Rapid Point-of-Care Assay for Diagnosis of Neurocysticercosis in Seizure Patients

用于诊断癫痫患者神经囊尾蚴病的快速护理点检测

• 批准号: 10084274
• 负责人: Andrew E. Levin
• 金额: $ 30万
• 依托单位: KEPHERA DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-10 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10084274
• 关键词: Address; Adult; Affect; Anthelmintics; Antigens; Antiparasitic Agents; Biological Assay; Blood donor; Blood specimen; Brain; Brain Diseases; Centers for Disease Control and Prevention (U.S.); Chemistry; Clinical; Collaborations; Complex; Computer software; Cyst; Data; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Electroencephalogram; Electroencephalography; Engineering; Ensure; Enzymes; Epilepsy; Etiology; Europe; Family suidae; Frequencies; Goals; Gold; Human; Hygiene; Image; Immigration; Immunoassay; Income; Individual; Infection; Infrastructure; Label; Laboratories; Lateral; Location; Magnetic Resonance Imaging; Measurement; Medical; Membrane; Methods; Neurocysticercosis; Parasitic Diseases; Parasitic infection; Patients; Performance; Phase; Preparation; Price; Procedures; Publishing; Reader; Reagent; Recombinants; Reproducibility; Resistance; Running; Sampling; Seizures; Sensitivity and Specificity; Serology test; Serum; Specificity; Structural defect; Synthetic Antigens; Taenia solium; Temperature; Test Result; Testing; Tissues; Training; Travel; Variant; Whole Blood; Wireless Technology; World Health Organization; antibody detection; base; clinical Diagnosis; cost; design; detection sensitivity; effective therapy; follow-up; imaging study; infection rate; lateral flow assay; medical specialties; nervous system disorder; nervous system infection; novel; performance tests; point of care; point of care testing; prototype; relating to nervous system; research clinical testing; scale up; statistics; tool; validation studies

Project Summary Epilepsy, a disorder of the brain manifested by seizures, is the fourth most prevalent neurological disease, affecting over 50 million people worldwide, or about 1 out of 150 individuals on average. The frequency of epilepsy is distributed unevenly, however, with the vast majority of cases occurring in less developed regions of the world. The explanation for this distribution is most likely that one third of all epilepsy cases are due to Neurocysticercosis, known to be the most common parasitic infection of the nervous system. Neurocysticercosis is caused by the presence of larval cysts of Taenia solium, the pork tapeworm, in the brain, which can cause seizures and illness ranging from mild to fatal depending on their location, number and viability. In contrast to idiopathic epilepsy, a complex disease which can be difficult to treat and resistant to cure, Neurocysticercosis can be treated and in many cases cured with inexpensive and available anti- helminthic drugs. Distinguishing whether the cause of seizures is idiopathic epilepsy or Neurocysticercosis is thus a critical part of the diagnostic workup and essential to determine the appropriate course of treatment for patients. The established procedures for diagnosing epilepsy comprise electroencephalography and imaging via MRI, but these sophisiticated tools are of limited availability in the less developed world where Neurocysticercosis is most frequent. On the other hand, Neurocysticercosis can be diagnosed with a serological test that detects antibodies to T. solium cysts. The gold standard serological test, the Enzyme Immunotransfer Blot (EITB) developed at CDC, is a laboratory-based test, however, that is not widely available and requires significant training to carry out. Thus there is a critical need for a rapid, commercially available point-of-care test for Neurocysticercosis that can be used to test patients with seizures, in order to identify those with the parasitic infection so that they can be treated effectively. Development of such a test has been identified as an urgent priority by the World Health Organization. In the Phase I project, we will utilize recombinant and synthetic T. solium antigens corresponding to those used in the EITB to develop a point-of-care serological test for Neurocysticercosis that will meet the criteria in the World Health Organization’s Target Product Profile. These antigens have shown high sensitivity and specificity in prior studies, and will be combined to further increase sensitivity for detection of single viable cysts, the most challenging case. The point-of-care Neurocysticercosis test will be evaluated for sensitivity on a well- characterized panel of sera from Neurocysticercosis patients confirmed by EITB or clinical diagnosis, and for specificity on healthy controls and other disease state sera. Test results will be read using a field-friendly, ultraportable, low-cost reader that will provide objective interpretation and enable wireless upload of data to local devices or remote servers. Phase II will support complete development to commercial stage, clinical evaluation and preparation for CE mark and FDA submission of the Neurocysticercosis point-of-care test.

项目概要 癫痫是一种以癫痫发作为表现的大脑疾病，是第四大最常见的神经系统疾病， 影响全球超过 5000 万人，即平均每 150 人中就有 1 人受到影响。 然而，癫痫分布不均，绝大多数病例发生在欠发达地区 对这种分布的解释很可能是所有癫痫病例的三分之一是由于 神经囊尾蚴病，已知是神经系统最常见的寄生虫感染。 神经囊尾蚴病是由大脑中存在猪带绦虫（猪肉绦虫）幼虫包囊引起的， 它们可能导致癫痫发作以及从轻微到致命的各种疾病，具体取决于它们的位置、数量和 与特发性癫痫相反，特发性癫痫是一种难以治疗且具有耐药性的复杂疾病。 神经囊尾蚴病可以通过廉价且可用的抗药来治疗，并且在许多情况下可以治愈。 区分癫痫发作的原因是特发性癫痫还是神经囊尾蚴病。 因此，这是诊断检查的关键部分，对于确定适当的治疗方案至关重要 诊断癫痫的既定程序包括脑电图和成像。 通过 MRI，但这些复杂的工具在欠发达国家的可用性有限 神经囊尾蚴病是最常见的。另一方面，神经囊尾蚴病可以通过以下方法诊断。 检测猪绦虫包囊抗体的血清学测试 金标准血清学测试，即酶。 CDC 开发的免疫转移印迹 (EITB) 是一种基于实验室的测试，但尚未广泛应用 并且需要大量的培训才能进行，因此迫切需要一种快速的、商业化的方法。 神经囊尾蚴病即时检测，可用于检测癫痫患者，以便识别 已经开发出这样的测试来治疗那些患有寄生虫感染的人，以便他们能够得到有效的治疗。 被世界卫生组织确定为紧急优先事项。 在第一阶段项目中，我们将利用与所使用的抗原相对应的重组和合成的T. solium抗原 EITB 开发一种针对神经囊尾蚴病的即时血清学检测，该检测将符合 EITB 中的标准 世界卫生组织的目标产品概况这些抗原显示出高敏感性和特异性。 在之前的研究中，并将结合起来以进一步提高检测单个活包囊的灵敏度，最 具有挑战性的病例将评估护理点神经囊尾蚴病测试的敏感性。 经 EITB 或临床诊断证实的神经囊尾蚴病患者的血清特征组，以及 健康对照和其他疾病状态血清的特异性将使用现场友好的、 超便携、低成本阅读器，将提供客观解释并支持无线上传数据 第二阶段将支持本地设备或远程服务器的完整开发到商业阶段、临床阶段。 评估和准备 CE 标志以及 FDA 提交的神经囊尾蚴病即时检测。