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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.

Original publication

DOI

10.1016/j.xcrm.2022.100842

Type

Journal

Cell reports. Medicine

Publication Date

12/2022

Volume

3

Addresses

Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, 240 Pasteur Dr., Biomedical Innovation Building, Room 1553, Stanford, CA, USA; Immunology Graduate Program, Department of Medicine, Stanford University, Stanford, CA, USA.

Keywords

Humans, Bacterial Infections, Virus Diseases, Sensitivity and Specificity, Prospective Studies, Transcriptome