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

项目摘要/摘要 全球抗生素耐药性的急剧增加引发了人们对抗生素回归前的幽灵。 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 在不必要使用抗生素的情况下，临床医学是在对患有 急性呼吸道感染，通常由病毒引起。我们工作的长期目标是 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。现在可以用高灵敏的分子检测方法来检测呼吸道病毒。 然而，它们的高敏感度导致在它们不是 病人患病的原因。我们提出了利用宿主反应，包括宿主基因 表达式，以提供更准确的诊断信息。大多数以前的工作评估 宿主对呼吸道感染的反应是使用血液样本进行的，但我们最近这样做了 表明人类的基因表达可以在鼻腔样本中测量，并且有能力 识别和区分有症状感染、无症状感染和无症状感染 感染对鼻腔样本和血液的影响至少一样大。这里提出的工作代表了 华盛顿大学和BioFire诊断公司之间的学术和行业合作伙伴关系 将开发一种新的诊断测试，在鼻部样本上进行，结合病毒检测 与人类的基因表达有关。我们的意图是将测试转向监管部门的批准，因此 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，该系统已经被广泛用于多重病原体检测。这个 病毒成分是基于BioFire开发的分析方法和基因表达 组件将使用华盛顿大学团队根据我们最近的 知情同意/同意。每个受试者的鼻拭子将使用原型测试进行测试 将获取设备和血液样本进行降钙素原测定，以帮助确定 病人患病的原因。样机测试装置的结果将与 由将使用患者临床信息的专家临床医生小组进行分类 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，两者都有，或者都不是。我们还将分析在以下方面使用测试结果的潜在影响 抗生素的使用。在研究的第二阶段，病毒之间不一致的样本 检测和宿主反应将使用rna-seq和定量病毒学进行分析，以 理解为什么结果会不一致。如果这个项目成功，它将直接导致 旨在确定临床疗效的临床试验，用于支持FDA的申请 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.