Predicting prolonged bovine tuberculosis breakdowns in Great Britain as an aid to control

Bovine tuberculosis (bTB) is an important notifiable disease in cattle in Great Britain (GB), and is subject to statutory control measures. Despite this, disease incidence has increased since the mid-1980s, and around 30% of herd breakdowns continue for more than 240 days. This is twice the shortest possible time for confirmed breakdowns to test clear from infection (≈120 days), and four times the shortest possible time for unconfirmed breakdowns (≈60 days). These "prolonged" breakdowns consume substantial resources and may act as an ongoing source of infection. It is not clear why some breakdowns become prolonged. Existing detailed case-control data have been re-analysed to determine risk factors for breakdowns lasting longer than 240 days, the strongest of which was the confirmation status of the breakdown: OR 12.6 (95%CI: 6.7-25.4). A further model restricted to data available early on in a breakdown for all breakdowns nationally, can predict 82-84% of prolonged breakdowns with a positive predictive value of 44-49% when validated using existing national datasets over a 4-year period. Identification of prolonged breakdowns at an earlier stage could help to target bTB controls in GB.     

Investigations of cattle herd breakdowns with bovine tuberculosis in four counties of England and Wales using VETNET data

Cattle herd breakdown (HBR) with bovine tuberculosis (BTB) was investigated for farms in four counties of England and Wales outside southwest England from 1986 to early 2000. Data from the national database of TB testing history (VETNET) were used. Factors that influenced HBR included calendar time, herd size, number of cattle tested, the test type, the inter-test interval and spatial grouping of farms. Herd tests other than routine herd tests had an increased risk of HBR in all four counties. In all counties, the risk of HBR increased with calendar time and in Shropshire a test interval of 3 years was associated with an increased risk of HBR compared with a 1-year test interval. In Staffordshire and Sussex, a 4-year test interval was associated with a lower risk of HBR compared with a 1-year test interval. There was no evidence of spatial clustering of HBR in West Glamorgan (equal spatial risk in a 15–30 km radius) and weak evidence of spatial clustering in Shropshire (7–15 km) and Sussex (5–10 km). In Staffordshire, there was evidence of spatial (2–4 km) and time (3–4 years) clustering of HBR. The locally increased rate of testing following a confirmed HBR increased the detection of infected herds but did not prevent local spread in two of the four counties (Shropshire and Staffordshire) since the rate of HBR increased linearly from 1988 to 2000. The main conclusion is that there were both local and distant components of spread.     

Breakdown severity during a bovine tuberculosis episode as a predictor of future herd breakdowns in Ireland

A retrospective cohort study of Irish cattle herds investigated whether the severity of a herd’s bovine tuberculosis (BTB) breakdown was a predictor of the hazard of a future BTB breakdown in that herd. Data on 10,926 herds not having had BTB in 1995 (the “non-exposed” group) were obtained using a 10% random sample from all herds without BTB in 1995. Data on 6757 herds that had a new BTB breakdown in 1995 (the “exposed” group) were obtained and categorized into five increasing exposure-severity classes based on the total number of standard reactors (to the single intra-dermal comparative cervical tuberculin test) detected during the breakdown. Exposed herds were deemed to be free of BTB after they passed a 6-month check test; non-exposed herds were deemed free as of the date of the first negative herd-test in 1995.

In the 5 years after 1995, 18% of the non-exposed herds had a BTB breakdown, whereas 31% of the exposed herds had a subsequent breakdown. Relative to the hazard for non-exposed herds, the hazard for the first future singleton standard reactor breakdown, was 1.6-times higher for exposed herds with only 1 standard reactor in 1995, and 1.8-times higher for those exposed herds with 4–8 standard reactors during the 1995 episode. When the outcome for future breakdowns was 2 or more standard reactors, the hazard ratios ranged from 1.6 for exposed herds with only 1 standard reactor in 1995 up to 2.9 in exposed herds with 8 or more standard reactors during the 1995 episode. The latter hazard ratio varied over time, decreasing to 1.7 after 3 years of risk. The hazard of a future BTB breakdown increased directly with number of cattle in the herd, a positive history of previous BTB in the herd, and the local herd prevalence of BTB. The presence of confirmed BTB lesions in reactor cattle was not predictive of the future breakdown hazard when the effects of other factors were controlled.     

