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 癫痫是一种以癫痫为表现的大脑紊乱，是第四大最常见的神经疾病， 影响到全球超过5000万人，平均每150人中就有1人受到影响。的频率 然而，癫痫的分布并不均匀，绝大多数病例发生在欠发达地区。 这个世界。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，已知是神经系统最常见的寄生虫感染。 脑囊虫病是由猪带绦虫幼虫在大脑中的存在而引起的。 可导致癫痫发作和疾病，从轻微到致命不等，具体取决于它们的位置、数量和 生存能力。与特发性癫痫不同，特发性癫痫是一种复杂的疾病，很难治疗，也很难抵抗 治愈，脑囊虫病是可以治疗的，在许多情况下可以用廉价的可用的抗囊虫药物治愈 蠕虫类药物。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疗程是必不可少的 病人。诊断癫痫的既定程序包括脑电和成像。 但这些诡辩的工具在欠发达世界的可获得性有限 脑囊虫病是最常见的。另一方面，脑囊虫病可以被诊断为 检测弓形虫包囊抗体的血清学试验。黄金标准的血清学检测，酶 CDC开发的免疫转移印迹(EITB)是一种以实验室为基础的检测方法，但并未广泛应用 而且需要大量的培训才能进行。因此，迫切需要一种快速的、商业上可用的 脑囊虫病的看护点测试，可用于测试癫痫患者，以确定 那些有寄生虫感染的人，这样他们才能得到有效的治疗。这样的测试已经开发出来了 被世界卫生组织确定为紧急优先事项。 在第一阶段项目中，我们将利用重组和合成的沙门氏菌抗原 在EITB开发一种针对脑囊虫病的护理点血清学测试，该测试将满足 世界卫生组织的目标产品简介。这些抗原表现出高度的敏感性和特异性。 在先前的研究中，将结合使用，以进一步提高对单个可存活包囊的检测灵敏度，最 具有挑战性的案子。医疗点脑囊虫病测试将在井上进行敏感性评估- 经EITB或临床诊断证实的脑囊虫病患者的特征性血清样本，并用于 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型、 超便携、低成本阅读器，将提供客观解释，并支持将数据无线上传到 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，临床 CE标志和FDA提交的脑囊虫病护理点检测的评估和准备。