Trial design to estimate the effect of vaccination on tuberculosis incidence in badgers

The principal wildlife reservoir of Mycobacterium bovis in Ireland is the European badger. Studies in the Republic of Ireland (RoI) have shown that badgers culled in association with cattle herd tuberculosis breakdowns (focal culling) have a higher prevalence of infection than the badger population at large. This observation is one rationale for the medium term national strategy of focal badger culling. A vaccination strategy for the control of bovine tuberculosis (bTB) in badgers is a preferred long-term option. The Bacillus Calmette-Guérin (BCG) vaccine has been shown to decrease disease severity in captive badgers under controlled conditions. As the vaccine has been tested in a controlled environment with precise information on infection pressure, it cannot be assumed a priori that the effects of vaccination are similar in the wild, where other environmental and/or ecological factors prevail. For this reason we have designed a vaccine field trial to assess the impact of vaccination on the incidence of TB infection in a wild badger population. The selected study area for the vaccine trial (approximately 755 square kilometers) is divided into three zones each of which has similar characteristics in terms of size, number of main badger setts, cattle herds, cattle and land classification type. Three vaccination levels (100%, 50% and 0%) will be allocated to the three zones in a way that a gradient of vaccination coverage North to South is achieved. The middle zone (zone B) will be vaccinated at a 50% coverage but zone A and C will be randomly allocated with 100% or 0% vaccination coverage. Vaccination within zone B will be done randomly at individual badger level. The objective of this paper is to describe the design of a field tuberculosis vaccination trial for badgers, the epidemiological methods that were used to design the trial and the subsequent data analysis. The analysis will enable us to quantify the magnitude of the observed vaccination effect on M. bovis transmission in badgers under field conditions and to improve our knowledge of the biological effects of vaccination on susceptibility and infectiousness.     

Advances and prospects for management of TB transmission between badgers and cattle

Bovine tuberculosis (bTB) is the most serious endemic disease facing the livestock industry in the United Kingdom (UK) and Republic of Ireland (RoI), where its management has been confounded by the presence of persistent infection in the Eurasian badger (Meles meles). Field evidence suggests that the social structure of badger populations can have an important influence on disease dynamics, and on the outcome of management interventions. Recent, large-scale badger culling experiments in the UK and RoI had complex epidemiological outcomes. In the UK, proactive culling led to reduced bTB incidence in cattle herds inside culled areas, but a temporary increase in adjacent areas. Reactive culling in response to herd breakdowns was associated with an increase in the incidence of bTB in cattle. In contrast, badger culling in RoI was reported to have only beneficial effects on bTB incidence in cattle. The reasons for these differences are not clear. The complexity of the evidence base for culling is highlighted by the different management approaches currently being adopted by the different authorities of the UK and RoI. It is generally accepted that a holistic approach to bTB management, which targets both cattle and wildlife, is necessary. Consequently recent research activities have also focussed on cattle and badger vaccines, and biosecurity on farms. This paper describes recent advances in our understanding of the epidemiology of bTB in badgers and the consequences of culling, and current research to develop approaches for the vaccination of badgers, and methods of managing the risks of contact between badgers and cattle in farm buildings.     

An ecological and comparative perspective on the control of bovine tuberculosis in Great Britain and the Republic of Ireland

Disease ecology involves a systematic approach to understanding the interactions and evolution of host-pathogen systems at the population level, and is essential for developing a comprehensive understanding of the reasons for disease persistence and the most likely means of control. This systems or ecological approach is being increasingly recognised as a progressive method in disease control and is exploited in diverse fields ranging from obesity management in humans to the prevention of infectious disease in animal populations. In this review we discuss bovine tuberculosis (bTB) in Great Britain (GB) within a disease ecology context, and suggest how a comparative ecological perspective helps to reconcile apparent conflicts with the evidence on the effectiveness of badger culling to assist in the control of bTB in GB and the Republic of Ireland (ROI). Our examination shows that failure of past measures to control bTB and the disparity in outcomes of badger culling experiments are the result of a complex relationship amongst the agent, host and environment, i.e. the episystem, of bTB. Here, we stress the role of distinctive bTB episystems and badger culling trial design in the ambiguity and resulting controversy associated with badger culling in GB and ROI. We argue this episystem perspective on bTB control measures in cattle and badger populations provides a useful and informative perspective on the design and implementation of future bTB management in GB, particularly at a time when both scientific and lay communities are concerned about the ongoing epidemic, the cost of current control measures and the execution of future control procedures.     

