Host-response transcriptional biomarkers accurately discriminate bacterial and viral infections of global relevance

Emily R. Ko*, Megan E. Reller, L. Gayani Tillekeratne, Champica K. Bodinayake, Cameron Miller, Thomas W. Burke, Ricardo Henao, Micah T. McClain, Sunil Suchindran, Bradly Nicholson, Adam Blatt, Elizabeth Petzold, Ephraim L. Tsalik, Ajith Nagahawatte, Vasantha Devasiri, Matthew P. Rubach, Venance P. Maro, Bingileki F. Lwezaula, Wasantha Kodikara-Arachichi, Ruvini KurukulasooriyaAruna D. De Silva, Danielle V. Clark, Kevin L. Schully, Deng Madut, J. Stephen Dumler, Cecilia Kato, Renee Galloway, John A. Crump, Geoffrey S. Ginsburg, Timothy D. Minogue, Christopher W. Woods

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Diagnostic limitations challenge management of clinically indistinguishable acute infectious illness globally. Gene expression classification models show great promise distinguishing causes of fever. We generated transcriptional data for a 294-participant (USA, Sri Lanka) discovery cohort with adjudicated viral or bacterial infections of diverse etiology or non-infectious disease mimics. We then derived and cross-validated gene expression classifiers including: 1) a single model to distinguish bacterial vs. viral (Global Fever-Bacterial/Viral [GF-B/V]) and 2) a two-model system to discriminate bacterial and viral in the context of noninfection (Global Fever-Bacterial/Viral/Non-infectious [GF-B/V/N]). We then translated to a multiplex RT-PCR assay and independent validation involved 101 participants (USA, Sri Lanka, Australia, Cambodia, Tanzania). The GF-B/V model discriminated bacterial from viral infection in the discovery cohort an area under the receiver operator curve (AUROC) of 0.93. Validation in an independent cohort demonstrated the GF-B/V model had an AUROC of 0.84 (95% CI 0.76–0.90) with overall accuracy of 81.6% (95% CI 72.7–88.5). Performance did not vary with age, demographics, or site. Host transcriptional response diagnostics distinguish bacterial and viral illness across global sites with diverse endemic pathogens.

Original languageEnglish (US)
Article number22554
JournalScientific Reports
Volume13
Issue number1
DOIs
StatePublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s).

ASJC Scopus subject areas

  • General

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