Diagnostic array for aseptic encephalitis

描述(申请人提供)：脑炎和脑膜炎是一种潜在的致命疾病，定义为大脑的急性炎症或覆盖在大脑和脊髓上的保护膜。这些疾病可由病毒、细菌、真菌、寄生虫或阿米巴引起，并对儿童、老年人或免疫功能低下者造成不成比例的影响。病毒是脑炎最常见的原因，大多数无菌性脑炎病例是由肠道病毒、人类疱疹病毒和虫媒病毒引起的。不幸的是，脑膜炎和脑炎的临床表现和最初的实验室结果通常太不特异，不能进行病因学诊断。中枢神经系统(CNS)感染引起的并发症和适当的治疗策略取决于所涉及的机体。因此，重要的是要区分那些特定治疗已被证明有效的病例，以及那些只指示进行支持性治疗的病例。十多年来，核酸扩增和检测分析一直被认为是中枢神经系统感染的首选检测方法，但目前只有两种FDA批准的分子诊断测试用于脑脊液(CSF)，每一种都只能检测肠道病毒。考虑到腰椎穿刺术的侵袭性，脑脊液检测的低限需要，引起无菌性脑膜炎或脑炎的细菌的范围，检测在促进适当的 鉴于这些疾病的治疗方法、在单个小样本上获得多种检测结果的许多实际优势、缺乏FDA批准的诊断检测以及全球监测活动在疾病控制和预防中的重要性，开发一种针对这些疾病的灵敏、多重诊断检测非常重要。在第一阶段开发的检测方法来自沃兹沃斯中心病毒疾病实验室开发的一套实时聚合酶链式反应和逆转录酶聚合酶链式反应分析、Akonni单室扩增微阵列和低成本的仪器组件。病毒在每个反应中可以检测到100个基因拷贝，达到了第一阶段的敏感性里程碑。第二阶段的目标是完成样本到答案系统，评估其临床性能，并根据FDA的质量体系法规21 CFR 820为商业生产做准备。

DESCRIPTION (provided by applicant): Encephalitis and meningitis are potentially fatal diseases defined by acute inflammation of the brain or protective membranes covering the brain and spinal cord. These diseases can be caused by viruses, bacteria, fungi, parasites or amoeba, and disproportionately affect children, the elderly, or the immunocompromised. Viruses are the most common cause of encephalitis, with the majority of aseptic encephalitis cases caused by enterovirus, human herpesviruses, and arboviruses. Unfortunately, clinical presentation and initial laboratory findings in cases of meningitis and encephalitis are usually too nonspecific to permit an etiologic diagnosis. Complications arising from central nervous system (CNS) infection and appropriate treatment strategies depend on the organism involved. It is therefore important to differentiate between those cases for which a specific treatment has been shown effective, and those for which only supportive treatment is indicated. Nucleic acid amplification and detection assays have been considered the test of choice for CNS infections for more than a decade, yet there are only two FDA-approved molecular diagnostic tests for use with cerebrospinal fluid (CSF), each of which only detects enterovirus. Given the invasiveness of lumbar puncture, the need for low limits of detection in CSF, the range of organisms causing aseptic meningitis or encephalitis, the clinical advantage of detection in facilitating appropriate treatment, the many practical advantages of achieving multiple test results on a single small sample volume, the lack of FDA-cleared tests for diagnosis, and the importance of global surveillance activity in disease control and prevention, it is important to develop a sensitive, multiplexed diagnostic test for these diseases. The assay developed in Phase 1 was derived from a set of real-time PCR and reverse transcriptase PCR assays developed by the Laboratory of Viral Diseases at the Wadsworth Center, Akonni single-chamber amplification microarrays, and a low-cost instrument package. Viruses are detectable at d 100 gene copies per reaction, meeting the Phase 1 sensitivity milestone. The objectives of Phase 2 are to complete a sample- to-answer system, evaluate its clinical performance, and prepare for commercial production in compliance with the 21 CFR 820, the FDA's Quality System Regulation.