Long-term temporal trends and estimated transmission rates for Mycobacterium bovis infection in an undisturbed high-density badger (Meles meles) population.

We describe epidemiological trends in Mycobacterium bovis infection in an undisturbed wild badger (Meles meles) population. Data were derived from the capture, clinical sampling and serological testing of 1803 badgers over 9945 capture events spanning 24 years. Incidence and prevalence increased over time, exhibiting no simple relationship with host density. Potential explanations are presented for a marked increase in the frequency of positive serological test results. Transmission rates (R0) estimated from empirical data were consistent with modelled estimates and robust to changes in test sensitivity and the spatial extent of the population at risk. The risk of a positive culture or serological test result increased with badger age, and varied seasonally. Evidence consistent with progressive disease was found in cubs. This study demonstrates the value of long-term data and the repeated application of imperfect diagnostic tests as indices of infection to reveal epidemiological trends in M. bovis infection in badgers.

Social group size affects Mycobacterium bovis infection in European badgers (Meles meles).

1. In most social animals, the prevalence of directly transmitted pathogens increases in larger groups and at higher population densities. Such patterns are predicted by models of Mycobacterium bovis infection in European badgers (Meles meles). 2. We investigated the relationship between badger abundance and M. bovis prevalence, using data on 2696 adult badgers in 10 populations sampled at the start of the Randomized Badger Culling Trial. 3. M. bovis prevalence was consistently higher at low badger densities and in small social groups. M. bovis prevalence was also higher among badgers whose genetic profiles suggested that they had immigrated into their assigned social groups. 4. The association between high M. bovis prevalence and small badger group size appeared not to have been caused by previous small-scale culling in study areas, which had been suspended, on average, 5 years before the start of the current study. 5. The observed pattern of prevalence might occur through badgers in smaller groups interacting more frequently with members of neighbouring groups; detailed behavioural data are needed to test this hypothesis. Likewise, longitudinal data are needed to determine whether the size of infected groups might be suppressed by disease-related mortality. 6. Although M. bovis prevalence was lower at high population densities, the absolute number of infected badgers was higher. However, this does not necessarily mean that the risk of M. bovis transmission to cattle is highest at high badger densities, since transmission risk depends on badger behaviour as well as on badger density.

Bovine tuberculosis in cattle and badgers in localized culling areas.

Bovine tuberculosis (TB) is a zoonotic disease that can have serious consequences for cattle farming and, potentially, for public health. In Britain, failure to control bovine TB has been linked to persistent infection of European badger (Meles meles) populations. However, culling of badgers in the vicinity of recent TB outbreaks in cattle has failed to reduce the overall incidence of cattle TB. Using data from a large-scale study conducted in 1998-2005, we show that badgers collected on such localized culls had elevated prevalence of Mycobacterium bovis, the causative agent of bovine TB, suggesting that infections in cattle and badgers were indeed associated. Moreover, there was a high degree of similarity in the M. bovis strain types isolated from cattle and associated badgers. This similarity between strain types appeared to be unaffected by time lags between the detection of infection in cattle and culling of badgers, or by the presence of purchased cattle that might have acquired infection elsewhere. However, localized culling appeared to prompt an increase in the prevalence of M. bovis infection in badgers, probably by disrupting ranging and territorial behavior and hence increasing intraspecific transmission rates. This elevated prevalence among badgers could offset the benefits, for cattle, of reduced badger densities and may help to explain the failure of localized culling to reduce cattle TB incidence.

Impacts of widespread badger culling on cattle tuberculosis: concluding analyses from a large-scale field trial.

BACKGROUND: Bovine tuberculosis (TB) has re-emerged as a major problem for British cattle farmers. Failure to control the infection has been linked to transmission from European badgers; badger culling has therefore formed a component of British TB control policy since 1973. OBJECTIVES AND DESIGN: To investigate the impact of repeated widespread badger culling on cattle TB, the Randomised Badger Culling Trial compared TB incidence in cattle herds in and around ten culling areas (each 100 km2) with those in and around ten matched unculled areas. RESULTS: Overall, cattle TB incidence was 23.2% lower (95% confidence interval (CI) 12.4-32.7% lower) inside culled areas, but 24.5% (95% CI 0.6% lower-56.0% higher) higher on land

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.

Social organization and movement influence the incidence of bovine tuberculosis in an undisturbed high-density badger Meles meles population.

