Using machine learning to improve bovine tuberculosis control in herd level outbreaks.

Bovine tuberculosis (bTB), a chronic disease of cattle, is caused by the Mycobacterium bovis infection. Despite having a serious social and economic impact in the United Kingdom and Ireland, there is no antemortem gold standard diagnostic test. Tuberculin skin tests (CICT) are commonly used as a control measure with the interferon gamma (IFN-γ) assay being applied in certain circumstances. This paper utilizes data gathered describing tuberculin regression in reactors (test positive cattle) following the CICT at 72 ± 4 h post injection in herds with large bTB outbreaks. The work then applies machine learning techniques (Decision Trees, Bagging Trees and Random Forests, alongside several balancing approaches) to predict which cattle were likely to be truly infected with tuberculosis, enabling identification of atypical breakdowns that require extra investigation and providing a mechanism for quality assurance of the existing CICT bTB surveillance scheme. The analysis showed that Random Forests (RF) trained using SMOTE balancing had the joint best performance and accuracy (0.90). The importance of the two components of the interferon gamma assay within the RF model also indicated that varying the assay threshold for large outbreaks would be beneficial. Furthermore, the combined use of the RF and IFN- γ models could lead to the improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. An additional use of these models would be for quality assuring the current bTB surveillance based on CICT and post mortem inspection. Quality control is well recognized as an essential component of a disease surveillance/eradication programme.Clinical Relevance- Bovine tuberculosis remains a disease that is hard to control on a national level. The use of the machine learning model could lead to significant improved detection of infection within breakdown herds, reducing the scale and duration of outbreaks. Advanced modelling, such as this, has the potential to strengthen the efficacy of disease surveillance and the eradication strategy and can meaningfully contribute to animal disease national control plans.

Assessing the impact of a test and vaccinate or remove badger intervention project on bovine tuberculosis levels in cattle herds.

Bovine tuberculosis (bTB) is a chronic, zoonotic infection of domestic and wild animals caused mainly by Mycobacterium bovis. The Test and Vaccinate or Remove (TVR) project was a 5-year intervention (2014-2018) applied to Eurasian badgers (Meles meles) in a 100 km2 area of County Down, Northern Ireland. This observational study used routine bTB surveillance data of cattle to determine if the TVR intervention had any effect in reducing the infection at a herd level. The study design included the TVR treatment area (Banbridge) compared to the three adjacent 100 km2 areas (Dromore, Ballynahinch, and Castlewellan) which did not receive any badger intervention. Results showed that there were statistically lower bTB herd incidence rate ratios in the Banbridge TVR area compared to two of the other three comparison areas, but with bTB herd history and number of bTB infected cattle being the main explanatory variables along with Year. This finding is consistent with other study results conducted as part of the TVR project that suggested that the main transmission route for bTB in the area was cattle-to-cattle spread. This potentially makes any wildlife intervention in the TVR area of less relevance to bTB levels in cattle. It must also be noted that the scientific power of the TVR study (76%) was below the recommended 80%, meaning that results must be interpreted with caution. Even though statistical significance was achieved in two cattle-related risk factors, other potential risk factors may have also demonstrated significance in a larger study.

The impact of BCG strains and repeat vaccinations on immunodiagnostic tests in Eurasian badgers (Meles meles).

