CruziScreen, a recombinant antigen-based screening test for Chagas disease

项目摘要 恰加斯病是一种由感染原生动物引起的严重炎症性综合征。 寄生虫，克氏锥虫。虽然传播主要是通过中间昆虫 宿主，感染是沉默的，慢性携带者通过转移 由这些人捐献的血液制成的受感染产品。最多500,000 南美洲和中美洲国家每年报告的新增病例和6.6万人死亡 寄生虫生活的地方。移民和范围的扩大相结合， 然而，寄生虫的寄主生活在一些国家导致了大量的感染者 直到最近才患上恰加斯病。美国在这些国家中居于首位。控制 恰加斯病的预防有赖于对感染的准确检测。改进了 需要当前可用的诊断程序。 在我们的研究中，我们发现了一种新的方法来识别寄生虫的片段(某些蛋白质) 可以作为新的诊断测试的组成部分。因为它们有能力紧紧地绑在一起 抗体来自受感染的个体，通常选自各种个体诊断 我们将它们缝合成“多个抗体结合表位”，以提高诊断能力。 权力。这些“多蛋白”最大限度地提高了与受感染血清的反应能力，从而使新的 测试。我们已经使用计算机搜索来确定一些新的诊断候选 在T.ruzi和我们的初步数据中，有几个很有希望成为重要成分 用一种新的诊断测试。这项建议中的研究将开发一种改进的和成本- 有效的诊断测试，以允许筛查毛滴虫感染/恰加斯病。 拟议的研究将分两步进行：在第一步中，我们将优化并严格定义 两种铅多蛋白的生产参数。在第2步中，我们将集成这些诊断线索 转换成与标准参考实验室/血液中心使用的格式一致的格式 将它们分发给我们广泛的合作者网络，这些合作者是克氏锥虫的广泛流行 需要进一步评估的地区。如果成功，在第二阶段应用、原型测试和附属设备 测试格式将作为潜在的商业测试进行制作和广泛评估。

Project Summary Chagas disease is a severe inflammatory syndrome caused by infection with a protozoan parasite, Trypanosoma cruzi. Although transmission occurs mostly through an intermediate insect host, the infection is silent and chronic carriers pose a significant risk through the transfer of infected products made from donated blood of these individuals to blood recipients. Up to 500,000 new cases and 66,000 deaths are reported annually in countries in South and Central America where the parasite lives. The combination of immigration and expansion of the range where the parasite host lives is, however, leading to large numbers of infected individuals in countries that until recently did not have Chagas disease. The United States is foremost amongst these. Control and prevention of Chagas disease relies on the accurate detection of infection. Improvements in the currently available diagnostics are required. In our research we have found a novel way to identify pieces of the parasite (certain proteins) that could be used as components of a new diagnostic test. Since they have the ability to tightly bind antibodies from infected individuals and are often selected from a variety of individual diagnostic leads, we stitch them together as “multiple antibody-binding epitopes” to enhance the diagnostic power. These “polyproteins” maximize the ability to react with infected serum, enabling the new test. We have used computational searches to identify a number of novel diagnostic candidates in T. cruzi and our preliminary data indicate several that hold promise as important components with a new diagnostic test. The research in this proposal will develop an improved and cost- effective diagnostic test to permit screening for T. cruzi infection / Chagas disease. The proposed research will proceed in two steps: In step 1 we will optimize and tightly define the production parameters of two lead polyproteins. In step 2 we will integrate these diagnostic leads into a format consistent with use in standard reference laboratories/ blood centers as well distribute them to our extensive network of collaborators in a wide variety of T. cruzi-endemic regions for further evaluation. If successful, in the phase II application, prototype tests and adjunct test formats will be produced and extensively evaluated as potential commercial tests.