Emerging infections: surveillance, epidemiology and pathogenesis

新发感染：监测、流行病学和发病机制

• 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
• 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

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.

总结 为了应对下一次新出现的感染，我们的目标是建立一个最先进的新兴 传染病研究中心负责监测关键疾病综合征-呼吸道疾病， 不明原因的脑炎和发热-最常观察到的与新出现的 病毒在过去的几十年里与此同时，当局亦会监察动物和昆虫传病媒介， 确定这些新出现的病毒的起源并确定与之相关的传播模式。的 该中心包括四个国际监测站点-中国，香港，尼泊尔和埃塞俄比亚- 根据已确定的病毒出现史或高潜力， 捕捉这样的事件。中国，香港和尼泊尔都位于东南亚，历史上 一直是许多新出现的病毒，如H5 N1流感，SARS冠状病毒，严重发烧和 血小板减少症病毒和最近报道的阿龙山病毒。埃塞俄比亚、沿着与东北 非洲，由于MERS在骆驼中的地方性， 这是该地区的一个主要水库。为了识别新的或新出现的病毒，我们将使用互补病毒家族- 特异性共有PCR和无偏倚的下一代测序方法，然后对其进行测序。 完整的基因组随后，我们将生产建立诊断试剂盒所必需的关键试剂。 检测和病毒发病机理、流行病学和免疫控制的基本方面的研究。这些 包括开发细胞培养系统、靶向RT-PCR/PCR测定、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，以及如果 合适的雪貂病毒传播模型该中心的另一个组成部分是国际能力 建设最初的努力集中在两种典型的病毒上：MERS CoV，一种最近出现的病毒，和一种高度流行的病毒。 变异登革病毒，登革病毒5，这是具有流行和出现的潜力。MERS-CoV是一种 致命的人畜共患呼吸道病原体，迄今病死率约为35%。我们将实施监视 并开发其他试剂和检测方法来表征其流行病学特征， 致病潜力这些努力将建立和验证必要的关键基础设施， 一种新出现的传染病如果发生新的疫情，将重新调整工作重点， 应对新出现的威胁。优先事项依次为：（1）人类和动物监测， 新型/新兴病毒;（2）检测和试剂开发;（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。