TB vaccine trials in Kenya Preparation and implementation

BCG, the only licensed vaccine against tuberculosis in use today, protects against severe extrapulmonary forms of TB in humans (miliary and meningeal forms), but offers variable protection against the most common respiratory form of the disease (pulmonary TB), with ranges of efficacy from 0-80% and can produce severe adverse effects in immunocompromised individuals. New vaccines are key to the global effort to eliminate TB. New vaccines will need to protect against pulmonary, extrapulmonary and disseminated TB in all populations and are urgently needed. A vaccine strategy that targets adults and adolescents to reduce TB transmission and infants to reduce TB morbidity and mortality would have great impact on the TB epidemic. TB vaccine trial sites will need to be located in high burden settings and have the infrastructure, staffing and necessary experience to conduct such trials. At the time of conducting epidemiological studies reported in this thesis, Kenya was ranked 10^th by the WHO among countries with the greatest burden of tuberculosis. Western Kenya had a high burden of TB (400/100,000 population) and HIV prevalence (15%), with 75% of TB cases also HIV infected. Epidemiological studies were conducted among adolescents and infants to determine the burden of tuberculosis and inform future TB vaccine trial design. Subsequently, the site took part in two multicenter TB vaccine trials in infants and adults that are also reported in this thesis.