New Tuberculosis Vaccine Trials in Infants: design, diagnostics and trial site development

Tuberculosis is a major public health problem, with particularly high morbidity and mortality among infants. The only licensed TB vaccine, BCG confers only partial protection against pulmonary disease, the most common and most transmissible form of the disease. Novel TB vaccines with better efficacy are urgently needed as part of the armoury of tools to eliminate TB by 2050. To properly design and implement these trials, several factors need to be borne in mind. These include, the most suited trial population, estimates of disease incidence, cohort retention and mortality. There are also diagnostic considerations, such as the utility of the chest radiograph and the possible role of the more prevalent non-tuberculous mycobacteria in confounding TB diagnosis. Finally, there are practical factors related to selection and development of research sites with the required trial infrastructure and expertise in high burden countries. This thesis explored the factors of design of new tuberculosis vaccine trials, diagnostic considerations and process of site development.