Bacille Calmette-Guerin (BCG) is a potential tool in the control of Mycobacterium bovis in European badgers (Meles meles). A five year Test and Vaccinate or Remove (TVR) research intervention project commenced in 2014 using two BCG strains (BCG Copenhagen 1331 (Years 1-3/ BadgerBCG) and BCG Sofia SL2222 (Years 4-5). Badgers were recaptured around 9 weeks after the Year 5 vaccination and then again a year later. The Dual-Path Platform (DPP) Vet TB assay was used to detect serological evidence of M. bovis infection. Of the 48 badgers, 47 had increased Line 1 readings (MPB83 antigen) between the Year 5 vaccination and subsequent recapture. The number of BCG Sofia vaccinations influenced whether a badger tested positive to the recapture DPP VetTB assay Line 1 (p < 0.001) while the number of BadgerBCG vaccinations did not significantly affect recapture Line 1 results (p = 0.59). Line 1 relative light units (RLU) were more pronounced in tests run with sera than whole blood. The results from an in_house MPB83 ELISA results indicated that the WB DPP VetTB assay may not detect lower MPB83 IgG levels as well as the serum DPP VetTB assay. Changes in interferon gamma assay (IFN-γ) results were seen in 2019 with significantly increased CFP-10 and PPDB readings. Unlike BadgerBCG, BCG Sofia induces an immune response to MPB83 (the immune dominant antigen in M. bovis badger infection) that then affects the use of immunodiagnostic tests. The use of the DPP VetTB assay in recaptured BCG Sofia vaccinated badgers within the same trapping season is precluded and caution should be used in badgers vaccinated with BCG Sofia in previous years. The results suggest that the DPP VetTB assay can be used with confidence in badgers vaccinated with BadgerBCG as a single or repeated doses.

Evaluating the risk of bovine tuberculosis posed by standard inconclusive reactors identified at backward-traced herd tests in Northern Ireland that disclosed no reactors.

Bovine tuberculosis is a notifiable disease in Northern Ireland with the national eradication programme of compulsory testing and slaughter of reactor animals costing approximately £40 million per year. Backward tracing, known as Backward Check Tests (BCTs), of reactor animals is used to identify previous herds where the bTB positive animal has resided. The aim of this study was to quantify the bovine tuberculosis (bTB) risk posed by inconclusive reactors (ICs) at BCTs at both the individual animal and the herd level. ICs to the Comparative Intradermal Tuberculin Test (CITT) at a BCT, in which no reactors were found, were matched with CITT negative animals, based on age, sex, test ID and follow up period, in Northern Ireland between 1st January 2008 and 31st December 2017 (inclusive). A retrospective matched cohort study design was used with the outcome of interest being the bTB status of each animal and subsequent bTB herd breakdowns. After adjusting for herd size, IC animals at a BCT had 16 times the odds (95% confidence interval: 7.75 to 38.28, p < 0.001) of becoming bTB positive compared to CITT negative animals. The percentage population attributable risk was 0.0001%. The majority 75% (n = 71) of ICs that became bTB positive were identified at the 42 day retest. Of those that were not disclosed at the 42 day retest (n = 24), almost a third (29%) had moved to an unrestricted herd. However, after adjusting for herd size and type, herds that had ICs only identified at a BCT did not have an increased odds of a subsequent bTB herd breakdown compared to herds that had a CITT negative BCT. Given the increased risk posed by ICs at a BCT, it may be justifiable to remove them from the herd immediately or place them under lifetime movement restrictions to the herd where they were detected. However, further action regarding the herd of origin does not appear to be justified.

The regression of the bovine tuberculin reaction: Results from the Reactor Quality Assurance study in Northern Ireland.

Tuberculin skin tests remain widely used in the control of bovine tuberculosis (bTB) in cattle. Little is known about the rate of regression of tuberculin reactions after the comparative intradermal cervical test (CICT) in cattle. This study aimed to collect data to describe tuberculin regression in reactors following the CICT at 72 ± 4 h post injection. Reactors were also tested using the interferon gamma (IFN-γ) assay to establish if any pattern existed between these results and the CICT reaction regression. The data were derived from 108 herds, 112 herd-level CICTs and 1008 animals. A multivariable linear mixed model was built to explore the regression of the bovine tuberculin reaction over time and the influence of potential predictors. The results confirmed a proportional decline in the bovine tuberculin reaction occurred over time. The predictors in the final model demonstrated that regression of the tuberculin reaction differed between reactors according to their IFN-γ test results and whether visible lesions were present at slaughter. Follow-up measurement of tuberculin reactions and the serial use of the IFN-γ assay in large breakdowns has the potential to provide both a mechanism for quality assurance of the current CICT bTB surveillance and the identification of atypical breakdowns or reactors requiring further investigation.

