Molecular epidemiology of tuberculosis in the Midlands

Data from this thesis has extended our understanding of the molecular epidemiology and transmission of Mycobacterium tuberculosis in the Midlands. A novel DNA fingerprinting method called Mycobacterial Interspersed Repetitive Units containing Variable Number Tandem Repeats (MIRU-VNTR) typing provided equivalent results when compared to the current gold standard for DNA fingerprinting (IS6110 RFLP). To improve our understanding of TB in the Midlands, MIRU-VNTR typing was then developed to be assayed by non-dHPLC for the first time. Using this high-throughput rapid method a prospective and universal typing study was undertaken. This work identified the predominance of the Euro-American and East African Indian global clades in the Midlands and linked them to particular human population groups using novel software based on names. DNA fingerprinting also discovered the most prevalent single strain in the Midlands. This strain is geographically restricted to the West Midlands within the UK and globally. From this geographical association, we have called this strain the "Mercian" strain. The Mercian strain was not associated with patients who originated from the Indian Sub-Continent but was significantly associated with UK-born, Black Caribbean patients in Wolverhampton. These findings show that strains have been imported into the Midlands from around the world and there has also been continued transmission of these and other strains which may have been present in the Midlands for years. Molecular tools developed in this thesis will have regional, national, and international impact on TB control.EThOS - Electronic Theses Online ServiceGBUnited Kingdo