To further investigate the influence of background LTBI on classifier performance, separate comparisons were made between active TB and symptomatic controls either with or without LTBI. In both comparisons, active TB could be distinguished from symptomatic controls with overall classifier accuracies of at least 87% (Table 2, Table 3 , Figure 5 c-f, Tables S1 and 2). Active TB was readily distinguishable from symptomatic controls without LTBI using both crude and fractionated plasma, with overall accuracies, sensitivities and specificities of at least 90% (Table 2,  Table 3 , Figure 5 e,f and Table S1 and S2). The main influence of LTBI among the symptomatic controls was to reduce classifier specificity, reflected in a higher proportion of false positives. Strikingly, plasma pre-fractionation improved specificity from 75% to 82% only using four m/z clusters (Table 2, Table 3 , Figure 5 c,d, p,0.001) .