Test and vaccinate or remove: Methodology and preliminary results from a badger intervention research project.

BACKGROUND: In the British Isles, it is generally accepted that the Eurasian badger (Meles meles) plays a role in the maintenance of bovine tuberculosis (bTB) in cattle. Non-selective culling is the main intervention method deployed in controlling bTB in badgers along with smaller scale Bacillus Calmette-Guérin (BCG) vaccination areas. This paper describes the use of selective badger culling combined with vaccination in a research intervention trial. METHODS: In Northern Ireland, a 100 km2 area was subjected to a test and vaccinate or remove (TVR) badger intervention over a 5-year period. Badgers were individually identified and tested on an annual basis. Physical characteristics and clinical samples were obtained from each unique badger capture event. RESULTS: A total of 824 badgers were trapped with 1520 capture/sampling events. There were no cage-related injuries to the majority of badgers (97%). A low level of badger removal was required (4.1%-16.4% annually), while 1412 BCG vaccinations were administered. A statistically significant downward trend in the proportion of test positive badgers was observed. CONCLUSION: This is the first project to clearly demonstrate the feasibility of cage side testing of badgers. The results provide valuable data on the logistics and resources required to undertake a TVR approach to control Mycobacterium bovis in badgers.

A Bayesian analysis of a Test and Vaccinate or Remove study to control bovine tuberculosis in badgers (Meles meles).

A novel five year Test and Vaccinate or Remove (TVR) wildlife research intervention project in badgers (Meles meles) commenced in 2014 in a 100km2 area of Northern Ireland. It aimed to increase the evidence base around badgers and bovine TB and help create well-informed and evidence-based strategies to address the issue of cattle-to-cattle spread and spread between cattle and badgers. It involved real-time trap-side testing of captured badgers and vaccinating those that tested negative for bTB (BadgerBCG-BCG Danish 1331) and removal of those that tested bTB positive using the Dual-Path Platform VetTB test (DPP) for cervids (Chembio Diagnostic Systems, Medford, NY USA). Four diagnostic tests were utilised within the study interferon gamma release assay (IGRA), culture (clinical samples and post mortem), DPP using both whole blood and DPP using serum. BCG Sofia (SL222) was used in the final two years because of supply issues with BadgerBCG. Objectives for this study were to evaluate the performance of the DPP in field conditions and whether any trend was apparent in infection prevalence over the study period. A Bayesian latent class model of diagnostic test evaluation in the absence of a gold standard was applied to the data. Temporal variation in the sensitivity of DPP and interferon gamma release assay (IGRA) due to the impact of control measures was investigated using logistic regression and individual variability was assessed. Bayesian latent class analysis estimated DPP with serum to have a sensitivity of 0.58 (95% CrI: 0.40-0.76) and specificity of 0.97 (95% CrI: 0.95-0.98). The DPP with whole blood showed a higher sensitivity (0.69 (95% CrI: 0.48-0.88)) but similar specificity (0.98 (95% Crl: 0.96-0.99)). The change from BCG Danish to BCG Sofia significantly impacted on DPP serum test characteristics. In addition, there was weak evidence of increasing sensitivity of IGRA over time and differences in DPP test sensitivity between adults and cubs. An exponential decline model was an appropriate representation of the infection prevalence over the 5 years, with a starting prevalence of 14% (95% CrI: 0.10-0.20), and an annual reduction of 39.1% (95% CrI: 26.5-50.9). The resulting estimate of infection prevalence in year 5 of the study was 1.9% (95% CrI: 0.8-3.8). These results provide field evidence of a statistically significant reduction in badger TB prevalence supporting a TVR approach to badger intervention. They give confidence in the reliability and reproducibility in the DPP Whole Blood as a real time trap-side diagnostic test for badgers, and describe the effect of vaccination and reduced infection prevalence on test characteristics.

