Preface

A dissertation submitted to the University of Bristol in accordance with the requirements of the degree of Doctor of Philosophy in the Faculty of Health Sciences.

Abstract

Bacillus Calmette–Guérin (BCG) remains the only licensed vaccine against Tuberculosis (TB). In 2005, England changed from universal vaccination of school-age children to targeted vaccination of high-risk neonates. Little work has been done to assess the impact of this policy change. This thesis evaluates the impact of this change. Whilst the characteristics of TB in England have been reported elsewhere, little attention has been given to the role of BCG. Consequently, I explored and combined, the available data sources. Reporting on data quality issues, trends in incidence rates and differences in outcomes stratified by BCG status. Prior to the change in policy, several studies were carried out to assess the impact. I recreated one such study and found that there was a greater impact than previously thought. Determining the benefits of being BCG vaccinated is necessary to properly assess the impact of the policy change. I evaluated the evidence that vaccination may improve outcomes for TB cases in England and found that there was some evidence of an association between vaccination and reduced mortality. Surveillance data can help assess whether changes in vaccination policy have influenced incidence rates. I used surveillance data to determine whether those at school-age, or neonates, were affected by the policy change. I found that the policy change was associated with increased notifications in the UK born but this was outweighed by a reduction in notifications in the non-UK born. Statistical modelling is restricted by the available data. Therefore, I developed a dynamic model of TB, fit to available data, to forecast the impact of the policy change. Although the fit to the data was poor, the forecasts suggested that continuing school-age vaccination reduced TB incidence in the UK born compared with neonatal vaccination. Neonatal vaccination reduced incidence in children but had little impact on other age groups.

Acknowledgements

Thank you to Ellen Brooks-Pollock and Hannah Christensen, for supervising this thesis and for providing guidance and support. I would also like to thank Matthew Hickman for providing additional supervisory support. This thesis could not have been completed with out the support of the Tuberculosis section at Public Health England. Of particular help were: Maeve K Lalor, Dominik Zenner, and Colin Campbell. Mary Ramsay, also at Public Health England, provided invaluable insights. Nicky Welton provided support with the statistical methodology used in Chapter 7 - thank you. This work was funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Evaluation of Interventions at University of Bristol in partnership with Public Health England. Thank you for this opportunity. Thank you to my friends and family for providing support over 4 years.

Finally, thank you to my partner, Venexia Walker, without whom this would definitely have gone unfinished.