Plasma multiomics distinguishes pulmonary tuberculosis from other respiratory infections

Novel blood-based biomarkers for tuberculosis (TB) are needed to develop rapid, point-of-care diagnostics. We sought to use combined plasma metabolomics and high-density cytokine profiling to identify a biomarker signature that can differentiate pulmonary TB (PTB) from patients hospitalized with other respiratory diseases and ambulatory household contacts with TB symptoms. We analyzed plasma concentrations of 28 cytokines and 118 metabolites from 391 adults (≥18 years) presenting with respiratory symptoms suggestive of TB, of which 187 had PTB confirmed by Xpert MTB and/or M. tuberculosis sputum culture and 204 were controls in whom PTB was excluded. Our study identified a 5-marker signature (IFN.gamma, IL.22, IL.10, methionine and oxoproline) with an AUC of 0.97 (95% CI: 0.95-1.00) in the test set. The signature had 98% and 84% sensitivity at 70% and 98% specificity respectively, which meet WHO target product profiles for both non-sputum triage and diagnostic TB tests.