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.

Full Text

Duke Authors

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

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


  • eng

Conference Location

  • United States