New Diagnostics for Amebiasis

描述(申请人提供)：溶组织内阿米巴，阿米巴病的原因，是一种B类病原体，被认为是前三大生物防御寄生虫，因为它很难诊断。由这种原生动物病原体引起的疾病是由肠道和肠外感染引起的，这两种感染都是发展中国家的主要问题。由于这些原因，迫切需要对这种有机体及其疾病进行新的和改进的诊断。在第一阶段，我们将继续和扩大我们在肠道阿米巴病粪便试纸抗原检测测试方面的开发工作，包括在孟加拉国、越南和土耳其进行关键的临床评估。临床研究人员将利用聚合酶链式反应技术来评估测试性能。我们将把这项技术转让给一家快速薄膜测试制造商，并建立GMP生产的滴尺的测试性能。提交给食品和药物管理局的510(K)计划的数据将从内部绩效研究和现场临床评估中收集。作为这项工作的合理延伸，将评估试纸用于检测阿米巴肝脓肿患者的循环抗原。我们将继续努力建立一种用于军用和参考实验室检测固定标本中凝集素的酶联免疫吸附试验。该ELISA将在TechLab的GMP下生产，并在美国的参考实验室进行现场评估。510(K)提交的数据将被收集并提交给FDA。除了酶联免疫吸附试验外，还将继续努力开发一种粪便抗原检测试纸，该试纸可用于美国和其他工业化国家的固定标本。对于肠外阿米巴病，最敏感的诊断方法是同时检测血清抗原和抗体。因此，我们将以凝集素的重组多肽LecA作为捕获抗原，建立一种新的肠外阿米巴病的血清学诊断方法。在第二阶段，临床评估将扩大到包括在其他国家的现场研究。此外，我们将进一步努力开发溶组织埃希氏菌包囊测试，以及开发溶组织埃希氏菌/隐孢子虫/贾第鞭毛虫的小组测试。该项目将导致一系列在阿米巴病诊断中有广泛应用的测试，使这些测试适合于生物防御目的和改善全球医疗保健。

DESCRIPTION (provided by applicant): Entamoeba histolytica, the cause of amoebiasis, is a Category B pathogen considered in the top three biodefense parasites because it is difficult to diagnose. The disease caused by this protozoan pathogen occurs due to intestinal and extra-intestinal infections, both of which are major problems in developing countries. For these reasons, there is an urgent need for new and improved diagnostics for this organism and its disease. In Phase I we will continue and expand our developmental work on stool dipstick antigen detection tests for intestinal amebiasis, including critical clinical evaluations in Bangladesh, Vietnam, and Turkey. Clinical investigators will utilize PCR technology to evaluate test performance. We will transfer the technology to a manufacturer of rapid membrane tests and establish test performance of dipsticks manufactured under GMP. Data for 510(k) submissions to the Food and Drug Administration will be collected from in-house performance studies and on-site clinical evaluations. As a logical extension of this work, the dipsticks will be evaluated for the detection of circulating antigen in persons with amebic liver abscess. We will extend efforts on an ELISA for use by military and reference labs for the detection of lectin in fixed specimens. The ELISA will be manufactured under GMP at TechLab and evaluated on-site at reference laboratories in the U.S. The data for a 510(k) submission will be collected and submitted to the FDA. In addition to the ELISA, efforts will continue on a stool antigen detection dipstick that works with fixed specimens for use in the U.S. and other industrialized countries. For extra-intestinal amebiasis, the highest sensitivity diagnostic approach utilizes detection of both serum antigen and antibody. Therefore, we will develop a new serodiagnostic test for extra-intestinal amebiasis utilizing lecA (a recombinant peptide of the lectin) as the capture antigen. In Phase II, clinical evaluations will be extended to include on-site studies in other countries. In addition, we will expand efforts to develop tests for E. histolytica cysts as well as develop a panel test for E. histolytica/Cryptosporidium/Giardia. This project will lead to a battery of tests that have broad application in the diagnosis of amebiasis, making these tests suitable for biodefense purposes and for improving global healthcare.