A randomised controlled trial (RCT) to evaluate a scalable active case finding primary care-based intervention for tuberculosis using a point-of-care TB remains the foremost infectious disease killer globally. A starling statistic is that 2 out of every 5 TB cases globally (40%) remain undiagnosed and untreated. These 'missed' or undiagnosed cases are disproportionately concentrated in large peri-urban 'slums' and informal settlements of large cities in Africa and Asia (they are frequently minimally symptomatic but remain infectious). TB will never be brought under control unless this large reservoir of transmission is wiped out. The lack of a sensitive low cost same-day test represented a major challenge to active community-based case finding (ACF) compared to the current model where patients 'self-seek' care (passive case finding). More recently, sensitive TB DNA-detection tests called Gene Xpert (Xpert) have become available. Small portable battery-operated versions of these tests are now available (OMNI). We conducted a large study in South Africa and Zimbabwe (published in 2016) that showed that using the old non-portable version of Xpert on a mini-truck equipped with a generator was feasible and highly effective for ACF. In a subsequent study funded by the American government (XACT II) we showed that using the portable version of Xpert on the back of a small low-cost scalable panel van (in effect a mobile mini clinic) was feasible and had a very high pick-up rate of TB in peri-urban communities (~10% of those undergoing targeted screening; see preliminary data).   In the proposed study (XACT III) we will use the same approach, but we need to be sure that such a strategy is scalable and feasible in different settings where the challenges and conditions vary. More importantly, we need to methodologically optimise the ACF model. Thus, we need to determine where Xpert (the diagnostic test) should be optimally placed from a physical location point-of-view, i.e. do we really need to install it on the mobile mini clinic, or, can it be located in centralised laboratories (as it is now) with samples being sent to these laboratories? This is a very important question: we know that sending collected sputum samples to centralised laboratories will be much easier as it uses existing infrastructure, however, the downside is between 20 and 40% of patients fail to come back to collect their results (pre-treatment loss to follow-up; PTLF). Using the diagnostic in the mobile mini van (at point-of-care; POC) dramatically reduces this PTLF enabling quick diagnosis and interrupting transmission. To definitively settle the question we need a study using the 2 different strategies to find out which strategy is most cost-effective yet can rapidly pick up the most cases and minimise transmission.  There are 2 other important sub-questions that the study will answer. Chest x-rays, which can identify people at high risk of having TB, can now be automatically read by a computer algorithm (called computer-assisted diagnosis of TB; CAD-TB). It will be very important to know whether mass screening using CAD-TB can triage individuals i.e. narrow the net so that we target the ACF only to those at high risk of having TB. This could save even more money yet be just as effective.  Secondly, a fundamental unanswered question is why individuals with minimal or no symptoms can be highly infectious (transmit disease)? We need to study this phenomenon in greater detail using cough aerosol readouts, chest x rays, and looking at the TB strains. This might provide medical science with the information it needs to design diagnostic or therapeutic interventions to address this important problem.   However, the key priority now is to show that the XACT approach is feasible in different settings and to clarify how the molecular diagnostics should be optimally located. Answering these questions will allow the initiation of ACF programmes in many countries and will contribute critical data to policy makers so that guidelines on ACF can be disseminated and implemented. 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.