1. The culling of European badgers Meles meles has been a central part of attempts to control bovine tuberculosis (TB) in British cattle for many years. Recent results, however, indicate that this approach could in practice enhance disease spread. 2. This paper looks at the relationship between TB incidence and badger ecology in a high-density population in south-west England, which has been the subject of a long-term intensive study. The principal aims were to relate the probability of TB incidence, as detected by culture of clinical samples (i.e. excretion of bacilli), at the level of the individual and of the social group to demographic processes, movement, social organization and disease dynamics. 3. The probability of an individual being an incident case was greater in groups where TB was already present, although this was less influential in groups that were subject to some instability in numbers. Both individuals and groups were more likely to be incident cases where the social group was diminishing in size, although no relationship was observed with group size itself. This suggests that the process of group size reduction rather than group size per se has most influence on disease dynamics. The likelihood that either an individual or a group was an incident case was positively correlated with both individual and group-level movement. When the proportion of females in a social group was high, the positive association between movement and incidence was found to be more pronounced and there was a significantly higher probability of incident cases among males. 4. These relationships highlight the importance of social structure in driving TB transmission dynamics in this stable, high-density badger population. The results support the idea that a stable social structure mitigates against new incident cases of disease, and are consistent with the contention that badger culling may create the social circumstances for enhanced transmission of TB.

Bovine tuberculosis infection in wild mammals in the South-West region of England: a survey of prevalence and a semi-quantitative assessment of the relative risks to cattle.

In the United Kingdom, badgers are implicated in the transmission of Mycobacterium bovis to cattle, but little information is available on the potential role of other wild mammals. This paper presents the results of the largest systematic UK survey of M. bovis infection in other wild mammals. Mammal carcasses (4715) from throughout the South-West region of England were subjected to a systematic post mortem examination, microbiological culture of tissues and spoligotyping of isolates. Infection was confirmed in fox, stoat, polecat, common shrew, yellow-necked mouse, wood mouse, field vole, grey squirrel, roe deer, red deer, fallow deer and muntjac. Prevalence in deer may have been underestimated because the majority were incomplete carcasses, which reduced the likelihood of detecting infection. Infected cases were found in Wiltshire, Somerset, Devon and Cornwall, Gloucestershire and Herefordshire. Lesions were found in a high proportion of spoligotype-positive fallow, red and roe deer, and a single fox, stoat and muntjac. M. bovis spoligotypes occurred in a similar frequency of occurrence to that in cattle and badgers. Data on prevalence, pathology, abundance and ecology of wild mammals was integrated in a semi-quantitative risk assessment of the likelihood of transmission to cattle relative to badgers. Although most species presented a relatively low risk, higher values and uncertainty associated with muntjac, roe, red and in particular fallow deer, suggest they require further investigation. The results suggest that deer should be considered as potential, although probably localised, sources of infection for cattle.

Positive and negative effects of widespread badger culling on tuberculosis in cattle.

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. For three decades, European badgers (Meles meles) have been culled by the British government in a series of attempts to limit the spread of Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Despite these efforts, the incidence of TB in cattle has risen consistently, re-emerging as a primary concern for Britain's cattle industry. Recently, badger culling has attracted controversy because experimental studies have reached contrasting conclusions (albeit using different protocols), with culled areas showing either markedly reduced or increased incidence of TB in cattle. This has confused attempts to develop a science-based management policy. Here we use data from a large-scale, randomized field experiment to help resolve these apparent differences. We show that, as carried out in this experiment, culling reduces cattle TB incidence in the areas that are culled, but increases incidence in adjoining areas. These findings are biologically consistent with previous studies but will present challenges for policy development.

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.

The status of Mycobacterium bovis infection in UK wild mammals: a review.

Bovine tuberculosis caused by Mycobacterium bovis is a zoonotic infection with a wide range of mammalian hosts. In parts of the UK M. bovis infection in cattle is a persistent problem. The European badger (Meles meles) is implicated in the transmission of M. bovis to cattle, and is widely believed to constitute the most important reservoir of infection in UK wildlife. However, few studies have been carried out on the status of M. bovis infection in other UK mammals. In this review we present information on the incidence and pathology of M. bovis infection in UK wild mammals from both published and previously unpublished sources. Although the evidence does not support the existence of a significant self-maintaining reservoir of infection in any wild mammal other than the badger, there is a clear lack of sufficient data to rule out the involvement of other species. In the light of this and the dynamic nature of epidemiological patterns, further surveillance for M. bovis infection in UK wild mammals, using modern methods of diagnosis, is essential.

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.

Wildlife disease reservoirs: the epidemiology of Mycobacterium bovis infection in the European badger (Meles meles) and other British mammals.

