Understanding the epidemiology and natural history of unrecognized Ebola virus infection

项目概要/摘要 大量埃博拉病毒感染病例可能在2013-2016年西方 非洲爆发，既有未确诊的埃博拉病毒病（EVD），也有轻度症状， 无症状感染者。在这个未被识别的人群中的流行病学和感染的自然史， 这是由埃博拉血清学阳性和接触史定义的，人们对此知之甚少。例如， 不清楚未识别感染的个体是否有类似的临床和心理后遗症， 公认的情况下，如葡萄膜炎，抑郁症，和工作相关的残疾。了解在多大程度上 感染后后遗症的发生和未被识别的感染的预测将加强努力， 将未被识别的感染者-有症状的和无症状的-与幸存者服务联系起来， 在未来的疫情中更好地识别这一人群。 我将研究一组特征明确的个体，这些个体具有过去的，未被识别的， 埃博拉病毒感染。我将利用由国家卫生研究院开发的现有EVD幸存者密切接触者队列， 利比里亚国家过敏和传染病研究所埃博拉病毒研究伙伴关系 （生效）。PREVAIL项目开始对EVD幸存者及其密切接触者进行自然史研究， 2015年6月。已入组超过1，100名EVD幸存者，目的是表征其EVD后临床 后遗症、病毒持久性和抗体应答的持久性。超过2，300名密切接触者也被 作为对照人群。共发现230名（10%）EVD幸存者的密切接触者， 通过定量FANG埃博拉EIA检测为血清阳性，并且未报告患有EVD。在研究 基线时，57%的人群报告在暴露后三周内出现症状， 埃博拉病毒，43%没有。这将是第一个系统的，纵向研究未被承认的幸存者， 埃博拉病毒感染。 这项K23提案旨在：（1）确定未被识别的、有症状的埃博拉病毒的临床后遗症 感染，（2）确定未识别的无症状埃博拉病毒感染的预测因子和临床后遗症， 和（3）识别未识别的、有症状的EVD幸存者的心理社会后遗症。我的职业生涯 发展目标包括：（1）观察性研究的设计，（2）先进的生物统计学，（3）领域 低资源环境下的流行病学。该计划将与课程作业，指导性学习和 国际导师团队的指导。除了未来对EVD长期后遗症的研究外，我将 我将这些技能和专业知识应用到R 01应用程序中，在该应用程序中，我研究了 其他病毒性出血热和新发传染病，如马尔堡病毒和猴痘。

PROJECT SUMMARY/ABSTRACT A large number of Ebola virus infections may have been unrecognized during the 2013-2016 West African outbreak, both undiagnosed Ebola virus disease (EVD) as well as mildly symptomatic and asymptomatic infection. The epidemiology and natural history of infection in this unrecognized population, which is defined by positive Ebola serology and a history of exposure, are poorly understood. For instance, it is unknown if individuals with unrecognized infection have similar clinical and psychosocial sequelae as recognized cases, such as uveitis, depression, and work-related disability. Understanding the extent to which post-infectious sequelae occur and the predictors of unrecognized infection will bolster efforts to screen and link unrecognized, infected individuals - both symptomatic and asymptomatic - to survivor services and to better identify this population in future outbreaks. I will study a well characterized cohort of individuals with serological evidence of past, unrecognized, Ebola virus infection. I will utilize an existing cohort of close contacts of EVD survivors developed by the National Institute of Allergy and Infectious Diseases' Partnership for Research on Ebola Virus in Liberia (PREVAIL). The PREVAIL program began a natural history study of EVD survivors and their close contacts in June 2015. Over 1,100 EVD survivors have been enrolled with the aim of characterizing their post-EVD clinical sequelae, viral persistence, and durability of antibody response. Over 2,300 close contacts have also been enrolled as the comparison population. A total of 230 (10%) close contacts of EVD survivors were found to be seropositive by the quantitative FANG Ebola EIA and had not been reported as having had EVD. At study baseline, 57% of this population reported having had symptoms in the three-week period after exposure to Ebola virus, and 43% did not. This will be the first systematic, longitudinal study of unrecognized survivors of Ebola virus infection. This K23 proposal aims to: (1) identify the clinical sequelae of unrecognized, symptomatic Ebola virus infection, (2) identify the predictors and clinical sequelae of unrecognized, asymptomatic Ebola virus infection, and (3) identify psychosocial sequelae among unrecognized, symptomatic EVD survivors. My career development aims involve: (1) design of observational studies, (2) advanced biostatistics, and (3) field epidemiology in low-resource settings. This plan will be carried out with coursework, directed study, and the guidance of an international team of mentors. In addition to future study of longer-term sequelae of EVD, I will apply these skills and expertise to an R01 application in which I study the epidemiology and natural history of other viral hemorrhagic fever and emerging infectious diseases such as Marburg virus and monkeypox.