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Persistent tuberculosis (TB) in cattle populations in England has been associated with an exchange of infection with badgers ( Meles meles ). A badger control policy (BCP) commenced in 2013. Its aim was to decrease TB incidence in cattle by reducing the badger population available to provide a wildlife reservoir for bovine TB. Monitoring data from 52 BCP intervention areas 200–1600 km 2 in size, starting over several years, were used to estimate the change in TB incidence rate in cattle herds, which was associated with time since the start of the BCP in each area. A difference in differences analysis addressed the non-random selection and starting sequence of the areas. The herd incidence rate of TB reduced by 56% (95% Confidence Interval 41–69%) up to the fourth year of BCP interventions, with the largest drops in the second and third years. There was insufficient evidence to judge whether the incidence rate reduced further beyond 4 years. These estimates are the most precise for the timing of declines in cattle TB associated with interventions primarily targeting badgers. They are within the range of previous estimates from England and Ireland. This analysis indicates the importance of reducing transmission from badgers to reduce the incidence of TB in cattle, noting that vaccination of badgers, fertility control and on farm biosecurity may also achieve this effect.

Bovine tuberculosis (bTB) is an important animal health and economic problem for the cattle industry and a potential zoonotic threat. Wild badgers ( Meles meles ) play a role on its epidemiology in some areas of high prevalence in cattle, particularly in the UK and Republic of Ireland and increasingly in parts of mainland Europe. However, little is known about the involvement of badgers in areas on the spatial edge of the cattle epidemic, where increasing prevalence in cattle is seen. Here we report the findings of a study of found-dead (mainly road-killed) badgers in six counties on the edge of the English epidemic of bTB in cattle. The overall prevalence of Mycobacterium tuberculosis complex (MTC) infection detected in the study area was 51/610 (8.3%, 95% CI 6.4–11%) with the county-level prevalence ranging from 15 to 4–5%. The MTC spoligotypes of recovered from badgers and cattle varied: in the northern part of the study area spoligotype SB0129 predominated in both cattle and badgers, but elsewhere there was a much wider range of spoligotypes found in badgers than in cattle, in which infection was mostly with the regional cattle spoligotype. The low prevalence of MTC in badgers in much of the study area, and, relative to in cattle, the lower density of sampling, make firm conclusions difficult to draw. However, with the exception of Cheshire (north-west of the study area), little evidence was found to link the expansion of the bTB epidemic in cattle in England to widespread badger infection.

Culling badgers to control the transmission of bovine tuberculosis (TB) between this wildlife reservoir and cattle has been widely debated. Industry‐led culling began in Somerset and Gloucestershire between August and November 2013 to reduce local badger populations. Industry‐led culling is not designed to be a randomized and controlled trial of the impact of culling on cattle incidence. Nevertheless, it is important to monitor the effects of the culling and, taking the study limitations into account, perform a cautious evaluation of the impacts. A standardized method for selecting areas matched to culling areas in factors found to affect cattle TB risk has been developed to evaluate the impact of badger culling on cattle TB incidence. The association between cattle TB incidence and badger culling in the first 2 years has been assessed. Descriptive analyses without controlling for confounding showed no association between culling and TB incidence for Somerset, or for either of the buffer areas for the first 2 years since culling began. A weak association was observed in Gloucestershire for Year 1 only. Multivariable analysis adjusting for confounding factors showed that reductions in TB incidence were associated with culling in the first 2 years in both the Somerset and Gloucestershire intervention areas when compared to areas with no culling (incidence rate ratio (IRR): 0.79, 95% CI: 0.72–0.87, p < .001 and IRR: 0.42, 95% CI: 0.34–0.51, p < .001, respectively). An increase in incidence was associated with culling in the 2‐km buffer surrounding the Somerset intervention area (IRR: 1.38, 95% CI: 1.09–1.75, p = .008), but not in Gloucestershire (IRR: 0.91, 95% CI: 0.77–1.07, p = .243). As only 2 intervention areas with 2 years of data are available for analysis, and the biological cause–effect relationship behind the statistical associations is difficult to determine, it would be unwise to use these findings to develop generalizable inferences about the effectiveness of the policy at present. We describe the effects of industry‐led badger culling in England on bTB incidents in cattle herds in the first two years of the intervention. Descriptive analyses without controlling for confounding showed no association between the intervention and TB incidence for Somerset, or for either of the buffer areas for the first or second year since culling began. Multivariable analysis adjusting for confounding factors showed that reductions in cattle TB incidence were associated with the industry‐led badger culling in the first two years in both the Somerset and Gloucestershire intervention areas, and an increase in incidence was associated with culling in the 2‐km buffer surrounding the Somerset intervention area , but not in Gloucestershire. As only two intervention areas with two years of follow‐up data are available for analysis here, it is unwise to develop generalizable inferences about the effectiveness of the policy at present.

