Accession Number : ADA585214


Title :   A Host Transcriptional Signature for Presymptomatic Detection of Infection in Humans Exposed to Influenza H1N1 or H3N2


Descriptive Note : Journal article


Corporate Author : DUKE UNIV DURHAM NC DEPT OF ELECTRICAL AND COMPUTER ENGINEERING


Personal Author(s) : Woods, Christopher W ; McClain, Micah T ; Chen, Minhua ; Zaas, Aimee K ; Nicholson, Bradly P ; Varkey, Jay ; Veldman, Timothy ; Kingsmore, Stephen F ; Huang, Yongsheng ; Lambkin-Williams, Robert


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a585214.pdf


Report Date : 09 Jan 2013


Pagination or Media Count : 10


Abstract : There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003 H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent.


Descriptors :   *INFECTIOUS DISEASES , *INFLUENZA , *VIRUS DISEASES , BLOOD , CLINICAL MEDICINE , DIAGNOSIS(MEDICINE) , PATIENTS , RESPIRATORY SYSTEM , SIGNS AND SYMPTOMS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE