New Rapid Diagnostic Tests for Amebiasis

描述（由申请方提供）：溶组织内阿米巴是一种原生动物寄生虫，是人类阿米巴病的病原体。肠道阿米巴病会导致衰弱性腹泻和痢疾，而肠外阿米巴病则发生在寄生虫从肠道迁移到全身器官时，最常见的是肝脏。NIAID生物防御剂B&C蓝带小组针对E。溶组织病原体是最优先研究的3种寄生病原体之一，因为它是环境稳定的，在低剂量下具有传染性，并且是全世界发病率和死亡率的重要原因。E.溶组织囊肿主要是通过摄入受污染的食物和水获得的，每年导致5 000万例阿米巴结肠炎和阿米巴肝脓肿，估计有10万人因感染而死亡。通过粪便显微镜检查、抗原检测、PCR或IFA准确诊断感染可导致成功治疗和完全康复。几个问题混淆了正确的诊断，包括一连串的其他生物体，可以导致类似的肠道症状，非致病性内阿米巴属的存在。在粪便标本，以及缺乏粪便阳性结果一旦阿米巴感染成为侵入性。E.由于内阿米巴属的非致病性菌株，以E. histolytica，使E.具有特殊价值的溶组织特异性诊断。正确的识别可以消除症状的误诊以及使用不必要且可能危险的药物进行治疗。此外，必须提供一种简单的诊断方法，以在粪便检测不阳性的情况下识别侵袭性阿米巴病。该STTR II期申请描述了用于识别人类肠道和肠外阿米巴感染的2种集成快速诊断检测试剂的GMP生产。具体目标1强调了E. HISTOLYTICA ANGIENQUIK CHEKTM检测，用于鉴定大肠杆菌。阿米巴性结肠炎患者粪便标本和肠外阿米巴病患者血清、全血、唾液和尿液中的溶组织特异性抗原。具体目标#2强调了E. HISTOLYTICA ANTIBODY QUIK CHEKTM测试，旨在检测抗E。暴露于大肠杆菌的患者血清样本中的溶组织抗体。抗原阴性的溶组织菌。测试将在TechLab，Inc.生产。使用我们与弗吉尼亚大学合作开发的试剂。检测将提供给UVA和我们在孟加拉国和德国的联盟研究中心进行临床检测。这两个中心都可以从阿米巴病流行地区获得标本和病人。此外，具体目标#3强调了在护理点环境中对这两种测试的分析，以确定识别人类阿米巴病的最有效诊断策略。

DESCRIPTION (provided by applicant): Entamoebga histolytica is a protozoan parasite and the causative agent of amebiasis in humans. Intestinal amebiasis causes debilitating diarrhea and dysentery, while extraintestinal amebiasis occurs when the parasite migrates from the intestinal tract to organs throughout the body, most commonly the liver. The NIAID Blue Ribbon Panel on Biodefense Agents B&C targeted E. histolytica as 1 of the 3 parasitic pathogens of highest priority for research because it is environmentally stable, infectious at a low dose, and is a significant cause of morbidity and mortality worldwide. E. histolytica cysts are predominantly acquired through ingestion of contaminated food and water, leading to 50 million cases of amebic colitis and amebic liver abscess annually, and an estimated 100,000 deaths occurring due to infection. Accurate diagnosis of infection by fecal microscopy, antigen testing, PCR, or IFA leads to successful treatment and full recovery. Several issues confound proper diagnosis, including the litany of other organisms that can cause similar intestinal symptoms, the presence of non-pathogenic Entamoeba spp. in the fecal specimen, and the lack of fecal positive results once amebic infections become invasive. E. histolytica must be specifically identified since non-pathogenic strains of Entamoeba spp. colonize the human intestine at 3-10 fold the rate of E. histolytica, making E. histolytica-specific diagnostics of particular value. Proper identification eliminates misdiagnosis of symptoms and treatment with unnecessary and possibly dangerous drugs. Further, a simple method of diagnosis must be made available to identify invasive amebiasis in the absence of positive fecal testing. This STTR Phase II application describes the GMP manufacture of 2 integrated rapid diagnostic tests used for the identification of intestinal and extraintestinal amebic infections in humans. Specific Aim #1 highlights production and FDA clearance of the E. HISTOLYTICA ANTIGEN QUIK CHEKTM test, which is designed to identify E. histolytica-specific antigen in fecal specimens from patients with amebic colitis, and in serum, whole blood, saliva and urine from patients with extraintestinal amebiasis. Specific Aim #2 highlights production and FDA clearance of the E. HISTOLYTICA ANTIBODY QUIK CHEKTM test, which is designed to detect anti-E. histolytica antibodies in serum samples of patients exposed to E. histolytica who are antigen negative. The tests will be manufactured at TechLab, Inc. using reagents developed through our partnership with the University of Virginia. The tests will be provided to UVA and our consortium sites in Bangladesh and Germany for clinical testing. Both sites have access to specimens and patients from areas where amebiasis is endemic. Further, Specific Aim #3 highlights analysis of these 2 tests together in point-of-care environments in order to identify the most effective diagnostic strategy for identifying amebiasis in humans.