REVIEW ARTICLE

Bovine Tuberculosis Risk Factors for British Herds Before andAfter the 2001 Foot-and-Mouth Epidemic: What have weLearned from the TB99 and CCS2005 Studies?F. Vial1,*, E. Miguel1, W. T. Johnston2, A. Mitchell3 and C. A. Donnelly1

1 Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analysis and Modelling, School of Public Health, Imperial College

London, London, UK2 Department of Health Sciences, University of York, York, UK3 Animal Health and Veterinary Laboratories Agency (AHVLA), New Haw, Addlestone, UK

Keywords:

biosecurity; bovine tuberculosis; cattle

trading; foot-and-mouth; randomized badger

culling trial

Correspondence:

C. A. Donnelly. Department of Infectious

Disease Epidemiology, MRC Centre for

Outbreak Analysis and Modelling, Imperial

College London, School of Public Health, St

Mary’s Campus, London W2 1PG, UK.

Tel.: +44 (0)20 7594 3394;

E-mail: c.donnelly@imperial.ac.uk

*Current address: Veterinary Public Health

Institute, DCR-VPH Vetsuisse Faculty, Bern

University, Bern, Switzerland

Received for publication March 13, 2012

doi:10.1111/tbed.12184

Summary

Over the last couple of decades, the UK experienced a substantial increase in the

incidence and geographical spread of bovine tuberculosis (TB), in particular since

the epidemic of foot-and-mouth disease (FMD) in 2001. The initiation of the

Randomized Badger Culling Trial (RBCT) in 1998 in south-west England pro-

vided an opportunity for an in-depth collection of questionnaire data (covering

farming practices, herd management and husbandry, trading and wildlife activity)

from herds having experienced a TB breakdown between 1998 and early 2006 and

randomly selected control herds, both within and outside the RBCT (the so-called

TB99 and CCS2005 case–control studies). The data collated were split into four

separate and comparable substudies related to either the pre-FMD or post-FMD

period, which are brought together and discussed here for the first time. The find-

ings suggest that the risk factors associated with TB breakdowns may have chan-

ged. Higher Mycobacterium bovis prevalence in badgers following the FMD

epidemic may have contributed to the identification of the presence of badgers on

a farm as a prominent TB risk factor only post-FMD. The strong emergence of

contact/trading TB risk factors post-FMD suggests that the purchasing and move-

ment of cattle, which took place to restock FMD-affected areas after 2001, may

have exacerbated the TB problem. Post-FMD analyses also highlighted the poten-

tial impact of environmental factors on TB risk. Although no unique and univer-

sal solution exists to reduce the transmission of TB to and among British cattle,

there is an evidence to suggest that applying the broad principles of biosecurity

on farms reduces the risk of infection. However, with trading remaining as an

important route of local and long-distance TB transmission, improvements in the

detection of infected animals during pre- and post-movement testing should

further reduce the geographical spread of the disease.

Introduction

Bovine tuberculosis (TB) is a chronic debilitating bacterial

disease of cattle that has been experiencing a re-emergence

in parts of the European Union as a result of limitations in

control measures targeting the spread of its causative agent

Mycobacterium bovis (Thoen et al., 2006). In Great Britain,

the disease was eliminated from most cattle herds by 1960,

with the exception of infection hot spots in south-west

England, after the implementation of a herd testing and

slaughter policy (Proud, 2006), but the maintenance of

M. bovis in badger populations (Meles meles) (Cheeseman

et al., 1989) has hampered efforts to completely eradicate

the disease. In the last twenty years, TB infection has

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases. 1

Transboundary and Emerging Diseases

become more geographically widespread, and there has

been a substantial increase in the incidence of TB (Fig. 1)

(Krebs et al., 1997), in particular since the epidemic of

foot-and-mouth disease (FMD) in 2001 (Defra, 2011).

More than 8 million British cattle were tested for TB

between January and December 2012 (Defra, 2013), and

one in nine herds had at least one animal failing the single

intradermal comparative cervical tuberculin test or showing

lesions consistent with TB during the slaughterhouse

inspection – an event known as a ‘herd breakdown’.