The potential of oral vaccines for disease control in wildlife species

Numerous infectious diseases caused by bacteria or viruses persist in developed and developing countries due to ongoing transmission among wildlife reservoir species. Such diseases become the target of control and management programmes in cases where they represent a threat to public health (for example rabies, sylvatic plague, Lyme disease), or livestock production (for example bovine tuberculosis, brucellosis, pseudorabies), or where they threaten the survival of endangered animal populations. In the majority of cases, lethal control operations are neither economically feasible nor publicly supported as a practical means for disease management. Prophylactic vaccination has emerged over the last 15 years as an alternative control strategy for wildlife diseases, mainly driven by the success of widescale oral rabies vaccination programmes for meso-carnivores in North America and Northern Europe. Different methods have been trialled for the effective delivery of wildlife vaccines in the field, however oral vaccination remains the most widely used approach. Successful implementation of an oral wildlife vaccine is dependent on a combination of three components: an efficacious immunogen, a suitable delivery vehicle, and a species-specific bait. This review outlines the major wildlife disease problems for which oral vaccination is currently under consideration as a disease management tool, and also focuses on the technological challenges that face wildlife vaccine development. The major conclusion is that attenuated or recombinant live microbes represent the most widely-used vaccines that can be delivered by the oral route; this in turn places major emphasis on effective delivery systems (to maintain vaccine viability), and on selective baiting systems, as the keys to wildlife vaccine success. Oral vaccination is a valuable adjunct or alternative strategy to culling for the control of diseases which persist in wildlife reservoirs.     

BCG vaccination against tuberculosis in European badgers (Meles meles): a review

Tuberculosis (TB) is a significant animal health problem in many parts of the world, and reservoirs of infection in wild animals complicate disease control efforts in farmed livestock, particularly cattle. Badgers (Meles meles) are a significant wildlife reservoir of Mycobacterium bovis infection for cattle in the United Kingdom (UK) and Republic of Ireland (ROI). Vaccination of badgers using an M. bovis strain bacille Calmette-Guérin (BCG) vaccine could potentially be an option in the national TB eradication strategy. Wildlife vaccination has been used successfully for other diseases in wildlife species, and may have a role to play in reducing M. bovis transmission at the wildlife-livestock interface. Research to date has provided evidence that BCG is protective in badgers, and a parenteral badger BCG vaccine has been licensed in the UK. Further research is required to develop effective strategies for vaccine deployment and to determine the effect of badger vaccination on cattle TB incidence.     

A cost-benefit analysis of culling badgers to control bovine tuberculosis

Bovine tuberculosis (TB) is an important economic problem. The incidence of TB in cattle herds has steadily risen in the UK, and badgers are strongly implicated in spreading disease. Since the mid-1970s the UK government has adopted a number of badger culling strategies to attempt to reduce infection in cattle. In this report, an established model has been used to simulate TB in badgers, transmission to cattle, and control by badger culling. Costs were supplied by the UK Government's Department for Environment Food and Rural Affairs (Defra) for badger trapping and gassing. Regardless of culling intensity or area simulated, an overall reduction in the herd breakdown rate was seen. With a high culling efficacy and no social perturbation, the mean Net Present Value of a few simulated culling strategies in an "ideal world" was positive, meaning the economic benefits outweighed the costs. Further work is required before these results could be considered definitive, as it is necessary to evaluate uncertainties and simulate less than perfect conditions.     

