Our present findings confirm the utility of defining the host proteomic response in distinguishing clinically overlapping patient (5) Total number of mass/charge (m/z) clusters obtained from SELDI-ToF profiling of crude and pre-fractionated plasma. In brackets number of relevant discriminatory m/z clusters selected by the RFE algorithm. F1 = fraction 1 at pH 9; F2 = fraction 2 at pH 7; F3 = fraction 3 at pH 5; F4 = fraction 4 at pH 4; F5 = fraction 5 at pH 3; F6 = fraction 6 organic phase. doi:10.1371/journal.pone.0038080.t003 groups in a TB clinic setting. Moreover, this study shows that active TB can be identified by a blood test in a population of community TB clinic attenders, on a background of non-TB attributable symptoms, despite the coexistence of LTBI. Ultimately, a significant impact on control of TB in high prevalence settings will depend on the ability to translate these findings into a robust, affordable point-of-care format. Incorporation of a panel of biomarkers derived from this study into a lateral flow device or similar platform is the logical next step. Finally, the utility of defining proteomic patterns in TB may extend beyond diagnostics to provide new methods for monitoring treatment response and disease stage.