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: 10699435
• 负责人: Andrew E. Levin
• 金额: $ 99.9万
• 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 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10699435
• 关键词: Address; Adult; Affect; Anthelmintics; Antigens; Antiparasitic Agents; Biological Assay; Brain; Brain Diseases; Buffers; Chemistry; Clinical; Clinical Research; Complex; Country; Cyst; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Electroencephalography; Ensure; Enzyme-Linked Immunosorbent Assay; Enzymes; Epilepsy; Etiology; Europe; FDA approved; Family suidae; Frequencies; Goals; Gold Colloid; Human; Hygiene; Image; Immigration; Immunoassay; Income; Individual; Infection; Infrastructure; Label; Laboratories; Lateral; Location; Magnetic Resonance Imaging; Measurement; Measures; Methods; Multi-site clinical study; Neurocysticercosis; Neurologic; Neurologic Symptoms; Parasitic Diseases; Parasitic infection; Patients; Performance; Persons; Phase; Preparation; Price; Procedures; Prospective Studies; Reagent; Recombinants; Reference Standards; Reflex action; Resistance; Retrospective Studies; Sampling; Seizures; Sensitivity and Specificity; Serology test; Serum; Specificity; Structural defect; Symptoms; Taenia solium; Temperature; Testing; Tissues; Training; Travel; Western Blotting; Whole Blood; World Health Organization; antibody detection; clinical diagnosis; clinical research site; commercial launch; cost; design; detection sensitivity; diagnostic tool; effective therapy; imaging study; in-vitro diagnostics; infection rate; lateral flow assay; manufacture; manufacturing scale-up; medical specialties; meetings; nervous system disorder; nervous system infection; neural; patient screening; point of care; point of care testing; prospective; prototype; research clinical testing; scale up; skills; 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 likely explanation for this distribution is 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 sophisticated 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, it 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 utilized recombinant and synthetic T. solium antigens corresponding to those used in the EITB to develop a prototype lateral flow, point-of-care serological test for neurocysticercosis aimed at meeting the criteria in the World Health Organization’s Target Product Profile. These antigens have shown high sensitivity and specificity in prior studies, and in combination further increase the sensitivity for detection of single viable cysts, the most challenging disease manifestation. In Phase II, the lateral flow neurocysticercosis test will be evaluated in prospective studies on neurological patients with symptoms suggestive of neurocysticercosis, and in retrospective studies on well-characterized sera from neurocysticercosis patients confirmed by EITB or clinical diagnosis, and for specificity on healthy controls and other disease state sera. 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。 整个世界。对这种分布的可能解释是，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引起的，这可能会导致 癫痫发作和疾病从轻微到致命不等，视其位置、数量和生存能力而定。与之形成鲜明对比的是 特发性癫痫，一种难以治疗和难以治愈的复杂疾病，脑囊虫病 可以用廉价和可用的抗寄生虫药物治疗，在许多情况下还可以治愈。与众不同 因此，癫痫发作的原因是特发性癫痫还是脑囊虫病是诊断的关键部分。 体检对确定患者的适当疗程是必不可少的。既定的程序 诊断癫痫的方法包括脑电和核磁共振成像，但这些复杂的工具 在脑囊虫病最常见的欠发达世界，这些药物的可获得性有限。另一方面 另一方面，脑囊虫病可以通过检测弓形虫包囊抗体的血清学测试来诊断。这个 CDC开发的金标血清学检测--酶免疫转移印迹(EITB)是一种以实验室为基础的 然而，测试并不广泛，需要大量的培训才能进行。因此，有一个迫切的需要 为了获得一种快速的、商业上可用的脑囊虫病护理点测试，可以用来测试患有 抽搐，以确定谁与寄生虫感染，以便他们可以得到有效的治疗。发展 世界卫生组织已将此类检测确定为一项紧迫的优先事项。 在第一阶段项目中，我们使用了重组和合成的沙门氏菌抗原，这些抗原与 EITB将开发一种针对脑囊虫病的原型横向流动、护理点血清学测试，旨在 符合世界卫生组织目标产品简介中的标准。这些抗原已经显示出很高的 敏感度和特异度在以前的研究中，并结合进一步提高了对单一 活体包囊，最具挑战性的疾病表现。在第二阶段，侧流性脑囊虫病测试将 在对症状提示脑囊虫病的神经科患者的前瞻性研究中进行评估， 并对EITB或EITB证实的脑囊虫病患者的特征良好的血清进行了回顾性研究 临床诊断，以及对健康对照和其他疾病状态血清的特异性。第二阶段将支持 完成CE标志和FDA的商业化开发、临床评估和准备工作 提交脑囊虫病护理点测试。