Tuberculosis in cattle herds are sentinels for Mycobacterium bovis infection in European badgers (Meles meles): the Irish Greenfield Study

In Ireland badgers are removed in response to tuberculosis (TB) breakdowns in cattle herds (focal culling). Prevalence studies, conducted using a detailed post mortem and bacteriological examination, showed that 36-50% of badgers were infected with Mycobacterium bovis. Focal culling forms part of the medium term national strategy for the control of bovine TB in cattle and is based on the premise that badgers in areas with herd breakdowns have a higher prevalence of infection than the badger population at large. However, the hypothesis that cattle can be used as sentinels for infection in the badger population has never been formally tested. In this study we tested the hypothesis by determining the infection prevalence in badgers in areas where there had been historically, a consistently low prevalence of infection in cattle. Low cattle TB prevalence areas were defined as those herds with ≤ 2 standard reactors in the annual round of skin testing over the preceding 5 years (Greenfield sites). Using GIS, and adjusting for variation in land use, previous culling and cattle density, 198 Greenfield sites were identified and surveyed, and 138 areas with badger setts or signs of badger activity were identified. A single badger was removed from 87 sites and all were examined using detailed post mortem and bacteriological procedures. A prevalence of M. bovis infection of 14.9% was found in the Greenfield site badgers. This prevalence was significantly lower (P<0.001) than in badgers removed during focal culling (36.6%). The results validate the use of cattle as sentinels for TB in badgers and support the medium term national strategy for the control of bovine TB. The geographic variation in M. bovis infection prevalence in the Irish badger populations will be used when devising strategies for the incorporation of badger vaccination into the long term bovine TB control programme.     

Public attitudes towards badger culling to control bovine tuberculosis in cattle

In 1999, a questionnaire survey was conducted to evaluate public preferences towards badger culling to control bovine tuberculosis in cattle. Three alternative treatments were considered: (1) widespread culling, (2) the current experimental trials, and (3) no culling. One hundred residents from Glastonbury and York were interviewed in person and asked to give preference ratings to each of the three treatments. The single most preferred treatment was no culling, and the least preferred was the widespread cull. Respondents who favoured either the widespread cull or the experimental trials tended to be more knowledgeable about the problem and cited the level of tuberculosis in cattle as the primary factor guiding their preferences. Respondents who favoured the no culling option tended to be less knowledgeable, and cited the conservation and welfare impacts on badger populations as the most important factors. Analysis of the distribution of preference scores suggested that although it was not necessarily the most preferred treatment the experimental trial may be a relatively acceptable alternative.     

The effect of varying levels of population control on the prevalence of tuberculosis in badgers in Ireland

We examined the effect of varying levels of badger population control on the prevalence of Mycobacterium bovis infection in badgers in four counties of Ireland. In the 'Removal' and 'Buffer' areas, proactive culling was conducted to substantially reduce and subsequently maintain badger populations at a low level for five years. In the 'Reference' areas, localised reactive culling was conducted in association with herd breakdowns. The infection status of badgers was determined using bacteriology. A total of 2696 badgers were recruited into the study, and 19.0% were found to be infected with M. bovis. The two population control strategies had differing effects on the subsequent prevalence of tuberculosis in badger populations. Proactive culling led to a long term decrease in the prevalence of tuberculosis in the re-emergent populations. Although there was an overall decline in the disease prevalence, no consistent trend in disease prevalence as a result of reactive culling was observed.     

Progress in the development of tuberculosis vaccines for cattle and wildlife

Vaccination against bovine tuberculosis is likely to become an important disease control strategy in developing countries, which cannot afford a test and slaughter control programme, or in countries which have a wildlife reservoir of Mycobacterium bovis infection. In the past decade, considerable progress has been made in the development and evaluation of tuberculosis vaccines for cattle and for a range of wildlife maintenance hosts including possums, badgers, deer and African buffaloes. Experimental challenge systems have been established for the different target species and the resulting disease process has mimicked that seen in the field. In cattle, neonatal vaccination with BCG appeared to be more effective than vaccination of 6-month-old calves and in most situations no other vaccine has been shown to be better than BCG. However, prime-boost strategies involving combinations of BCG with a protein or DNA vaccine, to improve on BCG vaccination alone, have produced very encouraging results. Differential diagnostic tests have been developed using mycobacterial antigens that are only present in virulent M. bovis to differentiate between BCG-vaccinated and M. bovis-infected cattle. BCG vaccine has been shown to reduce the spread of tuberculous lesions in a range of wildlife species and a prototype oral bait delivery system has been developed. Prospects for the development of improved vaccines against bovine tuberculosis are promising and vaccination approaches could become very valuable in the control and eradication of bovine tuberculosis.     

