Serological tests are simple, do not require significant laboratory infrastructure, and have been commercialized into user-friendly platforms for a variety of diseases. microbead immunoassay to measure antibody responses to 28 (antigens using an in-house multiplex microbead immunoassay. We compared the median difference of the antibody response to each antigen between patients with and without culture-confirmed TB, ranked each antigen according to variable importance (VIM), and assessed the sensitivity and specificity of combinations of antibody responses using an advanced classification algorithm, SuperLearner. Results Among the 237 patients included in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and 113 (48%) had TB. Median antibody levels to eight antigens were significantly different between patients with and without TB. A panel including eight of the top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a specificity of 88.6% NOS3 (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38, Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be 90%, specificity remained close to 70% with as few as 3 antigens included in the panels. Conclusions Measuring antibody responses to combinations of antigens could facilitate TB screening and should be further evaluated in populations SJ572403 being targeted for systematic screening. Background In order to meet ambitious tuberculosis (TB) elimination targets, the World Health Organization (WHO) now recommends systematic screening of high-risk groups[1]. Screening for active disease has several benefits, including improved patient outcomes and reduced transmission through detection and treatment of TB at an earlier stage[2]. To facilitate screening, the WHO target product profile for a TB screening test recommends a minimum sensitivity of 90% and minimum specificity of 70% [3, 4]. These targets were selected to minimize the number of false-negative results in those with TB, and to limit the need for unnecessary and costly diagnostic testing in those without TB. In addition, the target product profile calls for a low-cost and simple-to-perform assay that could be performed by front-line health workers at community health centers[4, 5]. Unfortunately, the lack of a screening strategy that meets all of these criteria is a major challenge for uptake of the systematic screening guidelines. Current algorithms for TB screening typically include symptoms (cough greater that 2 weeks in duration, or any TB symptom such as cough of any duration, night sweats, fevers or weight loss) and/or chest radiography[1]. The sensitivity and specificity of symptom-based screening are highly variable depending on the population being screened. For SJ572403 example, sensitivity is high and specificity is low in people living with HIV, but the opposite is true in people without HIV infection[6]. Chest radiography more consistently meets minimum accuracy requirements for a TB screening tests, but requires infrastructure and personnel often not found in community health centers where patients first seek care. Thus, there is an urgent need for a point-of-care screening test to rapidly and accurately screen patients for active TB[7]. Serologic tests are a promising approach to screening as they meet the nontechnical requirements for a TB screening test. Serological tests are simple, do not require significant laboratory infrastructure, and have been commercialized into user-friendly platforms for a variety of diseases. However, current commercial TB serologic tests detect responses to one or at most two (antigens in TB individuals and healthy settings in Pakistan inside a multiplex microbead immunoassay using the Luminex platform (Austin, TX). SJ572403 They recognized a panel of antibody reactions to 8 antigens that experienced high level of sensitivity and specificity (90% and 80%, respectively)[10]. This multiplex assay can be performed inside a user-friendly and high-throughput format. Studies in additional settings and that enroll individuals with a medical suspicion of.