiel, D. ; Bruce, M. ; Frankena, K. ; Udo, H.M.J. ; Zijpp, A.J. van der; Rushton, J. - \ 2015
    Preventive Veterinary Medicine 118 (2015)4. - ISSN 0167-5877 - p. 247 - 259.
    bovine brucellosis - serological tests - economic-impact - risk-factors - melitensis - vaccination - health
    Brucellosis is an endemic disease in small-scale goat husbandry systems in Mexico. It is a zoonosis and the economic consequences can be large, although estimates are not available for the Mexican goat sector. Our objective was to conduct a financial analysis of brucellosis control in a prominent dairy goat production area of the Bajío region, Mexico. We used three models: (1) a brucellosis transmission model at village flock level (n = 1000 head), (2) a flock growth model at smallholder flock level (n = 23 head) using output of model 1 and (3) cost-benefit analysis of several brucellosis control scenarios based on output of model 2. Scenarios consisted of test-and-slaughter or vaccination or a combination of both compared to the base situation (no control). The average net present values (NPV) of using vaccination over a five-year period was 3.8 US$ (90% CI: 1.3 – 6.6) and 20 US$ (90% CI: 11.3 – 28.6) over a ten- year period per goat. The average benefit-cost ratios over a five-year period and ten- year period were 4.3 US$ (90% CI: 2.2 – 6.9) and 12.3 US$ (90% CI: 7.5 – 17.3) per goat, respectively. For the total dairy goat population (38,462 head) of the study area (the Bajío of Jalisco and Michoacán) the NPV’s over a five-year and ten-year period were 0.15 million US$ and 0.8 million US$. However, brucellosis prevalence was predicted to remain relatively high at about 12%. Control scenarios with test-and-slaughter predicted to reduce brucellosis prevalence to less than 3%, but this produced a negative NPV over a five-year period ranging from -31.6 to -11.1 US$ and from -31.1 to 7.5 US$ over a ten-year period). A brucellosis control campaign based on vaccination with full coverage is economically profitable for the goat dairy sector of the region although smallholders would need financial support in case test-and-slaughter is applied to reduce the prevalence more quickly.
    Economic Analysis of HPAI Control in the Netherlands II: Comparison of Control Strategies
    Longworth, N.J. ; Mourits, Monique C.M. ; Saatkamp, H.W. - \ 2014
    Transboundary and Emerging Diseases 61 (2014)3. - ISSN 1865-1674 - p. 217 - 232.
    pathogenic avian influenza - poultry farms - mouth-disease - epidemic - virus - transmission - vaccination - simulation - spread - h7n7
    A combined epidemiological-economic modelling approach was used to analyse strategies for highly pathogenic avian influenza (HPAI) control for the Netherlands. The modelling framework used was InterSpread Plus (ISP), a spatially based, stochastic and dynamic simulation model. A total of eight control strategies were analysed, including pre-emptive depopulation and vaccination strategies. The analysis was carried out for three different regions in the Netherlands: high-, medium- and low-density areas (HDA, MDA and LDA, respectively). The analysis included the veterinary impact (e.g. number of infected premises and duration), but was particularly focused on the impact on direct costs (DC) and direct consequential costs. The efficient set of control strategies for HDA and MDA included strategies based on either pre-emptive depopulation only or combined vaccination and pre-emptive depopulation: D2 (pre-emptive depopulation within a radius of 2 km), RV3 + D1 (ring vaccination within a radius of 3 km and additional pre-emptive depopulation within a radius of 1 km) and PV + D1 (preventive vaccination in non-affected HDAs and pre-emptive depopulation within a radius of 1 km in the affected HDA). Although control solely based on depopulation in most cases showed to be effective for LDA, pre-emptive depopulation showed to have an additional advantage in these areas, that is, prevention of 'virus jumps' to other areas. The pros and cons of the efficient control strategies were discussed, for example, public perception and risk of export restrictions. It was concluded that for the Netherlands control of HPAI preferably should be carried out using strategies including pre-emptive depopulation with or without vaccination. Particularly, the short- and long-term implications on export, that is, indirect consequential costs (ICC) and aftermath costs of these strategies, should be analysed further.