Genetic evidence further elucidates the history and extent of badger introductions from Great Britain into Ireland.

The colonization of Ireland by mammals has been the subject of extensive study using genetic methods and forms a central problem in understanding the phylogeography of European mammals after the Last Glacial Maximum. Ireland exhibits a depauperate mammal fauna relative to Great Britain and continental Europe, and a range of natural and anthropogenic processes have given rise to its modern fauna. Previous Europe-wide surveys of the European badger (Meles meles) have found conflicting microsatellite and mitochondrial DNA evidence in Irish populations, suggesting Irish badgers have arisen from admixture between human imported British and Scandinavian animals. The extent and history of contact between British and Irish badger populations remains unclear. We use comprehensive genetic data from Great Britain and Ireland to demonstrate that badgers in Ireland's northeastern and southeastern counties are genetically similar to contemporary British populations. Simulation analyses suggest this admixed population arose in Ireland 600-700 (CI 100-2600) years before present most likely through introduction of British badgers by people. These findings add to our knowledge of the complex colonization history of Ireland by mammals and the central role of humans in facilitating it.

The population and landscape genetics of the European badger (Meles meles) in Ireland.

The population genetic structure of free-ranging species is expected to reflect landscape-level effects. Quantifying the role of these factors and their relative contribution often has important implications for wildlife management. The population genetics of the European badger (Meles meles) have received considerable attention, not least because the species acts as a potential wildlife reservoir for bovine tuberculosis (bTB) in Britain and Ireland. Herein, we detail the most comprehensive population and landscape genetic study of the badger in Ireland to date-comprised of 454 Irish badger samples, genotyped at 14 microsatellite loci. Bayesian and multivariate clustering methods demonstrated continuous clinal variation across the island, with potentially distinct differentiation observed in Northern Ireland. Landscape genetic analyses identified geographic distance and elevation as the primary drivers of genetic differentiation, in keeping with badgers exhibiting high levels of philopatry. Other factors hypothesized to affect gene flow, including earth worm habitat suitability, land cover type, and the River Shannon, had little to no detectable effect. By providing a more accurate picture of badger population structure and the factors effecting it, these data can guide current efforts to manage the species in Ireland and to better understand its role in bTB.

Pathogenic potential to humans of bovine Escherichia coli O26, Scotland.

Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin-producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx(2) in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26-associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx(2) phage acquisition.

BCG vaccination against tuberculosis in European badgers (Meles meles): a review.

Tuberculosis (TB) is a significant animal health problem in many parts of the world, and reservoirs of infection in wild animals complicate disease control efforts in farmed livestock, particularly cattle. Badgers (Meles meles) are a significant wildlife reservoir of Mycobacterium bovis infection for cattle in the United Kingdom (UK) and Republic of Ireland (ROI). Vaccination of badgers using an M. bovis strain bacille Calmette-Guérin (BCG) vaccine could potentially be an option in the national TB eradication strategy. Wildlife vaccination has been used successfully for other diseases in wildlife species, and may have a role to play in reducing M. bovis transmission at the wildlife-livestock interface. Research to date has provided evidence that BCG is protective in badgers, and a parenteral badger BCG vaccine has been licensed in the UK. Further research is required to develop effective strategies for vaccine deployment and to determine the effect of badger vaccination on cattle TB incidence.

Clinical factors associated with death before discharge and overall survival time in dogs with generalized megaesophagus.

