Understanding the epidemiology and natural history of unrecognized Ebola virus infection

项目摘要/摘要 在2013-2016年的西方，大量的埃博拉病毒感染可能没有被发现 非洲爆发，既有未诊断的埃博拉病毒病(EVD)，也有轻微的症状和 无症状感染。在这个未被识别的人群中感染的流行病学和自然病史， 由阳性埃博拉血清学和接触史来定义的疾病，人们知之甚少。例如，它是 不明原因的感染者是否有类似的临床和心理社会后遗症 公认的病例，如葡萄膜炎、抑郁症和与工作有关的残疾。了解以下内容的程度 感染后的后遗症会发生，未被识别的感染的预测因素将加强筛查和 将未被识别的感染者--包括有症状和无症状的人--与幸存者服务和 在未来的疫情中更好地识别这一群体。 我将研究一组特征良好的个体，这些个体有过去的、未被识别的、 埃博拉病毒感染。我将利用现有的埃博拉病毒幸存者的密切联系队列，该队列由 国家过敏和传染病研究所在利比里亚研究埃博拉病毒的伙伴关系 (以此为准)。年，该项目开始对埃博拉病毒幸存者及其密切接触者进行自然历史研究。 2015年6月。超过1100名EVD幸存者被登记，目的是描述他们EVD后的临床特征 后遗症、病毒持久性和抗体反应的持久性。超过2300名密切接触者也被 被登记为比较人群。共有230名(10%)埃博拉病毒幸存者的密切接触者被发现是 经FANG埃博拉EIA检测呈血清阳性，尚未有埃博拉病毒感染的报告。在学习中 基线，57%的人报告在暴露于 埃博拉病毒，43%的人没有。这将是第一次对未被确认的幸存者进行系统的纵向研究 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、无症状的埃博拉病毒感染的预测因素和临床后遗症， 以及(3)确定未被识别的、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)高级生物统计学；(3)实地研究 低资源环境下的流行病学。该计划将通过课程作业、指导学习和 国际导师团队的指导。除了未来对EVD的长期后遗症的研究外，我还将 将这些技能和专业知识应用到R01应用程序中，在该应用程序中，我学习了猪瘟的流行病学和自然病史 其他病毒性出血热和新出现的传染病，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.