Katharina Kranzer and colleagues investigate the operational characteristics of an active tuberculosis case-finding service linked to a mobile HIV testing unit that operates in underserviced areas in Cape Town, South Africa., Background The World Health Organization is currently developing guidelines on screening for tuberculosis disease to inform national screening strategies. This process is complicated by significant gaps in knowledge regarding mass screening. This study aimed to assess feasibility, uptake, yield, treatment outcomes, and costs of adding an active tuberculosis case-finding program to an existing mobile HIV testing service. Methods and Findings The study was conducted at a mobile HIV testing service operating in deprived communities in Cape Town, South Africa. All HIV-negative individuals with symptoms suggestive of tuberculosis, and all HIV-positive individuals regardless of symptoms were eligible for participation and referred for sputum induction. Samples were examined by microscopy and culture. Active tuberculosis case finding was conducted on 181 days at 58 different sites. Of the 6,309 adults who accessed the mobile clinic, 1,385 were eligible and 1,130 (81.6%) were enrolled. The prevalence of smear-positive tuberculosis was 2.2% (95% CI 1.1–4.0), 3.3% (95% CI 1.4–6.4), and 0.4% (95% CI 1.4 015–6.4) in HIV-negative individuals, individuals newly diagnosed with HIV, and known HIV, respectively. The corresponding prevalence of culture-positive tuberculosis was 5.3% (95% CI 3.5–7.7), 7.4% (95% CI 4.5–11.5), 4.3% (95% CI 2.3–7.4), respectively. Of the 56 new tuberculosis cases detected, 42 started tuberculosis treatment and 34 (81.0%) completed treatment. The cost of the intervention was US$1,117 per tuberculosis case detected and US$2,458 per tuberculosis case cured. The generalisability of the study is limited to similar settings with comparable levels of deprivation and TB and HIV prevalence. Conclusions Mobile active tuberculosis case finding in deprived populations with a high burden of HIV and tuberculosis is feasible, has a high uptake, yield, and treatment success. Further work is now required to examine cost-effectiveness and affordability and whether and how the same results may be achieved at scale., Editors' Summary Background In 2010, 8.8 million people developed active tuberculosis—a contagious bacterial infection—and 1.4 million people died from the disease. Most of these deaths were in low- and middle-income countries and a quarter were in HIV-positive individuals—people who are infected with HIV, the virus that causes AIDS, are particularly susceptible to tuberculosis because of their weakened immune system. Tuberculosis is caused by Mycobacterium tuberculosis, which is spread in airborne droplets when people with the disease cough or sneeze. Its characteristic symptoms are a persistent cough, unintentional weight loss, hemoptysis (coughing up blood from the lungs), fever, and night sweats. Diagnostic tests for tuberculosis include sputum smear microscopy (microscopic analysis of mucus brought up from the lungs by coughing) and culture (growth) of M. tuberculosis from sputum samples. Tuberculosis can be cured by taking several powerful antibiotics daily for at least 6 months. Why Was This Study Done? To improve tuberculosis control, active disease must be diagnosed quickly and treated immediately. Passive tuberculosis case finding, which relies on people seeking medical help because they feel unwell, delays the diagnosis and treatment of tuberculosis and increases M. tuberculosis transmission. By contrast, active tuberculosis case finding—where health workers seek out and diagnose individuals with TB who have not sought care on their own initiative—has the potential to reduce tuberculosis transmission by improving case detection. The World Health Organization (WHO), which already recommends active tuberculosis case finding in HIV-infected individuals as part of its HIV/TB “Three I's” strategy, is currently developing guidelines to inform the design of national tuberculosis screening strategies based on the local prevalence of HIV and TB and other context-specific factors that affect how many individuals need to be screened to identify each additional new tuberculosis case (the “yield” of active case finding). Large gaps in our knowledge about mass-screening strategies are complicating the development of these guidelines so, in this observational prospective study, the researchers assess the feasibility, uptake, yield, treatment outcomes, and costs of adding an active tuberculosis case-finding program to an existing mobile HIV testing service in South Africa. What Did the Researchers Do and Find? All HIVnegative adults with symptoms characteristic of tuberculosis and all HIV-positive adults regardless of symptoms who attended a mobile HIV testing service operating in deprived communities in ape Town, South Africa between May 2009 and February 2011 were eligible for inclusion in the study. Of the 6,309 adults who accessed the mobile clinic during this period, 1,385 met these eligibility criteria, and 1,130 were enrolled and referred for the collection of sputum samples, which were analyzed by microscopy and culture. The prevalence of smear-positive tuberculosis was 2.2%, 3.3%, and 0.4% among HIV-negative study participants, newly diagnosed HIV-positive participants, and people already known to have HIV, respectively. The corresponding prevalences for smear-negative/culture-positive tuberculosis were 5.3%, 7.4%, and 4.3%, respectively (culture detects more tuberculosis cases than microscopy but, whereas microscopy can provide a result within 1–2 days, culture can take several weeks). Fifty-six new tuberculosis cases were identified, 42 people started tuberculosis treatment, and 34 completed treatment (a treatment success rate of 81%). Finally, the incremental cost of the intervention was US$1,117 per tuberculosis case detected and US$2,458 per tuberculosis case cured. What Do These Findings Mean? These findings show that active case finding for tuberculosis delivered through a mobile HIV testing service is feasible and has a high uptake, yield and treatment success in deprived communities with a high prevalence of HIV and tuberculosis. The findings also highlight the challenges faced by mobile population-based services such as losses between tuberculosis diagnosis and treatment, which were greatest for smear-negative/culture-positive people who were more difficult to contact than smear-positive people because of the greater time lag between sputum collection and diagnosis. Because the study was done in a single city, these findings need to be confirmed in other settings—the yield of active tuberculosis case finding reported here, for example, is not likely to be generalizable to countries that rely on sputum smears for tuberculosis diagnosis. Finally, given that the incremental cost per case treated in this study is 3-fold higher than the incremental cost per case treated under passive case detection in South Africa, further studies are needed to determine the cost-effectiveness and affordability of population-based tuberculosis screening. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001281. The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis and HIV, and on the Three I?s for HIV/TB (some information is in several languages); details of a 2011 meeting on the development of guidelines on screening for active tuberculosis are available The Stop TB partnership is working towards tuberculosis elimination; patient stories about tuberculosis/HIV coinfection are available The US Centers for Disease Control and Prevention has information about tuberculosis, about tuberculosis and HIV co-infection, and about the diagnosis of tuberculosis disease The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis MedlinePlus has links to further information about tuberculosis (in English and Spanish) The Tuberculosis Survival Project, which aims to raise awareness of tuberculosis and provide support for people with tuberculosis, provides personal stories about treatment for tuberculosis; the Tuberculosis Vaccine Initiative also provides personal stories about dealing with tuberculosis