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.

项目摘要 癫痫是由癫痫发作表现出的大脑疾病，是第四大流行的神经系统疾病，是 全球影响超过5000万人，平均150人中有1人。频率 但是，癫痫的分布不均匀，绝大多数情况发生在较不发达的地区 世界。该分布的解释很可能是所有癫痫病的三分之一是由于 神经囊肿，已知是神经系统中最常见的寄生虫感染。 神经囊肿是由大脑中的Taenia solium（猪肉tape虫）的幼虫囊肿引起的 会导致癫痫发作和疾病，从轻度到致命，具体取决于其位置，数量和 生存能力。与特发性癫痫相比 治愈，神经囊肿病可以治疗，在许多情况下，可以用廉价且可用的抗 舵手药物。区分癫痫发作的原因是特发性癫痫还是神经囊肿是 因此，诊断检查的关键部分是确定适当治疗过程的至关重要的部分 患者。诊断癫痫的完整脑电图和成像的既定程序 通过MRI，但是这些sophiiticatienitic的工具在较不发达的世界中的可用性有限 神经囊肿最常。另一方面，可以诊断出神经囊肿 血清学测试检测到抗牛群囊肿的抗体。黄金标准血清学测试，酶 在CDC上开发的免疫转移印迹（EITB）是一种基于实验室的测试，但是并非广泛可用 并需要进行大量培训才能进行。迫切需要快速，市售的 可用于测试癫痫患者的神经囊肿的护理测试，以鉴定 患有寄生虫感染的人可以有效治疗。这种测试的开发已经 世界卫生组织被确定为紧急优先事项。 在第一阶段项目中，我们将利用重组和合成T. solium抗原，与所使用的抗原相对应 在EITB中，为神经囊虫病的临时血清学检验，该测试将符合该标准 世界卫生组织的目标产品概况。这些抗原表现出高灵敏度和特异性 在先前的研究中，并将合并以进一步提高检测单个可行囊肿的灵敏度，这是最多的 具有挑战性的案例。将评估护理点神经囊肿检验的敏感性 通过EITB或临床诊断证实的神经囊虫病患者的血清表征，用于 健康对照和其他疾病状态血清的特异性。测试结果将使用现场友好的读取 超实用的低成本阅读器，将提供客观的解释并使无线数据上传到 本地设备或远程服务器。第二阶段将支持到商业阶段的完整发展，临床 评估和准备神经囊虫病的CE Mark和FDA提交了护理点测试。