Bovine Brucellosis in Gauteng, South Africa: Seroprevalence amongst Cattle Handlers and Variables Associated with Seropositive Cattle Herds, 2014-2016.

In South Africa, the prevalence of cattle handler exposure to Brucella on cattle farms is unknown and risk factors and cattle symptoms associated with infected cattle herds are unavailable. To address this gap, a case-control study of cattle herds was conducted in Gauteng province and farm workers and veterinary officials were tested for exposure to Brucella. Seroprevalence amongst farm workers exposed to case herds ranged from 4.0% (BrucellaCapt®) to 16.7% (IgG ELISA®), compared to those exposed to control herds, where seroprevalence ranged from 1.9% (BrucellaCapt®) to 5.7% (IgG ELISA®). Seroprevalence amongst veterinary officials was significantly greater compared to farm workers exposed to case herds for the outcome RBT+ IgM- IgG+ (OR = 11.1, 95% CI: 2.5-49.9, p = 0.002) and RBT- IgM- IgG+ (OR = 6.3, 95% CI: 2.3-17.3, p < 0.001). Risk factors associated with being an infected herd were: being a government-sponsored farm vs. private farm (OR 4.0; 95% CI: 1.4-11.3; p = 0.009), beef vs. dairy herd (OR 7.9; 95% CI: 1.4-44.9; p = 0.020), open vs. closed herd (OR 3.3; 95% CI: 1.1-10.4; p = 0.038) and the presence of antelope on the farm (OR 29.4; 95% CI: 4.0-218.2; p = 0.001). Abortions (OR = 5.1; 95% CI: 2.0-13.3; p < 0.001), weak calves in the herd (OR = 8.0; 95% CI: 2.6-24.4; p < 0.001), reduction in number of calves born (OR = 9.0; 95% CI: 2.1-43.6; p < 0.001), reduction in conception rate (OR = 3.9; 95% CI: 0.8-18.3; p = 0.046), hygromas in cattle (p = 0.011) and farmers reporting brucellosis-like symptoms in their farm workers or in him/herself (OR = 3.4; 95% CI: 1.3-8.7; p = 0.006) were more likely to be associated with Brucella infected herds than control herds. This evidence can be used in strategic planning to protect both human and herd health.

Knowledge of Brucellosis, Health-Seeking Behaviour, and Risk Factors for Brucella Infection amongst Workers on Cattle Farms in Gauteng, South Africa.

Brucellosis in humans is under-detected and underreported in sub-Saharan Africa. Risk factors associated with Brucella infection and health seeking behaviour in response to brucellosis-like symptoms, amongst cattle farm workers and veterinary officials in South Africa, are unknown. Farm workers and veterinary officials (N = 230) were screened for brucellosis using commercial Rose Bengal Test (RBT®), IgM Enzyme-linked Immunoassay (ELISA)®, IgG ELISA® and the BrucellaCapt® test. Knowledge of brucellosis and risk factors for exposure to Brucella were also investigated. Seroprevalence varied according to test used: 10.1% (RBT®), 20.9% (IgG ELISA®) and 6.5% (BrucellaCapt®). Only 22.2% (6/27) of veterinary officials opt to visit a clinic, doctor, or hospital in response to self-experienced brucellosis-like symptoms, compared to 74.9% (152/203) of farm workers (p < 0.001). Of the BrucellaCapt® seropositive participants, 53% (7/15) did not visit a clinic in response to brucellosis-like symptoms. Weak evidence of an association between the handling of afterbirth or placenta and infection of a short evolution (RBT®, IgM ELISA® and IgG ELISA® seropositive) was found (OR = 8.9, 95% CI: 1.0-81.1, p = 0.052), and strong evidence of an association between this outcome and the slaughter of cattle (OR = 5.3, 95% CI: 1.4-19.6, p = 0.013). There was strong evidence of a positive association between inactive/resolved infection and veterinary officials vs. farm workers exposed to seropositive herds (OR = 7.0, 95% CI: 2.4-20.2, p < 0.001), with a simultaneous negative association with the handling of afterbirth or placenta (OR = 3.9, 95% CI: 1.3-11.3, p = 0.012). Findings suggest a proportion of undetected clinical cases of brucellosis amongst workers on cattle farms in Gauteng.

Methodology and preliminary results of a systematic literature review of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis.

A systematic review was conducted to identify studies with data for statistical meta-analyses of sensitivity (Se) and specificity (Sp) of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis (bTB) in cattle. Members of a working group (WG) developed and tested search criteria and developed a standardised two-stage review process, to identify primary studies with numerator and denominator data for test performance and an agreed range of covariate data. No limits were applied to year, language, region or type of test in initial searches of electronic databases. In stage 1, titles and available abstracts were reviewed. References that complied with stage 1 selection criteria were reviewed in entirety and agreed data were extracted from references that complied with stage 2 selection criteria. At stage 1, 9782 references were reviewed and 261 (2.6%) passed through to stage 2 where 215 English language references were each randomly allocated to two of 18 WG reviewers and 46 references in other languages were allocated to native speakers. Agreement regarding eligibility between reviewers of the same reference at stage 2 was moderate (Kappa statistic = 0.51) and a resolution procedure was conducted. Only 119 references (published 1934-2009) were identified with eligible performance estimates for one or more of 14 different diagnostic test types; despite a comprehensive search strategy and the global impact of bTB. Searches of electronic databases for diagnostic test performance data were found to be nonspecific with regard to identifying references with diagnostic test Se or Sp data. Guidelines for the content of abstracts to research papers reporting diagnostic test performance are presented. The results of meta-analyses of the sensitivity and specificity of the tests, and of an evaluation of the methodological quality of the source references, are presented in accompanying papers (Nuñez-Garcia et al., 2017; Downs et al., 2017).

