Meeting Urgent Needs in Surveillance and Diagnostics. Zika

满足监视和诊断方面的迫切需求。

• 批准号: 9402049
• 负责人: Barry Wilmer Alto
• 金额: $ 14.28万
• 依托单位: FIREBIRD BIOMOLECULAR SCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-15 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9402049
• 关键词: Address; Adopted; Age; American; Appearance; Arboviruses; Benchmarking; Bioinformatics; Biological; Biological Assay; Brazil; Caring; Centers for Disease Control and Prevention (U.S.); Clinic; Collaborations; Commercial Sectors; Communicable Diseases; Communities; Community Health; Complex; Conservatism; Coronavirus; Culicidae; DNA; Databases; Dengue; Developing Countries; Development; Diagnostic; Disease; Disease Outbreaks; Ebola virus; Economics; Emerging Communicable Diseases; Encephalitis; Environment; Evolution; Extramural Research Program; FDA approved; Florida; Future; Generations; Genomics; Geography; HIV; Health Personnel; Hepatitis B; Hepatitis C virus; Human; Human Development; Individual; Information Systems; Laboratories; Latin America; Learning; Liquid substance; Literature; Medical Entomology; Middle East Respiratory Syndrome Coronavirus; Modeling; Molecular; Monitor; National Institute of Allergy and Infectious Disease; Noise; Nucleic Acids; Nucleotides; Outcome; Paper; Patients; Phase; Population Surveillance; Preparation; Procedures; Public Health; Public Sector; RNA; RNA Viruses; Reagent; Reproducibility; Research; Research Personnel; Resources; Sales; Saliva; Sampling; Science; Sentinel; Sequence Analysis; Severe Acute Respiratory Syndrome; Sexual Transmission; Signal Transduction; Small Business Technology Transfer Research; Sterilization; Surveys; Symptoms; System; Technology; Testing; Time; Translating; United States; United States Public Health Service; Universities; Urine; Viral Load result; Virus; West Nile virus; Work; Writing; ZIKV infection; Zika Virus; base; chikungunya; cost; desert fever; design; field study; flexibility; genetic information; hazard; health management; in utero; innovation; instrument; medical attention; meetings; molecular recognition; new technology; news; pathogen; programs; research and development; response; success; synthetic biology; tool; viral RNA

Urgent Needs in Surveillance and Diagnostics. Zika Firebird Biomolecular Sciences LLC Florida Medical Entomology Laboratory, the University of Florida Steven A. Benner Barry W. Alto ABSTRACT The potential hazards of the Zika virus to both American citizenry and citizens of the world need no discussion. We are still learning the distribution and impact of the virus on human development in utero, as well as its distribution in patient saliva, sexual fluids, and urine. With several dozen cases in the US at the time of this writing, most obtained overseas, the extramural research programs of public health agencies are being asked to seek better public health surveillance technologies and immediate human diagnostics tools for Zika. For example, in Brazil, the immediate need is a test that to distinguish between dengue, chikungunya, and Zika in public clinics; at this time, this distinction is made based on interrogation of patients with respect to the timing of the appearance of various symptoms. The work proposed here will deliver those technologies and tools for Zika. However, this work will provide more. Today, the NIAID, CDC, and other public health units responsible for managing infectious disease outbreaks move from disease to disease, with each new outbreak and news cycle. This is inefficient, at best. Efficient public health services in an age of emerg- ing diseases need a robust and reproducible technology platform that is sufficiently flexible to sur- vey for any emerging infectious diseases without crisis. The work proposed here offers such a platform as part of its ability to survey for Zika, and distinguish it from other arboviruses, based on reagent innovations drawn from the field of “synthetic biology”, including artificially expanded genetic infor- mation systems (AEGIS), self-avoiding molecular recognition systems (SAMRS), biversal nucleotides, transliteration, and evolution-based arbovirus sequence analysis, in a collaboration between the Flor- ida Medical Entomology Laboratory (FMEL), which has live lab-infected mosquitoes with Zika, dengue, and chikungunya, and Firebird, a serial innovator in synthetic biology and diagnostics technology. This R21 project will first add Zika to an already established kit that detects 22 other arboviruses, common and exotic.13 We will benchmark that expanded kit, delivering it to beta testers in FMEL, where multiplexed readout is done using a Luminex instrument. This independent testing guarantees scientific rigor, and will be done by Month 12. In Year 2, we will seek a simpler system, focusing the multiplex on geography-specific target sets, adding biversals to manage sequence evolution of the RNA viruses, replacing Luminex in 10x target assays by a readout based on a 4x4 micro array, and going as far as possible towards a 10x multiplex system that can assay ~ 10 mosquitoes in the field. Towards these ends, we will meet the following specific aims: The outcome of this project will include new Zika science, as well as kits that will allow public health services to enjoy the advantages of these reagent innovations in managing the Zika outbreak, just as those advantages are now enjoyed in many products, including FDA-approved products, for human diagnostics.