Risk of tuberculosis cattle herd breakdowns in Ireland: effects of badger culling effort,density and historic large-scale interventions

Bovine tuberculosis (bTB) continues to be a problem in cattle herds in Ireland and Britain. It has been suggested that failure to eradicate this disease is related to the presence of a wildlife reservoir (the badger). A large-scale project was undertaken in the Republic of Ireland during 1997–2002 to assess whether badger removal could contribute to reducing risk of cattle herd breakdowns in four areas. During the period of that “four area” study, there was a significant decrease in risk in intensively culled (removal) areas relative to reference areas. In the present study, we revisit these areas to assess if there were any residual area effects of this former intervention a decade on (2007–2012). Over the study period there was an overall declining trend in bTB breakdown risk to cattle herds. Cattle herds within former removal areas experienced significantly reduced risk of breakdown relative to herds within former reference areas or herds within non-treatment areas (OR: 0.53; P < 0.001). Increased herd breakdown risk was associated with increasing herd size (OR: 1.92-2.03; P < 0.001) and herd bTB history (OR: 2.25-2.40; P < 0.001). There was increased risk of herd breakdowns in areas with higher badger densities, but this association was only significant early in the study (PD*YEAR interaction; P < 0.001). Badgers were culled in areas with higher cattle bTB risk (targeted culling). Risk tended to decline with cumulative culling effort only in three counties, but increased in the fourth (Donegal). Culling badgers is not seen as a viable long-term strategy. However, mixed policy options with biosecurity and badger vaccination, may help in managing cattle breakdown risk.

Electronic supplementary material

The online version of this article (doi:10.1186/s13567-014-0109-4) contains supplementary material, which is available to authorized users.     

Efficacy of trapping during the initial proactive culls in the randomised badger culling trial

The randomised badger culling trial (RBCT) has shown that widespread badger culling in predefined areas of approximately 100 km2 led to a reduction in the number of cattle herds testing positive for bovine tuberculosis (TB) ('herd breakdowns'), but was associated with an increase in cattle tb in surrounding areas. This study has tried to estimate the trapping efficacy and the level of reduction of the badger population during the initial proactive culls in the RBCT. For seven triplets trapping efficacy was estimated between 71 per cent and 85 per cent, and for three triplets between 35 per cent and 46 per cent. Two of the latter triplets had trapping coinciding with harsh climatic conditions. Badger population removal was estimated at 64 per cent to 77 per cent in the former and 32 per cent to 39 per cent in the latter triplets. In most of the treatment areas there was therefore a consistent and substantial reduction in the number of badgers at the end of the initial cull. All the proactive treatment areas were subjected to further culls, and it is therefore likely that greater reductions would have occurred by the end of 2005, when the analysis of cattle herd breakdowns took place.     

Does reactive badger culling lead to an increase in tuberculosis in cattle?

The conclusion from the randomised badger culling trial was that localised badger culling not only fails to control but can actually increase the incidence of bovine tuberculosis in cattle. Professor Simon More and colleagues from University College Dublin question that conclusion, arguing that the data do not provide sufficient evidence to rule out alternative hypotheses.     

The Northern Ireland programme for the control and eradication of Mycobacterium bovis

Bovine tuberculosis is endemic in Northern Ireland and a comprehensive eradication scheme has been in operation since 1959. The current programme involves annual testing, extensive computerized tracing, short-interval testing of herds contiguous to outbreaks and compulsory slaughter of positive cattle. Despite initial reductions in disease prevalence, eradication has proved elusive and potential explanatory factors include high cattle density and potential for between-herd contact, the impact of exotic diseases on resource priorities, and significant levels of bovine tuberculosis in a wildlife reservoir, the European badger (Meles meles). Both the role of the infected bovine and that of the badger in spreading disease have to be addressed to ensure progress towards eradication. Current measures are described and future options for enhancing the programme are outlined.     

