Veterinary Medicine International There are no guarantees that such studies would identify signiﬁcant risk factors, although the fundamental premise of epidemiology is that disease occurrence in populations is not random but rather is associated with identiﬁable factors. Not all of the studies summarized below are classical “risk factor” studies; instead they are observational studies and it is important to remember that risk factors identiﬁed in herd- and animal-level studies are associated with the measured outcome and are not necessarily causal. Some studies include analysis of wildlife-related risk factors, which have not been discussed in any detail here. Summaries of the studies assessed as part of this paper have been included below in two groups. The ﬁrst are classical case-control studies, the second are predominantly cohort-based studies or case-control studies focused on speciﬁc risk factors. Most of the studies listed under “other epidemiological studies” used preexisting data (e.g., cattle movement and bovine TB test data) and have addressed speciﬁc epidemiological questions, such as, the role of cattle movement. Previous (case-control) studies, mostly in the UK and Ireland, have identiﬁed a number of risk factors associated with TB herd breakdowns. These include the purchase of cattle [26–28], the occurrence of TB in contiguous herds, and/or the surrounding area [29, 30] as well as herd size [28, 30]. The most frequently identiﬁed risks for herd-herd transmission included cattle movements and trading, where general trading or purchase from markets or herds in hot- spot areas or from infected herds have all been linked with increased risk for the receiving herd [31]. The following are among the risk factors shown to inﬂuence the potential of direct and indirect (via faeces and urine) exposure of cattle to the wildlife reservoir (badgers in the UK and Ireland) when at pasture; stocking regime (set- stocking), rotational versus strip grazing, stocking densities, farm habitat types, and livestock production intensity [31]. Sharing feed or water between cattle and wildlife when housed or at pasture, housing type and storing manure indoors are associated with the diﬀerential risk of transmis- sion between cattle and wildlife. Results in relation to the association with the presence of badger setts or local badger density have been more variable with some studies reporting an increased risk associated with the presence of badger setts on the farm [26, 29] or local badger density [4] while others have found no association with the presence of badger setts either on the farm or the surrounding area [27, 30]. Other evidence, and in particular observational studies on badgers in GB, has suggested possible routes of transmis- sion from badgers to cattle [32], including the possibilities of direct contact between cattle and badgers at pasture, indirect contact between cattle and infected badger faeces, urine and wound discharges, the likelihood of which is increased where cattle can access badger setts and latrines, and/or where badgers access cattle feed and/or water troughs. There is also substantial evidence in GB of badger visits to farmyards and buildings to access a range of feed sources including cattle feed in stores, maize silage, and accessing feed in troughs [33, 34], all of which would increase the likelihood of both direct and indirect transmission of infection. The physical 3 exclusion of badgers from farm buildings has been suggested as the simplest and potentially most eﬀective method of reducing contact between badgers and cattle [32], although issues of practicality, likely farmer uptake and compliance, require further investigation. Many farm and management variables are likely to be highly correlated with factors, such as, herd size, herd type, and to a lesser degree herd location. Herd size, for example, was a risk factor in a number of previous studies, although it is unclear whether this variable is acting as a risk factor per se, as a partial summary measure of other factors or because of inherent changes in the herd level sensitivity and speciﬁcity of the test as herd size increases. Other factors identiﬁed in some studies include farm and herd management practices, such as, the spreading of slurry [26]; the use of certain housing types [27]; farms having multiple premises [27]; the use of silage clamps [28]. In general, the most consistently identiﬁed risk factors are biologically plausible and consistent with known transmis- sion routes involving cattle to cattle and badger to cattle pathways. Whilst many of the general risk factors for the introduction and spread of bovine TB have been identiﬁed, less is known about the practical measures that herd keepers could reasonably take to minimize their risk and the possible impact of common biosecurity practices. 4. Case-Control Studies In bovine TB, several risk factors (e.g., cattle husbandry and environmental practices) have been suggested as pre- disposing farms to TB breakdowns [35]. However, they are not amenable to experimental investigation due to the large number of variables, the impracticality and cost of conduct- ing controlled experiments on commercial livestock farms, and the need for data from a large number of representative bovine TB breakdowns. In such circumstances, a “case- control” study provides the appropriate approach [1]. The essence of a case-control study is ﬁrstly to identify if speciﬁed risk factors are statistically associated with the occurrence of a disease or condition, while controlling for confounding and interaction and secondly to estimate the magnitude of any such risk. Within a case-control design, further options exist as to whether or not cases and control should be matched. The typical output of a case-control study is a list of risk factors associated with the disease, accompanied by the statistical signiﬁcance of each, the odds ratio (OR) for each, and the 95% conﬁdence interval (CI) for the OR. For example, the study may show that a farm that purchases cattle is twice as likely to experience a bovine TB breakdown as one that does not. The accompanying statistical signiﬁcance indicates the likelihood of such a ﬁnding not being true (i.e., that such a ﬁnding has arisen in the study purely by random chance) and therefore the weight that can be applied to the ﬁnding. The 95% CI of an odds ratio indicates the likely range of the predicted risk. An estimated OR of >1.0 indicates that the factor is associated with an increased risk of a breakdown, and the greater the numerical value of the OR, the greater the risk. By contrast an OR <1.0 suggests that the factor