Evaluation of the methodological quality of studies of the performance of diagnostic tests for bovine tuberculosis using QUADAS.

There has been little assessment of the methodological quality of studies measuring the performance (sensitivity and/or specificity) of diagnostic tests for animal diseases. In a systematic review, 190 studies of tests for bovine tuberculosis (bTB) in cattle (published 1934-2009) were assessed by at least one of 18 reviewers using the QUADAS (Quality Assessment of Diagnostic Accuracy Studies) checklist adapted for animal disease tests. VETQUADAS (VQ) included items measuring clarity in reporting (n = 3), internal validity (n = 9) and external validity (n = 2). A similar pattern for compliance was observed in studies of different diagnostic test types. Compliance significantly improved with year of publication for all items measuring clarity in reporting and external validity but only improved in four of the nine items measuring internal validity (p < 0.05). 107 references, of which 83 had performance data eligible for inclusion in a meta-analysis were reviewed by two reviewers. In these references, agreement between reviewers' responses was 71% for compliance, 32% for unsure and 29% for non-compliance. Mean compliance with reporting items was 2, 5.2 for internal validity and 1.5 for external validity. The index test result was described in sufficient detail in 80.1% of studies and was interpreted without knowledge of the reference standard test result in only 33.1%. Loss to follow-up was adequately explained in only 31.1% of studies. The prevalence of deficiencies observed may be due to inadequate reporting but may also reflect lack of attention to methodological issues that could bias the results of diagnostic test performance estimates. QUADAS was a useful tool for assessing and comparing the quality of studies measuring the performance of diagnostic tests but might be improved further by including explicit assessment of population sampling strategy.

Meta-analyses of the sensitivity and specificity of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis in the UK and Ireland.

Bovine Tuberculosis (bTB) in cattle is a global health problem and eradication of the disease requires accurate estimates of diagnostic test performance to optimize their efficiency. The objective of this study was, through statistical meta-analyses, to obtain estimates of sensitivity (Se) and specificity (Sp), for 14 different ante-mortem and post-mortem diagnostic tests for bTB in cattle. Using data from a systematic review of the scientific literature (published 1934-2009) diagnostic Se and Sp were estimated using Bayesian logistic regression models adjusting for confounding factors. Random effect terms were used to account for unexplained heterogeneity. Parameters in the models were implemented using Markov Chain Monte Carlo (MCMC), and posterior distributions for the diagnostic parameters with adjustment for covariates (confounding factors) were obtained using the inverse logit function. Estimates for Se and/or Sp of the tuberculin skin tests and the IFN-γ blood test were compared with estimates published 2010-2015. Median Se for the single intradermal comparative cervical tuberculin skin (SICCT) test (standard interpretation) was 0.50 and Bayesian credible intervals (CrI) were wide (95% CrI 0.26, 0.78). Median Sp for the SICCT test was 1.00 (95% CrI 0.99, 1.00). Estimates for the IFN-γ blood test Bovine Purified Protein Derivative (PPD)-Avian PPD and Early Secreted Antigen target 6 and Culture Filtrate Protein 10 (ESAT-6/CFP10) ESAT6/CFP10 were 0.67 (95% CrI 0.49, 0.82) and 0.78 (95% CrI 0.60, 0.90) respectively for Se, and 0.98 (95% CrI 0.96, 0.99) and 0.99 (95% CrI 0.99, 1.00) for Sp. The study provides an overview of the accuracy of a range of contemporary diagnostic tests for bTB in cattle. Better understanding of diagnostic test performance is essential for the design of effective control strategies and their evaluation.

A matched cohort study investigating the risk of Mycobacterium bovis infection in the progeny of infected cows.

The aim of this study was to quantify the risk of bovine tuberculosis in the progeny of cows confirmed as having bovine tuberculosis. Historical computerised records were used to undertake a retrospective cohort study. The exposed cohort was defined as the last calf of dams that were diagnosed as having bovine tuberculosis during 2002. The progeny were only retained for subsequent analysis if they were born in the 9 months preceding slaughter of the dam and if they lived for more than 15 months. The unexposed cohort comprised of animals born in the same herd within 1 month of the exposed cohort and was matched one-to-one. The resultant dataset contained 1156 matched cohorts. Forty-two animals from the exposed cohort and 35 from the unexposed cohort had bovine tuberculosis. The relative risk was estimated at 1.2 (95% confidence interval 0.8-1.79). It was concluded that progeny of tuberculous dams were not at a significantly increased risk of Mycobacterium bovis infection.

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.