Risk of tuberculosis cattle herd breakdowns in Ireland: effects of badger culling effort,density and historic large-scale interventions

Bovine tuberculosis (bTB) continues to be a problem in cattle herds in Ireland and Britain. It has been suggested that failure to eradicate this disease is related to the presence of a wildlife reservoir (the badger). A large-scale project was undertaken in the Republic of Ireland during 1997–2002 to assess whether badger removal could contribute to reducing risk of cattle herd breakdowns in four areas. During the period of that “four area” study, there was a significant decrease in risk in intensively culled (removal) areas relative to reference areas. In the present study, we revisit these areas to assess if there were any residual area effects of this former intervention a decade on (2007–2012). Over the study period there was an overall declining trend in bTB breakdown risk to cattle herds. Cattle herds within former removal areas experienced significantly reduced risk of breakdown relative to herds within former reference areas or herds within non-treatment areas (OR: 0.53; P < 0.001). Increased herd breakdown risk was associated with increasing herd size (OR: 1.92-2.03; P < 0.001) and herd bTB history (OR: 2.25-2.40; P < 0.001). There was increased risk of herd breakdowns in areas with higher badger densities, but this association was only significant early in the study (PD*YEAR interaction; P < 0.001). Badgers were culled in areas with higher cattle bTB risk (targeted culling). Risk tended to decline with cumulative culling effort only in three counties, but increased in the fourth (Donegal). Culling badgers is not seen as a viable long-term strategy. However, mixed policy options with biosecurity and badger vaccination, may help in managing cattle breakdown risk.

Electronic supplementary material

The online version of this article (doi:10.1186/s13567-014-0109-4) contains supplementary material, which is available to authorized users.     

Mycobacterium nonchromogenicum in nasal mucus from cattle in a herd infected with bovine tuberculosis

Skin test negative cattle from a herd containing an unusually high proportion (194/382) of tuberculin skin test positive cattle were investigated for remaining Mycobacterium bovis infected animals. Blood samples from the skin test negative cattle, analysed by an antibody ELISA and an interferon-gamma assay, were mostly test negative for M. bovis. Radiometric culture of nasal mucus samples from 48 of the cattle yielded 22 culture positives with acid-fast bacilli and cording in 6 of these. Subculture on solid media was successful for 7, including 2 with cording of the 22 radiometric culture positives. Mycobacterium tuberculosis complex DNA probe testing using the Accuprobe (Gen-Probe, Inc.) and M. tuberculosis complex-specific PCR amplification, performed on the solid media subcultures, were negative. 16S rRNA PCR and sequence analysis were successful for 6 of the 7 solid media subcultures obtained and revealed the presence of Mycobacterium nonchromogenicum in all 6 subcultures. This is the first report of M. nonchromogenicum in nasal mucus of cattle. The observation highlights the importance of integrating definitive tests such as the PCR for diagnosis of bovine tuberculosis and indicates a possible zoonotic risk.     

Meta-analysis of field studies on bovine tuberculosis skin tests in United States cattle herds

Our objective was to summarize information on the diagnostic accuracy, in terms of test sensitivity (Se) and specificity (Sp), for bovine tuberculosis (bTb) tuberculin skin tests as currently used in the United States. Meta-analyses including Se and Sp estimates from field studies of bTb tuberculin tests conducted in North American cattle were conducted to provide a distribution of estimates and central tendency for Se and Sp of the caudal fold tuberculin (CFT) and serial interpretation of the CFT and comparative cervical tuberculin (CFT-CCT) tests. In total, 12 estimates for CFT and CFT-CCT test Se and Sp were identified from seven publications matching inclusion criteria. Estimates for CFT test Se ranged from 80.4% to 93.0% and CFT test Sp from 89.2% to 95.2%. Estimates for CFT-CCT test Se ranged from 74.4% to 88.4% and CFT-CCT test Sp ranged from 97.3% to 98.6%. These distributions of test Se and Sp are intended to provide a more realistic representation for U.S. bTb skin tests than previously reported. Estimation and discussion of herd-level CFT and CFT-CCT test parameters is also included. These results should be considered at the herd and individual animal level when evaluating results from tuberculin skin test results in North American cattle herds.     

Risk of bovine tuberculosis for cattle sold out from herds during 2005 in Ireland

A retrospective cohort study was conducted to determine the risk of bovine tuberculosis (TB) among animals sold out from herds that were free to trade animals during the year 2005 according to their bovine TB testing history during the year 2005. The present study sample comprised of 338,960 animals, of which 124,360 animals were sold out from herds that were restricted from trading at some stage during 2005 (bovine TB 'exposed') and 214,600 animals that were sold from herds which did not have their trading status withdrawn in 2005 (bovine TB 'non-exposed'). The overall risk of a diagnosis of bovine TB during the two-year period after the animals were sold out was 0.69 per cent. The odds of bovine TB were 1.91 higher for animals sold out from bovine TB 'exposed' herds compared with animals sold out from bovine TB 'non-exposed' herds (OR 95 per cent CI: 1.76 to 2.07, P<0.0001). Ten per cent of animals identified during field surveillance with bovine TB did so less than two months after being sold out in 2005, and similarly, 10 per cent of the animals classified as bovine TB positive by finding a bovine TB lesion at slaughter did so within 25 days (or less) of being sold out in 2005.     