    Contagious animal diseases: The science behind trade policies and standards (Personal View)
    Boqvist, S. ; Dekker, A. ; Depner, K. ; Grace, D. ; Hueston, W. ; Stark, K.D.C. ; Sternberg Lewerin, S. - \ 2014
    The Veterinary Journal 202 (2014)1. - ISSN 1090-0233 - p. 7 - 10.
    pcr detection methods - swine-fever virus - mouth-disease - ring test - vaccination - transmission - products - drivers - impacts - trends
    Economics of eradicating Foot-and-Mouth disease epidemics with alternative control strategies
    Bergevoet, R.H.M. ; Asseldonk, M.A.P.M. van - \ 2014
    Archivos de Medicina Veterinaria 46 (2014)3. - ISSN 0301-732X - p. 381 - 388.
    vaccination - consequences - model
    The paper presents an economic analysis of Foot-and-Mouth Disease (FMD) control strategies for livestock herds. Alternative vaccination-to-live control strategies were compared to the strategy that involves culling of all susceptible animals in an area of 1 km around infected herds in addition to standard measures as culling of infected herds, pre-emptive slaughter of contact herds, establishment of control and surveillance zones. Vaccination strategies differed with respect to the radius of vaccination around infected farms (2 km versus 5 km). As an example to illustrate the economic consequences the Netherlands was used. These strategies were evaluated for a Sparsely Populated Livestock Areas (SPLA) with less than 2 farms/km2 and a Densely Populated Livestock Areas (DPLA) with more than 4 farms/km2. Results of the partial budgeting FMD model revealed that for DPLA a control strategy which includes a vaccination radius of 2 km is most cost effective. For SPLA a control strategy which includes a 1 km culling radius around an infected farm is most cost effective.
    Economic impact of foot and mouth disease outbreaks onsmallholder farmers in Ethiopia
    Jemberu, W.T. ; Mourits, Monique C.M. ; Woldehanna, T. ; Hogeveen, H. - \ 2014
    Preventive Veterinary Medicine 116 (2014)1-2. - ISSN 0167-5877 - p. 26 - 36.
    southern cambodia - livelihoods - vaccination
    Foot and mouth disease is endemic in Ethiopia with occurrences of several outbreaks everyyear. Quantitative information about the impact of the disease on smallholder farming sys-tems in the country is, however, scarce. This study presents a quantitative assessment ofthe clinical and direct economic impacts of foot and mouth disease outbreaks on house-hold level in smallholder livestock farming systems. Impacts were assessed based on dataobtained from case outbreaks in cattle in crop–livestock mixed and pastoral smallholderfarming systems that occurred in 2012 and 2013. Data were collected by using question-naires administered to 512 smallholder farmers in six districts within two administratezones that represent the two smallholder farming systems. Foot and mouth disease morbid-ity rates of 85.2% and 94.9% at herd level; and 74.3% and 60.8% at animal level in the affectedherds were determined for crop–livestock mixed system and pastoral system, respectively.The overall and calf specific mortality rates were 2.4% and 9.7% for the crop–livestock mixedsystem, and 0.7% and 2.6% for the pastoral system, respectively. Herd level morbidity ratewas statistically significantly higher in the pastoral system than in the crop–livestock mixedsystem (P <0.001). The economic losses of foot and mouth disease outbreak due to milkloss, draft power loss and mortality were on average USD 76 per affected herd and USD 9.8per head of cattle in the affected herds in crop–livestock mixed system; and USD 174 peraffected herd and USD 5.3 per head of cattle in the affected herds in the pastoral system.The herd level economic losses were statistically significantly higher for the pastoral sys-tem than for the crop–livestock mixed system (P <0.001). The major loss due to the diseaseoccurred as a result of milk losses and draft power losses whereas mortality losses wererelatively low. Although the presented estimates on the economic losses accounted only forthe visible direct impacts of the disease on herd level, these conservative estimates signifya potential socioeconomic gain from a control intervention.
    Good memories for details improve fish health
    Wiegertjes, G.F. - \ 2014
    Wageningen : Wageningen University, Wageningen UR - ISBN 9789461739759 - 20
    vissen - diergezondheid - immunologie - aquacultuur - celbiologie - vaccinatie - fishes - animal health - immunology - aquaculture - cellular biology - vaccination
    Immune escape mutants of highly pathogenic avian influenza H5N1 selected using polyclonal sera: Identification of key amino acids in the HA protein
    Sitaras, I. ; Kalthof, D. ; Beer, M. ; Peeters, B.P.H. ; Jong, M.C.M. de - \ 2014
    PLoS ONE 9 (2014)2. - ISSN 1932-6203 - 13 p.
