TY - JOUR
T1 - Validation of a Host Gene Expression Test for Bacterial/Viral Discrimination in Immunocompromised Hosts
AU - Mahle, Rachael E.
AU - Suchindran, Sunil
AU - Henao, Ricardo
AU - Steinbrink, Julie M.
AU - Burke, Thomas W.
AU - McClain, Micah T.
AU - Ginsburg, Geoffrey S.
AU - Woods, Christopher W.
AU - Tsalik, Ephraim L.
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2021/8/15
Y1 - 2021/8/15
N2 - 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 (Pa=a.04 relative to immunocompetent subjects) and 75.4% for viral infection (Pa=a.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.
AB - 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 (Pa=a.04 relative to immunocompetent subjects) and 75.4% for viral infection (Pa=a.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.
UR - https://academic.oup.com/cid/article/73/4/605/6104215
UR - http://www.scopus.com/inward/record.url?scp=85114338761&partnerID=8YFLogxK
U2 - 10.1093/cid/ciab043
DO - 10.1093/cid/ciab043
M3 - Article
SN - 1058-4838
VL - 73
SP - 605
EP - 613
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -
