New test for the diagnosis of acute respiratory infection that detects viruses and evaluates host gene expression in a nasal sample

项目总结/摘要 世界范围内抗生素耐药性的急剧增加，使人们担心会回到以前的水平。 抗生素时代过度使用抗生素是这一过程的主要驱动力。的主要领域之一 发生不必要的抗生素使用的临床医学是在管理患者 急性呼吸道感染，通常由病毒引起。我们工作的长期目标 是开发更好的诊断测试，帮助医生避免使用抗生素治疗病毒感染。 感染.目前，高度敏感的分子检测方法可用于检测呼吸道病毒。 然而，它们的高灵敏度导致在它们不是病毒的情况下检测到病毒。 患者的疾病原因。我们已经提出利用宿主反应，包括宿主基因 表达，以提供更准确的诊断信息。以前的工作评价 宿主对呼吸道感染的反应是通过血液样本进行的，但我们最近 显示人类基因表达可以在鼻样本中测量，并且能够 识别并区分有症状感染者、无症状感染者和无症状感染者， 感染至少对鼻腔样本和血液样本一样好。这里提出的工作代表了 华盛顿大学和BioFire Diagnostics之间的学术-工业合作伙伴关系， 将开发一种新的诊断测试，对鼻样本进行结合病毒检测 与人类基因表达有关。我们的目的是将测试推向监管批准， 它可以用来帮助病人和医生。BioFire将准备一个原型测试设备 使用他们的FilmArray系统，该系统已广泛用于多重病原体检测。的 病毒成分是基于BioFire开发的检测方法， 该组件将使用华盛顿大学团队根据我们最近的研究结果选择的基因。 知情同意/同意。将使用原型测试对每名受试者的鼻拭子进行测试 将获得器械和血液样本用于降钙素原测量，以帮助确定 患者的疾病原因。原型测试装置的结果将与 由专家临床医生小组进行分类，他们将使用患者的临床信息 包括降钙素原结果，以确定患者是否患有病毒感染、细菌感染、 感染，两者都有，或者都没有。我们还将分析使用测试结果对 抗生素利用在研究的第二阶段， 将使用RNA-seq和定量病毒学分析检测和宿主应答， 理解为什么结果不一致。如果这个项目成功，它将直接导致一个 旨在确定临床疗效的临床试验，用于支持FDA申请 批准

Project Summary / Abstract Dramatic worldwide increases in antibiotic resistance raise the specter of a return to the pre- antibiotic era. Overuse of antibiotics is the main driver of this process. One of the main areas of clinical medicine where unnecessary antibiotic use occurs is in the management of patients with acute respiratory infections, which are often caused by viruses. The long-term goal of our work is to develop better diagnostic tests that will help physicians avoid using antibiotics to treat viral infections. Highly sensitive molecular assays are now available to detect respiratory viruses. However, their high sensitivity leads to detection of viruses in cases in which they are not the cause of the patient’s illness. We have proposed using host response, including host gene expression, to provide more accurate diagnostic information. Most previous work evaluating host response to respiratory infections was done using blood samples but we have recently shown that human gene expression can be measured in nasal samples, and the ability to recognize and discriminate between symptomatic infection, asymptomatic infection, and no infection is at least as good for nasal samples as for blood. The work proposed here represents an academic-industry partnership between Washington University and BioFire Diagnostics that will develop a new diagnostic test performed on a nasal sample that combines virus detection with human gene expression. Our intention is to move the test towards regulatory approval so that it can be used to help patients and physicians. BioFire will prepare a prototype test device using their FilmArray system, which is already widely used for multiplex pathogen detection. The viral component is based on assays that BioFire has developed, and the gene expression component will use genes selected by the Washington University team based on our recent with informed consent/assent. A nasal swab from each subject will be tested using the prototype test device and a blood sample will be obtained for procalcitonin measurement to help determine the cause of the patient’s illness. The results of the prototype test device will be compared to classification by a panel of expert clinicians who will use the patient’s clinical information including the procalcitonin result to determine whether the patient had a viral infection, bacterial infection, both, or neither. We will also analyze the potential impact of using the test results on antibiotic utilization. In a second phase of the study, samples that are discrepant between virus detection and host response will be analyzed using RNA-seq and quantitative virology to understand why results were discrepant. If this project is successful, it will lead directly to a clinical trial designed to establish clinical efficacy, used to support an application for FDA approval.