Mycobacterium bovis infection has been confirmed in a wide range of mammals hosts throughout the world. The European badger (Meles meles) and the brushtail possum (Trichosurus vulpecula) are implicated as significant sources of infection for domestic cattle in the UK and New Zealand respectively. The risk of transmission of infection between a wildlife population and domestic animals will be determined by both the epidemiology of the disease and the ecology of the host. In the UK, surveys by the UK Ministry of Agriculture, Fisheries and Food (MAFF) have identified M. bovis infection in deer (Cervus sp., Capreolus sp., Dama sp.), red fox (Vulpes vulpes), mink (Mustela vison), feral ferret (Mustela furo), mole (Talpa europaea), brown rat (Rattus norvegicus) and feral cat (Felis catus). However, the potential contribution to cattle herd breakdowns, of reservoirs of M. bovis infection in mammals other than the badger is poorly understood and is the subject of current research. In contrast, M. bovis infection in the badger has been the subject of a long term ecological and epidemiological study at Woodchester Park in South-West England, where the prevalence and distribution of infection in a wild population has been intensively monitored. The pattern of infection in the population and potential risks to cattle, are profoundly influenced by badger social organization and behaviour. The pattern of land use and cattle farming practices in the UK brings badgers into close contact with domestic animals and provides conditions that may enhance the likelihood of disease transfer.

High-affinity ivermectin binding to recombinant subunits of the Haemonchus contortus glutamate-gated chloride channel.

Glutamate-gated chloride channels (GluCls) are targets for the avermectin anthelmintics. A family of five GluCl subunit genes encoding seven subunits has been identified in Caenorhabditis elegans. We have previously shown that two orthologous genes in the parasite, Haemonchus contortus, encode three GluCl subunits (HcGluClbeta, Hcgbr-2A and Hcgbr-2B) with high amino-acid identity (>80%) to their C. elegans counterparts. We amplified and cloned a further subunit cDNA, HcGluClalpha, from H. contortus eggs. Sequence comparisons suggested that this subunit was closely related to, but not orthologous with, the C. elegans GluClalpha1, alpha2 or alpha3/GBR-2 subunits ( approximately 55% amino-acid identity). The HcGluClalpha cDNA from an ivermectin-resistant isolate contained no coding changes from the wild-type. All of the known H. contortus GluCl cDNA clones were subcloned into the expression vector pcDNA3.1 and transiently expressed in COS-7 cells. As predicted by functional data from the C. elegans orthologues, the Hcgbr-2A and HcGluClbeta subunits failed to bind [3H]ivermectin. The Hcgbr-2B and HcGluClalpha subunits bound [3H]ivermectin with high affinity; the K(d) values were 70+/-16 and 26+/-12 pM, respectively. This binding was inhibited by a variety of avermectins, though cold ivermectin was the most potent inhibitor of [3H] ivermectin binding. Picrotoxin, fipronil, glutamate and GABA all failed to compete for ivermectin binding to either subunit. The affinity of [3H]ivermectin binding to H. contortus L3 P2 larval membrane preparations was re-examined and found to be 70+/-7 pM. The properties of orthologous GluCl subunits are likely to be conserved across species, but the repertoire and relative importance of those subunits may vary.

Spatial perturbation caused by a badger (Meles meles) culling operation: implications for the function of territoriality and the control of bovine tuberculosis (Mycobacterium bovis).

1. The spatial organization of a badger population (North Nibley) is described before and after it was subjected to a UK Ministry of Agriculture, Fisheries and Food badger removal operation (BRO) intended to control bovine tuberculosis. Comparison is made with an undisturbed badger population (Woodchester Park). 2. The Woodchester Park population was organized in group territories with clearly defined boundaries that remained stable during the 3 years of study (1995-97). In North Nibley, however, the badgers' spatial organization was severely perturbed in the first year and, to a lesser extent, also in the second year after the BRO, with badgers using latrines further away from their setts. This resulted in enlarged social group ranges that were difficult to define and overlapped considerably. 3. The disturbance was observed in the removal groups, those immediately adjacent, as well as those at a distance of one or two social groups from the removal area, with an unexpected indication that the latter groups may have been the most affected. 4. The apparent increase in the size of the group ranges in North Nibley was likely to have been caused by an increased proportion of badgers making extra-group excursions in the aftermath of the BRO. 5. Initial recolonization was almost exclusively by females. 6. Although such perturbation might be expected to facilitate disease transmission between badger social groups, there was no evidence that any infectious animals had survived the BRO. However, there were further cattle breakdowns in the area. 7. The behaviour of badgers after the BRO also provided an opportunity to test predictions made by competing hypotheses about the main determinants of the badger's socio-spatial behaviour.

