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.     

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.     

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.     

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.     

Geographical association between the genotype of bovine tuberculosis in found dead badgers and in cattle herds

In a survey, 457 badgers that had been found dead in Wales were postmortem-examined, and samples were examined by histology and by extended culture (for up to 12 weeks). Mycobacterium bovis was cultured from 55 badgers (12.0 per cent), and the histology typical of M bovis infection was seen in a further six (1.3 per cent). The prevalence in badgers in each of 10 geographical areas varied between 0 and 26 per cent (P<0.001), and was associated with the incidence of confirmed M bovis infection in cattle herds in the same areas (P<0.01). In northern Wales, bTB was rare in both hosts. An infected badger was 12.3 times more likely to be within 5 km of a confirmed cattle bTB breakdown than an uninfected badger. The M bovis isolates from badgers belonged to one of four genotypes defined by spoligotype and variable number tandem repeat type. These genotypes were also found in 290 concurrent confirmed herd breakdowns, and tended to be similar to the genotypes in badgers in the same geographical areas. When badgers and cattle no more than 30 km apart were compared, the genotype diversity was greater in cattle than in badgers (P=0.016), suggesting that the movement of cattle plays a greater part in the spatial distribution of M bovis than the movement of badgers.     

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.     

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.     

Farmers' confidence in vaccinating badgers against bovine tuberculosis

This paper examines UK farmers' levels of confidence in vaccinating badgers against bovine tuberculosis (bTB) and their trust in the Government's ability to deal with bTB. In 2010, a badger vaccine based on the BCG vaccine was licensed following field trials and used as part of the UK Government's Badger Vaccination Deployment Project. A stratified random sample of cattle farmers in five different locations of England was surveyed using a telephone survey to elicit their views of badger vaccination. The survey provided a total of 341 responses with a response rate of 80 per cent. Results suggest that the farmers are cautious about badger vaccination, appearing to be neither overly confident nor unconfident in it. However, the farmers did not reveal high levels of trust in the Government to manage bTB policy or badger vaccination. There were no differences in the levels of confidence or trust between farms that were under bTB restrictions at the time of the survey and those that were not or between farms with historically high levels of bTB. Analysis of principal components suggests that 33 per cent of the farmers accepted badger vaccination, but that acceptance is dependent on the wider social and political environment.     

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.     

Husbandry practices, badger sett density and habitat composition as risk factors for transient and persistent bovine tuberculosis on UK cattle farms

Bovine tuberculosis (bTB) is a persistent problem in cattle herds in Great Britain and Ireland. Farm management and cattle husbandry practices can influence the risk of transmission of bTB and hence the likelihood of bTB breakdown (>or=1 reactor to the tuberculin skin test). Biological differences are expected in the transmission dynamics, and hence risk factors for bTB breakdown, on farms where infection persists in the herd compared to farms where infection is more sporadic or short-lived. Comparative case-control studies were performed to test farm management practices as potential risk factors for transient (under breakdown restrictions for 6 months) bTB breakdown over 5 years (1995-1999) on 179 and 171 UK cattle farms, respectively. Farms were characterised for badger sett density and farm habitat composition by ground survey, farmers were questioned retrospectively on management practices, and cases and controls were identified from national tuberculin test records. Controlling for routine tuberculin testing interval, log-transformed herd size, regional location, badger sett density and farm habitat complexity, multivariable logistic regression identified increased odds of both transient and persistent breakdown on farms that bought-in cows (odds ratio (OR)>or=4.9; 95% confidence interval (CI)>or=1.1;22.8). In addition, the purchase of >50 head of cattle (OR=4.0, 95% CI=1.0;16.0) and the storage of manure for >or/=6 months (OR=4.4; 95% CI=1.3;15.4) were risk factors for transient breakdown, whereas the use of silage clamps (OR=9.1; 95% CI=2.0;40.8) increased the risk of persistent breakdown. Decreased odds of both transient and persistent breakdown were associated with higher stocking densities (>3cattle/ha) (OR相似文献   

Vaccinating badgers (Meles meles) against Mycobacterium bovis: the ecological considerations

