Richard S. Clifton-Hadley

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 Britains 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.

Bottlenecks and broomsticks: the molecular evolution of Mycobacterium bovis

Mycobacterium bovis is the cause of tuberculosis in cattle and is a member of the Mycobacterium tuberculosis complex. In contrast to many other pathogenic bacterial species, there is little evidence for the transfer and recombination of genes between cells. The clonality of this group of organisms indicates that the population structure is dominated by reductions in diversity, caused either by population bottlenecks or selective sweeps as entire chromosomes become fixed in the population. We describe how these forces have shaped not only the phylogeny of this group but also, at a very local level, the population structure of Mycobacterium bovis in the British Isles. We also discuss the practical implications of applying this knowledge to understanding the spread of infection and the development of improved vaccines and diagnostic tests.

Cattle movements and bovine tuberculosis in Great Britain

For 20 years, bovine tuberculosis (BTB) has been spreading in Great Britain (England, Wales and Scotland) and is now endemic in the southwest and parts of central England and in southwest Wales, and occurs sporadically elsewhere. Although its transmission pathways remain poorly understood, the diseases distribution was previously modelled statistically by using environmental variables and measures of their seasonality. Movements of infected animals have long been considered a critical factor in the spread of livestock diseases, as reflected in strict import/export regulations, the extensive movement restrictions imposed during the 2001 foot-and-mouth disease outbreak, the tracing procedures after a new case of BTB has been confirmed and the Governments recently published strategic framework for the sustainable control on BTB. Since January 2001 it has been mandatory for stock-keepers in Great Britain to notify the British Cattle Movement Service of all cattle births, movements and deaths. Here we show that movements as recorded in the Cattle Tracing System data archive, and particularly those from areas where BTB is reported, consistently outperform environmental, topographic and other anthropogenic variables as the main predictor of disease occurrence. Simulation distribution models for 2002 and 2003, incorporating all predictor categories, are presented and used to project distributions for 2004 and 2005.

Culling and cattle controls influence tuberculosis risk for badgers

Human and livestock diseases can be difficult to control where infection persists in wildlife populations. In Britain, European badgers (Meles meles) are implicated in transmitting Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), to cattle. Badger culling has therefore been a component of British TB control policy for many years. However, large-scale field trials have recently shown that badger culling has the capacity to cause both increases and decreases in cattle TB incidence. Here, we show that repeated badger culling in the same area is associated with increasing prevalence of M. bovis infection in badgers, especially where landscape features allow badgers from neighboring land to recolonize culled areas. This impact on prevalence in badgers might reduce the beneficial effects of culling on cattle TB incidence, and could contribute to the detrimental effects that have been observed. Additionally, we show that suspension of cattle TB controls during a nationwide epidemic of foot and mouth disease, which substantially delayed removal of TB-affected cattle, was associated with a widespread increase in the prevalence of M. bovis infection in badgers. This pattern suggests that infection may be transmitted from cattle to badgers, as well as vice versa. Clearly, disease control measures aimed at either host species may have unintended consequences for transmission, both within and between species. Our findings highlight the need for policymakers to consider multiple transmission routes when managing multihost pathogens.

Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers

Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (Meles meles). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of Mycobacterium bovis infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle.

Introduction of bovine tuberculosis to north-east England by bought-in cattle.

The source of bovine tuberculosis was investigated in 31 herds in north-east England that experienced confirmed breakdowns between January 2002 and June 2004; nine of the herds had been restocked after the uk outbreak of foot-and-mouth disease in 2001. In all but one of the breakdowns the most likely source of infection was identified as one or more purchased animals. In 17 of the breakdowns, reactor animals were traced to herds from which the same combination of spoligotype and variable number tandem repeats was isolated, and in five breakdowns a different spoligotype was isolated. The most likely sources were located in Wales and the west and north of England, and included a Cheshire herd that was the most likely source of nine of the breakdowns. Three breakdowns were traced to Irish imports. Reactors in five of the breakdowns included homebred as well as purchased animals, providing evidence for the likely spread of the disease within the herds. The lack of geographical clustering of molecular types pointed to the overwhelming source of infection being cattle that had been bought-in.