Geographical association between the genotype of bovine tuberculosis in found dead badgers and in cattle herds

In a survey, 457 badgers that had been found dead in Wales were postmortem-examined, and samples were examined by histology and by extended culture (for up to 12 weeks). Mycobacterium bovis was cultured from 55 badgers (12.0 per cent), and the histology typical of M bovis infection was seen in a further six (1.3 per cent). The prevalence in badgers in each of 10 geographical areas varied between 0 and 26 per cent (P<0.001), and was associated with the incidence of confirmed M bovis infection in cattle herds in the same areas (P<0.01). In northern Wales, bTB was rare in both hosts. An infected badger was 12.3 times more likely to be within 5 km of a confirmed cattle bTB breakdown than an uninfected badger. The M bovis isolates from badgers belonged to one of four genotypes defined by spoligotype and variable number tandem repeat type. These genotypes were also found in 290 concurrent confirmed herd breakdowns, and tended to be similar to the genotypes in badgers in the same geographical areas. When badgers and cattle no more than 30 km apart were compared, the genotype diversity was greater in cattle than in badgers (P=0.016), suggesting that the movement of cattle plays a greater part in the spatial distribution of M bovis than the movement of badgers.     

Prevalence of bovine tuberculosis in pastoral cattle herds in the Oromia region,southern Ethiopia

A cross-sectional study of bovine tuberculosis (BTB) was conducted in pastoral cattle herds in southern Ethiopia, from February to August 2008 using the comparative intradermal tuberculin test. The prevalence of BTB and the risk factors for having positive reactor herds were assessed in four pastoral associations in two districts of southern Ethiopia, namely Goro-Dola with 242 cattle in 16 herds and Liben with 231 cattle in 15 herds. A herd was considered positive if there was at least one reactor animal in a herd. The test results were interpreted based on the Office Internationale des Epizooties recommended 4-mm and a recently suggested 2-mm cut-off. The apparent individual animal prevalence of tuberculin reactors was 5.5% (95% confidence interval (CI), 4.0–8.0%) and 7.0% (95% CI, 5.0–10.0%), whereas the true prevalence estimate was 4.4% (95% CI, 0.8–8.0%) and 6.1% (95% CI, 2.6–9.5%), when using the 4-mm and the 2-mm cut-offs, respectively. The overall herd apparent prevalence of tuberculin reactor animals was 41.9% (95% CI, 24.9–60.9%) and 48.4% (95% CI, 30.2–66.9%) with the 4-mm and 2-mm cut-offs, respectively. A positive tuberculin test was associated with the age of animals and the main drinking water sources during dry seasons. In order to investigate the public health risks and the epidemiological importance of BTB in the area, we recommend to include other livestock species (camels and goats) as well as humans in future studies.     

Effect of paratuberculosis on the diagnosis of bovine tuberculosis in a cattle herd with a mixed infection using interferon-gamma detection assay

Interferon-gamma (IFN-gamma) detection assay is being applied as an ancillary test to tuberculin tests in the diagnosis of bovine tuberculosis to detect the maximum number of infected animals. Among possible factors influencing the performance of tuberculosis-diagnostic tests, paratuberculosis, a widespread disease in Spain and other European countries, has been pointed out as a cause of false positive reactions. Still, its effect on the sensitivity of these tests in cattle has yet to be fully characterized. The impact of paratuberculosis in the apparent sensitivity of IFN-gamma assay was studied in a bullfighting cattle herd with a mixed tuberculosis-paratuberculosis infection, using culture of Mycobacterium bovis and Mycobacterium avium paratuberculosis as the gold standard to determine the infection status of every animal. A total of 218 animals were slaughtered and sampled for bacteriology after blood sampling. IFN-gamma assay showed a lower apparent sensitivity in animals with a mixed infection (50%) compared to all animals suffering tuberculosis (78.3%). This finding indicates that the presence of paratuberculosis in tuberculosis-infected herds could imply a serious impairment in the sensitivity of IFN-gamma detection test.     