Following further investigation, herd breakdowns were tra-

ditionally classified as ‘confirmed’ (post-mortem examina-

tion of slaughtered cattle led to detection of TB lesions or

culture of M. bovis) or ‘unconfirmed’ (one or more cattle

reacted to the tuberculin test, but infection was not con-

firmed at post-mortem or by culture). Since 2011, the offi-

cial terminology has been changed to ‘officially TB-free

suspended’ or ‘officially TB-free withdrawn’ instead of

‘unconfirmed’ and ‘confirmed’, respectively.

Development of the TB99 and CCS2005 case–controlstudies

The initiation of the Randomized Badger Culling Trial

(RBCT) in 1998 in England provided an opportunity for an

in-depth collection of farm data on herds experiencing a

TB breakdown (case herds) and on herds not experiencing

one (control herds) within the RBCT triplets (100 km2

trial areas recruited as matched sets of three). The TB99

questionnaire was designed to be used by State Veterinary

Service (SVS, renamed Animal Health in April 2007). Vet-

erinary officers in interviews with farmers and herd manag-

ers following each TB breakdown were intended to collect a

wide range of detailed information on both the herd and

the farm (including herd composition and health, type of

farm enterprise, animal movements, husbandry factors and

wildlife presence/control on the farm). Following the dis-

ruption to TB99 activities during and after the 2001 FMD

epidemic, the TB99 study for the calendar year 2004 was

restricted to the collection of 98 cases across RBCT triplets

(Fig. 2) and their associated controls. Furthermore, in line

with the recommendation made by the House of Commons

Environment, Food and Rural Affairs Select Committee

and an independent auditor, during 2004, a substantially

revised questionnaire was developed, and a reorientation of

the study into what became known as the Case Control

Study 2005 (CCS2005) occurred. The CCS2005 study was

designed as a 1-year study and launched at the end of Janu-

ary 2005 in four geographical regions of varying TB preva-

lence. Unlike previous investigations, the case and control

herds were to be recruited both inside and outside RBCT

areas and included one area of newly emerging TB, Cum-

bria (Fig. 2).

Given the variability in the conditions under which the

TB99 and CCS2005 data had been collected over nearly

nine years (1998–2006), the aggregate data set was split intofour separate substudies, whose analyses were carried out

in a standardized fashion, making them directly compara-

ble. The first analysis related to the pre-FMD period (John-

ston et al., 2005), the second to the 2 years immediately

post-FMD, the third solely to the calendar year 2004 [both

of which can be found in the final report of the Indepen-

dent Scientific Group on Cattle TB (Bourne et al., 2007)]

and finally an analysis on the reformulated CCS2005 (John-

ston et al., 2011).

A general review of the literature on herd-level risk factor

studies can be found in the study by Skuce et al. (2012).

While other studies have investigated risk factors of TB

herd breakdowns post-FMD, they have mainly focused on

the TB risk associated with UK herds, which had been

restocked after the FMD epidemic (Carrique-Mas et al.,

2008), or compared the TB risk of herds, which had been

restocked with herds that remained continuously stocked

throughout the FMD epidemic (Ram�ırez-Villaescusa et al.,

2010). The TB99 and CCS2005 studies were the first studies

to explicitly investigate the contribution of farming prac-

tices, herd management and husbandry, trading and wild-

life activity to the herd-level TB risk in areas of high

incidence post-FMD.

Here, we synthesize and review the results from all four

RBCT case–control substudies to draw a picture of TB risk

factors for British herds before and after the 2001 FMD epi-

1996 2000 2004 2008 2012

Year

20 000

40 000

60 000

80 000

0

2000

4000

6000

8000

10 000Number of TB herd testsNumber of herds with status 'officially TB free' withdrawnNumber of new TB incidents

Fig. 1. Defra statistics for TB in GB between January 1996 and Decem-

ber 2012 (Defra, 2013). Trends in the number of TB herd tests per-

formed (left y-axis), the number of herds with status ‘officially TB-free

withdrawn’ and the number of new TB incidents (right y-axis) in Great

Britain between 1996 and 2012. The arrow symbolizes the 2001 foot-

and-mouth disease epidemic.

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases.2

TB Risk Factors in British Herds Pre- and Post-FMD F. Vial et al.

demic and discuss the possible implications of this scientific

evidence for policy makers.

