Skip to main content
Duke University Libraries
DukeSpace Scholarship by Duke Authors
  • Login
  • Ask
  • Menu
  • Login
  • Ask a Librarian
  • Search & Find
  • Using the Library
  • Research Support
  • Course Support
  • Libraries
  • About
View Item 
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
  •   DukeSpace
  • Duke Scholarly Works
  • Scholarly Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.

Thumbnail
View / Download
1.0 Mb
Date
2022-04
Authors
Ko, Emily R
Henao, Ricardo
Frankey, Katherine
Petzold, Elizabeth A
Isner, Pamela D
Jaehne, Anja K
Allen, Nakia
Gardner-Gray, Jayna
Hurst, Gina
Pflaum-Carlson, Jacqueline
Jayaprakash, Namita
Rivers, Emanuel P
Wang, Henry
Ugalde, Irma
Amanullah, Siraj
Mercurio, Laura
Chun, Thomas H
May, Larissa
Hickey, Robert W
Lazarus, Jacob E
Gunaratne, Shauna H
Pallin, Daniel J
Jambaulikar, Guruprasad
Huckins, David S
Ampofo, Krow
Jhaveri, Ravi
Jiang, Yunyun
Komarow, Lauren
Evans, Scott R
Ginsburg, Geoffrey S
Tillekeratne, L Gayani
McClain, Micah T
Burke, Thomas W
Woods, Christopher W
Tsalik, Ephraim L
Antibacterial Resistance Leadership Group
Show More
(36 total)
Repository Usage Stats
7
views
1
downloads
Abstract
<h4>Importance</h4>Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship.<h4>Objective</h4>To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI.<h4>Design, setting, and participants</h4>This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc.<h4>Interventions</h4>The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection.<h4>Main outcomes and measures</h4>Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score <0.19], viral likely [probability score of 0.19-0.40], bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability score >0.73]) and compared with procalcitonin measurement.<h4>Results</h4>Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P < .001), the specificity was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%; P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9% (95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants (90.9%) with acute COVID-19 as having a viral infection.<h4>Conclusions and relevance</h4>In this study, the HR-B/V test accurately discriminated bacterial from viral infection among patients with febrile ARI and was superior to procalcitonin measurement. The findings suggest that an accurate point-of-need host response test with high NPV may offer an opportunity to improve antibiotic stewardship and patient outcomes.
Type
Journal article
Subject
Antibacterial Resistance Leadership Group
Humans
Bacteria
Bacterial Infections
Virus Diseases
Fever
Gene Expression
Adult
Child
Female
Male
Procalcitonin
COVID-19
Permalink
https://hdl.handle.net/10161/24951
Published Version (Please cite this version)
10.1001/jamanetworkopen.2022.7299
Publication Info
Ko, Emily R; Henao, Ricardo; Frankey, Katherine; Petzold, Elizabeth A; Isner, Pamela D; Jaehne, Anja K; ... Antibacterial Resistance Leadership Group (2022). Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection. JAMA network open, 5(4). pp. e227299. 10.1001/jamanetworkopen.2022.7299. Retrieved from https://hdl.handle.net/10161/24951.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
Collections
  • Scholarly Articles
More Info
Show full item record

Scholars@Duke

Ginsburg

Geoffrey Steven Ginsburg

Adjunct Professor in the Department of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
McClain

Micah Thomas McClain

Associate Professor of Medicine
Tillekeratne

Gayani Tillekeratne

Assistant Professor of Medicine
Global healthAntimicrobial resistance/ stewardshipAcute respiratory tract infections Emerging infections/ dengue
Tsalik

Ephraim Tsalik

Adjunct Associate Professor in the Department of Medicine
My research is focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease.  This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance. With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of presentation
Alphabetical list of authors with Scholars@Duke profiles.
Open Access

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy

Rights for Collection: Scholarly Articles


Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info

Make Your Work Available Here

How to Deposit

Browse

All of DukeSpaceCommunities & CollectionsAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit DateThis CollectionAuthorsTitlesTypesBy Issue DateDepartmentsAffiliations of Duke Author(s)SubjectsBy Submit Date

My Account

LoginRegister

Statistics

View Usage Statistics
Duke University Libraries

Contact Us

411 Chapel Drive
Durham, NC 27708
(919) 660-5870
Perkins Library Service Desk

Digital Repositories at Duke

  • Report a problem with the repositories
  • About digital repositories at Duke
  • Accessibility Policy
  • Deaccession and DMCA Takedown Policy

TwitterFacebookYouTubeFlickrInstagramBlogs

Sign Up for Our Newsletter
  • Re-use & Attribution / Privacy
  • Harmful Language Statement
  • Support the Libraries
Duke University