Quantifying badger exposure and the risk of bovine tuberculosis for cattle herds in county Kilkenny, Ireland

The objectives of the study were to quantify the levels of badger exposure for cattle and to test the hypothesis that increased badger exposure does not increase the risk of bovine tuberculosis (BTB) in a herd. Information that became available from the targeted removal of badgers over the study period, and from a badger-removal project in county Kilkenny, during 1996-1999 was used. The specific location of cattle within each farm, and the length of time that cattle spent in each farm field during the grazing season, and in the barnyard during winter, was used to build an exposure coefficient to quantify the amount of badger exposure that cattle encountered either on pasture or in the barn. The study design was a matched case-control study in which the control herds were selected using incidence density sampling. During the 4-year study period, 543 badgers were removed and of these 96 badgers were classified as tuberculosis positive; 96 BTB herd breakdowns occurred. There was a significant association between case herds and having a higher badger sett exposure coefficient during 1996-1998. No significant association between case herds and having a higher exposure coefficient based on the number of badgers, or the number of tuberculous badgers, during September 1997-December 1999 was found.     

Targeted badger removal and the subsequent risk of bovine tuberculosis in cattle herds in county Laois, Ireland

We investigated the impact of targeted removal of badgers on the subsequent bovine tuberculosis (BTB) risk in cattle herds in county Laois, Ireland. The study period was 1989-2005. For each of 122 targeted badger-removal licenses (permit to remove badgers in the proximity of cattle herds undergoing a serious BTB episode), the herd number (index herd) for which the license was given was obtained. The herds in the proximity of the index herd were identified from another database. The main "exposure" in our study was the geographical location of herds relative to the area in which targeted badger removal was conducted. We categorized herds into five different exposure groups: herds were classified as non-exposed and denoted as group 0 (reference group) if they were located 500 m or more from the edge of any parcel of land of the index herd; group 1, was the index herds, group 2 the immediate (contiguous) neighbors of the index herd, group 3 herds were not immediate neighbors but within 150 m and group 4 herds were between 150 m and 500 m distance from the edge of any parcel of land of the index herd, respectively. We conducted a survival analysis (allowing multiple failures per herd) to compare the hazard of having a BTB episode in any of the four groups of exposed herds vs. the hazard in herds in the reference group. We controlled for other known risk factors as well taking into account a temporal component. Our analysis showed that the hazard ratio for the index herds (group 1) were non-significantly increased, indicating that there was no difference in the hazard of failing a BTB test (after the targeted badger removal was conducted) between index herds and reference herds. For the rest of the herds farther away from badger removal activities the hazards were lower than herds in areas not under badger removal. The hazard in the reference group decreased over the study period.     

Farm-level risk factors for the occurrence,new infection or persistence of tuberculosis in cattle herds from South-Central Spain

Eradication of tuberculosis (TB) in cattle is a priority in the EU. However, and despite the resources invested, TB eradication is still a goal yet to be accomplished. As a consequence, the identification of risk factors contributing to TB transmission and persistence is key to a better understand and, ultimately, more cost-effectively control and eradicate this complex zoonotic disease worldwide. This study aimed to identify the factors contributing to the TB occurrence, new infection, and persistence in one of the most TB-prevalent regions in the South-Central part of Spain (SCS), Ciudad Real (CR), and for which high quality and detailed information on cattle and wild ungulate demographics, management, and sanitary status was available for up to 5 years (2007–2011). Multilevel logistic modeling was used for this purpose. Results of this study revealed that the risk for TB (occurrence, new infection, and/or persistence) in cattle herds from CR is related to TB-persistence on farm in previous years, extensive production systems (beef and bullfighting being more risky that dairy) and large farm in terms of cattle number. Also, the presence and proximity of fenced hunting estates (which are usually intensively managed) significantly contributed to the risk of TB occurrence and persistence in CR. This association suggests that wild ungulates may play a role as TB-reservoirs and transmit TB to cattle in the CR, a region where TB is endemic and is associated with extensive farming of beef cattle. To the best of author's knowledge this is the first study to (i) evaluate the wild ungulate-domestic interface at a farm level using detailed information over an extensive region and period of time (2007–2011) and (ii) to identify a direct association between TB in cattle and the proximity and management practices of wild ungulates. Methods and results presented here may support policies to better prevent and control TB in the SCS and in other regions/countries with similar epidemiological conditions.     

Herd-level seroprevalence and risk-mapping of bovine hypodermosis in Belgian cattle herds

Our objective was to determine the seroprevalence of Hypoderma spp. and to develop a spatial model describing the risk surface of warble-fly infection in Belgian cattle herds (adjusting for herd size, herd type, local temperature, rainfall, relative air humidity and land-cover). This survey was carried out in 390 selected herds of all types (dairy, mixed and beef) from December 1997 to March 1998, which were included in a national infectious bovine rhinotracheitis and paratuberculosis (Johne's-disease) survey. All animals >24 months old were blood sampled and an ELISA was used on pooled serum samples (10 animals per pool). The herd seroprevalence was 48.7% (95% confidence interval: 43.6-53.8); positive herds were mainly in the south of the country and along the North Sea coast. The logistic multiple-regression model of herd-level seropositivity indicated that mixed-type and beef-cattle herds have more than four-fold and two-fold increases in the odds of being Hypoderma-positive, respectively, compared with dairy herds.     

