Diagnostic array for aseptic encephalitis

无菌性脑炎诊断芯片

• 批准号: 8992890
• 负责人: DARRELL P CHANDLER
• 金额: $ 97.31万
• 依托单位: AKONNI BIOSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-15 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992890
• 关键词: Acute; Affect; Amoeba genus; Arboviruses; Area; Aseptic Meningitis; Bacteria; Biological Assay; Brain; Brain Diseases; Cells; Central Nervous System Infections; Cerebrospinal Fluid; Child; Clinical; Clinical Sensitivity; Communicable Diseases; Cytomegalovirus; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disease; Elderly; Encephalitis; Enterovirus; FDA approved; Genes; Guidelines; Health; Herpesviridae; Herpesvirus 1; Human; Human Herpesvirus 2; Human Herpesvirus 6; Immunocompromised Host; Infection; Laboratories; Laboratory Finding; Lateral; Life; Membrane; Meningitis; Molecular Diagnostic Testing; Nucleic Acids; Organism; Parasites; Performance; Phase; Predisposition; Preparation; Principal Investigator; Production; RNA-Directed DNA Polymerase; Reaction; Reagent; Regulation; Reproducibility; Reverse Transcriptase Polymerase Chain Reaction; Reverse Transcription; Sampling; Sensitivity and Specificity; Specificity; Specimen; Spinal Cord; Spinal Puncture; System; Test Result; Testing; Time; Translating; Virus; Virus Diseases; West Nile virus; amplification detection; base; cost; disorder control; disorder prevention; fungus; instrument; meetings; programs; research study; treatment strategy

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.

描述（由申请人提供）：脑炎和脑膜炎是由大脑急性炎症或覆盖大脑和脊髓的保护膜急性炎症定义的潜在致命疾病。这些疾病可能是由病毒，细菌，真菌，寄生虫或变形虫引起的，并且会对儿童，老年人或免疫副强化产生不成比例的影响。病毒是脑炎的最常见原因，大多数由肠病毒，人疱疹病毒和刺刺病毒引起的大多数无菌性脑炎病例。不幸的是，在脑膜炎和脑炎病例中，临床表现和初始实验室发现通常过于非特异性，无法进行病因。中枢神经系统（CNS）感染和适当的治疗策略引起的并发症取决于所涉及的生物。因此，重要的是要区分那些表现出特定治疗有效的情况，以及仅指示支持性治疗的情况。十多年来，核酸的扩增和检测测定法被认为是CNS感染的首选测试，但是只有两个FDA批准的分子诊断测试，用于与脑脊液（CSF）一起使用，每种脑脊液仅检测肠病毒。鉴于腰刺穿的侵入性，需要在CSF中检测到较低的限制，导致无菌性脑膜炎或脑炎的生物范围，在促进适当的临床优势方面的临床优势 治疗，在单个小样本量，缺乏FDA清除测试的诊断测试以及全球监测活动在疾病控制和预防中的重要性，在疾病控制和预防中的重要性，在单个小样本量上获得多次测试结果的许多实际优势，这对于开发这些疾病的敏感，多重诊断测试很重要。在第1阶段开发的测定源自一组实时PCR和由病毒疾病实验室在Wadsworth Center，Akonni单室放大微阵列和低速仪器包开发的逆转录酶PCR分析。每个反应的D 100基因拷贝可检测到病毒，符合第1阶段的灵敏度里程碑。第2阶段的目标是完成样品待办事项系统，评估其临床性能，并根据21 CFR 820（FDA的质量系统调节）准备商业生产。