OBJECTIVE: To investigate the association of 6 clinical features with outcome of dogs with generalized megaesophagus. DESIGN: Retrospective cohort study. ANIMALS: 71 client-owned dogs with radiographic evidence of generalized esophageal dilation. PROCEDURES: Medical records were reviewed for data on signalment, age at onset of clinical signs, body weight, evidence of undernutrition, and the administration of drugs to treat or prevent esophagitis. Radiographs were reviewed for evidence of aspiration pneumonia (AP) and to calculate the relative esophageal diameter. Details of outcome were collected from the medical records and by contacting owners and referring veterinarians. The association of 6 factors with death before discharge and overall survival time was assessed. RESULTS: Overall median survival time was 90 days. Nineteen (26.7%) patients died before discharge from the hospital. Radiographic evidence of AP was both positively associated with death before discharge and negatively associated with overall survival time. An age at onset of clinical signs of >13 months was negatively associated with overall survival time. No evidence of an association of the degree of esophageal dilation or the use of drugs to prevent or treat esophagitis with death before discharge or overall survival time was found. CONCLUSIONS AND CLINICAL RELEVANCE: Radiographic evidence of AP and the age at onset of clinical signs were the only variables found to be significantly associated with survival time in this study, and this should be considered when advising on prognosis in dogs with megaesophagus.

Radiographic diameter of the colon in normal and constipated cats and in cats with megacolon.

Radiographs of 50 cats with no history of gastrointestinal disease were evaluated to establish a normal reference range for radiographic diameter of the feline colon. Thirteen cats with constipation and 26 with megacolon were also evaluated and compared with the normal cats to characterize the accuracy of the reference range and to identify a cutoff to distinguish constipation from megacolon. A ratio of maximal diameter of the colon to L5 length was the most repeatable and accurate measurement. A ratio <1.28 is a strong indicator of a normal colon (sensitivity 96%, specificity 87%). A value >1.48 is a good indicator of megacolon (sensitivity 77%, specificity 85%).

Epidemiological analysis of tick-borne diseases in Zambia.

Tick-borne diseases are a constraint to livestock production in many developing countries as they cause high morbidity and mortality, which results in decreased production of meat, milk and other livestock by-products. The most important tick-borne diseases of livestock in sub-Saharan Africa are East Coast fever (caused by Theileria parva), babesiosis (caused by Babesia bigemina and B. bovis), anaplasmosis (caused by Anaplasma marginale) and heartwater (caused by Ehrlichia ruminantium). Despite their economic importance, information on the epidemiology of these diseases in many countries, including Zambia, is often inadequate, making rational disease control strategies difficult to implement. In this study 18S and 16S rRNA gene PCR assays were used for a comprehensive epidemiological analysis of tick-borne disease of cattle in three provinces of Zambia (Lusaka, Central and Eastern). All the disease pathogens under study (T. parva, T. mutans, T. taurotragi, B. bovis, B. bigemina, Anaplasma spp and E. ruminantium) were prevalent in each of the provinces surveyed. However, variation was observed in prevalence between regions and seasons. There was no association between live vaccination against East Coast fever and being PCR positive for T. parva. A number of risk factors were shown to be associated with (a) the occurrence of tick-borne pathogens in cattle and (b) cattle tick burdens in the wet season. A negative association was observed between the number of co-infecting pathogens and the erythrocyte packed cell volume (PCV) of carrier cattle.

Prevalence and risk factors for feline obesity in a first opinion practice in Glasgow, Scotland.

A cross-sectional questionnaire study of cat owners registered with a first opinion veterinary practice was undertaken in July 2008. The body condition score (BCS) of the cats was assessed by the interviewer using a validated five point scale. Owners also rated their cat's BCS using five word descriptions. In total, 118 questionnaires were collected. The prevalence of overweight or obese cats (BCS 4 or 5) was 39% (30.2-47.8%, n=61). Risk factors associated with overweight or obesity were frequency of feeding and neutered status. There was moderate agreement between owner and interviewer rating of BCS. Owner misperception was more likely when owners rated cats with BCS 1 (very thin) and 4 (overweight) and in longhaired cats. The study highlights the continuing need for owner education in feline nutrition and specifically the requirement for veterinarians to develop strategies to help owners correct their assessment of their cat's BCS.

A comparison of the effects of two different doses of ketamine used for co-induction of anaesthesia with a target-controlled infusion of propofol in dogs.

