Long term studies to tuberculosis and HIV in Karonga District, Malawi (360G-Wellcome-081825_Z_06_Z)

The natural history of tuberculosis has not been completely elucidated. This is attributable to two factors: the length and complexity of its pathogenesis (involving primary, reactivation or reinfection disease which may develop over decades), and the complexity of its immune regulation (which involves T cell mechanisms which may only contain but not eradicate infection, and which are influenced by cross-reactive antigens from related mycobacterial species). Tuberculosis in Karonga district has been studied over a period of 20 years and we have accumulated a unique body of data examining from many different perspectives. In addition, Karonga is representative of areas where tuberculosis is a significant source of morbidity and mortality especially in conjunction with HIV, and thus information gained from this community can be generalised to other areas in sub-Saharan Africa. In addition to monitoring of disease incidence, based on sputum culture of all TB suspects in the district since 1986, there have been major studies of infection risk (based on more than 100,000 tuberculin tests during the 1980s), drug sensitivity, BCG efficacy (including a trial of two versus one dose), immunotherapy, chemoprophylaxis, risk factors for infection and disease (including HIV, genetics, helminth infection, and contact, as well as socio-economic factors), infection transmission (based on molecular fingerprinting) and a series of studies probing the immune response to BCG. In more recent studies which are in preparation for publication, I and my colleagues have explored recurrent disease (distinguishing relapse and reinfection), contact patterns during illness, and risk of infection and disease and associated immune responses among spouses of cases (the latter study led by the late Frank Mwaungulu [epidemiologist] and Anne Ben-Smith [immunologist]). The intention of this proposal is to add important pieces to this wealth of information, and to integrate all these data into a comprehensive analysis and description of tuberculosis in this population.