Integrated point-of-care diagnostic and data reporting platform for emerging arboviruses

总结 超过20亿人生活在受节肢动物传播病毒影响的地区 在一些实施方案中，所述病毒包括病毒（虫媒病毒），例如登革热黄病毒（DENV）和寨卡病毒（ZIKV），以及基孔肯雅甲病毒（CHIKV）。 这些虫媒病毒是致病性的，每年造成数百万人感染。虽然监视对于 了解感染率，控制疫情，并告知患者治疗措施，没有FDA- 在护理点同时检测多种虫媒病毒抗原并进行分析的获批方法， 文档和实时报告数据。在第一阶段，我们开发了用于泛DENV的非多重测试， 非结构蛋白1（NS 1）、ZIKV NS 1和CHIKV包膜（E）（Simplified）和三合一多重检测 所有三种病毒抗原（3 IgM）。这些测试在实验室进行了评估，并使用存档的，去识别的 患者样本。此外，我们开发了一个移动的智能手机应用程序，以图像捕获测试结果，地理位置， 定位图像拍摄的位置，并将数据上传到中央服务器进行流行病学绘图。在 在第二阶段，我们建议完成Simplified和3Simplified测试的开发，并加强我们的数字平台 用于实时元数据报告，以支持治疗干预和疫情管理。我们提出的 Simplified和3D检测是低成本的即时检测，可以在现场进行，无需移动部件，或 需要经过培训的人员、昂贵的设备或集中实验室。在目标1中，我们将扩大 产生特异于DENV、ZIKV和CHIKV抗原的先导单克隆抗体。在目标2中，我们将 优化用于DENV、ZIKV和CHIKV抗原的全血检测的Simplification和3D检测。在目标3中， 将根据GMP生产多个批次的Simplification和3000检测试剂盒，用于前瞻性临床前评价 在哥伦比亚和巴西采集样本。在目标4中，我们将开发和信息化的医疗保健数据库， Simplified和3GPP测试结果数据与电子健康记录存储库的集成;数字平台 将在哥伦比亚和巴西进行评估。这个项目是创新的，因为它是第一个平台， 基于虫媒病毒抗原的即时检测和实时数据分析，用于感染地理标记， 爆发管理。在第二阶段项目顺利完成后，我们将开发出第一个- 该平台为虫媒病毒检测和数据报告提供一体化解决方案， 用于监管验证。

Summary Over 2 billion people live in areas that are affected by the transmission of arthropod-borne viruses (arboviruses) such as the flaviviruses dengue (DENV) and Zika (ZIKV), and the alphavirus chikungunya (CHIKV). These arboviruses are pathogenic and cause millions of infections annually. While the surveillance is critical to understanding infection rates, controlling outbreaks, and informing patient therapeutic efforts, there is no FDA- approved method to simultaneously detect multiple arboviral antigens at the point-of-care and analyze, document, and report data in real-time. In Phase I, we developed non-multiplexed tests for pan-DENV nonstructural protein 1 (NS1), ZIKV NS1, and CHIKV envelope (E) (SimPlex) and a 3-in-1, multiplexed test for all three viral antigens (3Plex). These tests were evaluated in the laboratory and using archived, de-identified patient samples. Additionally, we developed a mobile smartphone application to image capture test results, geo- locate where the image was captured, and upload the data to a central server for epidemiological mapping. In Phase II, we propose to finalize development of the SimPlex and 3Plex tests and enhance our digital platform for real-time metadata reporting to support therapeutic intervention and outbreak management. Our proposed SimPlex and 3Plex tests are low-cost, point-of-care tests that can be done in the field without moving parts, or the necessity of trained personnel, expensive equipment, or a centralized laboratory. In Aim 1, we will scale up production of lead monoclonal antibodies specific for DENV, ZIKV, and CHIKV antigens. In Aim 2, we will optimize SimPlex and 3Plex tests for whole blood detection of DENV, ZIKV, and CHIKV antigens. In Aim 3, we will produce multiple lots of SimPlex and 3Plex tests under GMP for pre-clinical evaluation using prospectively collected samples in Colombia and Brazil. In Aim 4, we will develop and informatic healthcare databased for fast integration of SimPlex and 3Plex test result data with electronic health record repositories; the digital platform will be evaluated in Colombia and Brazil. This project is innovative because it is the first platform that allows point-of-care arboviral antigen-based detection and real-time data analytics for infection geotagging and outbreak management. Upon successful completion of this Phase II project, we will have developed a first-of- its-kind platform, which provides an all-in-one solution to arboviral detection and data reporting, that will be ready for regulatory validation.