Validation of a host response test to distinguish bacterial and viral respiratory infection.
Abstract
BACKGROUND:Distinguishing bacterial and viral respiratory infections is challenging.
Novel diagnostics based on differential host gene expression patterns are promising
but have not been translated to a clinical platform nor extensively tested. Here,
we validate a microarray-derived host response signature and explore performance in
microbiology-negative and coinfection cases. METHODS:Subjects with acute respiratory
illness were enrolled in participating emergency departments. Reference standard was
an adjudicated diagnosis of bacterial infection, viral infection, both, or neither.
An 87-transcript signature for distinguishing bacterial, viral, and noninfectious
illness was measured from peripheral blood using RT-PCR. Performance characteristics
were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness.
Subjects with bacterial-viral coinfection and microbiologically-negative suspected
bacterial infection were also evaluated. Performance was compared to procalcitonin.
FINDINGS:151 subjects with microbiologically confirmed, single-etiology illness were
tested, yielding AUROCs 0•85-0•89 for bacterial, viral, and noninfectious illness.
Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial
infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness,
the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection
was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified
95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects
with bacterial infection superimposed on chronic viral infection, the RT-PCR test
identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected
bacterial infection; the RT-PCR test identified bacterial infection more frequently
than procalcitonin (82% vs 64%, p = 0•02). INTERPRETATION:The RT-PCR test offered
similar diagnostic performance to procalcitonin in some subgroups but offered better
discrimination in others such as viral vs. non-infectious illness and bacterial/viral
coinfection. Gene expression-based tests could impact decision-making for acute respiratory
illness as well as a growing number of other infectious and non-infectious diseases.
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https://hdl.handle.net/10161/19461Published Version (Please cite this version)
10.1016/j.ebiom.2019.09.040Publication Info
Lydon, Emily C; Henao, Ricardo; Burke, Thomas W; Aydin, Mert; Nicholson, Bradly P;
Glickman, Seth W; ... Tsalik, Ephraim L (2019). Validation of a host response test to distinguish bacterial and viral respiratory
infection. EBioMedicine. 10.1016/j.ebiom.2019.09.040. Retrieved from https://hdl.handle.net/10161/19461.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.
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Show full item recordScholars@Duke
Thomas Burke
Manager, Systems Project
Vance Garrison Fowler Jr.
Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial
ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
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.
Ricardo Henao
Associate Professor in Biostatistics & Bioinformatics
Emily Ray Ko
Assistant Professor of Medicine
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for
infectious disease.
Micah Thomas McClain
Associate Professor of Medicine
Ephraim Tsalik
Adjunct Associate Professor in the Department of Medicine
My research at Duke has 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 pre
Christopher Wildrick Woods
Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance
for communicable diseases 7. Antimicrobial resistance
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