Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts.
Journal Article (Journal Article)
BACKGROUND: Host gene expression has emerged as a complementary strategy to pathogen detection tests for the discrimination of bacterial and viral infection. The impact of immunocompromise on host-response tests remains unknown. We evaluated a host-response test discriminating bacterial, viral, and noninfectious conditions in immunocompromised subjects. METHODS: An 81-gene signature was measured using real-time-polymerase chain reaction in subjects with immunocompromise (chemotherapy, solid-organ transplant, immunomodulatory agents, AIDS) with bacterial infection, viral infection, or noninfectious illness. A regularized logistic regression model trained in immunocompetent subjects was used to estimate the likelihood of each class in immunocompromised subjects. RESULTS: Accuracy in the 136-subject immunocompetent training cohort was 84.6% for bacterial versus nonbacterial discrimination and 80.8% for viral versus nonviral discrimination. Model validation in 134 immunocompromised subjects showed overall accuracy of 73.9% for bacterial infection (Pā =ā .04 relative to immunocompetent subjects) and 75.4% for viral infection (Pā =ā .30). A scheme reporting results by quartile improved test utility. The highest probability quartile ruled-in bacterial and viral infection with 91.4% and 84.0% specificity, respectively. The lowest probability quartile ruled-out infection with 90.1% and 96.4% sensitivity for bacterial and viral infection, respectively. Performance was independent of the type or number of immunocompromising conditions. CONCLUSIONS: A host gene expression test discriminated bacterial, viral, and noninfectious etiologies at a lower overall accuracy in immunocompromised patients compared with immunocompetent patients, although this difference was only significant for bacterial infection classification. With modified interpretive criteria, a host-response strategy may offer clinically useful diagnostic information for patients with immunocompromise.
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Duke Authors
- Burke, Thomas
- Ginsburg, Geoffrey Steven
- Henao, Ricardo
- McClain, Micah Thomas
- Steinbrink, Julie
- Tsalik, Ephraim
- Woods, Christopher Wildrick
Cited Authors
- Mahle, RE; Suchindran, S; Henao, R; Steinbrink, JM; Burke, TW; McClain, MT; Ginsburg, GS; Woods, CW; Tsalik, EL
Published Date
- August 16, 2021
Published In
- Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America
Volume / Issue
- 73 / 4
Start / End Page
- 605 - 613
PubMed ID
- 33462581
Pubmed Central ID
- PMC8366815
Electronic International Standard Serial Number (EISSN)
- 1537-6591
Digital Object Identifier (DOI)
- 10.1093/cid/ciab043
Language
- eng
Conference Location
- United States