Bovine tuberculosis (TB) is a serious zoonotic disease, which despite a largely successful test and slaughter programme has persisted in cattle herds in parts of the UK. The badger (Meles meles) is widely considered to represent a significant wildlife reservoir for the transmission of Mycobacterium bovis to cattle, and has been the subject of a variety of culling strategies since the mid 1970s. Nevertheless, the incidence of herd breakdowns has continued to rise, and the efficacy of culling is currently the subject of a large-scale field trial. One potential alternative tool for the management of disease in wildlife populations is vaccination. However, the successful development of an effective vaccine and a strategy for its delivery will require careful consideration of the practical constraints imposed by ecological factors. In the current paper, we discuss relevant ecological and epidemiological characteristics of badger populations and practical aspects of vaccine delivery in the field.     

Factors influencing the incidence and scale of bovine tuberculosis in cattle in southwest England

Bovine tuberculosis (TB) in cattle is a major economic problem in Britain. In the past 25 years, the infection has been concentrated in the southwest region of England. We investigated the effects of agricultural and farm-management characteristics on the occurrence and scale of TB in cattle in the region (1988-1996) using logistic and linear regression. Factors relating to the existence of previous infection in cattle and the management of cattle and badgers are all linked to the incidence of the infection--but those related specifically to the management of cattle are of overriding importance in determining the scale of the problem. Although our analysis was conducted at a large spatial scale, the results suggest that improvements to the procedure for testing and managing TB in cattle, reductions in cattle stocking density, a greater human input in herd management and more-carefully targeted badger culling all might contribute to reducing the incidence and/or number of herd breakdowns.     

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.     

Effects of farm management practices on cattle grazing behaviour and the potential for transmission of bovine tuberculosis from badgers to cattle

Despite the large body of circumstantial evidence to suggest a link, the means by which bovine tuberculosis is passed from badgers to cattle remains unclear; pasture contamination with the urine, faeces and/or sputum of infectious badgers is believed to be the main route of transmission. Therefore the behaviour of grazing cattle was studied to determine whether they avoided investigating and/or grazing pasture contaminated with badger excreta, and whether different farm management practices enhanced the potential for disease transmission. Active latrines were avoided by most cattle until the sward length in the rest of the field was reduced, after which there was an increasing likelihood that active badger latrines would be grazed. Most of the cattle grazed active badger latrines, but cattle of low rank within the herd grazed latrines more heavily. Farm management practices that reduced the availability of long swards shortened the period of investigative behaviour and greatly enhanced the risk that cattle would graze active badger latrines. Cattle were more likely to graze pasture away from latrines that was contaminated either with badger urine or single faeces. Because bacilli remain viable in the soil for up to 2 years, there is the potential for bacilli to accumulate at active badger latrines, and these could pose a significant risk to cattle, even when the latrine is no longer being used by badgers. Cattle readily grazed the lush sward at disused latrines, during which they could ingest contaminated soil; the amount of soil ingested increases as sward length decreases.     

Spatial relationship between Mycobacterium bovis strains in cattle and badgers in four areas in Ireland

We investigated whether strains (restriction fragment length polymorphism, RFLP-types) of Mycobacterium bovis isolated from badgers and from cattle clustered among and within four areas in Ireland. The spatial scan test and nearest-neighbor analysis were used as the spatial cluster-detection techniques. In addition, for each of the major strains, associations between the distance to badger setts and the "centroid" of the cattle farm were assessed in a logistic model. Overall, between September 1997 and May 2000, 316 and 287 M. bovis samples, from badgers and cattle, respectively, were strain-typed. The distribution of strains in badgers, and separately in cattle, differed among areas. Within each of the four large areas, badgers and cattle tended to have similar strains; this is consistent with the sharing of M. bovis strains within an area. In more detailed within-area analyses, some spatial clusters of M. bovis strains were detected, separately, in both cattle and badgers. Almost half of the infected badger setts with a specific strain were located outside of the "detected" clusters. There was no association between the number of infected badgers with a specific M. bovis strain within 2 or 5 km distances to cattle herds, and the risk of the same strain in cattle. We speculate about the dynamic nature of badger movements, as an explanation for the absence of more clusters of most of the strains of M. bovis isolated from badgers, and its impact on trying to study transmission of M. bovis between cattle and badger.     

