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Abstract
In October 2018, the United Nations General Assembly confirmed its commitment to eliminate tuberculosis by 2030. To achieve this goal, it would be required to urgently reduce the incident cases around the world. This dissertation was designed to further our understanding of what factors contribute to tuberculosis incidence in high and medium burden tuberculosis countries. We founded our work in the model of the cycle of tuberculosis transmission, studying factors that affect both individual and population levels. At the individual level, exposure leads to infection and then disease. The risk from exposure to infection increases according to the contact rate, but the definition of adequate contact for transmission is still poorly understood. In the first and second aims of the study we examined the nature of the interaction between tuberculosis cases and their social contacts in a high-burden country, Uganda and developed a method to estimate adequate contact for transmission of My cobacterium tuberculosis as the conjunction of two domains-setting and relationship. We proved that these domains affected the likelihood of infection with M. tuberculosis for members of a social network of a tuberculosis case, particularly children contacts. At the population level, clustering of cases might indicate a recent transmission chain that feeds again into new infections. In the third aim of this research we characterized the proportion of clustered tuberculosis cases based on genotypic matching in Guatemala between 2010 and 2014, providing for the first time an insight in the molecular epidemiology of tuberculosis in this middle-burden country. We found high levels of ongoing transmission of M. tuberculosis in Guatemala as indicated by clustering in a convenience sample. Moreover, we detected previously unreported strains of M. tuberculosis that contribute to tuberculosis morbidity in the country. Tuberculosis affects disproportionally to the marginalized population. Continued efforts like ours to increase our knowledge and understanding of the factors that contribute to the burden of tuberculosis in low-income settings are urgently required. This work could provide the basis for innovative measures and evidence-based policies that would effectively halt tuberculosis transmission and occurrence in these areas, leading the pathway for a feasible global elimination.