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疾病，由大脑或覆盖大脑和脊髓的保护膜的急性炎症定义。这些疾病可由病毒、细菌、真菌、寄生虫或变形虫引起，对儿童、老年人或免疫功能低下者的影响尤为严重。病毒是脑炎最常见的病因，大多数无菌性脑炎病例由肠病毒、人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结果通常是非特异性的，无法进行病因学诊断。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生物体。因此，重要的是要区分那些特定治疗已被证明有效的病例，以及那些只需要支持性治疗的病例。十多年来，核酸扩增和检测试验一直被认为是检测中枢神经系统感染的首选方法，但目前只有两种经fda批准的用于脑脊液（CSF）的分子诊断试验，每一种都只能检测肠道病毒。鉴于腰椎穿刺的侵入性、脑脊液中检测限低的必要性、引起无菌性脑膜炎或脑炎的微生物的范围，便于适当的临床优势检测

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.