Bovine tuberculosis trends in the UK and the Republic of Ireland, 1995–2010

Selected demographic features and trends in bovine tuberculosis (BTB) from 1995 to 2010 are described for the countries of the UK and the Republic of Ireland, using standardised definitions and measures. All countries experienced a reduction in the number of cattle and herds and in the proportion of dairy herds, while average herd size increased. In general, the trends indicate a stable situation of very low BTB prevalence in Scotland and, over most of the period, a rising prevalence in England and Wales. The prevalence in the Republic of Ireland declined while Northern Ireland experienced both a rise and fall. Differences in demography, BTB programme structure and test results were noted, particularly between the island of Ireland and Great Britain. Further investigation of these differences may provide valuable insights into risk factors for BTB and optimisation of existing BTB programmes.

Estimating the Hidden Burden of Bovine Tuberculosis in Great Britain

The number of cattle herds placed under movement restrictions in Great Britain (GB) due to the suspected presence of bovine tuberculosis (bTB) has progressively increased over the past 25 years despite an intensive and costly test-and-slaughter control program. Around 38% of herds that clear movement restrictions experience a recurrent incident (breakdown) within 24 months, suggesting that infection may be persisting within herds. Reactivity to tuberculin, the basis of diagnostic testing, is dependent on the time from infection. Thus, testing efficiency varies between outbreaks, depending on weight of transmission and cannot be directly estimated. In this paper, we use Approximate Bayesian Computation (ABC) to parameterize two within-herd transmission models within a rigorous inferential framework. Previous within-herd models of bTB have relied on ad-hoc methods of parameterization and used a single model structure (SORI) where animals are assumed to become detectable by testing before they become infectious. We study such a conventional within-herd model of bTB and an alternative model, motivated by recent animal challenge studies, where there is no period of epidemiological latency before animals become infectious (SOR). Under both models we estimate that cattle-to-cattle transmission rates are non-linearly density dependent. The basic reproductive ratio for our conventional within-herd model, estimated for scenarios with no statutory controls, increases from 1.5 (0.26–4.9; 95% CI) in a herd of 30 cattle up to 4.9 (0.99–14.0) in a herd of 400. Under this model we estimate that 50% (33–67) of recurrent breakdowns in Britain can be attributed to infection missed by tuberculin testing. However this figure falls to 24% (11–42) of recurrent breakdowns under our alternative model. Under both models the estimated extrinsic force of infection increases with the burden of missed infection. Hence, improved herd-level testing is unlikely to reduce recurrence unless this extrinsic infectious pressure is simultaneously addressed.

Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot‐and‐mouth disease epidemic

A case–control study of the factors associated with the risk of a bovine tuberculosis (TB) breakdown in cattle herds was undertaken within the randomized badger culling trial (RBCT). TB breakdowns occurring prior to the 2001 foot-and-mouth disease epidemic in three RBCT triplets were eligible to be cases; controls were selected from the same RBCT area. Data from 151 case farms and 117 control farms were analysed using logistic regression. The strongest factors associated with an increased TB risk were movement of cattle onto the farm from markets or farm sales, operating a farm over multiple premises and the use of either covered yard or ‘other’ housing types. Spreading artificial fertilizers or farmyard manure on grazing land were both associated with decreased risk. These first case–control results from the RBCT will be followed by similar analyses as more data become available.

Evidence of genetic resistance of cattle to infection with Mycobacterium bovis.

Anecdotal evidence points to genetic variation in resistance of cattle to infection with Mycobacterium bovis, the causative agent of bovine tuberculosis (BTB), and published experimental evidence in deer and cattle suggests significant genetic variation in resistance and reactivity to diagnostic tests. However, such genetic variation has not been properly quantified in the United Kingdom dairy cattle population; it is possible that it exists and may be a factor influencing the occurrence of BTB. Using models based on the outcome of the process of diagnosis (ultimate fate models) and on the outcome of a single stage of diagnosis (continuation ratio models, herd test-date models), this study shows that there is heritable variation in individual cow susceptibility to BTB, and that selection for milk yield is unlikely to have contributed to the current epidemic. Results demonstrate that genetics could play an important role in controlling BTB by reducing both the incidence and the severity of herd breakdowns.