Diagnostic array for aseptic encephalitis

描述（由申请人提供）：脑炎和脑膜炎是潜在的致命性疾病，定义为大脑或覆盖大脑和脊髓的保护膜的急性炎症。这些疾病可能由病毒、细菌、真菌、寄生虫或阿米巴虫引起，并且不成比例地影响儿童、老年人或免疫功能低下者。病毒是脑炎最常见的原因，大多数无菌性脑炎病例由肠道病毒、人类疱疹病毒和虫媒病毒引起。不幸的是，脑膜炎和脑炎病例的临床表现和最初的实验室检查结果通常太不特异，无法进行病原学诊断。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生物体。因此，重要的是要区分那些情况下，一个特定的治疗已被证明是有效的，和那些只支持治疗的迹象。十多年来，核酸扩增和检测试验一直被认为是CNS感染的首选试验，但只有两种FDA批准的用于脑脊液（CSF）的分子诊断试验，每种都只能检测肠道病毒。考虑到腰椎穿刺的侵入性，CSF中检测下限的需要，引起无菌性脑膜炎或脑炎的微生物的范围，检测在促进适当的 由于疾病控制和预防的重要性、在单个小样本体积上获得多个测试结果的许多实际优点、缺乏FDA批准的诊断测试以及全球监测活动的重要性，开发用于这些疾病的敏感的多重诊断测试是重要的。第1阶段开发的检测方法源自沃兹沃斯中心病毒疾病实验室开发的一组实时PCR和逆转录酶PCR检测方法、Akonni单室扩增微阵列和低成本仪器包。病毒在d100基因拷贝/反应时可检出，符合1期敏感性里程碑。第2阶段的目标是完成一个样品-应答系统，评价其临床性能，并准备按照21 CFR 820（FDA质量体系法规）进行商业生产。

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.