New Diagnostics for Amebiasis

描述（由申请人提供）：阿米巴原虫是阿米巴病的病因，是前三大生物防御寄生虫中的B类病原体，因为诊断困难。由这种原生动物病原体引起的疾病是由于肠道和肠外感染引起的，这两者都是发展中国家的主要问题。由于这些原因，迫切需要对这种生物体及其疾病进行新的和改进的诊断。在第一阶段，我们将继续并扩大针对肠道阿米巴病的粪便试纸抗原检测试验的开发工作，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PCR技术来评估测试性能。我们将把这项技术转让给一家快速膜测试制造商，并建立在GMP下生产的试纸的测试性能。提交给食品和药物管理局的510(k)数据将从内部绩效研究和现场临床评估中收集。作为这项工作的逻辑延伸，将评估试纸检测阿米巴肝脓肿患者的循环抗原。我们将继续努力开发一种ELISA，用于军事和参考实验室检测固定标本中的凝集素。该ELISA将在TechLab按照GMP生产，并在美国的参考实验室进行现场评估。提交510(k)申请的数据将被收集并提交给FDA。除了酶联免疫吸附试验外，美国和其他工业化国家还将继续研制一种适用于固定标本的粪便抗原检测试纸。对于肠外阿米巴病，灵敏度最高的诊断方法是同时检测血清抗原和抗体。因此，我们将开发一种新的肠外阿米巴病的血清诊断测试，利用lecA（一种凝集素的重组肽）作为捕获抗原。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，我们将扩大努力，开发溶组织芽胞杆菌囊肿的检测方法，以及开发溶组织芽胞杆菌/隐孢子虫/贾第鞭毛虫的小组检测方法。该项目将导致一系列在阿米巴病诊断中具有广泛应用的测试，使这些测试适用于生物防御目的和改善全球卫生保健。

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.