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

针对新兴虫媒病毒的综合护理点诊断和数据报告平台

• 批准号: 10080060
• 负责人: Bobby Brooke Herrera
• 金额: $ 79.99万
• 依托单位: E25BIO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-10 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080060
• 关键词: Absorbent Pads; Acute; Aedes; Affect; Alphavirus; Antibodies; Antigens; Arboviruses; Archives; Area; Arthropod Vectors; Bar Codes; Bedside Testings; Biological Assay; Blood group antigen S; Brazil; Buffers; Car Phone; Care Technology Points; Characteristics; Chikungunya virus; Clinical; Clinical Decision Support Systems; Colombia; Culicidae; Data; Data Analytics; Data Reporting; Databases; Dengue; Detection; Development; Diagnostic; Diagnostic tests; Disease Outbreaks; Electronic Health Record; Enzyme-Linked Immunosorbent Assay; Epidemiology; Equipment; Evaluation; FDA approved; Feasibility Studies; Flavivirus; Funding; Gold; Health; Health Personnel; Healthcare; Human; Human Resources; Image; Incidence; Individual; Infection; Infection Control; Informatics; Instruction; Laboratories; Lateral; Lead; Metadata; Methods; Mexico; Monitor; Monoclonal Antibodies; National Institute of Allergy and Infectious Disease; Nonstructural Protein; Pathogenicity; Patients; Performance; Phase; Plasma; Preparation; Process; Production; Recombinants; Reporting; Reproducibility; Resources; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Serological; Serum; Site; Small Business Innovation Research Grant; Source; System; Telephone; Test Result; Testing; Therapeutic; Therapeutic Intervention; Time; Training; Validation; Viral; Viral Antigens; Virus; Virus Diseases; Whole Blood; ZIKA; Zika Virus; accurate diagnosis; base; chikungunya; clinical decision support; commercialization; cost; cross reactivity; data dictionary; design; digital; evidence base; field study; health care service organization; infection burden; infection rate; innovation; interoperability; new technology; novel; pathogen; point of care; point-of-care diagnostics; preclinical evaluation; prospective; prospective test; prototype; repository; scale up; skills; smartphone Application; tool; transmission process; viral detection

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.

概括 超过20亿人生活在受节肢动物传播病毒影响的地区 （Arboviruses），例如Flaviviruess登革热（DENV）和Zika（Zikv）和Alphavirus chikungunya（Chikv）。 这些arbovirus是致病性的，每年引起数百万个感染。而监视对于 了解感染率，控制爆发并告知患者的治疗工作，没有FDA- 批准的方法是在护理点和分析处同时检测多种弧病毒抗原， 记录并实时报告数据。在第一阶段，我们开发了Pan-denv的非培训测试 非结构蛋白1（NS1），ZIKV NS1和CHIKV INVELOPE（E）（E）和3合1的多路复用测试 所有三种病毒抗原（3Plex）。这些测试在实验室中进行了评估，并使用存档的，被识别的 病人样本。此外，我们开发了一个移动智能手机应用程序来图像捕获测试结果，地理位置 - 找到捕获图像的位置，然后将数据上传到中央服务器以进行流行病学映射。在 第二阶段，我们建议最终确定单纯形和3Plex测试的开发，并增强我们的数字平台 用于实时元数据报告，以支持治疗干预和暴发管理。我们提出的 单纯形和3plex测试是低成本的，即护理点测试，可以在没有运动部件的情况下进行，或者 训练有素的人员，昂贵的设备或集中实验室的必要性。在AIM 1中，我们将扩大规模 针对DENV，ZIKV和CHIKV抗原特异的铅单克隆抗体的产生。在AIM 2中，我们将 优化单纯糖和3个复合测试，以全血检测DENV，ZIKV和CHIKV抗原。在AIM 3中，我们 将在GMP下产生多个单纯形和3Plex测试，以进行前瞻性评估 在哥伦比亚和巴西收集了样品。在AIM 4中，我们将开发和提供信息的医疗保健数据库 与电子健康记录存储库的单纯形和3plex测试结果数据集成；数字平台 将在哥伦比亚和巴西进行评估。该项目具有创新性，因为它是第一个允许的平台 基于促弧病毒抗原的抗原抗原检测和实时数据分析，用于感染地面和 爆发管理。成功完成此II阶段项目后，我们将开发首个 ITS-BIND平台提供了一个多合一的解决方案，可用于arboviral检测和数据报告，这将准备就绪 用于监管验证。