Determining the importance of different locations to Mycobacterium tuberculosis transmission in high tuberculosis burden settings Over nine and a half million people worldwide developed tuberculosis (TB) in 2014, and 1.5 million died from the disease. Current control strategies are insufficient, with global TB incidence falling by only 1-2% per year. Despite its importance as a global public health problem, very little is known about where Mycobacterium tuberculosis transmission (M.tb., the bacterium that causes the majority of TB disease) occurs, particularly in high burden countries such as South Africa. This is primarily because it is difficult to know whether someone has been recently infected, and it can be decades between infection and disease. Studies of social contacts have been useful in giving some indication of which locations may be important to M.tb. transmission. However, these studies are insufficient to estimate where the majority of transmission occurs, for three main reasons:  1) There is a lot of variation in the infectiousness of people with TB disease, and in how susceptible people are to infection and disease (e.g. people living with HIV are at increased risk). For this reason, chance meetings between the most infectiousness and susceptible people are likely be very important to overall transmission in a population. These meetings are most likely to occur in the places where numbers of new people met are highest, but these locations may not be the places where people spend most time, or where people meet the most other people per visit. 2) Transmission is likely to occur more often in crowded, badly ventilated buildings with little natural light. 3) Transmission is likely to be more common in places that are both visited by people with TB, and also visited by the people most susceptible to TB (e.g. clinics).   In this study, we will develop a better understanding of where M.tb. transmission occurs in high TB burden countries, and use this information to inform strategies to reduce TB death and suffering. We will use Cape Town, South Africa, as a case study. We have four main tasks:  1) Develop a model of people's contacts and infection transmission to investigate how variation in susceptibility and infectiousness affects where transmission occurs, for M.tb. and other infections. 2) Collect new data using questionnaires that will allow us to estimate the proportion of contacts that are between people who have not met before, by location. We will also collect data on the levels of ventilation and natural light in different types of location. 3) Using the new data we have collected, as well as existing data, build a model of M.tb. transmission by location. Using this model, we will estimate the proportion of transmission that occurs in different locations in Cape Town. 4) Adapt the model to represent contact patterns, susceptibility levels (e.g. HIV prevalence), and levels of M.tb. transmission in other high burden sub-Saharan African settings. We can then estimate in what types of location transmission may be common in other countries. We will also investigate what the most effective locations are to target using infection control interventions (e.g. improving ventilation or installing ultraviolet (U.V.) lights).  This study will help to fill a major gap in our understanding of TB: where does transmission occur? This has very real, practical implications. Trials of U.V. lights suggest that they may reduce transmission by 70-80%, and improving ventilation can also be very effective in preventing infections. These infection control measures are often implemented in TB clinics, but we currently do not know where else they should be targeted. Our results will inform the targeting of infection control measures, and if successful, should lead to reductions in M.tb. transmission, and in TB death and suffering. Our new understanding should also contribute to meeting the 2025 WHO End TB Strategy targets in high TB burden settings, the settings most in need of novel, innovative, and cost effective prevention strategies. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.