Tuberculosis in England, a high-income Western European setting with low incidence: Recent trends, Social determinants and Prevention through BCG vaccination.

While the tuberculosis (TB) burden in England is low compared to some parts of the word, annual incidence rates have not declined in over two decades, and remain among the highest in developed countries. In the first part of my thesis, I examined trends in TB notifications rates in England with emphasis on the UK-born population, which because of its relatively lower incidence, has received less attention than foreign-born groups. This analysis showed that for nearly two decades, rates have remained mostly stagnant in White UK-born populations, except in the elderly in which rates continue to decline, whereas TB rates have been declining in foreign-born subjects and UK-born ethnic minority groups in the past decade. Given the strong link between poverty and TB, I also investigated the association between socioeconomic deprivation and the risk of TB in England. An ecological analysis suggested that the association between small-area level deprivation and TB rates in a recent 5-year period was much stronger in the UK-born population than in the foreign-born population. To investigate the role of deprivation in the UK-born White population further, I used data from a case-control study of UK-born White young adults in which information was collected on individual-level socio-economic determinants of health. The analysis showed a four times higher risk of TB in subjects with an education level below O-levels compared to those with a degree, as well as an association between increased TB risk and area-level deprivation, tobacco smoking, drug use, and homelessness. In the second part of the thesis, I focused on BCG vaccination, a longstanding part of the TB prevention toolkit, and which has been somewhat overlooked compared to case finding and treatment. I reported a survey of the implementation at the local level of the 2005 change to England’s BCG policy replacing the universal vaccination of schoolchildren by targeted vaccination of higher-risk infants. Heterogeneity in the healthcare service pathways for BCG vaccination was noted, as well as challenges to the identification of, and service delivery to, the targeted groups. I also conducted an ecological study estimating the vaccine uptake in a 3-year period (2006-2008) following the policy change and its association to some area-level factors, with results suggesting that about one third of eligible infants may have missed vaccination. Finally, I conducted a historical cohort study measuring the long-term duration of BCG-derived protection against tuberculosis using data from Norway, a low-incidence setting comparable to England. I found that BCG effectiveness lasts for at least 20 years, longer than previously estimated. Overall, my thesis highlights the existence of stagnant TB rates in UK-born White young adults, and particular social determinants such as tobacco smoking, drug use and homelessness, that are amenable to specific interventions to reduce the risk of TB in a currently neglected population group. It also presents evidence to improve BCG policies targeted at high-risk groups in low-incidence settings and vaccination uptake. The new information on the duration of BCG protection can also help inform any review of the costeffectiveness of BCG vaccination in the general population.