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）：脑炎和脑膜炎是潜在致命的疾病，其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、寄生虫或阿米巴原虫引起，尤其影响儿童、老年人或免疫功能低下的人。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，脑膜炎和脑炎病例的临床表现和初步实验室检查结果通常过于非特异性，无法进行病因诊断。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微生物。因此，区分特定治疗已显示有效的病例和仅支持性治疗的病例非常重要。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测试，但 FDA 批准的仅两种用于脑脊液 (CSF) 的分子诊断测试，每种测试仅检测肠道病毒。鉴于腰椎穿刺的侵入性、脑脊液检测低限的需要、引起无菌性脑膜炎或脑炎的微生物范围、检测在促进适当治疗方面的临床优势 治疗、在单个小样本量上获得多种测试结果的许多实际优势、缺乏 FDA 批准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，为这些疾病开发一种敏感的多重诊断测试非常重要。第一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套实时 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。每次反应可检测到 d 100 个基因拷贝的病毒，达到了第一阶段敏感性里程碑。第二阶段的目标是完成样本到答案系统，评估其临床性能，并为符合 FDA 质量体系法规 21 CFR 820 的商业生产做好准备。