Emerging infections: surveillance, epidemiology and pathogenesis

摘要 为了为下一次新出现的感染做准备，我们的目标是建立一个最先进的新兴 传染病研究中心重点疾病证候监测--呼吸道疾病， 原因不明的脑炎和发烧--最常被观察到的与新出现的 在过去的几十年里，病毒。同时，将对动物和昆虫媒介进行监测，以 确定这些新出现的病毒的来源并确定与之相关的传播模式。这个 该中心包括四个国际监测点-中国、香港、尼泊尔和埃塞俄比亚-这四个地点 精心挑选的基础上，要么有明确的病毒出现史，要么有很高的 捕捉这样的事件。中国、香港和尼泊尔都位于东南亚，历史上 是许多新出现的病毒，如H5N1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，以及东北部 非洲，由于MERS在骆驼中的地方性流行，MERS冠状病毒(MERS-CoV)出现的风险很高， 这是该地区的一个重要水库。为了识别新病毒或新出现的病毒，我们将使用互补病毒家族- 特异性共识聚合酶链式反应和无偏下一代测序方法 完整的基因组。随后，我们将生产建立诊断所必需的关键试剂 病毒检测和研究病毒发病机制、流行病学和免疫控制的基本方面。这些 包括发展细胞培养系统、靶向RT-PCR/PCR检测、血清学检测、单抗 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 适当的，雪貂模型的病毒传播。该中心的另一个组成部分是国际运力 大楼。最初的努力集中在两种样本病毒上：MERS-CoV，一种新出现的病毒，以及一种高度 变种登革病毒，登革病毒5号，具有流行和出现的潜力。MERS冠状病毒是一种 致命性人畜共患呼吸道病原体，迄今病死率约为35%。我们将实施监控 并开发额外的试剂和化验方法来表征它们的流行病学和 致病潜力。这些努力将建立和验证响应所需的关键基础设施 一种新出现的传染病。在发生新的疫情时，将重新确定工作的优先顺序，将重点放在 应对新出现的威胁。优先事项依次为：(1)人类和动物监测 新出现的病毒；(2)检测和试剂开发；(3)确定新出现的病毒的流行病学 病毒；(4)新病毒的发病机制、免疫控制、传播和治疗。

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.