Penn-Nicholson A, et al. - For ultimate translation into a point-of-care diagnostic, researchers sought to develop a proteomic biomarker of risk of tuberculosis (TB) progression in this prospective cohort study. Through either active (every 6 months) or passive 2-year follow-up, proteomic TB risk signatures were found in a longitudinal cohort of 6,363 Mycobacterium tuberculosis-infected, HIV-negative South African adolescents (aged 12-18 years) who partook in the Adolescent Cohort Study (ACS) between July 6, 2005, and April 23, 2007. Within a year of diagnosis, both proteomic TB risk signatures predicted progression to incident TB. These were the first proteomic prognostic signatures for TB that have been validated, though neither fulfill the minimum criteria described for a progression test in the WHO Target Product Profile. There is a need for more work to create such a test for the real-world identification of individuals in whom to investigate incipient, subclinical, or active TB disease for appropriate treatment and care.