Now showing 1 - 3 of 3
  • Publication
    Quantification of Mycobacterium bovis transmission in a badger vaccine field trial
    In the UK and Ireland, Bacille Calmette-Guérin (BCG) vaccination of badgers has been suggested as one of a number of strategies to control or even eradicate Mycobacterium bovis infection in badgers. In this manuscript, we present the results of a badger field trial conducted in Ireland and discuss how the novel trial design and analytical methods allowed the effects of vaccination on protection against infection and, more importantly, on transmission to be estimated. The trial area was divided into three zones North to South (A, B and C) where vaccination coverages of 0, 50 and 100%, respectively, were applied. Badgers were trapped over a 4 year period. Badgers were assigned to either placebo or vaccine treatment, with treatment allocation occurring randomly in zone B. Blood samples were collected at each capture, and serology was performed in these samples using a chemiluminescent multiplex ELISA system (Enfer test). The analysis aimed to compare new infections occurring in non-infected non-vaccinated badgers to those in non-infected vaccinated ones, while accounting for the zone in which the badger was trapped and the infection pressure to which this individual badger was exposed. In total, 440 records on subsequent trappings of individual non-infected badgers were available for analysis. Over the study period, 55 new infections occurred in non-vaccinated (out of 239 = 23.0%) and 40 in vaccinated (out of 201 = 19.9%) badgers. A Generalized Linear Model (GLM) with a cloglog link function was used for analysis. Statistical analysis showed that susceptibility to natural exposure with M. bovis was reduced in vaccinated compared to placebo treated badgers: vaccine efficacy for susceptibility, VES, was 59% (95% CI = 6.5%–82%). However, a complete lack of effect from BCG vaccination on the infectivity of vaccinated badgers was observed, i.e. vaccine efficacy for infectiousness (VEI) was 0%. Further, the basic reproduction ratio as a function of vaccination coverage (p) (i.e. R(p)) was estimated. Given that the prevalence of M. bovis infection in badgers in endemic areas in Ireland is approximately 18%, we estimated the reproduction ratio in the unvaccinated population as R(0) = 1.22. Because VESwas now known, the reproduction ratio for a fully vaccinated population was estimated as R(1) = 0.50. These results imply that with vaccination coverage in badgers exceeding 30%, eradication of M. bovis in badgers in Ireland is feasible, provided that the current control measures also remain in place.
    Scopus© Citations 32  370
  • Publication
    Quantification of Mycobacterium bovis transmission in a badger vaccine field trial
    In the UK and Ireland, Bacille Calmette-Guérin (BCG) vaccination of badgers has been suggested as one of a number of strategies to control or even eradicate Mycobacterium bovis infection in badgers. In this manuscript, we present the results of a badger field trial conducted in Ireland and discuss how the novel trial design and analytical methods allowed the effects of vaccination on protection against infection and, more importantly, on transmission to be estimated. The trial area was divided into three zones North to South (A, B and C) where vaccination coverages of 0, 50 and 100%, respectively, were applied. Badgers were trapped over a 4 year period. Badgers were assigned to either placebo or vaccine treatment, with treatment allocation occurring randomly in zone B. Blood samples were collected at each capture, and serology was performed in these samples using a chemiluminescent multiplex ELISA system (Enfer test). The analysis aimed to compare new infections occurring in non-infected non-vaccinated badgers to those in non-infected vaccinated ones, while accounting for the zone in which the badger was trapped and the infection pressure to which this individual badger was exposed. In total, 440 records on subsequent trappings of individual non-infected badgers were available for analysis. Over the study period, 55 new infections occurred in non-vaccinated (out of 239 = 23.0%) and 40 in vaccinated (out of 201 = 19.9%) badgers. A Generalized Linear Model (GLM) with a cloglog link function was used for analysis. Statistical analysis showed that susceptibility to natural exposure with M. bovis was reduced in vaccinated compared to placebo treated badgers: vaccine efficacy for susceptibility, VES, was 59% (95% CI = 6.5%–82%). However, a complete lack of effect from BCG vaccination on the infectivity of vaccinated badgers was observed, i.e. vaccine efficacy for infectiousness (VEI) was 0%. Further, the basic reproduction ratio as a function of vaccination coverage (p) (i.e. R(p)) was estimated. Given that the prevalence of M. bovis infection in badgers in endemic areas in Ireland is approximately 18%, we estimated the reproduction ratio in the unvaccinated population as R(0) = 1.22. Because VEs was now known, the reproduction ratio for a fully vaccinated population was estimated as R(1) = 0.50. These results imply that with vaccination coverage in badgers exceeding 30%, eradication of M. bovis in badgers in Ireland is feasible, provided that the current control measures also remain in place.
    Scopus© Citations 32  417
  • Publication
    Optimising and evaluating the characteristics of a multiple antigen ELISA for detection of Mycobacterium bovis infection in a badger vaccine trial
    A long-term research programme has been underway in Ireland to evaluate the usefulness of badger vaccination as part of the national bTB (bovine tuberculosis) control strategy. This culminated in a field trial which commenced in county Kilkenny in 2009 to determine the effects of badger vaccination on Mycobacterium bovis transmission in badgers under field conditions. In the present study, we sought to optimise the characteristics of a multiplex chemiluminescent assay for detection of M. bovis infection in live badgers. Our goal was to maximise specificity, and therefore statistical power, during evaluation of the badger vaccine trial data. In addition, we also aimed to explore the effects of vaccination on test characteristics. For the test optimisation, we ran a stepwise logistic regression with analytical weights on the converted Relative Light Units (RLU) obtained from testing blood samples from 215 badgers captured as part of culling operations by the national Department of Agriculture, Food and the Marine (DAFM). The optimised test was applied to two other datasets obtained from two captive badger studies (Study 1 and Study 2), and the sensitivity and specificity of the test was attained separately for vaccinated and non-vaccinated badgers. During optimisation, test sensitivity was maximised (30.77%), while retaining specificity at 99.99%. When the optimised test was then applied to the captive badger studies data, we observed that test characteristics did not vary greatly between vaccinated and non-vaccinated badgers. However, a different time lag between infection and a positive test result was observed in vaccinated and non-vaccinated badgers. We propose that the optimized multiplex immunoassay be used to analyse the vaccine trial data. In relation to the difference in the time lag observed for vaccinated and non-vaccinated badgers, we also present a strategy to enable the test to be used during trial evaluation.
    Scopus© Citations 9  225