American and Asian Centers for Arboviral Research and Enhanced Surveillance (A2CARES)

摘要 最近的人类病原体大流行暴露了当前监测系统的局限性。这个 美洲相继爆发的虫媒病毒疫情表明，疫情检测可能会被推迟，并有机会 错过了为监测、基础科学、临床研究和研究收集具有良好特征的标本和数据 疫苗和新诊断技术的发展。作为回应，我们召集了一个世界知名的财团 植物病毒学、流行病学、免疫学、病毒诊断学、系统发育和临床研究的研究人员， 同时在长期队列和基于医院的研究中利用研究基础设施和专业知识。这有 经过30年的国际合作研究，发表了200多份联合出版物，内容广泛 与当地和国际卫生机构密切合作准备和应对疫情的经验 当局和NIAID。在亚洲和美洲的关键地点，我们将使用创新的分子和血清学 识别新出现的病原体并解决登革热和其他虫媒病毒的基本问题的方法 沿坡度的地点之间差异的流行病学和测试病毒、宿主和环境决定因素 都市化。我们的首要目标是发展一个相互联系、协调的临床和 加强研究计划的实验室地点，比较疾病流行病学和严重程度 不同地区，开发和实施尖端诊断方法，并高效和 有效地应对疫情。厄瓜多尔、尼加拉瓜的标准化医院研究和社区队列 斯里兰卡将对城市、城市周边和农村地区的人类树枝病毒疾病进行特征和比较 并与卫生部一起发展可持续的基础设施，以迅速应对流行病， 通过疫情调查、对非人类灵长类动物的监测和病媒入罪。我们将实施- MET研究管理、数据和临床管理以及统计分析的标准化计划 网站，在广泛的现场培训计划的支持下。目标1将建立标准和新型的综合影院 在每个地点进行虫媒病毒和其他病原体的监测、诊断和研究。AIM 2 COM- 在位于不同生态区域的队列研究中比较登革热/虫媒病毒的流行病学和传播 在城市化的连续体上。在目标3中，我们将描述完整的病毒基因组序列，以便进行比较 虫媒病毒系统发育、系统地理学和分子流行病学研究。目标4包括监视， 从严重住院病例中鉴定和表征新的和未识别的人类病原体， 意外爆发、病媒和非人类灵长类动物。将开发分子和血清学检测方法 用于新发现的病原体，并在研究地点快速实施，以确定流行病学和 临床表现，并将提供给EIDRC网络。总而言之，我们的A2CARES联盟将 在拉丁美洲和南亚提供有价值的新工具和知识以及3个互联中心 将能够应对疫情，并在遥远的未来研究新出现的和地方性的传染病。

ABSTRACT Recent pandemics of human pathogens have revealed the limitations of current surveillance systems. The sequential arboviral epidemics in the Americas showed how outbreak detection can be delayed and opportunities missed to collect well-characterized specimens and data for surveillance, basic science, clinical research, and development of vaccines and new diagnostics. In response, we have assembled a consortium of world-renowned investigators in arbovirology, epidemiology, immunology, viral diagnostics, phylogenetics, and clinical research, while leveraging research infrastructure and expertise in long-term cohort and hospital-based studies. This has resulted from 3 decades of collaborative international research, with over 200 joint publications, and extensive experience in preparing for and responding to outbreaks working closely with local and international health authorities and NIAID. With key sites in Asia and the Americas, we will use innovative molecular and serological methods to identify emerging pathogens and to address fundamental questions in dengue and other arboviral epidemiology and test viral, host and environmental determinants of differences between sites along a gradient of urbanicity. Our overarching goal is to develop an interconnected, harmonized network of clinical and laboratory sites to strengthen research programs, compare disease epidemiology and severity in different regions, develop and implement cutting-edge diagnostic methods, and respond efficiently and effectively to outbreaks. Standardized hospital studies and community-based cohorts in Ecuador, Nicaragua and Sri Lanka will characterize and compare human arboviral illnesses across urban, peri-urban and rural sites and develop sustainable infrastructure to rapidly respond to epidemics together with Ministries of Health, comple- mented by outbreak investigation, surveillance of non-human primates, and vector incrimination. We will imple- ment standardized plans for study administration, data and clinical management, and statistical analysis across sites, supported by an extensive on-site training program. Aim 1 will establish standard and novel multiplex assays at each site for surveillance, diagnosis and research of arboviruses and other pathogens. Aim 2 com- pares dengue/arbovirus epidemiology and transmission in cohort studies located in ecologically distinct regions over a continuum of urbanicity. In Aim 3, we will characterize complete viral genome sequences for comparative studies of arboviral phylogenetics, phylogeography and molecular epidemiology. Aim 4 consists of surveillance, identification, and characterization of novel and unrecognized human pathogens from severe hospitalized cases, unexpected outbreaks, vectors and non-human primates. Molecular and serological assays will be developed for newly identified pathogens and quickly implemented across study sites to characterize the epidemiology and clinical manifestations and will be made available to the EIDRC network. In sum, our A2CARES Consortium will provide valuable new tools and knowledge and 3 interconnected centers in Latin America and South Asia that will be able to respond to outbreaks and to study emerging and endemic infectious diseases far into the future.