Bovine tuberculosis (TB) is an important animal health issue in many parts of the world. In England and Wales, the primary test to detect infected animals is the single intradermal comparative cervical tuberculin test, which compares immunological responses to bovine and avian tuberculins. Inconclusive test reactors (IRs) are animals that demonstrate a positive reaction to the bovine tuberculin only marginally greater than the avian reaction, so are not classified as reactors and immediately removed. In the absence of reactors in the herd, IRs are isolated, placed under movement restrictions and re-tested after 60 days. Other animals in these herds at the time of the IR result are not usually subject to movement restrictions. This could affect efforts to control TB if undetected infected cattle move out of those herds before the next TB test. To improve our understanding of the importance of IRs, this study aimed to assess whether median survival time and the hazard of a subsequent TB incident differs in herds with only IRs detected compared with negative-testing herds. Survival analysis and extended Cox regression were used, with herds entering the study on the date of the first whole herd test in 2012. An additional analysis was performed using an alternative entry date to try to remove the impact of IR retesting and is presented in the Supplementary Material. Survival analysis showed that the median survival time among IR only herds was half that observed for clear herds (2.1 years and 4.2 years respectively; < 0.001). Extended Cox regression analysis showed that IR-only herds had 2.7 times the hazard of a subsequent incident compared with negative-testing herds in year one (hazard ratio: 2.69; 95% CI: 2.54, 2.84; < 0.001), and that this difference in the hazard reduced by 63% per year. After 2.7 years the difference had disappeared. The supplementary analysis supported these findings showing that IR only herds still had a greater hazard of a subsequent incident after the IR re-test, but that the effect was reduced. This emphasizes the importance of careful decision making around the management of IR animals and indicates that re-testing alone may not be sufficient to reduce the risk posed by IR only herds in England and Wales.

The objective was to measure the association between badger culling and bovine tuberculosis (TB) incidents in cattle herds in three areas of England between 2013–2017 (Gloucestershire and Somerset) and 2015–2017 (Dorset). Farming industry-selected licensed culling areas were matched to comparison areas. A TB incident was detection of new Mycobacterium bovis infection (post-mortem confirmed) in at least one animal in a herd. Intervention and comparison area incidence rates were compared in central zones where culling was conducted and surrounding buffer zones, through multivariable Poisson regression analyses. Central zone incidence rates in Gloucestershire (Incidence rate ratio (IRR) 0.34 (95% CI 0.29 to 0.39, p < 0.001) and Somerset (IRR 0.63 (95% CI 0.58 to 0.69, p < 0.001) were lower and no different in Dorset (IRR 1.10, 95% CI 0.96 to 1.27, p = 0.168) than comparison central zone rates. The buffer zone incidence rate was lower for Gloucestershire (IRR 0.64, 95% CI 0.58 to 0.70, p < 0.001), no different for Somerset (IRR 0.97, 95% CI 0.80 to 1.16, p = 0.767) and lower for Dorset (IRR 0.45, 95% CI 0.37 to 0.54, p < 0.001) than comparison buffer zone rates. Industry-led culling was associated with reductions in cattle TB incidence rates after four years but there were variations in effects between areas.

The role of badgers in the geographic expansion of the bovine tuberculosis (bTB) epidemic in England is unknown: indeed there have been few published studies of bTB in badgers outside of the Southwest of England where the infection is now endemic in cattle. Cheshire is now on the edge of the expanding area of England in which bTB is considered endemic in cattle. Previous studies, over a decade ago when bovine infection was rare in Cheshire, found no or only few infected badgers in the south eastern area of the county. In this study, carried out in 2014, road-killed badgers were collected through a network of local stakeholders (farmers, veterinarians, wildlife groups, government agencies), and Mycobacterium bovis was isolated from 21% (20/94) badger carcasses. Furthermore, there was strong evidence for co-localisation of M. bovis SB0129 (genotype 25) infection in both badgers and cattle herds at a county scale. While these findings suggest that both badgers and cattle are part of the same geographically expanding epidemic, the direction of any cross-species transmission and the drivers of this expansion cannot be determined. The study also demonstrated the utility of using road-killed badgers collected by stakeholders as a means of wildlife TB surveillance.

