New Rapid Diagnostic Tests for Amebiasis

阿米巴病的新快速诊断测试

• 批准号: 7155831
• 负责人: Joel F Herbein
• 金额: $ 100万
• 依托单位: TECHLAB, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155831
• 关键词: amebiasis; antibody; antigens; clinical research; diagnostic tests; human; serum

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.

描述(申请人提供)：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的腹泻和痢疾，而肠外阿米巴病则是当寄生虫从肠道迁移到全身器官时发生的，最常见的是肝脏。NIAID生物防御剂B和C蓝带小组将溶解组织埃希氏菌作为最优先研究的3种寄生性病原体之一，因为它环境稳定，低剂量具有传染性，是世界范围内发病率和死亡率的重要原因。主要通过摄入受污染的食物和水获得溶组织埃希氏囊肿，每年导致5000万例阿米巴结肠炎和阿米巴肝脓肿，估计有100,000人死于感染。通过粪便镜检、抗原检测、聚合酶链式反应或间接免疫荧光法对感染进行准确诊断，可确保治疗成功和完全康复。有几个问题混淆了正确的诊断，包括可引起类似肠道症状的其他生物体的连锁反应，非致病性内阿米巴的存在。在粪便标本中，阿米巴感染一旦变为侵袭性，便缺乏粪便阳性结果。由于内阿米巴属非致病菌株，因此必须对溶组织埃希菌进行特异性鉴定。在人体肠道的定殖率是溶组织埃希氏菌的3-10倍，这使得溶组织埃希菌的特异性诊断具有特殊的价值。正确的识别消除了对症状的误诊和用不必要的和可能危险的药物治疗。此外，在没有阳性粪便检测的情况下，必须提供一种简单的诊断方法来识别侵袭性阿米巴病。这个STTR第二阶段的应用描述了GMP生产的2种用于识别人类肠道和肠外阿米巴感染的综合快速诊断试验。具体目标#1强调了溶解组织埃希氏菌抗原Quik CHEKTM检测的产生和FDA的清除，该检测旨在从阿米巴结肠炎患者的粪便标本以及肠外阿米巴病患者的血清、全血、唾液和尿液中鉴定溶组织埃希菌特异性抗原。特殊目的#2强调了溶组性肠杆菌抗体Quik CHEKTM检测的产生和FDA的批准，该检测旨在检测抗E.抗原阴性的溶组织埃希氏菌暴露患者血清标本中的溶组虫抗体。这些测试将在TechLab，Inc.使用我们与弗吉尼亚大学合作开发的试剂进行生产。这些测试将被提供给UVA和我们在孟加拉国和德国的财团地点进行临床测试。这两个网站都可以接触到阿米巴病流行地区的标本和患者。此外，具体目标#3强调在护理地点环境中对这两种测试一起进行分析，以确定识别人类阿米巴病的最有效的诊断策略。