Evaluation of a Mask Aerosol Sampling System (MASS) as an Active Case Finding Approach Focused on Infectious TB in Low-Resource Settings. Globally, tuberculosis (TB) is the most important cause of death and disease due to a single bacterial agent. TB is transmitted by aerosols (tiny droplets expelled by coughing and other respiratory efforts) generated by infected individuals. The bacteria-containing droplets are breathed deep into the lungs where, over months and years, disease is produced in about one in ten of those who get the initial infection.  Over one quarter of humanity is infected with the bacterium that causes TB, Mycobacterium tuberculosis (Mtb), but only people who go on to develop lung disease can spread the infection. Mtb must cause lung disease and be spread by aerosols to survive in the long term; if we prevent transmission, eventually the organism will die out and the disease will be eliminated. Thus, detection and treatment of infectious cases is of paramount importance. TB is a disease associated with poverty and, in resource constrained settings, many cases of TB go undiagnosed. This is particularly so in sub-Saharan Africa where healthcare is resource limited. Here, detection of individuals with suggestive symptoms (e.g.  prolonged cough) and Mtb positive sputum (coughed up mucus) provides the main means of diagnosis. However, many symptomatic individuals do not access healthcare, even when enabled to do so by community health workers (CHWs) and a significant proportion (20-50%) are not able to produce sputum. The Leicester team have been developing the use of adapted face masks to capture aerosols in a way that allows detection of Mtb in the World Health Organisation-recommended Mtb detection system, called Xpert MTB/RIF. The mask samples allow detection of Mtb positive individuals at a similar frequency to sputum analysis. However, unlike sputum samples, everyone who can wear a mask produces a sample in our mask aerosol sampling system (MASS). MASS is very low cost and requires only modest expertise to take and analyse the samples. In this project we shall evaluate use of the MASS as a low cost community screening tool. Our study is based in the Tshwane district of South Africa (around 1% are estimated to have lung TB) where the Pretoria team have developed a community oriented primary care (COPC) programme (http://www.up.ac.za/en/family-medicine/article/2077127/launch-video) directed to patient and household (HH) centred health promotion. Building on our established TB aerosol collaboration (MRC and Wellcome Trust funded) and, critically, with the support of the 1670 COPC CHWs, we now plan to evaluate application of MASS as a TB screening tool in Tshwane. If favourable, this evaluation will enable us to develop a large scale intervention trial where we will compare the in-practice capacity of MASS-based screening to detect infectious cases with the conventional approach of symptom and sputum screening. If a high proportion of such cases can be detected and treated, the approach has clear potential to reduce the overall frequency of TB in this and other poor communities. We will first test MASS in the CHWs to optimise the 15 minute procedure and train them for the study. We will then use the standard CHW review programme to detect HHs with individuals showing TB-related symptoms. Following informed consent, all members of such HHs aged 5 years and above will be mask sampled. We aim to sample 120 HHs with symptomatic individuals and expect to detect at least 20-40 positives. In parallel, through data collected from the near 300,000 individuals registered on the COPC programme we will identify 120 HHs matched for key socioeconomic indicators. All members of these HHs will be sampled as above. Symptomatic individuals and MASS positive individuals will all be referred to local clinics for standard diagnosis and treatment. We believe MASS could enable resource-constrained health systems to focus control efforts on the most infectious TB cases and their contacts, thereby reducing transmission and consequently reducing disease. 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.