Movement of badgers (Meles meles) in a high-density population: individual, population and disease effects.

The movement of 1763 badgers trapped between 36 social groups in Woodchester Park, Gloucestershire, over 18 years was analysed to determine the frequency and duration of moves, the factors associated with a predisposition to move and the spatial pattern of movements. Of those badgers whose capture history could be categorized, nearly half had moved. Of these, 73.1% were classified as 'occasional movers', 22.1% as 'permanent movers' and 4.8% as 'frequent movers'. Most adult badgers that moved made occasional moves (78.8%, n = 67). Cubs made all types of move including permanent moves (29%, n = 10). Seventy per cent of females were non-movers compared with 37% of males. Badgers were significantly more likely to move to smaller groups, whereas male badgers were significantly more likely to move to groups with a greater proportion of females. The spatial pattern of movement differed from the distribution of groups with bovine tuberculosis in the study area. However, temporal changes in movement were significantly related to the incidence of Mycobacterium bovis infection in the following year, indicating that as the movement of badgers between groups varies so does the incidence of bovine tuberculosis in the population. This finding is of central importance in the formulation of badger control policy.

A comparison of fertility control and lethal control of bovine tuberculosis in badgers: the impact of perturbation induced transmission.

In this paper we use mathematical modelling to consider the broad advantages and disadvantages of fertility control over lethal control for bovine tuberculosis in badger populations. We use a deliberately simple model, attempting to capture only the key transmission processes. The model is parametrized with reference to the long-term Woodchester Park study. Estimates of mortality rate from this study suggest no significant extra mortality risk for animals with evidence of infection as indicated by the presence of anti-Mycobacterium bovis antibodies or M. bovis isolation. We find that large reductions in prevalence are sometimes the consequence of only moderate reductions in population numbers. If we assume that the act of control does not in itself affect transmission rates, then as far as eradication is concerned, both fertility control and mortality control operate through the same epidemiological mechanism, the removal of susceptibles: if one is in principle capable of keeping a population low enough to be infection free then so is the other. It is necessary to continue either form of control at regular intervals to maintain a constant level of infection in the long term. If control were to be stopped, return to precontrol levels of badger population and infection prevalence would be expected within a few years. Fertility control is less effective in reducing population density than lethal control since it can only act, at maximum, to remove one age cohort per year. It is also less effective in reducing transmission as it can only ever remove susceptibles, while lethal control also removes infectious badgers. However, if the social disturbance caused by lethal control does in fact increase contact rates for the remaining infectious badgers, the relative efficacies of the two strategies become a great deal less clear. While we have no quantitative data on the extent to which social perturbation does act to promote transmission, model simulations show that it is possible to develop plausible scenarios in which the lethal control may actually act to increase the absolute numbers of animals infected, while reducing the number of uninfected animals to very low numbers.

The kinetics of serum antibody responses to natural infections with Mycobacterium bovis in one badger social group.

Bovine tuberculosis remains a significant problem in some parts of Great Britain and Ireland largely because of a reservoir of infection in badgers. Little is currently known about the immunopathology of Mycobacterium bovis infection in the badger. Badgers, from 31 social groups, in a study area of the Cotswold escarpment, have been trapped and sampled from 1981 to 1995. Serum antibody responses directed against the 25 kDa antigen (MPB83) of M. bovis have been studied in detail in a selected social group (JM) which has endemic infection. Sequential sera from 44 badgers were studied and results compared with culture from faeces, urine, tracheal aspirates, bite wound swabs and at post mortem. The results indicate that some badgers (about 10%) remain uninfected despite exposure to endemic M. bovis infection within the social group. In culture-positive animals active excretion of organisms is not necessarily concomitant with seropositivity. Conversely, seropositivity is not an indicator that culture positivity is present or imminent. This is particularly true in cubs when a transient seropositivity can occur within the first 6-8 months of life but these animals can remain culture-negative for up to 5 years. Western blotting confirms that at least some of these antibodies, detectable by ELISA in the culture-negative cubs, are directed against the 25 kDa M. bovis antigen. In contrast antibodies detectable in the culture-positive animals do not Western blot prior to a positive culture. Thus, differential reactivity in Western blotting may distinguish between serum antibodies indicative of potentially culture-positive animals and animals which will remain culture-negative.