监测和诊断的迫切需求。寨卡病毒 火鸟生物分子科学有限责任公司 佛罗里达大学佛罗里达医学昆虫学实验室 史蒂文·A·本纳 巴里·W·阿尔托 抽象的 寨卡病毒对美国公民和世界公民的潜在危害无需担心 讨论。我们仍在了解病毒的分布以及对人类发展的影响 子宫内及其在患者唾液、性液和尿液中的分布。已有数十起案件 在撰写本文时，美国大部分是在海外获得的，公共的校外研究项目 卫生机构被要求寻求更好的公共卫生监测技术并立即采取行动 寨卡病毒的人体诊断工具。例如，在巴西，迫切需要进行一项测试 在公共诊所区分登革热、基孔肯雅热和寨卡病毒；此时，这个区别就是 根据对患者的询问，了解各种情况出现的时间 症状。这里提出的工作将为寨卡病毒提供这些技术和工具。 然而，这项工作将提供更多。如今，NIAID、CDC 和其他公共卫生部门 负责管理传染病暴发，从一种疾病转移到另一种疾病，每一个新的疾病 爆发和新闻周期。这充其量是低效的。新兴时代的高效公共卫生服务 疾病需要一个强大且可重复的技术平台，该平台具有足够的灵活性来应对 应对任何新出现的传染病，没有危机。这里提出的工作提供了这样一个平台 作为其调查寨卡病毒能力的一部分，并根据试剂将其与其他虫媒病毒区分开来 来自“合成生物学”领域的创新，包括人工扩展的遗传信息 信息系统（AEGIS）、自回避分子识别系统（SAMRS）、双核苷酸、 音译和基于进化的虫媒病毒序列分析，由 Flor- ida 医学昆虫学实验室 (FMEL)，该实验室拥有实验室感染寨卡病毒、登革热和登革热病毒的活蚊子 基孔肯雅热，以及合成生物学和诊断技术领域的连续创新者火鸟。 该 R21 项目将首先将寨卡病毒添加到已建立的试剂盒中，该试剂盒可检测其他 22 种虫媒病毒，常见的 13 我们将对扩展套件进行基准测试，将其交付给 FMEL 中的 beta 测试人员，其中复用 使用 Luminex 仪器进行读数。这种独立测试保证了科学严谨性，并将 在第 12 个月之前完成。在第 2 年，我们将寻求一个更简单的系统，将多路复用的重点放在特定地理位置上 目标集，添加 biversals 来管理 RNA 病毒的序列进化，取代 10x 目标中的 Luminex 通过基于 4x4 微阵列的读数进行测定，并尽可能采用 10x 多重系统 可以在现场检测约 10 只蚊子。为了实现这些目标，我们将实现以下具体目标： 该项目的成果将包括新的寨卡科学，以及允许公共卫生服务的套件 享受这些试剂创新在控制寨卡疫情方面的优势，就像这些优势一样 现在，许多产品都使用这种技术，包括 FDA 批准的用于人体诊断的产品。

项目成果

Multiplexed Isothermal Amplification Based Diagnostic Platform to Detect Zika, Chikungunya, and Dengue 1.

• DOI: 10.3791/57051
• 发表时间: 2018-03-13
• 期刊: Journal of visualized experiments : JoVE
• 作者: Yaren O;Alto BW;Bradley KM;Moussatche P;Glushakova L;Benner SA
• 通讯作者: Benner SA

Point of sampling detection of Zika virus within a multiplexed kit capable of detecting dengue and chikungunya.

• DOI: 10.1186/s12879-017-2382-0
• 发表时间: 2017-04-20
• 期刊: BMC infectious diseases
• 影响因子: 3.7
• 作者: Yaren O;Alto BW;Gangodkar PV;Ranade SR;Patil KN;Bradley KM;Yang Z;Phadke N;Benner SA
• 通讯作者: Benner SA

Chikungunya virus vector competency of Brazilian and Florida mosquito vectors.

• DOI: 10.1371/journal.pntd.0006521
• 发表时间: 2018-06
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Honório NA;Wiggins K;Câmara DCP;Eastmond B;Alto BW
• 通讯作者: Alto BW

High-Throughput Method for Detection of Arbovirus Infection of Saliva in Mosquitoes Aedes aegypti and Ae. albopictus.

• DOI: 10.3390/v12111343
• 发表时间: 2020-11-23
• 期刊: Viruses
• 作者: Honório NA;Câmara DCP;Wiggins K;Eastmond B;Alto BW
• 通讯作者: Alto BW

Transmission Potential of Zika Virus by Aedes aegypti (Diptera: Culicidae) and Ae. mediovittatus (Diptera: Culicidae) Populations From Puerto Rico.

埃及伊蚊（双翅目：库蚊科）和伊蚊传播寨卡病毒的潜力。

• DOI: 10.1093/jme/tjaa286
• 发表时间: 2021
• 期刊: Journal of medical entomology
• 影响因子: 2.1
• 作者: Zimler,RebeccaA;Yee,DonaldA;Alto,BarryW
• 通讯作者: Alto,BarryW