A comparison of badger activity in two areas of high and low bovine tuberculosis incidence of Northern Ireland

During 2005, a field survey of badger activity was carried out to evaluate differences between two areas with different levels of bovine tuberculosis (annual herd incidences of 16% and 4%) and to assess the awareness of herd keepers in relation to badgers. A random selection of herd keepers was interviewed and their farm land surveyed for the presence of badgers. The survey end point for each farm was the discovery of an active badger sett. Participation was very high in both areas (>80%). Evidence of badger activity was recorded on a higher proportion of farms in the area with a high tuberculosis herd incidence. However, when the difference in quality of agricultural land within each area was taken into account, a statistically significant association was not demonstrated. This suggests that the quality of agricultural land is a major determinant in the location of active badger setts. Nevertheless, the study did demonstrate the potential for increased exposure of cattle to badgers in the high incidence area. Herd keepers accurately identified the presence of badger setts on their land (positive predictive value=97%) but herd keepers reporting the absence of badger setts/activities on their land were found to be less accurate. Overall, the conclusions from this study tend to reflect the findings observed in other studies.     

Value of existing serological tests for identifying badgers that shed Mycobacterium bovis

In the UK there has been a sharp rise in the incidence of bovine tuberculosis since the early 1990s and the badger has been identified as an important wildlife reservoir for this infection. Infected badgers can excrete Mycobacterium bovis, putting other badgers and cattle at risk of becoming infected. Vaccination has been proposed as an approach to reducing the excretion of M. bovis by tuberculous badgers. In order to evaluate the efficacy of a badger vaccine it will be necessary to accurately determine the number of badgers excreting M. bovis without removing them for post-mortem evaluation. The existing live tests for tuberculosis in the badger (culture, indirect ELISA, Western blot) have not been assessed for their ability to detect badgers excreting M. bovis. Over the past 18 years, badgers from 31 social groups have been trapped and sampled in a study area of the Cotswold escarpment. We have examined the serological responses of 128 badgers trapped between 1985 and 1998 from social groups where M. bovis infection was endemic. These responses were compared with culture from faeces, urine, tracheal aspirates and bite wound swabs taken from these animals while alive. ELISA was found to be more sensitive than Western blot in detecting badgers excreting M. bovis. The majority of culture-positive badgers excreted M. bovis intermittently over the period of study. As a result, there was only a 27.5% chance of sampling a badger for culture when it was excreting M. bovis. In contrast, a positive ELISA result correctly predicted 68.2% of badgers with a history of excreting M. bovis. In the absence of alternative live tests for the badger, the Brock Test indirect ELISA appears to be more valuable than culture for measuring the effect of vaccination on reducing the number of badgers at risk of transmitting tuberculosis.     

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.     

Quantifying badger exposure and the risk of bovine tuberculosis for cattle herds in county Kilkenny, Ireland

The objectives of the study were to quantify the levels of badger exposure for cattle and to test the hypothesis that increased badger exposure does not increase the risk of bovine tuberculosis (BTB) in a herd. Information that became available from the targeted removal of badgers over the study period, and from a badger-removal project in county Kilkenny, during 1996-1999 was used. The specific location of cattle within each farm, and the length of time that cattle spent in each farm field during the grazing season, and in the barnyard during winter, was used to build an exposure coefficient to quantify the amount of badger exposure that cattle encountered either on pasture or in the barn. The study design was a matched case-control study in which the control herds were selected using incidence density sampling. During the 4-year study period, 543 badgers were removed and of these 96 badgers were classified as tuberculosis positive; 96 BTB herd breakdowns occurred. There was a significant association between case herds and having a higher badger sett exposure coefficient during 1996-1998. No significant association between case herds and having a higher exposure coefficient based on the number of badgers, or the number of tuberculous badgers, during September 1997-December 1999 was found.