OBJECTIVE: To assess the cardiorespiratory and hypnotic-sparing effects of ketamine co-induction with target-controlled infusion of propofol in dogs. STUDY DESIGN: Prospective, randomized, blinded clinical study. ANIMALS: Ninety healthy dogs (ASA grades I/II). Mean body mass 30.5 +/- SD 8.6 kg and mean age 4.2 +/- 2.6 years. METHODS: All dogs received pre-anaesthetic medication with acepromazine (0.03 mg kg(-1)) and morphine (0.2 mg kg(-1)) administered intramuscularly 30 minutes prior to induction of anaesthesia. Heart rate and respiratory rate were recorded prior to pre-medication. Animals were allocated into three different groups: Group 1 (control) received 0.9% NaCl, group 2, 0.25 mg kg(-1) ketamine and group 3, 0.5 mg kg(-1) ketamine, intravenously 1 minute prior to induction of anaesthesia, which was accomplished using a propofol target-controlled infusion system. The target propofol concentration was gradually increased until endotracheal intubation was possible and the target concentration at intubation was recorded. Heart rate, respiratory rate and noninvasive blood pressure were recorded immediately prior to induction, at successful intubation and at 3 and 5 minutes post-intubation. The quality of induction was graded according to the amount of muscle twitching and paddling observed. Data were analysed using a combination of chi-squared tests, Fisher's exact tests, Kruskal-Wallis, and anova with significance assumed at p < 0.05. RESULTS: There were no significant differences between groups in the blood propofol targets required to achieve endotracheal intubation, nor with respect to heart rate, noninvasive blood pressure or quality of induction. Compared with the other groups, the incidence of post-induction apnoea was significantly higher in group 3, but despite this dogs in this group had higher respiratory rates overall. CONCLUSIONS AND CLINICAL RELEVANCE: Under the conditions of this study, ketamine does not seem to be a useful agent for co-induction of anaesthesia with propofol in dogs.

Ex vivo evaluation of the effect of tibial plateau osteotomy on the proximal tibial soft tissue envelope with and without the use of protective gauze sponges.

OBJECTIVE: To investigate the effect of tibial plateau leveling osteotomy (TPLO) on the proximal tibial soft tissue envelope with and without use of protective gauze sponges, and to determine whether the action of an oscillating saw blade on the gauze sponges would result in retention of particulate cotton debris. STUDY DESIGN: Cadaveric study. ANIMALS: Medium to large breed dog cadavers (n=10; 20 pelvic limbs). METHODS: TPLO was performed using the currently recommended technique involving dissection of the proximal tibial soft tissue envelope and its protection using cotton gauze sponges. In paired limbs, the procedure was repeated but no attempt was made to retract and protect the proximal tibial soft tissue envelope. Damage to the soft tissue envelope and presence of gross particulate cotton debris were investigated by direct observation and photographic analysis. Presence of microscopic cotton debris was investigated using light microscopic analysis of wound lavage fluid. RESULTS: No soft-tissue trauma was found in gauze sponge-protected specimens. When protective gauze sponges were not used, full-thickness (sagittal plane) lacerations to the caudoproximal tibial muscle group occurred in all specimens with a mean craniocaudal width of 9.5 mm (range 2-12 mm). The cranial tibial muscle was traumatized in only 1 specimen without protective gauze sponges. Trauma to the popliteal vessels was not identified in any specimen. No gross cotton debris was identified, but microscopic cotton fibers (diameter, 7-35 microm) were identified in lavage fluid from all gauze sponge-protected specimens. CONCLUSIONS: Use of protective gauze sponges is effective in protecting the proximal tibial soft tissue envelope from an oscillating TPLO saw blade, but results in retention of microscopic cotton particulate debris within the operative site. Significant soft tissue trauma is seen only in the caudoproximal tibial muscle group if protective gauze sponges are not used. CLINICAL RELEVANCE: Retraction and protection of the caudoproximal tibial soft tissue envelope is recommended during TPLO; however, to prevent retention of microscopic particulate cotton debris, alternatives to cotton gauze sponges should be considered as protective devices.