Field-deployable Assay for Differential Diagnosis of Malaria and Viral Febrile Illnesses

用于疟疾和病毒性发热性疾病鉴别诊断的现场部署检测

• 批准号: 9004780
• 负责人: Robert James Meagher
• 金额: $ 18.88万
• 依托单位: SANDIA CORP-SANDIA NATIONAL LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-24 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9004780
• 关键词: Africa; Animal Model; Antimalarials; Arboviruses; Area; Biological Assay; Biomedical Engineering; Biotechnology; Blood; Blood specimen; Case Study; Cellular Phone; Chemistry; Chikungunya virus; Clinic; Clinical; Cold Chains; Collection; Communities; Contact Tracing; Data; Data Analyses; Data Reporting; Dengue Virus; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Disease; Disease Outbreaks; Drops; Early Diagnosis; Ebola virus; Engineering; Environment; Epidemic; Fatigue; Fever; Fever Chills; Fluorescence; Fluorescent Probes; Genomics; Goals; Guinea; Health; Home environment; Human; Immunity; Infection; Infection Control; Institutes; Knowledge; Laboratories; Lassa virus; Lead; Liberia; Location; Malaria; Measures; Medical; Microfluidics; Modeling; Monitor; Myalgia; Nausea; Nucleic Acids; Parasites; Pathogen detection; Patient Care; Patients; Performance; Phase; Plasmodium falciparum; Prevalence; Public Health; Qualifying; RNA; RNA Viruses; Reaction; Reagent; Resistance; Resources; Sampling; Sensitivity and Specificity; Sierra Leone; Specimen; Supportive care; Symptoms; Techniques; Testing; Texas; Time; Triage; Tube; Universities; Viral; Virus; Virus Diseases; West Nile virus; Wireless Technology; Work; Yellow fever virus; assay development; authority; base; biothreat; cost; follow-up; manufacturing scale-up; member; molecular diagnostics; multidisciplinary; multiplex detection; novel; pathogen; prototype; public health relevance; research clinical testing; transmission process

 DESCRIPTION (provided by applicant): The ongoing Ebola epidemic in West Africa (primarily Guinea, Liberia, and Sierra Leone) provides a valuable case study in the importance of diagnostics for febrile illness. Prior to widespread knowledge of the Ebola outbreak, a patient presenting with fever and chills might be diagnosed with malaria, purely on the basis of symptoms with no follow-up tests. If this diagnosis is incorrect, the patient does not get the appropriate therapy, and if the patient in fact has Ebola or other contagious virus, this can lead to spread of the virus which complicates infection control. We propose to develop a simple, inexpensive, portable diagnostic device to detect a panel of viruses that may be endemic in West Africa: Ebola virus, Lassa virus, Yellow Fever virus, Chikungunya virus, Dengue virus, and West Nile virus; as well as Plasmodium falciparum (the most serious cause of human malaria). The device will be simple enough to operate at a simple field clinic, triage center, airport, or other resource-poor location, utilizing a novel assay cartridge with stabilized reagents to eliminate reliance on cold chain. Supporting hardware will be battery- or solar-powered, and uses a smart phone camera for assay detection, data analysis and reporting. The assay is based on isothermal amplification of pathogen RNA, using a novel chemistry that allows single-step, closed tube multiplex detection of targets using fluorescent probes and quenchers. The proposed work is a collaborative effort between the Biotechnology and Bioengineering group at Sandia National Laboratories, and the Institute for Human Health and Immunity at the University of Texas Medical Branch. The proposed work begins with proof-of-concept (R21) phase, during which the assays and prototype hardware are tested and verified for sensitivity and specificity for model strains of pathogens. If successful, the work proceeds to a development (R33) phase, during which the prototype assay and hardware are refined, and validated by testing with clinical specimens and blood from animal model infections.

 描述（由申请人提供）：西非（主要是几内亚、利比里亚和塞拉利昂）正在发生的埃博拉疫情为发热性疾病诊断的重要性提供了一个有价值的案例研究。在埃博拉疫情被广泛了解之前，一个出现发热和寒战的病人可能会被诊断为疟疾，纯粹是根据症状，没有后续测试。如果这种诊断是错误的，病人没有得到适当的治疗，如果病人实际上有埃博拉病毒或其他传染性病毒，这可能导致病毒的传播，使感染控制复杂化。我们建议开发一种简单，廉价，便携式诊断设备，以检测一组可能在西非流行的病毒：埃博拉病毒，拉沙病毒，黄热病病毒，基孔肯雅病毒，登革热病毒和西尼罗河病毒;以及恶性疟原虫（人类疟疾的最严重原因）。该设备将足够简单，可以在简单的现场诊所、分诊中心、机场或其他资源贫乏的地点操作，利用具有稳定试剂的新型测定盒来消除对冷链的依赖。支持硬件将由电池或太阳能供电，并使用智能手机摄像头进行检测，数据分析和报告。该检测基于病原体RNA的等温扩增，使用一种新的化学方法，允许使用荧光探针和猝灭剂对靶标进行单步、闭管多重检测。这项拟议中的工作是桑迪亚国家实验室生物技术和生物工程小组与德克萨斯大学医学分支人类健康和免疫研究所之间的合作努力。拟议的工作从概念验证（R21）阶段开始，在此期间，对检测试剂盒和原型硬件进行测试，并验证病原体模型菌株的灵敏度和特异性。如果成功，工作将进入开发（R33）阶段，在此期间，原型检测和硬件将得到完善，并通过使用来自动物模型感染的临床标本和血液进行测试进行验证。