    virus hemagglutinin - antigenic drift - a viruses - monoclonal-antibodies - evolution - poultry - egypt - vaccination - molecule - neutralization
    Evolution of Avian Influenza (AI) viruses – especially of the Highly Pathogenic Avian Influenza (HPAI) H5N1 subtype – is a major issue for the poultry industry. HPAI H5N1 epidemics are associated with huge economic losses and are sometimes connected to human morbidity and mortality. Vaccination (either as a preventive measure or as a means to control outbreaks) is an approach that splits the scientific community, due to the risk of it being a potential driving force in HPAI evolution through the selection of mutants able to escape vaccination-induced immunity. It is therefore essential to study how mutations are selected due to immune pressure. To this effect, we performed an in vitro selection of mutants from HPAI A/turkey/Turkey/1/05 (H5N1), using immune pressure from homologous polyclonal sera. After 42 rounds of selection, we identified 5 amino acid substitutions in the Haemagglutinin (HA) protein, most of which were located in areas of antigenic importance and suspected to be prone to selection pressure. We report that most of the mutations took place early in the selection process. Finally, our antigenic cartography studies showed that the antigenic distance between the selected isolates and their parent strain increased with passage number.
    Identification of factors associated with increased excretion of foot-and-mouth disease virus
    Bravo De Rueda, C. ; Dekker, A. ; Eble, P.L. ; Jong, M.C.M. de - \ 2014
    Preventive Veterinary Medicine 113 (2014)1. - ISSN 0167-5877 - p. 23 - 33.
    immune-responses - dairy-cows - transmission - vaccination - pigs - infection - quantification - epidemiology - calves - lambs
    We investigated which variables possibly influence the amount of foot-and-mouth disease virus (FMDV) shed in secretions and excretions by FMDV infected animals, as it is likely that the amount of FMDV shed is related to transmission risk. First, in a separate analysis of laboratory data, we showed that the total amount of FMDV in secretions and excretions from infected animals is highly correlated with maximum titres of FMDV. Next, we collected data from 32 published scientific articles in which FMDV infection experiments were described. The maximum titres of FMDV reported in different secretions and excretions (the response variable) and the experimental conditions in which they occurred (the explanatory variables), were recorded in a database and analyzed using multivariate regression models with and without random effects. In both types of models, maximum titres of FMDV were significantly (p <0.05) associated with types of secretions and excretions, animal species, stage of the disease and days post infection. These results can be used to prioritize biosecurity measures in contingency plans.
    Immune adjuvants as critical guides directing immunity triggered by therapeutic cancer vaccines
    Schijns, V.E.J.C. ; Tartour, E. ; Michalek, J. ; Stathopoulos, A. ; Dobrovolskiene, N.T. ; Strioga, M.M. - \ 2014
    Cytotherapy 16 (2014)4. - ISSN 1465-3249 - p. 427 - 439.
    dendritic cells induce - human langerhans cells - cd8 t-cells - melanoma patients - messenger-rna - lymph-nodes - in-vivo - alpha-galactosylceramide - antigen - vaccination
    Tumor growth is controlled by natural antitumor immune responses alone or by augmented immune reactivity resulting from different forms of immunotherapy, which has demonstrated clinical benefit in numerous studies, although the overall percentage of patients with durable clinical responses remains limited. This is attributed to the heterogeneity of the disease, the inclusion of late-stage patients with no other treatment options and advanced tumor-associated immunosuppression, which may be consolidated by certain types of chemotherapy. Despite variable responsiveness to distinct types of immunotherapy, therapeutic cancer vaccination has shown meaningful efficacy for a variety of cancers. A key step during cancer vaccination involves the appropriate modeling of the functional state of dendritic cells (DCs) capable of co-delivering four critical signals for proper instruction of tumor antigen–specific T cells. However, the education of DCs, either directly in situ, or ex vivo by various complex procedures, lacks standardization. Also, it is questioned whether ex vivo–prepared DC vaccines are superior to in situ–administered adjuvant-guided vaccines, although both approaches have shown success. Evaluation of these variables is further complicated by a lack of consensus in evaluating vaccination clinical study end points. We discuss the role of signals needed for the preparation of classic in situ and modern ex vivo DC vaccines capable of proper reprogramming of antitumor immune responses in patients with cancer.
    Economic assessment of Q fever in the Netherlands
    Asseldonk, M.A.P.M. van; Prins, J. ; Bergevoet, R.H.M. - \ 2013
    Preventive Veterinary Medicine 112 (2013)1-2. - ISSN 0167-5877 - p. 27 - 34.
    vaccination - epidemics - zoonosis - benefits - outbreak - disease - burden
    In this paper the economic impact of controlling the Q fever epidemic in 2007-2011 in the Netherlands is assessed. Whereas most of the long-term benefits of the implemented control programme stem from reduced disease burden and human health costs, the majority of short-term intervention costs were incurred in the dairy goat sector. The total intervention cost in agriculture amounted approximately 35,000 Euro per DALY occurred. By culling of infected animals, breeding prohibition and vaccination, the epidemic seems to be under control. As the dairy goat vaccination programme continues, future expenses in maintaining the current protected status are relatively low. (C) 2013 Elsevier B.V. All rights reserved.