The single intradermal comparative cervical tuberculin (SICCT) test is the primary test for ante-mortem diagnosis of bovine tuberculosis (TB) in England and Wales. When an animal is first classified as an inconclusive reactor (IR) using this test, it is not subject to compulsory slaughter, but it must be isolated from the rest of the herd. To understand the risk posed by these animals, a case-control study was conducted to measure the association between IR status of animals and the odds of them becoming a reactor to the SICCT at a subsequent test. The study included all animals from herds in which only IR animals were found at the first whole herd test in 2012 and used data from subsequent tests up until the end of 2016. Separate mixed-effects logistic regression models were developed to examine the relationship between IR status and subsequent reactor status for each risk area of England and for Wales, adjusting for other explanatory variables. The odds of an animal becoming a subsequent reactor during the study period were greater for IR animals than for negative animals in the high-risk area (odds ratio (OR): 6.85 (5.98–7.86)) and edge area (OR: 8.79 (5.92–13.04)) of England and in Wales (OR: 6.87 (5.75–8.22)). In the low-risk area of England, the odds were 23 times greater, although the confidence interval around this estimate was larger due to the smaller sample size (11–48, p < 0.001). These findings support the need to explore differential controls for IR animals to reduce the spread of TB, and they highlight the importance of area-specific policies.

Persistent tuberculosis (TB) in cattle populations in England has been associated with an exchange of infection with badgers (Meles meles). A badger control policy (BCP) commenced in 2013. Its aim was to decrease TB in cattle by reducing the badger population available to provide a wildlife reservoir for bovine TB. Monitoring data from 52 BCP intervention areas 200-1600 km2 in size, starting over several years, were used to estimate the change in TB incidence rate in cattle herds, which was associated with time since the start of the BCP in each area. A Difference in Differences analysis addressed the non-random selection and starting sequence of the areas. Herd incidence rate of TB reduced by 56% (95% Confidence Interval 43-67%) up to the fourth year of BCP interventions, with the largest reductions in the second and third years. There was insufficient evidence to judge whether incidence rate reduced further beyond four years. These estimates are the most precise for the timing of decline in cattle TB associated with interventions primarily targeting badgers. They are within the range of previous estimates from England and Ireland. This analysis indicates the importance of reducing transmission from badgers to reduce the incidence of TB in cattle, noting that vaccination of badgers, fertility control and on farm biosecurity may also achieve this effect.

This thesis explores the role of patient preferences in treatment decisions and in the cost-effectiveness of three treatments for patients with multiple sclerosis (MS). The first chapter reports the results of a survey conducted to measure utilities for six health states and three treatment states in multiple sclerosis. Patients assign high utilities to milder MS health states and disutility is associated with the treatment health states. Mean utilities for the treatment health states were lower than those for the milder MS health states. These results provide support for a hypothesis that a patient's decision to discontinue treatment is rational. The second chapter examines the role of risk attitude and treatment choice in patients with multiple sclerosis. Patients' risk profiles regarding health and money were assessed using standard-gamble questions. The main finding of this chapter is that risk attitude is related to treatment choice for patients with MS. As patients become more risk seeking, they are more likely to forgo treatment. Treatment discontinuation, however, is not associated with risk attitude. Patients who discontinue do so because they have experienced moderate or severe side effects, regardless of risk preference. An additional finding of this paper is that risk attitude varies across domains. While respondents were, on average, risk averse with respect to money, they were risk neutral on health. Therefore, risk attitude regarding money may not be an appropriate proxy for risk attitude regarding health. The third chapter evaluates the cost-effectiveness of interferon beta- I a, interferon beta-lb, and glatiramer acetate in patients with multiple sclerosis. A computer simulation to model the effects and costs of treatments in multiple sclerosis was developed. Cost-effectiveness ratios for all three treatments are unfavorable under most assumptions, unless the cost of the drug is substantially reduced. All three treatment strategies are strongly dominated in the base case analysis; for treatment duration of five years or less, benefits are not large enough to overcome disutility associated with the treatments. Using alternative assumptions, cost-effectiveness ratios are still greater than$1,000,000/QALY in most cases. Under favorable assumptions, cost-effectiveness ratios may be as low as $ 460,000/QALY for IFNB-1a.