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 癫痫是一种表现为癫痫发作的大脑疾病，是第四大流行的神经系统疾病， 影响到全世界5000多万人，平均每150人中就有一人受到影响。的频率 然而，癫痫分布不均，绝大多数病例发生在欠发达地区 of the world.对这种分布的解释很可能是，三分之一的癫痫病例是由于 脑囊虫病，已知是最常见的寄生虫感染的神经系统。 脑囊虫病是由脑中存在猪带绦虫（猪肉绦虫）的幼虫包囊引起的， 根据其位置、数量和 生存能力。与特发性癫痫相反，特发性癫痫是一种复杂的疾病，很难治疗， 治愈，脑囊虫病可以治疗，在许多情况下治愈廉价和可用的抗- 驱虫药区分癫痫发作的原因是特发性癫痫还是脑囊虫病， 因此，这是诊断检查的关键部分，对于确定适当的治疗过程至关重要。 患者诊断癫痫的既定程序包括脑电图和成像 但这些似是而非的工具在欠发达国家的可用性有限， 脑囊虫病是最常见的。另一方面，脑囊虫病可以用一种 检测T.包囊金标准血清学测试，酶 CDC开发的免疫转移印迹（EITB）是一种基于实验室的测试，但尚未广泛使用 并且需要大量的训练来执行。因此，迫切需要一种快速的、可商购的 脑囊虫病的即时检测，可用于检测癫痫患者，以确定 那些寄生虫感染，使他们能够得到有效的治疗。开发这样的测试已经 被世界卫生组织列为当务之急。 在第一阶段项目中，我们将利用重组和合成T。与所用抗原相对应的抗原 在EITB中，开发一种用于脑囊虫病的即时血清学检测， 世界卫生组织的目标产品简介。这些抗原已显示出高度的敏感性和特异性 在先前的研究中，将结合起来，以进一步提高检测单个活囊肿的灵敏度， 挑战性的案例将在微孔上评价床旁神经囊虫病检测的灵敏度- 来自经EITB或临床诊断证实的脑囊虫病患者的特征性血清组， 对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， 超便携，低成本的阅读器，将提供客观的解释，并使无线上传数据， 本地设备或远程服务器。第二阶段将支持完全开发到商业阶段， 评估和准备CE认证和FDA提交的脑囊虫病床旁检测。