Age-dependent patterns of bovine tuberculosis in cattle

Bovine tuberculosis (BTB) is an important livestock disease, seriously impacting cattle industries in both industrialised and pre-industrialised countries. Like TB in other mammals, infection is life long and, if undiagnosed, may progress to disease years after exposure. The risk of disease in humans is highly age-dependent, however in cattle, age-dependent risks have yet to be quantified, largely due to insufficient data and limited diagnostics. Here, we estimate age-specific reactor rates in Great Britain by combining herd-level testing data with spatial movement data from the Cattle Tracing System (CTS). Using a catalytic model, we find strong age dependencies in infection risk and that the probability of detecting infection increases with age. Between 2004 and 2009, infection incidence in cattle fluctuated around 1%. Age-specific incidence increased monotonically until 24–36 months, with cattle aged between 12 and 36 months experiencing the highest rates of infection. Beef and dairy cattle under 24 months experienced similar infection risks, however major differences occurred in older ages. The average reproductive number in cattle was greater than 1 for the years 2004–2009. These methods reveal a consistent pattern of BTB rates with age, across different population structures and testing patterns. The results provide practical insights into BTB epidemiology and control, suggesting that targeting a mass control programme at cattle between 12 and 36 months could be beneficial.     

Impact of the national full herd depopulation policy on the recurrence of bovine tuberculosis in Irish herds, 2003 to 2005

This study evaluated the impact of the Irish herd bovine tuberculosis (bTB) depopulation policy (depopulation, disinfection, contiguous testing and local badger removal where implicated) on the recurrence of bTB infection, by comparing the future risk in restocked herds following depopulation for either bTB or bovine spongiform encephalopathy (BSE) during 2003 to 2005. Each herd was assigned a 'previous bTB risk', based on bTB history during the five years before depopulation. Future bTB risk was estimated, using a multivariable Cox proportional hazard model for time-to-breakdown for each study herd, to identify risk factors associated with bTB. Future bTB risk varied significantly by reason for depopulation and previous bTB risk. Herds depopulated for bTB (by definition, at high bTB risk) were not significantly different from BSE herds with no or a low previous bTB risk. BSE herds with a high previous bTB risk were found to be at significantly greater future bTB risk. Herd bTB depopulation measures, as currently applied in Ireland, are shown to be effective in enabling herds to attain and retain bTB freedom following restocking. Based on the data presented, and consistent with current knowledge of the bTB epidemiology, local badger removal contributes to efforts to limit recurrence of bTB in Ireland.     

A review of tuberculosis science and policy in Great Britain

Bovine tuberculosis is one of the most complex animal health problems that the farming industry in Great Britain faces today. In leading and facilitating the changes to policy required to reverse the long-term upward trend in the disease, Government is heavily reliant on evidence emerging from its wide-ranging bovine tuberculosis research programme. The paper outlines development of policy in Great Britain and its relationship to research findings.     

Seroprevalence of bovine immunodeficiency-like virus and bovine leukemia virus in a dairy cattle herd.

To determine the prevalence of single vs. dual infection with bovine immunodeficiency virus (BIV) and bovine leukemia virus (BLV), sera (n = 95) from a dairy cattle herd were analyzed for anti-BIV and anti-BLV antibodies by an enzyme linked immunosorbent assay. Twenty-one percent (20/95) of samples were BIV-seropositive, while 52% (49/95) of the same samples were BLV-seropositive. A significantly greater percentage of BIV-seronegative samples were BLV-seropositive, 57% (43/75), than were BIV-seropositive samples, 30% (6/20). There was no significant correlation between data ranked from least to greatest amount of anti-viral antibody. Five cattle had persistent lymphocytosis (PL); all five were BLV-seropositive and two were BIV-positive. The mean anti-BLV titer was significantly greater in PL cattle, as compared at non-PL cattle, whereas there was no significant difference between the mean anti-BIV titer in PL cattle, as compared with non-PL cattle. These results provide additional information on the seroprevalence of naturally occurring BIV infection, and indicate that BIV can exist independent of other common infectious agents, such as BLV. Further, the results suggest that infection with BIV is not associated with an increased rate of infection with other infectious agents such as BLV.