“害怕漏诊致命性的感染如脑膜炎和败血症，使得医生经常处方抗生素并进行腰椎穿刺等诊断性操作以求结果安全。基于我们已经确定的两种基因的快速检测技术可以彻底改变儿科的做法，使得我们只给那些的确存在细菌感染的儿童使用抗生素。”Jethro Herberg博士如是说。 作者: wwwkkk83 时间: 2016-8-30 11:04
Preliminary Communication | August 23/30, 2016
INNOVATIONS IN HEALTH CARE DELIVERY
Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children
Jethro A. Herberg, PhD1; Myrsini Kaforou, PhD1; Victoria J. Wright, PhD1; Hannah Shailes, BSc1; Hariklia Eleftherohorinou, PhD1; Clive J. Hoggart, PhD1; Miriam Cebey-López, MSc2,3; Michael J. Carter, MRCPCH1; Victoria A. Janes, MD1; Stuart Gormley, MRes1; Chisato Shimizu, MD4,5; Adriana H. Tremoulet, MD4,5; Anouk M. Barendregt, BSc6; Antonio Salas, PhD2,3,7; John Kanegaye, MD4,5; Andrew J. Pollard, PhD8,9; Saul N. Faust, PhD10,11; Sanjay Patel, FRCPCH11; Taco Kuijpers, PhD6,12; Federico Martinón-Torres, PhD2,3; Jane C. Burns, MD4,5; Lachlan J. M. Coin, PhD13; Michael Levin, FRCPCH1 ; for the IRIS Consortium
[+] Author Affiliations
JAMA. 2016;316(8):835-845. doi:10.1001/jama.2016.11236.
http://jama.jamanetwork.com/article.aspx?articleid=2545687 作者: wwwkkk83 时间: 2016-8-30 11:05
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 (2-transcript) signature (FAM89A and IFI44L) was identified by removing highly correlated transcripts. When this 2-transcript signature was implemented as a disease risk score in the validation group (130 children, with 23 definite bacterial, 28 definite viral, and 79 indeterminate infections; median age, 17 months; 57% male), all 23 patients with microbiologically confirmed definite bacterial infection were classified as bacterial (sensitivity, 100% [95% CI, 100%-100%]) and 27 of 28 patients with definite viral infection were classified as viral (specificity, 96.4% [95% CI, 89.3%-100%]). When applied to additional validation datasets from patients with meningococcal and inflammatory diseases, bacterial infection was identified with a sensitivity of 91.7% (95% CI, 79.2%-100%) and 90.0% (95% CI, 70.0%-100%), respectively, and with specificity of 96.0% (95% CI, 88.0%-100%) and 95.8% (95% CI, 89.6%-100%). Of the children in the indeterminate groups, 46.3% (63/136) were classified as having bacterial infection, although 94.9% (129/136) received antibiotic treatment.
Conclusions and Relevance This study provides preliminary data regarding test accuracy of a 2-transcript host RNA signature discriminating bacterial from viral infection in febrile children. Further studies are needed in diverse groups of patients to assess accuracy and clinical utility of this test in different clinical settings.