Analysis

The case–control analysis approachThe case–control approach was not hypothesis-driven and

involved the screening of many different characteristics

derived from the questionnaires in the search for TB trans-

mission factors, which predisposed herds to infection. For

each case included in the study, the associated control herd/

herds was/were required to be from the same geographical

region, has/have undergone a whole herd test and not has/

have been under TB-related restrictions in the 12 months

prior to the case breakdown, and was matched on herd size,

herd type and parish testing interval for the CCS2005 study.

Cattle movement data for all TB99 studies were collected in

the questionnaire based on the farmer’s movement book,

while movement data were collected directly from the cattle

tracing system for the CCS2005 study. It is also worth not-

ing that while environmental data were collected directly

from the questionnaire for TB99, the geographical informa-

tion system (GIS) tools were used to derive the same infor-

mation, potentially more accurately, during CCS2005.

Logistic regression was used to examine potential risk

factors individually for differences between case and con-

trol farms. Those risk factors found to be significant at

P < 0.15 were further examined collectively using multivar-

iable binary logistic regression to identify a small set of sig-

nificant variables (P < 0.05). For each of these variables,

the odds ratio (OR) associated with the absence or presence

of a factor (or a doubling in a covariate) was calculated

along with its 95% confidence interval. It was recognized

that differences in risk could arise due to cases and controls

coming from different triplets (for the TB99 study), from

different herd types (i.e. beef, dairy or mixed) (Porphyre

Fig. 2. Location and numbers of case and control reports in the TB99 and CCS2005 studies.

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases. 3

F. Vial et al. TB Risk Factors in British Herds Pre- and Post-FMD

et al., 2008) and from different herd sizes (Reilly and Cour-

tenay, 2007), and therefore, these attributes were included

throughout the regression modelling process as forced co-

variates. Detailed methodology is available in the study by

Johnston et al. (2005). However, although sufficient con-

trol data were collected for meaningful analyses of pre-

FMD and 2004 data, the collection of control data fell short

of expectations in all pre-2005 studies. Only limited checks

for bias in the sample of control herds were possible with

the available information (RBCT consent status, herd type,

herd size); these checks revealed no evidence of bias.

TB risk factors identified pre-FMD

Table 1 provides a summary of the findings across the three

TB99 studies and the CCS2005 study. Factors are classified

into those found to increase or decrease the risk of a (con-

firmed or unconfirmed) TB breakdown and have been fur-

ther classified into farm management factors (e.g. housing),

contact and trading factors, wildlife and environmental fac-

tors. Odds ratios and 95% confidence intervals are summa-

rized in Fig. 3 and presented in more detail in the

Supplementary Information. Table 2 provides a summary

of factors linked to TB herd breakdowns in the UK as iden-

tified by non-RBCT studies pre- and post-FMD.

Farm management

The TB99 pre-FMD study revealed that cattle housing and

movement onto farms were prominent TB risk factors

before 2001(Johnston et al., 2005). Herds housed in cov-

ered yards (open-walled housing for larger groups of cattle

that may or may not be subdivided) experienced a greater

TB risk. It is possible that housing conditions are a proxy

for some other aspect of intensive management, which

may be more stressful for cattle than other types of hous-

ing, thereby potentially increasing the susceptibility of

cattle to TB or that such housing types facilitate access by

wildlife.

Spreading both artificial fertilizers and farmyard manure

on grazing land was associated with decreased TB risk

(Johnston et al., 2005), although ‘there were few instances

where farms did not use fertilizers on the grazing land’. It is

not clear why this should be so in RBCT herds, as other

pre-FMD studies have observed that the storage of manure

(Reilly and Courtenay, 2007) increased the risk of TB in

UK herds.

Several non-RBCT pre-FMD studies reported other TB

risk factors linked to farm management such as ratio of cat-

tle to farm workers (White and Benhin, 2004). Although

many of these variables were investigated by the pre-FMD

TB99 study, they were not retained as significant risk or

protective TB factors.

Contact/trading

Sourcing cattle from markets or farm sales increased a

herd’s TB risk, although in non-RBCT studies, this risk

was not found to increase with the number of cattle

moved onto the farm (Reilly and Courtenay, 2007).

The presence of contiguous cattle herds with confirmed

TB breakdown was only identified as a significant risk

factor in Northern Ireland (Denny and Wilesmith,

1999).

Environment & wildlife

The TB99 pre-FMD study did not highlight any significant

wildlife or environment factors that had been noted in

other British pre-FMD studies such as the protective effect

of hedgerows (Mathews et al., 2006) or the increased TB

risk in areas with badger setts (Denny and Wilesmith, 1999;

Garnett et al., 2002).

