Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts.
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2021-08
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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 (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.Type
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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. 605ā613. 10.1093/cid/ciab043 Retrieved from https://hdl.handle.net/10161/24295.
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Thomas Burke
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