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.

概括为了为下一次新出现的感染做好准备，我们的目标是建立一个最先进的新出现感染传染病研究中心负责监测关键疾病综合症——呼吸道疾病、脑炎和不明原因发烧——最常观察到与新出现的与此同时，将对动物和昆虫媒介进行监测，以防止病毒传播。确定这些新型病毒的起源并定义与之相关的传播模式。中心包括四个国际监测点——中国、香港、尼泊尔和埃塞俄比亚—— 精心挑选的基础是具有既定的病毒出现历史或高潜力中国、香港和尼泊尔都位于历史上曾发生过的东南亚。是许多新出现病毒的巢穴，例如 H5N1 流感、SARS 冠状病毒、严重发烧和血小板减少病毒、最近报道的阿龙山病毒以及埃塞俄比亚东北部病毒。由于骆驼中流行中东呼吸综合征 (MERS)，非洲出现中东呼吸综合征冠状病毒 (MERS-CoV) 的风险很高，为了识别新的或新出现的病毒，我们将使用互补病毒家族- 特定的 PCR 共识和公正的下一代测序方法，然后对其进行测序随后，我们将生成建立诊断所必需的关键试剂。病毒发病机制、流行病学和免疫控制的基本方面的分析和研究。包括细胞培养系统的开发、靶向 RT-PCR/PCR 检测、血清学检测、单克隆抗体检测用于抗原检测和潜在治疗应用的抗体、感染的小鼠模型，以及如果该中心的另一个组成部分是国际能力。最初的工作重点是两种典型病毒：中东呼吸综合征冠状病毒（MERS-CoV），一种最近出现的病毒，以及一种高度敏感的病毒。登革热病毒变种，登革热病毒 5，具有流行和出现的潜力。迄今为止，病死率约为 35% 的致命人畜共患呼吸道病原体，我们将实施监测。针对这些病毒并开发额外的试剂和测定法来表征其流行病学和这些努力将建立并验证应对疾病所需的关键基础设施。如果出现新的传染病，将重新调整工作重点。应对新出现的威胁的优先事项依次为： (1) 人类和动物监测新型/新兴病毒；(2) 检测方法和试剂开发；(3) 定义新型/新兴病毒的流行病学；病毒；（4）新型/新兴病毒的发病机制、免疫控制、传播和治疗。