TB risk factors identified post-FMD

The two-year post-FMD period for the TB99 study pro-

vided a larger number of cases and controls than were

studied from the same three triplets in the pre-FMD

study period. This led to the power of the study being

increased and to the more sensitive detection of potential

risk factors.

Contact/trading

While the data collected in 2002 and 2003 relate to the

same three RBCT triplets as the pre-FMD study, the TB99

questionnaire used had been reformatted, and following

the discovery of some biases in the original TB99 move-

ment data, information on cattle movements on and off the

farm was subsequently derived from the cattle tracing sys-

tem. It was found that cattle movement factors that led to a

decrease in the risk of TB (movements off the farm) were

prominent in the aftermath of the 2001 FMD epidemic.

Such differences could be related to the requirement for

control herds to have been free of TB-related restrictions in

the period prior to the case herd experiencing a TB break-

down, leading to unrestricted trading for control herds, but

decreased trading for case herds in the previous year. It is

important to note that some cattle types were moved by a

small proportion of herds, for example only 11% of control

farms and 3% of case farms moved on yearling stock. Risk

factors associated with contact/trading were prevalent

across the CCS2005 study, although none of the variables

explored resulted in a prominent (more than a 3-fold)

change in TB risk. Contact with high-risk herds either

through sourcing cattle from annually tested parishes (par-

ishes with high TB background risk) or through physical

contact with a neighbouring herd with a recent history of

TB increased the risk of a breakdown. These results were

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases.4

TB Risk Factors in British Herds Pre- and Post-FMD F. Vial et al.

Table

1.Farm

man

agem

ent,wildlife,

environmen

talandcontact/tradingTB

‘risk’

and‘protective’

factors

Pre-FM

Da

Post-FMD

Risk

Protective

Risk

Protective

Wildlife

Reportedpresence

ofbadgers

inhousing/stores

2001FMDepidemic

TB99(2004)

Eviden

ceofpresence

ofbad

gers

CCS2

005(2005)

Farm

ersaw

areofpresence

ofbad

ger

setts

TB99(2002/03)/(2004)

Rep

orted

presence

ofother

wildlifein

housing/stores

TB99(2004)

Controlo

fwildlifeother

than

dee

rs/bad

gers

TB99(2004)

Environmental

Sandyso

ils

TB99(2002/03)

Mixeddeciduouswoodlands

TB99(2002/03)/2004

Pasture,meadow,amenitygrass

TB99(2002/03)/2004

Loam

soil

TB99(2002/03)

Dee

pclay

soil

CCS2

005(2005)

Farmmanagement

Other

housingtypeb

TB99

≥2premises

TB99

Coveredyard

housing

TB99

TB99(2002/03)

Trea

tingherdforalisteddisea

seTB

99(2002/03)

Feedingsilage

TB99(2004)

Growinghay

TB99(2004)

Perm

ittinghau

liersto

theen

dofthelane

CCS2

005(2005)

More

groupsofan

imalsin

theherd

CCS2

005(2005)

Housingforcattleat

grazing

CCS2

005(2005)

Artificialfertilizers

TB99

Farm

yard

man

ure

TB99

Manure

fertilizer

TB99(2002/03)

Paddock

grazingsystem

TB99(2002/03)

Number

ofad

ditionalbee

fcows

CCS2

005(2005)

Number

ofcalves

added

toherdper

year

CCS2

005(2005)

Saltoutsidehousing

CCS2

005(2005)

Feed

outsidehousing

CCS2

005(2005)

Contacts/trading

Cattle

broughtonfrom

markets

TB99

Cattlebroughtonfrom

farm

sales

TB99

Number

ofherdcontacts

TB99(2002/03)

Sourcingfrom

cattleherdsin

annually

tested

parish

CCS2

005(2005)

Number

ofbreakdownsexperiencedby

contacted

herdsin

previous24months

CCS2

005(2005)

Number

ofan

imalsmovedoutofherd

CCS2

005(2005)

Movingonyearlystock

TB99(2002/03)

Movingoff

yearlystock

TB99(2002/03)

Movingcattleoffto

marke

tTB

99(2002/03)/(2004)

aPre-FM

DTB

99questionnaire

was

notas

extensive

asthat

usedin

post-FMD2002–2

003an

d2004TB

99studies.

b’Other’housingtypes

wererecorded

when

theherdusedneither

cubicleshed

s,coveredyardsnorloose

boxes,orcattlewerenothousedat

all,butgrazingonlywas

practised

onthefarm

.

