Developing a new rapid test for human African trypanosomiasis

描述（由申请人提供）：非洲人类锥虫病（HAT），又称昏睡病，是一种由原生动物寄生虫布鲁氏锥虫引起的严重疾病。HAT在撒哈拉以南非洲的36个国家流行，每年有30万至50万新病例，6.6万人死亡。由于这种致命的疾病是可以治疗的，所以对它的控制很大程度上依赖于对感染者的准确诊断。然而，目前可用的诊断要么是侵入性的，要么在敏感性和特异性方面不足。具有某些重复片段的蛋白质，“串联重复（TR）结构域”，已在各种原生动物寄生虫中发现，包括引起昏睡病的那种。人体似乎更倾向于识别这种具有TR结构域的蛋白质，因此当我们被感染时，我们的血液中有特异性抗体。这些抗体可以作为该疾病快速诊断测试的目标。我们最近通过计算搜索在相关的锥虫虫寄生虫婴儿利什曼原虫和克氏锥虫中发现了一些新的TR蛋白，并证明其中许多蛋白具有作为诊断的希望。这项研究申请是为了证明应用这种新的计算方法来开发改进的布鲁氏杆菌感染/ HAT的血清学测试的原理。一旦这个应用程序中的工作成功完成，我们将在未来测试来自这个应用程序的有希望的抗原的各种组合。最好的抗原组合将用于商业测试。公共卫生相关性：对非洲昏睡病进行有效、可部署的快速检测将极大地有助于防治这一致命疾病。通过发现和验证候选抗原，我们打算推进这种测试的商业原型，从而改善全球健康。

DESCRIPTION (provided by applicant): Human African trypanosomiasis (HAT), also known as sleeping sickness, is a severe disease caused by protozoan parasite Trypanosoma brucei. HAT is endemic in 36 countries in sub-Saharan Africa and there are 300,000 - 500,000 new cases with 66,000 deaths annually. Because this fatal disease is treatable, its control largely relies on accurate diagnosis of infected people. However, currently available diagnostics are either invasive or inadequate in sensitivity and specificity. Proteins with certain repeated pieces, "tandem repeat (TR) domains", have been found in various protozoan parasites including the one causing sleeping sickness. The human body appears to prefer to recognize such proteins with TR domains and we therefore have specific antibodies in our blood when we have been infected. These antibodies could serve as targets for a rapid diagnostic test for the disease. We have recently identified by computational search a number of novel TR proteins in the related trypanosomatid parasites Leishmania infantum and T. cruzi and demonstrated that many of them show promise as diagnostics. This research application is for a proof-of-principal in applying this novel computational approach for developing improved serological tests for T. brucei infection / HAT. Once the work in this application is completed successfully we would in the future test various combinations of the promising antigens from this application. The best antigen combination will be used to produce commercial tests. PUBLIC HEALTH RELEVANCE: An effective deployable rapid test for African sleeping sickness would greatly aid in the fight against this deadly disease. By discovering and validating candidate antigens we intend to progress toward a commercial prototype for such a test leading to an improvement in global health.