    C-strain vaccination against Classical Swine Fever: effects on epidemic and final screening
    Backer, J.A. ; Loeffen, W.L.A. ; Roermund, H.J.W. van - \ 2013
    Lelystad : Central Veterinary Institute
    varkenshouderij - klassieke varkenspest - vaccinatie - verspreide infecties - ziekteoverdracht - pig farming - classical swine fever - vaccination - disseminated infections - disease transmission
    In this project it is evaluated how the use of C-strain vaccine instead of E2-subunit vaccine will affect the effectiveness of controlling Classical Swine Fever (CSF). To this end a CSF transmission model was developed that describes virus transmission on three different levels: between animals, between pens and between herds. The results of transmission and vaccination experiments as well as the data from the 1997/1998 CSF epidemic in The Netherlands serve to parameterize the model. With the model hypothetical epidemics are simulated under different scenarios.
    Assessing and controlling health risks from animal husbandry
    Kimman, T.G. ; Hoek, M. ; Jong, M.C.M. de - \ 2013
    NJAS Wageningen Journal of Life Sciences 66 (2013)SI. - ISSN 1573-5214 - p. 7 - 14.
    resistant staphylococcus-aureus - virus transmission - infectious-diseases - quantification - vaccination - origin - netherlands - emergence - pathogens - vaccines
    A fierce debate is going on about the risks of animal husbandry for human health and the quality of control measures to reduce such risks. Risks include the occurrence of infectious diseases, in particular zoonoses, and the high antibiotic use in livestock production contributing to emergence of antibiotic resistance and its spread from animals to humans. On the other hand, many infectious diseases of animals and humans have been eliminated, including brucellosis, tuberculosis, leptospirosis, and BSE, resulting in an animal husbandry that perhaps has never been as safe as nowadays. So while many health risks have been brought under control, the public opinion appears to reflect a feeling of anxiety and mistrust in authorities and producers to deal with the potential and remaining public health risks associated with animal husbandry. These risks, often associated with the intensification of animal production, are nonetheless indeed real. An animal husbandry that is “completely” safe and healthy for humans and animals requires a central role for disease prevention in the design and management of animal husbandry systems. It also requires that rapid and adequate responses are taken by veterinary and medical authorities on both perceived and real risks. Communication on health risks must be complete and open. Because actions to protect the health of animals often also benefit human health, there is usually no conflict of interests between humans and animals regarding their health needs. We emphasize the need to use the precautionary principle in matters of human and animal health. This implies that there must not be a “clash of cultures” between medical and veterinary professionals and policy makers.
    Hoe - naar modern inzicht - een garnalenkwekerij op te zetten? : Gesprek met viroloog prof.dr. Just M. Vlak, over WSSV en de immunologische weerstand van een garnaal
    Vlak, Just - \ 2013
    shrimps - shrimp culture - white spot syndrome virus - animal viruses - vaccination - immunology - immune system
    Rapid generation of replication-deficient monovalent and multivalent vaccines for bluetongue virus: protection against virulent virus challenge in cattle and sheep
    Celma, C.C.P. ; Boyce, M. ; Rijn, P.A. van; Eschbaumer, M. ; Wernike, K. ; Hoffmann, B. ; Beer, M. ; Clercq, K. De; Roy, P. - \ 2013
    Journal of Virology 87 (2013)17. - ISSN 0022-538X - p. 9856 - 9864.
    time rt-pcr - synthetic rna - particles - europe - vaccination - serotype-8 - strains - epidemic - proteins - efficacy
    Since 1998, nine of the 26 serotypes of bluetongue virus (BTV) have spread throughout Europe and serotype 8 has suddenly emerged in northern Europe causing considerable economic losses, both direct (mortality and morbidity) but also indirect due to restriction in animal movements. Therefore many new types of vaccines, particularly subunit vaccines, with improved safety and efficacy for a broad range of BTV serotypes are currently being developed by different laboratories. Here we exploited a reverse genetics-based replication-deficient BTV-1 serotype (disabled infectious single cycle, DISC) to generate a series of DISC vaccine strains. Cattle and sheep were vaccinated with these viruses either singly or in cocktail as multivalent vaccine candidate. All vaccinated animals were seroconverted and developed a neutralizing antibody response against their respective serotype. After challenge with the virulent strains at 21 days post vaccination vaccinated animals showed neither any clinical reaction nor viremia. Further, there was no interference in protection with a multivalent preparation of six distinct DISC viruses. These data indicate that a very rapid response vaccine could be developed based on which serotypes are circulating in the population at the time of an outbreak.
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