Thesefactorswerefoundto

significantlyincrea

setherisk

ofTB

break

downs(confirm

edan

dunconfirm

ed)in

theRBCTTB

99an

dCCS2

005case–controlstudies.Variablesin

italicwereassociated

with

‘risk’

andin

bold

wereassociated

witha3-fold

(ormore)chan

gein

TBrisk.

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases. 5

F. Vial et al. TB Risk Factors in British Herds Pre- and Post-FMD

corroborated by other non-RBCT studies that identified

the purchase of cattle from high-frequency testing areas

(Carrique-Mas et al., 2008) and cattle movement from

infected areas (Gilbert et al., 2005; Green et al., 2008) post-

FMD as significant TB risk factors.

Farm management

Factors associated with farm management were also preva-

lent post-FMD: providing housing at grazing, feed outside

the housing or practising paddock grazing decreased TB

risk. There was also an evidence that treating land with

manure was protective, a finding at odds with another

post-FMD case–control study of English herds, which

found that both the storage and spreading of manure were

TB risk factors (Ram�ırez-Villaescusa et al., 2010). Although

other studies found that the use of salt/mineral licks

increased TB risk (Downs et al., 2008; Ram�ırez-Villaescusa

et al., 2010), we found that the provision of salt outside the

housing decreased TB risk. Feeding silage was associated

with a substantial increase in the risk of a TB breakdown, a

Fig. 3. Odds ratios and confidence intervals associated with TB ‘risk’ and ‘protective’ factors. The protective risk factors are highlighted by grey shad-

ing. The hatched bars correspond to OR estimates during TB99 2004 studies (see the Supplementary Information).

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases.6

TB Risk Factors in British Herds Pre- and Post-FMD F. Vial et al.

finding consistent with a pre-FMD study by Reilly and

Courtenay (2007) in which the odds of persistent TB were

increased 9-fold by the use of silage clamp.

Environment

The post-FMD studies were the first RBCT studies to reveal

the potential impact of environmental factors, possibly

linked to the suitability of the farm habitat for badgers, on

TB risk. The presence of mixed deciduous woodlands on a

Table 2. Factors linked to TB herd breakdowns in UK as identified by non-RBCT studies pre- and post-FMD

Explanatory variables TB risk UK (Pre-FMD) UK (Post-FMD)

Environmental Abundance of hedgerows (−) Mathews et al. (2006)[UK]

Wild Presence of badger setts

/carcasses near farm

(+) Denny and Wilesmith (1999) [NI]

Number of badger removal

operations

in previous years

(+) White and Benhin (2004)[SW England]

Badger sett exposure (+) Garnett et al. (2002) [UK]

Contacts/Trading Presence of contiguous cattle herds

with confirmed TB breakdown

(+) Denny and Wilesmith (1999) [NI]

Purchase of cows (+) Reilly and Courtenay (2007) [UK]

Purchase >50 cattle (+) Reilly and Courtenay (2007) [UK]

Purchase of cattle from markets (+) Ram�ırez-Villaescusa et al. (2010)

[SW England]

Restocking of herds within

12 months of FMD

(+) Ram�ırez-Villaescusa et al. (2010)

[SW England]

Restocking – reactors homebred

and purchased animals

(+) Gopal et al. (2006) [NE England]

Purchase of cattle from

high-frequency

testing areas

(+) Carrique-Mas et al. (2008) [UK]

High-risk areas (+) Green et al. (2008) [GB]

Cattle movement from

infected areas

(+) Gilbert et al. (2005) [GB]

(+) Green et al. (2008) [GB]

Farm

management

Herd size (+) Reilly and Courtenay (2007) [UK] Ram�ırez-Villaescusa et al. (2010)

[SW England]

Herd size (+) Denny and Wilesmith (1999) [NI] Carrique-Mas et al. (2008); [UK]

Herd size (+) Brooks-Pollock and Keeling (2009) [GB]

Use of mineral/salt licks (+) Ram�ırez-Villaescusa et al. (2010)

[SW England]

Use of mineral/salt licks (+) Downs et al. (2008) [England, Wales]

