Sputum host cytokine signatures for diagnosis of TB in children and adults.

Background: Tuberculosis (TB) still remains the world's leading infectious disease killer. New screening and diagnostic tests are urgently needed. We have previously identified a 3-marker host protein signature with high accuracy for TB in sputum from adult Gambian patients. The aim of this project was to analyse host sputum markers in a larger cohort of adults and children with presumptive TB from The Gambia, and to determine the global applicability of such a signature in samples from South Africa, Vietnam and Peru. Methods: Sputum samples were collected at baseline from all symptomatic participants and used for routine diagnostics and biomarker evaluation. Samples were also collected at 1 and 2 months after anti-TB treatment initiation from those who were subsequently found to have TB. For biomarker evaluation, an aliquot of sputum was digested with an equal volume of Sputolysin Results: For Gambian participants (n=428 TB and n=313 other respiratory diseases (ORD)) an 8-marker signature was able to differentiate between smear and culture positive TB from ORD with an AUC of 0.77, while a 3-marker signature classified smear negative TB with an AUC of 0.74. Additionally, a 4-marker signature could discriminate between children (<18 years) with TB (n=17) and those with ORD (n=23) with an AUC of 0.87, sensitivity of 82% and specificity of 87%. A 5-marker global signature was identified with an AUC of 0.71. Conclusion: This study describes the use of host markers in sputum for development of a rapid triage test for pulmonary TB in adults and children. Whilst the results are promising for regional-specific and treatment response signatures, our pilot data do not support development of a global test for TB triage based on sputum host signatures.