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

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.Project Narrative Epilepsy is the fourth most common neurological disorder in the U.S. and affects over 50 million people worldwide. This project addresses the critical need for a point-of-care test to diagnose Neurocysticercosis in patients with epileptic seizures, as this parasitic infection is responsible for about one third of all epilepsy and is the major cause of adult epilepsy worldwide. In Phase I, we propose to demonstrate the feasibility of a point- of-care test for Neurocysticercosis based on recombinant or synthetic antigens. In Phase II we will refine this assay into a manufactured product, carry out a validation study to support a 510(k) submission to FDA, and prepare for scale up and commercial launch of the assay.