Emerging infections: surveillance, epidemiology and pathogenesis

新发感染：监测、流行病学和发病机制

基本信息

批准号：
10163049
负责人：
DAVID WANG
金额：
$ 161.49万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-11 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10163049
关键词：
Africa Animal Model Animals Bioinformatics Biological Assay Camels Case Fatality Rates Cell Culture System China Clinical Consensus Consultations Coronavirus Dengue Dengue Virus Development Diagnostic Disease Disease Outbreaks Disease Surveillance Emerging Communicable Diseases Encephalitis Epidemiology Ethiopia Event Family Ferrets Fever Fever of Unknown Origin Genetic Genome Genomics Goals Hong Kong Human Immune Immunology Infection Infectious Diseases Research Influenza Influenza A Virus, H5N1 Subtype Infrastructure Insect Vectors International Lung diseases Malaysia Metadata Middle East Respiratory Syndrome Middle East Respiratory Syndrome Coronavirus Modeling Molecular Biology Monoclonal Antibodies National Institute of Allergy and Infectious Disease Nepal Pathogenesis Pathogenicity Pattern Prevalence Public Health Reagent Recording of previous events Reporting Reverse Transcriptase Polymerase Chain Reaction SARS coronavirus Serology Serology test Seroprevalences Site Southeastern Asia Specimen Syndrome Therapeutic Thrombocytopenia Time Variant Viral Viral Pathogenesis Virus Virus Receptors Zoonoses animal model development antigen detection assay development diagnostic assay high risk mouse model neutralizing antibody next generation sequencing novel novel virus respiratory pathogen respiratory virus response surveillance study therapeutic candidate transmission process vector viral transmission virology

项目摘要

SUMMARY To prepare for the next emerging infection, our goal is to establish a state-of-the-art Emerging Infectious Diseases Research Center with surveillance for the key disease syndromes – respiratory disease, encephalitis and fever of unknown origin– that have been observed most frequently associated with emerging viruses in the past few decades. In parallel, surveillance of animal and insect vectors will be performed to identify the origins of and define transmissions patterns associated with, these novel emerging viruses. The Center includes four international surveillance sites–China, Hong Kong, Nepal and Ethiopia– which were carefully selected on the basis of having either an established history of viral emergence or high potential to capture such events. China, Hong Kong and Nepal are all situated in Southeast Asia, which has historically been a nidus for many emerging viruses such as H5N1 influenza, SARS Coronavirus, Severe Fever and Thrombocytopenia virus, and the very recently reported Alongshan virus. Ethiopia, along with Northeastern Africa, is at high risk for emergence of MERS Coronavirus (MERS-CoV) due to endemicity of MERS in camels, a key reservoir in the region. To identify novel or emerging viruses, we will use complementary virus family- specific consensus PCR and unbiased next generation sequencing approaches and then sequence their complete genomes. Subsequently, we will generate key reagents essential for establishment of diagnostic assays and the study of fundamental aspects of viral pathogenesis, epidemiology, and immune control. These include development of cell culture systems, targeted RT-PCR/PCR assays, serological assays, monoclonal antibodies for antigen detection and potential therapeutic applications, mouse models of infection, and if appropriate, ferret models of virus transmission. An additional component of the center is international capacity building. Initial efforts focus on two exemplar viruses: MERS-CoV, a recently emerged virus, and a highly variant Dengue virus, Dengue virus 5, which is has prevalence and emergence potential. MERS-CoV is a deadly zoonotic respiratory pathogen with a case fatality rate of ~35% to date. We will implement surveillance for these viruses and develop additional reagents and assays to characterize their epidemiology and pathogenic potential. These efforts will establish and validate the critical infrastructure necessary to respond to a new emerging infectious disease. In the event of a new outbreak, efforts will be reprioritized to focus on response to the new emerging threat. The priorities, in order, are: (1) Human and animal surveillance for novel/emerging viruses; (2) Assay and reagent development; (3) Define epidemiology of novel/emerging viruses; (4) Pathogenesis, immune control, transmission and treatment of novel/emerging viruses.

概括为了为下一个新兴感染做准备，我们的目标是建立一个最先进的新兴传染病研究中心具有关键疾病综合征的监测 - 呼吸道疾病，脑炎和未知来源的发烧 - 已观察到与出现的最常相关的过去几十年的病毒。同时，将对动物和昆虫向量进行监视确定这些新兴病毒的起源并定义了与这些新型新兴病毒相关的传输模式。中心包括四个国际监视地点 - 中国，香港，尼泊尔和埃塞俄比亚 - 根据具有既定的病毒出现史或高潜力的史无前例的仔细选择捕获此类事件。中国，香港和尼泊尔都位于东南亚，历史上有历史我们是许多新兴病毒的Nidus 血小板减少症病毒，以及最近报道的沿Shan病毒。埃塞俄比亚，东北非洲，由于骆驼中MERS的内在性，MERS冠状病毒（MERS-COV）的出现风险很高，该地区的关键水库。为了识别新颖或新兴病毒，我们将使用完整的病毒家族 - 特定的共识PCR和公正的下一代测序方法，然后对其进行序列完整的基因组。随后，我们将生成对建立诊断必不可少的关键试剂测定和研究病毒发病机理，流行病学和免疫控制的基本方面。这些包括开发细胞培养系统，有针对性的RT-PCR/PCR分析，血清学测定，单克隆用于抗原检测和潜在治疗应用的抗体，感染的小鼠模型以及if 适当的病毒传播的雪貂模型。该中心的另一个组成部分是国际能力建筑。最初的努力侧重于两种示例病毒：MERS-COV，最近出现的病毒和高度变体登革热病毒，登革热病毒5，具有患病率和出现潜力。 MERS-COV是一个迄今为止，致命的人畜共患病病原体，病例死亡率约为35％。我们将实施监视对于这些病毒并开发其他试剂和测定，以表征其流行病学和致病潜力。这些努力将建立并验证回应所必需的关键基础设施一种新的新兴传染病。如果发生新的爆发，将重点放在重点上对新的新兴威胁的反应。优先事项是：（1）新颖/新兴病毒；（2）测定和试剂开发；（3）定义新颖/新兴的流行病学病毒；（4）新型/新兴病毒的发病机理，免疫控制，传播和治疗。