Tuberculosis: epidemiology and host susceptibility in north west England

UoM administered thesis: Master of Philosophy

  • Authors:
  • Marko Petrovic

Abstract

Tuberculosis (TB) is a highly infectious disease caused by the mycobacterium M.Tuberculosis. TB has a long history of causing major loss of life and has always been associated with poverty, poor living conditions and high population density. Although TB prevalence in developed countries has been significantly reduced in modern times through the introduction of antibiotics and better public hygiene, it has never been eliminated completely and it remains a major clinical and public health issue in third World and developing countries. Increased population movement, world travel and migration present significant additional exposure to infected and silent cases. In addition, antibiotic and drug resistant strains of TB are now causing a major concern. National surveillance and registration of TB cases provides an important mechanism for intelligence gathering and management. Various factors have been identified or considered to be important in determining who is susceptible or resistant to TB and affecting the course and outcome of the disease.The broad aim of the study was to contribute to the evidence base regarding the epidemiology of TB in the North West of England and to investigate the role of ultraviolet B, vitamin D receptor and regulatory genes in its underlying pathogenesis.A central objective of this study was to describe the epidemiology of TB in the North West of England and to identify key TB risk groups. This would enable recommendations for further public health actions. A further objective was to ascertain if dietary intake of vitamin D and level of sunlight exposure as determinants of vitamin D availability andiipolymorphisms of genes involved the regulation of Vitamin D levels (VDR and MCR1) were associated with being a TB case. As a strong biological case has previously been made for the involvement of immune pathway components in the resistance/susceptibility to TB, including both macrophage activation and the balance of T1 and T2 lymphocyte regulation of antibody versus cell mediated immunity, gene polymorphisms in TNFalpha, INFγ, IL4 and IL10 genes were examined as potential TB associated risk factors.A detailed review of the literature and data relating to the prevalence and incidence of TB and TB drug resistant forms in the UK and other countries across the world is included as a context for presenting and analysing the epidemiology of TB ETS surveillance data collected for the NW of the UK between 1999 and 2010. In 2010, there were 828 cases of TB in the NW which equates to an incidence of 12 cases per 100,000 and is the highest recorded NW regional incidence since ETS began. This rate was 42% higher than in 2004. The highest numbers of case reports and rates were consistently in the 15-34 year age group. Rates have increased in the 0-14 year age group, particularly in Greater Manchester, since 2004. The highest rates have, apart form 1999, been in those with Black African ethnicity, with an upward trend until 2008, and from then a year on year decrease. In 2010, 67% were resident in the most deprived quintile of the NW. A relationship between TB and multiple deprivation score was retained after the effect of ethnicity was statistically allowed for. The proportion of isolates with isoniazid resistance ranged between 3.1% and 7% per annum. The proportion with multi-drug resistance (i.e. resistance to at least rifampicin and isoniazid) ranged from 0.2%-1.8% per annum, with no overall trend.iiiFollowing gaining ethical approval, invitations to participate into the research project were extended to NW UK TB cases who had beenregistered in the study time window but whop were now TB free. The invitation was extended to both such cases and to a gender and age matched friend controls. The study included completion of an epidemiological questionnaire and proving a saliva sample for DNA extraction and genotyping. A range of approach methods were introduced to increase study participation. Of the 73 responders no significant difference in age or gender was observed as compared to these variables in non-responders. Response rates were significantly higher for those registered in 2009 compared to those registered 2004-2008. The highest non-response rate was seen in those of Pakistani origin. On examination of the data no differences were observed between cases and controls for intake of fish oils or dietary supplements containing vitamin D. No differences were seen for sunlight exposures. DNA samples from cases and matched controls were genotyped for a range of Tagging snp's from INF g, IL10, TNF a, IL4 and VDR genes using Sequenom Mass spectrometry. A further large control group DNA samples from the Manchester Aging Cohort were also genotyped for comparison and increase statistical power. No significant genetic associations were observed with TB status. The genotyping suffered from serious limitations of statistical power due to limited numbers of cases. These limitations are discussed. The public health implications of variations and trends in TB incidence rates and drug resistance are discussed.

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Original languageEnglish
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Award date31 Dec 2016