Imperial College London


Faculty of MedicineDepartment of Infectious Disease

Research Fellow



+44 (0)20 7594 3577v.wright




PaediatricsMedical SchoolSt Mary's Campus






BibTex format

author = {Herberg, JA and Kaforou, M and Wright, VJ and Shailes, H and Eleftherohorinou, H and Hoggart, CJ and Cebey-López, M and Carter, MJ and Janes, VA and Gormley, S and Shimizu, C and Tremoulet, AH and Barendregt, AM and Salas, A and Kanegaye, J and Pollard, AJ and Faust, SN and Patel, S and Kuijpers, T and Martinón-Torres, F and Burns, JC and Coin, LJ and Levin, M},
doi = {10.1001/jama.2016.11236},
journal = {Journal of the American Medical Association},
pages = {835--845},
title = {Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children},
url = {},
volume = {316},
year = {2016}

RIS format (EndNote, RefMan)

AB - IMPORTANCE: Because clinical features do not reliably distinguish bacterial from viral infection, many children worldwide receive unnecessary antibiotic treatment, while bacterial infection is missed in others. OBJECTIVE: To identify a blood RNA expression signature that distinguishes bacterial from viral infection in febrile children. DESIGN, SETTING, AND PARTICIPANTS: Febrile children presenting to participating hospitals in the United Kingdom, Spain, the Netherlands, and the United States between 2009-2013 were prospectively recruited, comprising a discovery group and validation group. Each group was classified after microbiological investigation as having definite bacterial infection, definite viral infection, or indeterminate infection. RNA expression signatures distinguishing definite bacterial from viral infection were identified in the discovery group and diagnostic performance assessed in the validation group. Additional validation was undertaken in separate studies of children with meningococcal disease (n = 24) and inflammatory diseases (n = 48) and on published gene expression datasets. EXPOSURES: A 2-transcript RNA expression signature distinguishing bacterial infection from viral infection was evaluated against clinical and microbiological diagnosis. MAIN OUTCOMES AND MEASURES: Definite bacterial and viral infection was confirmed by culture or molecular detection of the pathogens. Performance of the RNA signature was evaluated in the definite bacterial and viral group and in the indeterminate infection group. RESULTS: The discovery group of 240 children (median age, 19 months; 62% male) included 52 with definite bacterial infection, of whom 36 (69%) required intensive care, and 92 with definite viral infection, of whom 32 (35%) required intensive care. Ninety-six children had indeterminate infection. Analysis of RNA expression data identified a 38-transcript signature distinguishing bacterial from viral infection. A smaller
AU - Herberg,JA
AU - Kaforou,M
AU - Wright,VJ
AU - Shailes,H
AU - Eleftherohorinou,H
AU - Hoggart,CJ
AU - Cebey-López,M
AU - Carter,MJ
AU - Janes,VA
AU - Gormley,S
AU - Shimizu,C
AU - Tremoulet,AH
AU - Barendregt,AM
AU - Salas,A
AU - Kanegaye,J
AU - Pollard,AJ
AU - Faust,SN
AU - Patel,S
AU - Kuijpers,T
AU - Martinón-Torres,F
AU - Burns,JC
AU - Coin,LJ
AU - Levin,M
DO - 10.1001/jama.2016.11236
EP - 845
PY - 2016///
SN - 0002-9955
SP - 835
TI - Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children
T2 - Journal of the American Medical Association
UR -
UR -
VL - 316
ER -