Karonga Prevention Study (KPS) : whole genome sequencing in a whole population: supplementary proposal for tuberculosis whole genome sequencing (360G-Wellcome-096249_B_11_B)

HIV, tuberculosis and pneumococcal disease are leading causes of mortality and morbidity in Africa. They interact, and undermine development. Control measures exist but are inadequate (HIV, tuberculosis) or unproven (pneumococcus). By combining the established large-scale Karonga epidemiological studies and knowledge of long-term disease trends with detailed laboratory and genomic analysis we will: 1. measure pneumococcal carriage, transmission and serotype change at a household level fo llowing pneumococcal conjugate vaccine (PCV) introduction into the EPI schedule, trial alternate PCV schedules, and determine options to maximise vaccine benefits using modelling methods. 2. identify where M.tuberculosis is being transmitted by screening patients at antiretroviral clinics, by tuberculin testing and by defining transmission chains using whole genome sequencing, to target control efforts. 3. establish genomic determinants of virulence in M.tuberculosis by comparing s trains that have transmitted and caused disease with those that have not, and investigate long term non-progression of latent infection to better understand the host and pathogen determinants of M.tuberculosis natural history 4. assess the long-term direct and indirect benefits and limitations of antiretroviral therapy on adults and children. We will continue to develop the capacity of the site as a centre of excellence for research and training, relevant to Malawi.