Host gene expression in the Nasopharynx can discriminate microbiologically confirmed viral and bacterial lower respiratory tract infection

Sep 29, 2026

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Distinguishing viral versus bacterial lower respiratory tract infection (LRTI) remains challenging because clinical presentations overlap and current diagnostics often target specific pathogens with limited sensitivity or scope. This study evaluates a rapid host-response test (Biomeme HR-B/V assay) using nasopharyngeal samples on the Franklin platform, comparing a prior classifier with a newly developed predictive model using 24 gene targets. Performance is reported with receiver operating characteristics and validation on external nasal/NP RNA sequence datasets, supporting nasopharyngeal host gene expression as a discriminator of viral versus bacterial LRTI.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Introduction

Methods

Results

Conclusions

Introduction

Clinical challenge of LRTI etiology

Limitations of pathogen-based diagnostics

Role of host response-based diagnostics

Journal of Clinical and Translational Science [www.cambridge.org/cts](www.cambridge.org/cts) Research Article Cite this article: Tillekeratne LG, O’Grady N, Iglesias-Ussel MD, Anderson J, Brown A, Obale A, Nix C, Bodinayake CK, Nagahawatte A, Rolfe R, Woodhouse EW, Wijayaratne GB, Weerasinghe S, Dilshan UHBY, Gamage J, Kurukulasooriya R, Premamali M, Jayasinghearachchi HS, Nicholson BP, Ko ER, Tsalik EL, McClain MT, Myers RA, Woods CW, and Burke TW. Host gene expression in the Nasopharynx can discriminate microbiologically confirmed viral and bacterial lower respiratory tract infection. Journal of Clinical and Translational Science 9: e257, 1–11. doi: 10. 1017/cts.2025.10191 Received: 7 March 2025 Revised: 29 August 2025 Accepted: 20 October 2025 Keywords: Lower respiratory tract infection; host response; antimicrobial stewardship; nasopharynx; rapid diagnostic Corresponding author: L. G. Tillekeratne; Email: [gayani.tillekeratne@duke.edu](gayani.tillekeratne@duke.edu) *Co-first authors. **Co-senior authors. © The Author(s), 2025 . Published by Cambridge University Press on behalf of Association for Clinical and Translational Science. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence ([https://creativecommons.org/licenses/](https://creativecommons.org/licenses/)[ ](https://creativecommons.org/licenses/)[by/4.0/](by/4.0/)), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited. Host gene expression in the Nasopharynx can discriminate microbiologically confirmed viral and bacterial lower respiratory tract infection L. Gayani Tillekeratne1,2,3,4, * , Nicholas O’Grady1, * , Maria D. Iglesias-Ussel1,4 , Jack Anderson1,4, Alana Brown1, Armstrong Obale2,4, Christina Nix1, Champica K. Bodinayake2,3,4, Ajith Nagahawatte2,3,4, Robert Rolfe1,2, E. Wilbur Woodhouse1, Gaya B. Wijayaratne3,4, Senali Weerasinghe4, U. H. B.Y. Dilshan4, Jayani Gamage4, Ruvini Kurukulasooriya4, Madureka Premamali4, Himali S. Jayasinghearachchi5, Bradly P. Nicholson6, Emily R. Ko1, Ephraim L. Tsalik1,7, Micah T. McClain1, Rachel A. Myers1, Christopher W. Woods1,2,4, ** and Thomas W. Burke1, ** 1Duke University School of Medicine, Durham, NC, USA; 2Duke Global Health Institute, Durham, NC, USA; 3Faculty of Medicine, University of Ruhuna, Karapitiya, Galle, Sri Lanka; 4Duke-Ruhuna Collaborative Research Centre, Faculty of Medicine, University of Ruhuna, Karapitiya, Galle, Sri Lanka; 5Faculty of Medicine, General Sir John Kotelawala Defence University, Ratmalana, Sri Lanka; 6Institute for Medical Research, Durham Veterans Affairs Medical Center, Durham, NC, USA and 7Danaher Corporation, Washington, DC, USA Abstract Introduction: Distinguishing viral versus bacterial lower respiratory tract infection (LRTI) is challenging. We previously developed a rapid, host response-based test (Biomeme HR-B/Vassay) using peripheral blood samples to identify viral versus bacterial infection. We assessed the performance of this assay when using nasopharyngeal (NP) samples. Methods: Patients with LRTI were enrolled, and a NP swab sample was run using the HR-B/V assay (assessing 24 gene targets) on the FranklinTM platform. The performance of the prior classifier at identifying viral versus bacterial infection was assessed. A novel predictive model was generated for NP samples using the same 24 targets. Results were validated using external datasets with nasal/NP RNA sequence data. Results: Nineteen patients (median age 62 years, 52.1% male) were included. When using the prior HR-B/V classifier on NP samples of 19 patients with LRTI (12 viral, 7 bacterial), the area under the receiver operator curve (AUC) for viral versus bacterial infection was 0.786 (0.524–1), with accuracy 0.79 (95% CI 0.57–0.91), positive percent agreement (PPA) 0.43 (95% CI 0.16–0.75), and negative percent agreement (NPA) 1.00 (95% CI 0.76–1) . The novel mod

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What were the key findings about discriminating viral versus bacterial infections?

Nasopharyngeal host gene expression distinguished viral versus bacterial LRTI, with the novel NP model achieving improved AUC, accuracy, and agreement metrics, and external dataset validation showing high discriminative performance.

Sep 29, 2026

Upload by James