Recent advances in the management of bovine tuberculosis in free-ranging wildlife

Established foci of Mycobacterium bovis (the causative agent of bovine tuberculosis [bTB]) in free-ranging wildlife are currently under various stages of management on three continents (Africa, Europe and North America) and in New Zealand. Other, as yet undiagnosed, foci seem likely to exist elsewhere. The complex roles that these wildlife foci play in the ecology of bTB remain among the greatest challenges facing bTB control globally. Conceptually, management of bTB in free-ranging wildlife can be thought of as progressing from the discovery of an outbreak through frequently overlapping stages of epidemiological characterization, initial control, simulation and forecasting, focused control, and verification of eradication. Surveillance in its various forms remains a critical component of assessment throughout. Since the Fourth International M. bovis Conference in 2005, research on management of bTB in free-ranging wildlife has encompassed such areas as the human dimensions of wildlife management, mitigation of bTB risks from wildlife on cattle farms, vaccine biology, and epidemiology, with a major contribution from simulation modeling. In order to advance the actual field management of bTB, however, research must be sufficiently grounded to aid development of practical, affordable and politically defensible management interventions which stand a reasonable chance of being implemented. The current management of two wildlife reservoirs of bTB, brushtail possums (Trichosurus vulpecula) in New Zealand, and white-tailed deer (Odocoileus virginianus) in Michigan, USA, serve as contrasting examples of different wildlife management strategies aimed at achieving a common goal. In New Zealand, the importance of agricultural export markets and the status of the possum as a non-native pest have facilitated direct, aggressive management of the disease reservoir, resulting in considerable progress towards bTB freedom since 1994. In Michigan, the relative importance of the hunting economy and of whitetails as a game animal have made such aggressive culling politically untenable. This has forced reliance upon publicly supported, and implemented, management tools, and so provided impetus to better understand social support for wildlife management policy, its limitations, and ways to employ it in disease control policy development.     

Progress in the control of bovine tuberculosis in Spanish wildlife

Despite the compulsory test and slaughter campaigns in cattle, bovine tuberculosis (bTB) is still present in Spain, and the role of wildlife reservoirs is increasingly recognized. We provide an update on recent progress made in bTB control in Spanish wildlife, including aspects of epidemiology, surveillance, host-pathogen interaction and wildlife vaccination. At the high densities and in the particular circumstances of Mediterranean environments, wild ungulates, mainly Eurasian wild boar and red deer, are able to maintain Mycobacterium bovis circulation even in absence of domestic livestock. Infection is widespread among wild ungulates in the south of the country, local infection prevalence being as high as 52% in wild boar and 27% in red deer. Risk factors identified include host genetic susceptibility, abundance, spatial aggregation at feeders and waterholes, scavenging, and social behaviour. An increasing trend of bTB compatible lesions was reported among wild boar and red deer inspected between 1992 and 2004 in Southwestern Spain. Sporadic cases of badger TB have been detected, further complicating the picture. Gene expression profiles were characterized in European wild boar and Iberian red deer naturally infected with M. bovis. The comparative analysis of gene expression profiles in wildlife hosts in response to infection advanced our understanding of the molecular mechanisms of infection and pathogenesis, revealed common and distinctive host responses to infection and identified candidate genes associated with resistance to bTB and for the characterization of host response to infection and vaccination. Ongoing research is producing valuable knowledge on vaccine delivery, safety and efficacy issues. Baits for the oral delivery of BCG vaccine preparations to wild boar piglets were developed and evaluated. The use of selective feeders during the summer was found to be a potentially reliable bait-deployment strategy. Safety experiments yielded no isolation of M. bovis BCG from faeces, internal organs at necropsy and the environment, even after oral delivery of very high doses. Finally, preliminary vaccination and challenge experiments suggested that a single oral BCG vaccination may protect wild boar from infection by a virulent M. bovis field strain.     

