By: Sam Abbott
Supervised by: Hannah Christensen, and Ellen Brooks-Pollock
A dissertation submitted to the University of Bristol in accordance with the requirements for award of the degree of Doctor of Philosophy in the Faculty of Health Sciences on the 8th of August 2019.
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.
Links to external chapter resources are given below.
Chapter 3 - getTBinR: an R package for accessing and summarising World Health Organization Tuberculosis data
Chapter 6 - Exploring the effects of BCG vaccination in patients diagnosed with tuberculosis: observational study using the Enhanced Tuberculosis Surveillance system
Chapter 7 - Estimating the effect of the 2005 change in BCG policy in England: A retrospective cohort study
All links for Chapter 8 also apply to Chapters 9 and 10 as well.
Please cite the individual chapter papers/resources as appropriate if used in your work.
This repository has the following structure:
rmds: Thesis chapters as Rmd's.docs: Formatted PhD thesis (html+pdf).plan: Initial aims and objectives + in progress planning.packrat: All R packages required.projects: A backup of all analysis code used for this PhD. Not present on GitHub this folder can be restored usingbash bin/grab_projects.sh projects. Details of all analysis projects can be found in the thesis introduction.data: If using the local version of this thesis all data can be found zipped in this folder. If using a remote version then see the individual chapters for data sources and the following section for further details.review: Examiner comments and my responses from my viva.
See individual chapter text and Rmd documents for additional reproducibility information.
All chapters can be built using the data available in this repository. However the raw data cannot be shared freely. See tbinenglanddataclean for instructions as to the data sources that need to be applied for to reproduce each chapter in this thesis completely. The results in analysis chapters have been ported from their original, fully reproducible repositories. See these repositories for details.
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Install R (analysis run with
3.5.3) and Rstudio (alternatively use Docker as outlined below). -
Download the folder from https://github.com/seabbs/thesis/archive/master.zip or use
git clone, as follows, in the command line (not the R terminal).
git clone https://github.com/seabbs/thesis.git-
Once this has been downloaded click on the project file (
thesis.Rproj). -
Install thesis dependencies using the following.
#install.packages("packrat")
packrat::restore()
# If latex is not installed: tinytex::install_tinytex()-
Build the thesis using
make. Alternatively see theindexfolder for individual chapters. -
See the individual repositories for each chapter for full reproducibility details.
This thesis was developed in a docker container based on the tidyverse docker image. To run the docker image run:
docker run -d -p 8787:8787 --name thesis --mount type=bind,source=$(pwd)/data/tb_data,target=/home/rstudio/thesis/data -e USER=thesis -e PASSWORD=thesis seabbs/thesisThe rstudio client can be found on port :8787 at your local machines ip. The default username:password is thesis:thesis, set the user with -e USER=username, and the password with - e PASSWORD=newpasswordhere. The default is to save the analysis files into the user directory. If running without the accomanying data then remove --mount type=bind,source=$(pwd)/data/tb_data,target=/home/rstudio/thesis/data.
Alternatively the analysis environment can be accessed via binder.