New Diagnostics for Amebiasis

描述（由申请方提供）：溶组织内阿米巴是阿米巴病的病因，由于其难以诊断，因此被认为是前三大生物防御寄生虫中的B类病原体。由这种原生动物病原体引起的疾病是由于肠道和肠道外感染而发生的，这两者都是发展中国家的主要问题。由于这些原因，迫切需要针对该生物体及其疾病的新的和改进的诊断方法。在第一阶段，我们将继续并扩大我们在肠道阿米巴病粪便试纸抗原检测试验方面的开发工作，包括在孟加拉国、越南和土耳其的关键临床评价。临床研究者将利用PCR技术评价检测性能。我们将把该技术转让给一家快速膜检测制造商，并建立根据GMP生产的试纸的检测性能。将从内部性能研究和现场临床评价中收集向美国食品药品监督管理局提交的510（k）数据。作为这项工作的逻辑延伸，将评价试纸条用于检测阿米巴肝脓肿患者的循环抗原。我们将努力开发一种酶联免疫吸附试验，供军事和参考实验室用于检测固定标本中的凝集素。ELISA将在TechLab按照GMP生产，并在美国的参考实验室进行现场评价。将收集510（k）申报资料的数据并提交给FDA。除了ELISA，还将继续努力开发一种粪便抗原检测试纸，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，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血清学诊断试验肠外阿米巴病利用lecA（重组肽凝集素）作为捕获抗原。在第二阶段，临床评价将扩大到包括其他国家的现场研究。此外，我们将加大力度开发E。溶组织囊肿以及开发E.溶组织/隐孢子虫/贾第鞭毛虫。该项目将产生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.