Cattle Drive Salmonella Infection in the Wildlife–Livestock Interface

The genus Salmonella is found throughout the world and is a potential pathogen for most vertebrates. It is also the most common cause of food‐borne illness in humans, and wildlife is an emerging source of food‐borne disease in humans due to the consumption of game meat. Wild boar is one of the most abundant European game species and these wild swine are known to be carriers of zoonotic and food‐borne pathogens such as Salmonella. Isolation of the pathogen, serotyping and molecular biology are necessary for elucidating epidemiological connections in multi‐host populations. Although disease management at population level can be addressed using a number of different strategies, such management is difficult in free‐living wildlife populations due to the lack of experience with the wildlife–livestock interface. Herein, we provide the results of a 4‐year Salmonella survey in sympatric populations of wild boar and cattle in the Ports de Tortosa i Beseit National Game Reserve (NE Spain). We also evaluated the effects of two management strategies, cattle removal and increased wild boar harvesting (i.e. by hunting and trapping), on the prevalence of the Salmonella serovar community. The serovars Meleagridis and Anatum were found to be shared by cattle and wild boar, a finding that was confirmed by 100% DNA similarity patterns using pulse field gel electrophoresis. Cattle removal was more efficient than the culling of wild boar as a means of reducing the prevalence of shared serotypes, which underlines the role of cattle as a reservoir of Salmonella for wild boar. To our knowledge, this is the first attempt to manage Salmonella in the wild, and the results have implications for management.     

New generation vaccines and delivery systems for control of bovine tuberculosis in cattle and wildlife

Advances in the understanding of protective immune responses to tuberculosis are providing opportunities for the rational development of improved vaccines for bovine tuberculosis. Protection requires activation of macrophages through stimulation of a Th 1 type immune response. Ideally, a vaccine for cattle should induce protection without causing animals to react in a tuberculin test when exposed to Mycobacterium bovis. A number of new tuberculosis vaccines including attenuated M. bovis strains, killed mycobacteria, protein and DNA vaccines have been developed and many of these are being assessed in cattle. The requirements for a tuberculosis vaccine for wildlife differ from those for cattle. The major goal of a wildlife vaccine is to prevent the transmission of M. bovis to cattle and other wildlife. Although there are a number of technical problems associated with the development of a vaccine delivery system for wildlife, attenuated M. bovis vaccines administered via oral baits or aerosol spray to possums have already been shown to reduce the severity of a subsequent M. bovis infection.     

The role of wild animal populations in the epidemiology of tuberculosis in domestic animals: how to assess the risk

Tuberculosis is present in wild animal populations in North America, Europe, Africa and New Zealand. Some wild animal populations are a source of infection for domestic livestock and humans. An understanding of the potential of each wild animal population as a reservoir of infection for domestic animals is reached by determining the nature of the disease in each wild animal species, the routes of infection for domestic species and the risk of domestic animals encountering an infectious dose. The mere presence of infection in a wild animal population does not of itself provide evidence of a significant wildlife reservoir. Although at times counterintuitive, wildlife populations with high disease prevalence may not necessarily have a role in the epidemiology of disease in domestic livestock. The key concepts used in deciding whether an infected wild animal population is involved in the epidemiology of tuberculosis in domestic livestock is illustrated by reference to six well-researched cases: the feral pig (Suis scrofa) and feral Asian water buffalo (Bubalus bubalis) in Australia, white tailed deer (Odocoileus virginianus) in Michigan, and the brushtail possum (Trichosurus vulpecula) and other species, such as the ferret (Mustela furo), in New Zealand. A detailed analysis of Mycobacterium bovis infection in the Eurasian badger (Meles meles) in Ireland and their role as a reservoir of infection for cattle is also presented.     

The importance of localized culling in stabilizing chronic wasting disease prevalence in white-tailed deer populations

Strategies to contain the spread of disease often are developed with incomplete knowledge of the possible outcomes but are intended to minimize the risks associated with delaying control. Culling of game species by government agencies is one approach to control disease in wild populations but is unpopular with hunters and wildlife enthusiasts, politically unpalatable, and erodes public support for agencies responsible for wildlife management. We addressed the functional differences between hunting and government culling programs for managing chronic wasting disease (CWD) in white-tailed deer by comparing prevalence over a 10-year period in Illinois and Wisconsin. When both Illinois and Wisconsin were actively culling from 2003 – 2007, there were no statistical differences between state CWD prevalence estimates. Wisconsin government culling concluded in 2007 and average prevalence over the next five years was 3.09 ± 1.13% with an average annual increase of 0.63%. During that same time period, Illinois continued government culling and there was no change in prevalence throughout Illinois. Despite its unpopularity among hunters, localized culling is a disease management strategy that can maintain low disease prevalence while minimizing impacts on recreational deer harvest.