A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations

Aditya M Rao; Stephen J Popper; Sanjana Gupta; Viengmon Davong; Krista Vaidya; Anisone Chanthongthip; Sabine Dittrich; Matthew T Robinson; Manivanh Vongsouvath; Mayfong Mayxay; Pruksa Nawtaisong; Biraj Karmacharya; Simone A Thair; Isaac Bogoch; Timothy E Sweeney; Paul N Newton; Jason R Andrews; David A Relman; Purvesh Khatri

doi:10.1016/j.xcrm.2022.100842

A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations

Cell Rep Med. 2022 Dec 20;3(12):100842. doi: 10.1016/j.xcrm.2022.100842.

Authors

Aditya M Rao¹, Stephen J Popper², Sanjana Gupta³, Viengmon Davong⁴, Krista Vaidya⁵, Anisone Chanthongthip⁴, Sabine Dittrich⁶, Matthew T Robinson⁶, Manivanh Vongsouvath⁴, Mayfong Mayxay⁷, Pruksa Nawtaisong⁴, Biraj Karmacharya⁵, Simone A Thair³, Isaac Bogoch⁸, Timothy E Sweeney⁹, Paul N Newton⁶, Jason R Andrews², David A Relman¹⁰, Purvesh Khatri¹¹

Affiliations

¹ 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.
² Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.
³ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, 240 Pasteur Dr., Biomedical Innovation Building, Room 1553, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
⁴ Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR.
⁵ Dhulikhel Hospital, Kathmandu University Hospital, Kavrepalanchok, Nepal.
⁶ Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁷ Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit, Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Institute of Research and Education Development (IRED), University of Health Sciences, Ministry of Health, Vientiane, Lao PDR.
⁸ Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁹ Inflammatix Inc., Sunnyvale, CA, USA.
¹⁰ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, 240 Pasteur Dr., Biomedical Innovation Building, Room 1553, Stanford, CA, USA; Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA; Infectious Diseases Section, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
¹¹ Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, 240 Pasteur Dr., Biomedical Innovation Building, Room 1553, Stanford, CA, USA; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA. Electronic address: pkhatri@stanford.edu.

Abstract

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.

Keywords: antimicrobial resistance; bacterial vs. viral diagnosis; gene expression; global health; host response; infectious disease diagnosis; point-of-care diagnostics; public health.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

MeSH terms

Bacterial Infections* / diagnosis
Humans
Prospective Studies
Sensitivity and Specificity
Transcriptome
Virus Diseases* / diagnosis

Abstract

Publication types

MeSH terms

Grants and funding