The Molecular Epidemiology of Tuberculosis and the Impact of HIV Infection and Antiretroviral Therapy

This thesis investigates the epidemiology of tuberculosis (TB) disease in populations. It applies molecular epidemiological methods to elucidate the relative effects of HIV on TB disease following recent first infection, reactivation and recent reinfection with Mycobacterium tuberculosis (Mtb). Finally it aims to explore the impact of Antiretroviral Therapy (ART) on the incidence of TB in a population in rural Sub Saharan Africa. The data in chapters 2 and 3 is taken from a systematic literature review I performed of population based studies that reported TB molecular epidemiological data. In the subsequent chapters I analyse existing and newly collected data from the Karonga Prevention Study, set in Northern Malawi, to address the research questions. The results strongly suggest that HIV-infection increases an individual’s risk of TB disease due to recent Mtb (re)infection more than through reactivation in populations with generalised HIV epidemics. The last chapter suggests that patients on ART experience a high risk of TB compared to HIV positive/ART naive patients, especially in the first months after initiating ART. Also, it appears that after the introduction of ART in 2005 TB incidence in Karonga District plateaued after declining in the previous 10 years. These findings strongly suggest that TB programmes in areas with generalised HIV epidemics should focus more of their efforts on reducing Mtb transmission. Improved collaboration between TB and ART programmes may help to reduce TB rates in the highly vulnerable ART receiving population and subsequently in the general population.