Understanding Risk of Zoonotic Virus Emergence in EID Hotspots of Southeast Asia

项目摘要/摘要 东南亚是世界上风险最高的宰牲节热点地区之一，是SARS大流行、尼帕病毒、 以及反复爆发的流感。这是由野生动物的高度多样性和迅速扩大所推动的 人口结构使人类和野生动物种群更加紧密。这项提议将启动新兴的 传染病-东南亚研究合作中心(EID-Search)， 在美国、泰国、新加坡和马来西亚三个主要国家的新兴疾病研究领域处于领先地位 行政区划。这些研究人员拥有跨越50个诊所、实验室和研究的网络 几乎所有东南亚国家的机构，并将使用宰牲节搜索作为早期预警系统 疫情涉及信息、试剂、样本和技术的交换，以及一种协作的力量- 基础研究和翻译研究之家。开斋节搜索还将作为一项重要资产 在该区域爆发疫情的情况下扩大和部署资源。这个EIDRC将进行研究 到：1)通过分析，识别、表征和评级来自野生动物的高人畜共患潜在病毒的溢出风险 以前存档的野生动物样本，进行有针对性的野生动物监测，并使用血清学和聚合酶链式反应 用于识别新病毒的化验。这些特征将被用来评估对人的溢出风险，以及一系列 体外(受体结合、细胞培养)和体内(人源化小鼠和协作交叉模型)分析 用于评估它们感染人类和导致疾病的潜力；2)收集样本和问卷数据 来自生活在宰牲节热点地区并具有高动物文化和行为风险的人类社区 暴露(例如，狩猎野生动物、收集蝙蝠海鸟粪)。这些都将通过血清学检测来确定 新病毒溢出的证据，并对照元数据进行分析，以确定传播的关键风险途径； 3)确定临床队列中“隐蔽”暴发的病毒病原学并确定其特征。我们将进行综合征候 在AIM 2中为人群服务的诊所进行监测，招募有未诊断疾病和症状的患者 与新出现的病毒病原体一致，并用分子和后续血清学分析测试样本 确定这些症状和新病毒之间的因果联系。 这项研究将促进我们对新病毒出现的风险的理解，在一个独特的重要 区域。它还将通过将当地传染病科学家联系起来，加强国内研究能力 具有经证明有能力开展这项工作和生产 重大发现。来自EIDRC领导团队的大量高影响力协作研究 提供概念验证，证明EID-Search具有背景、协作网络、体验和 作为一种独特的早期预警系统，为可能出现的任何新的EID提供早期预警系统 这是开斋节最热的热点。

PROJECT SUMMARY/ABSTRACT Southeast Asia is one of the world’s highest-risk EID hotspots, the origin of the SARS pandemic, Nipah virus, and repeated outbreaks of influenza. This is driven by high diversity of wildlife and rapidly expanding demography that brings human and wildlife populations closer. This proposal will launch the Emerging Infectious Diseases - South East Asia Research Collaboration Hub (EID-SEARCH), a collaboration among leaders in emerging disease research in the USA, Thailand, Singapore and the 3 major Malaysian administrative regions. These researchers have networks that span >50 clinics, laboratories and research institutions across almost all SE Asian countries and will use the EID-SEARCH as an early warning system for outbreaks involving exchange of information, reagents, samples and technology, and a collaborative power- house for fundamental and translational research. The EID-SEARCH will also act as a significant asset to scale-up and deploy resources in the case of an outbreak in the region. This EIDRC will conduct research to: 1) Identify, characterize and rank spillover risk of high zoonotic potential viruses from wildlife, by analyzing previously-archived wildlife samples, conducting targeted wildlife surveillance, and using serology & PCR assays to identify novel viruses. These will be characterized to assess risk of spillover to people, and a series of in vitro (receptor binding, cell culture) and in vivo (humanized mouse and collaborative cross models) assays used to assess their potential to infect people and cause disease; 2) Collect samples and questionnaire data from human communities that live in EID hotspots and have high cultural and behavioral risk of animal exposure (e.g. wildlife hunting, bat guano collection). These will be tested with serological assays to identify evidence of novel virus spillover, and analyzed against metadata to identify key risk pathways for transmission; 3) Identify and characterize viral etiology of ‘cryptic’ outbreaks in clinical cohorts. We will conduct syndromic surveillance at clinics serving the populations in Aim 2, enroll patients with undiagnosed illness and symptoms consistent with emerging viral pathogens, and test samples with molecular and follow-up serological assays to identify causal links between these syndromes and novel viruses. This research will advance our understanding of the risk of novel viral emergence in a uniquely important region. It will also strengthen in-country research capacity by linking local infectious disease scientists with an international collaborative network that has proven capacity to conduct this work and produce significant findings. The large body of high impact collaborative research from this EIDRC leadership team provides proof-of-concept that EID-SEARCH has the background, collaborative network, experience, and skillset to act as a unique early warning system for novel EIDs of any etiology threatening to emerge in this hottest of the EID hotspots.