A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations.
Rao AM., Popper SJ., Gupta S., Davong V., Vaidya K., Chanthongthip A., Dittrich S., Robinson MT., Vongsouvath M., Mayxay M., Nawtaisong P., Karmacharya B., Thair SA., Bogoch I., Sweeney TE., Newton PN., Andrews JR., Relman DA., Khatri P.
Limited sensitivity and specificity of current diagnostics lead to the erroneous prescription of antibiotics. Host-response-based diagnostics could address these challenges. However, using 4,200 samples across 69 blood transcriptome datasets from 20 countries from patients with bacterial or viral infections representing a broad spectrum of biological, clinical, and technical heterogeneity, we show current host-response-based gene signatures have lower accuracy to distinguish intracellular bacterial infections from viral infections than extracellular bacterial infections. Using these 69 datasets, we identify an 8-gene signature to distinguish intracellular or extracellular bacterial infections from viral infections with an area under the receiver operating characteristic curve (AUROC) > 0.91 (85.9% specificity and 90.2% sensitivity). In prospective cohorts from Nepal and Laos, the 8-gene classifier distinguished bacterial infections from viral infections with an AUROC of 0.94 (87.9% specificity and 91% sensitivity). The 8-gene signature meets the target product profile proposed by the World Health Organization and others for distinguishing bacterial and viral infections.