Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts.

Abstract

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 (P = .04 relative to immunocompetent subjects) and 75.4% for viral infection (P = .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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1093/cid/ciab043

Publication Info

Mahle, Rachael E, Sunil Suchindran, Ricardo Henao, Julie M Steinbrink, Thomas W Burke, Micah T McClain, Geoffrey S Ginsburg, Christopher W Woods, et al. (2021). Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 73(4). pp. 605–613. 10.1093/cid/ciab043 Retrieved from https://hdl.handle.net/10161/24295.

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Scholars@Duke

Steinbrink

Julie Steinbrink

Assistant Professor of Medicine

I am a transplant infectious diseases physician. My clinical care focuses on the management of infections in immunocompromised patients, including solid organ and bone marrow transplant recipients, as well as cancer patients. My research focuses on developing noninvasive biomarker diagnostics and severity prognostic tools for infectious diseases in immunocompromised patients.


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