Rachael E Mahle1, Sunil Suchindran2, Ricardo Henao2,3, Julie M Steinbrink4, Thomas W Burke2, Micah T McClain2,4,5, Geoffrey S Ginsburg2, Christopher W Woods2,4,5, Ephraim L Tsalik2,4,6. 1. Duke University School of Medicine, Durham, North Carolina, USA. 2. Duke Center for Applied Genomics and Precision Medicine, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. 3. Department of Electrical and Computer Engineering, Pratt School of Engineering, Duke University, Durham, North Carolina, USA. 4. Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA. 5. Medical Service, Durham VA Health Care System, Durham, North Carolina, USA. 6. Emergency Medicine Service, Durham VA Health Care System, Durham, North Carolina, USA.
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.
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.
Authors: Ian S Jaffe; Anja K Jaehne; Eugenia Quackenbush; Emily R Ko; Emanuel P Rivers; Micah T McClain; Geoffrey S Ginsburg; Christopher W Woods; Ephraim L Tsalik Journal: Open Forum Infect Dis Date: 2021-11-10 Impact factor: 3.835
Authors: Ephraim L Tsalik; Ricardo Henao; Jesse L Montgomery; Jeff W Nawrocki; Mert Aydin; Emily C Lydon; Emily R Ko; Elizabeth Petzold; Bradly P Nicholson; Charles B Cairns; Seth W Glickman; Eugenia Quackenbush; Stephen F Kingsmore; Anja K Jaehne; Emanuel P Rivers; Raymond J Langley; Vance G Fowler; Micah T McClain; Robert J Crisp; Geoffrey S Ginsburg; Thomas W Burke; Andrew C Hemmert; Christopher W Woods Journal: Crit Care Med Date: 2021-10-01 Impact factor: 9.296
Authors: Emily R Ko; Ricardo Henao; Katherine Frankey; Elizabeth A Petzold; Pamela D Isner; Anja K Jaehne; Nakia Allen; Jayna Gardner-Gray; Gina Hurst; Jacqueline Pflaum-Carlson; Namita Jayaprakash; Emanuel P Rivers; Henry Wang; Irma Ugalde; Siraj Amanullah; Laura Mercurio; Thomas H Chun; Larissa May; Robert W Hickey; Jacob E Lazarus; Shauna H Gunaratne; Daniel J Pallin; Guruprasad Jambaulikar; David S Huckins; Krow Ampofo; Ravi Jhaveri; Yunyun Jiang; Lauren Komarow; Scott R Evans; Geoffrey S Ginsburg; L Gayani Tillekeratne; Micah T McClain; Thomas W Burke; Christopher W Woods; Ephraim L Tsalik Journal: JAMA Netw Open Date: 2022-04-01