Storage of manure indoors (+) Reilly and Courtenay (2007) [UK] Ram�ırez-Villaescusa et al. (2010)

[SW England]

Storing manure >6 months (+) Reilly and Courtenay (2007) [UK]

Spreading manure/slurry (+) Ram�ırez-Villaescusa et al. (2010)

[SW England]

Use of silage clamps (+) Reilly and Courtenay (2007) [UK]

Stocking density (>3 cattle/ha) (�) Reilly and Courtenay (2007) [UK]

Farming mixed herds (�) Reilly and Courtenay (2007) [UK]

Herds with dairy cattle (+) Ram�ırez-Villaescusa et al. (2010)

[SW England]

Number of farmers (+) White and Benhin (2004) [SW England]

Ratio cattle/farm workers (+) White and Benhin (2004) [SW England]

Other Number of animals tested (+) Green and Cornell (2005) [UK]

Test other than routine herd test (+) Green and Cornell (2005) [UK]

Length of test interval (+) Green and Cornell (2005) [UK]

TB historic incidence in the herd (+) White and Benhin (2004) [SW England] Carrique-Mas et al. (2008) [UK]

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases. 7

F. Vial et al. TB Risk Factors in British Herds Pre- and Post-FMD

farm increased its TB risk. Farms with sandy soils were also

found to experience a significantly higher TB risk although

such finding needs to be interpreted with caution as only

10% of cases had sandy soils compared with 5% of control

holdings. The presence of pasture, meadow or amenity grass

on a farm decreased TB risk, although factors with large odds

ratios and wide confidence intervals should be interpreted

cautiously. To our knowledge, no other post-FMD study

detected environmental variables as TB risk factors.

Wildlife

Post-FMD, there was evidence of wildlife factors becoming

prominent and the observation that badgers were more

likely to be reported present in housing or feed stores on

case farms, whereas on farms with managers more aware of

the presence of setts, there was less risk of a TB breakdown.

Wildlife factors were not mentioned in other UK studies

post-FMD.

Discussion

Did the 2001 FMD epidemic impact TB epidemiology in

the UK?

This review indicates that while cattle housing and move-

ment onto farms were identified as TB risk factors pre-

FMD, cattle movement factors that led to a decrease in the

risk of TB (movements off farms) and wildlife factors

became more prominent risk factors post-FMD. These

findings suggest that, at least in some areas, the risk factors

associated with breakdowns may have changed over time.

A recent review has highlighted the importance of the

local properties of the TB episystem (such as densities of

badgers, cattle herd size, national control policies, etc.), in

determining the severity of TB situation and the outcomes

of control measures (O’Connor et al., 2012). The FMD epi-

demic and the culling of 0.7 million cattle will have indi-

rectly resulted in major disruptions to the TB episystem in

the UK.

Limited TB testing of cattle during the 2001 FMD epi-

demic meant that most herds (including those in the

RBCT) experienced a delay in cattle testing of approxi-

mately 1 year resulting in delays in new TB reactors being

identified and removed from herds. Consequently, it was

predicted (Cox et al., 2005) and observed that the rate of

detection of TB herd breakdowns would double on

resumption of testing with the increase dying away after 1

to 2 years. By delaying the removal of M. bovis-infected

cattle from the environment, the FMD epidemic provided

increased opportunities for them to spread infection to

other cattle and/or badgers (Woodroffe et al., 2006).

Higher M. bovis prevalence in badgers following the

FMD epidemic (Woodroffe et al., 2006) may have contrib-

uted to the identification of the presence of badgers in cat-

tle housing/feed stores being recorded as a prominent TB

risk factor in the 2004 analyses. However, it is also possible

that farmers have become more aware/sensitive to the

presence of badgers near/on their farms as the RBCT

progressed, and protective measures may have been taken

more widely as a result of this (or an earlier TB break-

down), in particular post-FMD.

Foot-and-mouth disease also caused a considerable need

for restocking, and the patterns of purchasing and move-

ment of cattle that took place to restock FMD-affected

areas after the epidemic may have exacerbated the TB prob-

lem by spreading TB to areas of the country, which had

previously been unaffected. A retrospective cohort study of

148 cattle herds between October 2001 and November 2004

in SW England revealed that restocking of herds within

12 months of FMD was associated with an increased risk of

a TB breakdown on the farm receiving animals (Ram�ırez-

Villaescusa et al., 2010). It is perhaps not surprising to see

that purchase of cattle from high-frequency testing areas

(Carrique-Mas et al., 2008) and cattle movement from

infected areas (Gilbert et al., 2005) post-FMD were high-

lighted as significant TB risk factors in both the CCS2005

and non-RBCT studies. Post-restocking, trading continues

to carry TB risks, with long-distance cattle movements

exacerbating the TB epidemic (Gilbert et al., 2005) with

16% of herd infections in 2004 directly imputable to cattle

movements and a further 9% potentially resulting from

unrecorded movements (Green et al., 2008). In an attempt

to contain the spread of TB from high-risk areas, pre-

movement skin testing of cattle was introduced in Great

Britain in 2005–2006 (The Tuberculosis (England) Order

2005).

Limitations of the study and implications for future

research

The questionnaires used during the TB99 and CCS2005

studies provided interesting epidemiological insights into

TB risk factors for British herds and generated large

amounts of policy-relevant data during the RBCT. Inevita-

bly, although case–control studies are well suited for deter-

mining associations, they are also susceptible to bias. Bias

in the RBCT studies may have occurred as a result of

changes in the way some of the data were recorded between

the TB99 and CCS2005 studies (for example, animal move-

ment data). Furthermore, the criteria used to match case

herds and control herds slightly differed in the CCS2005

study. This review highlights the need for study design,

questionnaire design, data collection and data management

to be performed to high standards. The two RBCT studies

demonstrated the difficulty and importance of selecting

appropriate control groups in case–control studies [also see

(Wilson et al., 2000)] and showed that limiting statistical

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases.8

TB Risk Factors in British Herds Pre- and Post-FMD F. Vial et al.

adjustment (or matching) only to herd type may not always

be adequate. It is also worth bearing in mind that the

CCS2005 study had greater statistical power than the TB99

study (Wahl, 2006), for similarly posed questions, due to

the larger number of cases and controls recruited.

A large number of variables derived from the question-

naires were first screened individually before being further

examined collectively using multivariable binary logistic

regression and finally applying backward model selection.

Bayesian methods, such as Bayesian stochastic search vari-

able selection, have been shown to increase power and

decrease false-positive results when selecting factors to

model complex disease risk and could offer an interesting

alternative methodology for future identification and quan-

tification of TB risk factors (Swartz et al., 2008). Another

limitation of standard regression analyses, as performed

here, springs from its non-adequacy in capturing nonlinear

relationships between response variable (e.g. disease status)

and exposure (to various risk factors for example). When

such nonlinear relationship are demonstrated, alternative

methods such as statistical learning techniques can be

adapted and applied to epidemiological questions (Heine

et al., 2013).

Not all counties in the UK were equally affected by the

2001 FMD epidemic. To illustrate this point, in April 2001,

86 128 cattle were culled in Cumbria versus 7931 cattle

culled in Gloucestershire (both counties were investigated

as a part of the RBCT studies) (Defra, 2004). It is therefore

reasonable to expect that delays in cattle TB testing and the

need for restocking post-FMD would have differed in the

different counties, which were part of the RBCT studies,

possibly making the identification of strong common TB

risk factors post-FMD more difficult. The results of this

review therefore pertain to changes in the risk factors asso-

ciated with TB breakdowns in UK herds following the 2001

FMD epidemic and should not be generalized to other TB

areas in the British Isles, which were not affected by the epi-

demic.

Despite the limitations of the primary studies, the results

from the matched analyses performed on the TB99 and

CCS05 data are, to a large extent, supported by evidence

from other sources. We recognize that future studies (or

questionnaires) may benefit from testing specific hypothe-

ses and being targeted at providing information judged to

be most directly relevant to TB control. For example, the

identification of recurrent or prolonged breakdowns (last-

ing more than 240 days) at an early stage could help to bet-

ter target TB controls. More studies are needed to identify

risk factors for prolonged breakdowns, which may require

a different type of intervention (Karolemeas et al., 2010).

The large amount of data collected during the TB99 and

CCS2005 studies, as well as other routinely collected data

within VetNeta, could support more hypothesis-driven

analyses or allow the monitoring of the profile of break-

down farms over time.

The identification of disease risk or protective factors has

led, in the past, to the production of risk maps, which can

prove valuable for highlighting areas for targeting public

health interventions (e.g. vector borne disease). More

recently, new approaches such as multicriteria decision

analysis (MCDA) have been used to propose geospatial

models and spatially explicit decision support tools for the

management of diseases on the one hand (Hongoh et al.,

2013) and the identification and assessment of emerging

animal threats on the other (Del Rio Vilas et al., 2013).

These could constitute potentially fruitful new areas of

research for TB.

Conclusions

The TB99 and CCS2005 analyses indicate that there is no

universal solution that can be confidently adopted across

the whole of the UK to reduce the transmission of TB to

and from cattle. The apparent lack of a ‘silver bullet’ reflects

the fact that TB is a highly complex disease with risk factors

that change over both space and time. However, greater

insight into the possible dynamics of infection can be seen

when the risk factors are classified into management, con-

tact, wildlife and environment factors. Any attempt to

reduce TB risk must accept that environmental features are

not under a farmer’s control. The RBCT results suggest that

a farm-scale approach focussing on management factors,

such as the use of fertilizer, housing and feeding practices,

or on limiting the opportunities for contact with neigh-

bouring herds can realistically aim to reduce a herd’s risk of

experiencing a TB breakdown. While results such as these

can contribute towards that goal, ‘the natural science evi-

dence base cannot alone determine policy to control or

eradicate the disease’ (Godfray et al., 2013).

With trading remaining an important route of local and

long-distance TB transmission, DEFRA reported that

pre-movement testing (introduced in GB in 2006) and

post-movement testing (introduced in Scotland in 2007)

can be effective in reducing the risk of introduction of

infection into a herd via cattle movements in areas where

TB is sporadic (Defra, 2010). Improvements in the

detection of infected animals pre-movement (de la Rua-

Domenech et al., 2006) and ‘significant advances in both

effective vaccines and highly sensitive and specific diagnos-

tics […] would benefit disease control’ (Defra, 2005).

As in other similar settings, one must be cautious in

interpreting the findings from the TB99 and CCS2005

studies as they identify associations and not causes. Studies

are still needed to quantify the possible reduction in TB

risk following implementation of biosecurity measures.

Nevertheless, findings from the RBCT suggest that applying

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases. 9

F. Vial et al. TB Risk Factors in British Herds Pre- and Post-FMD

the broad principles of biosecurity on a farm (e.g. see the

advice developed by the Bovine TB Husbandry Working

Group in partnership with Defra: http://www.defra.gov.uk/

animal-diseases/a-z/bovine-tb/animal-keepers/biosecurity/)

could reduce the risk of cattle becoming infected by other

animals, including badgers, and thus reduce the risk of

infection.

Competing Interests

CAD was formerly a member of the Independent Scientific

Group on Cattle TB (ISG) for which she received fees for

time spent on ISG work and reimbursement of expenses

from Defra. WTJ was formerly employed as a research

assistant working with the ISG at Imperial College London.

FV was and ECM is employed as a research assistant

working with CAD at Imperial College London.

Authors’ Contributions

FV compiled the findings and drafted the manuscript.

WTJ, AM and CAD advised on the implementation of the

TB99 and CCS2005 studies. EM commented on the manu-

script and helped with the literature review and the produc-

tion of figures and tables. All authors critically reviewed the

results, their interpretation and their presentation within

the manuscript.

Acknowledgements

The authors thank all of the farmers who participated

in these studies; the SVS staff who collected the data;

the VLA (now part of AHVLA) who designed and wrote

the database and entered, stored and provided the data;

and the ISG Secretariat for support throughout these

studies. This work was funded by Defra. CAD, FV and

EM acknowledge the support of the Medical Research

Council for the Centre for Outbreak Analysis and

Modelling.

Note

aVetNet was Defra’s TB control and surveillance system [at the time

these studies were carried out]. The system had been in place since the

mid-1990s and recorded details of herds, TB tests, TB breakdowns and

the details of any slaughtered (reactors, slaughterhouse cases and direct

contacts) and inconclusive reactor cattle.

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Supporting Information

Additional supporting information may be found in the

online version of this article.

Suppl S1. A formal description of the model structure is

presented.

© 2013 Blackwell Verlag GmbH • Transboundary and Emerging Diseases. 11

F. Vial et al. TB Risk Factors in British Herds Pre- and Post-FMD