Ophthalmic Disease and Laboratory Surveillance in a Viral Hemorrhagic Fever Zone

项目摘要 新出现的传染病可能导致毁灭性的流行病，并对全球卫生安全构成威胁。世界 卫生组织已经确定了可能导致严重和即将爆发的病原体，其中包括 埃博拉病毒(EBOV)和拉沙热病毒，所有这些都需要在研究中迫切关注。西非埃博拉病毒 2013-2016年的埃博拉病毒(EVD)疫情是历史上最具破坏性的EBOV疫情，感染人数超过28,600人， 11,300人死亡。迄今为止，仍有个别疫情暴发，发病率和死亡率很高。确实有 大约17,000名埃博拉病毒病幸存者面临感染埃博拉病毒后疾病综合症的风险， 包括全身情况、眼部疾病和免疫特权部位的病毒持久性(房水， 精液和中枢神经系统)。鉴于病毒持续存在对公共卫生具有重要意义，因为它引发了EBOV 传播事件及其与终末器官损害的关联。 葡萄膜炎是一种潜在的致盲性炎症性眼病，是最常见的眼部并发症，发生在 西非约13-34%的埃博拉病毒幸存者。我们已经描述了由眼部并发症引起的视力丧失 塞拉利昂和利比里亚的回溯性队列。具体地说，在患有葡萄膜炎的利比里亚埃博拉病毒幸存者中 60%的EVD患者出现视力障碍，约40%的患者失明(视力低于20/400 幸存者。目前，我们对EVD相关性葡萄膜炎的长期病程了解不足。 视力结果，以及对这种威胁视力的疾病的适当治疗。除了我们最近的相关研究外， EVD幸存者的临床葡萄膜炎，我们最近对EBOV持久性的调查提出了关于 眼睛将作为传染病监测的新组织地点，特别是在病毒出血热地区 其他对公共卫生有意义的新病原体的地方性流行。 这项研究的目的是：1.确定葡萄膜炎的患病率、随时间发生的视力丧失以及危险因素 埃博拉病毒幸存者的葡萄膜炎发展2.探索拉沙热病毒幸存者的眼部表现3.验证 与儿童健康中心合作，将眼液采样作为传染病监测的检测方法 和死亡预防监测研究。 这项K-23计划的职业发展目标是：1.掌握疾病监测系统的方法技能 2.具备诊断感染性病原体的眼液分子诊断能力3.继续 在国际环境中培养临床研究技能4.进一步培训我的统计和流行病学方法 对于临床研究的成功来说是必不可少的。为了实现这些目标，我设计了一个培训计划，其中包括 课程工作，与国际领导人的指导，出席并在地方和国家研究中发表演讲 会议/会议，并指导实际操作培训。这个K23指导职业发展奖将是 为成为一名成功的独立临床医生科学家所需的技能奠定基础。

Project Summary Emerging infectious diseases can lead to devastating epidemics and pose a threat to global health security. The World Health Organization has identified pathogens that are likely to cause severe and imminent outbreaks, which include Ebolavirus (EBOV) and Lassa fever virus, all of which require urgent attention in research. The West African Ebola virus disease (EVD) outbreak of 2013-2016 is the most devasting EBOV outbreak in history with over 28,600 infected and 11,300 deaths. To date there continue to be isolated outbreaks with significant morbidity and mortality. There are approximately 17,000 EVD survivors who are at-risk for Post-Ebolavirus Disease Syndrome, a recently described entity, which includes systemic conditions, ocular disease, and viral persistence in immune privileged sites (aqueous humor, semen, and central nervous system). Viral persistence is of public health importance, given its initiation of EBOV transmission events and its association with end-organ damage. Uveitis, a potentially blinding inflammatory eye disease, is the most common ocular complication, occurring in approximately 13-34% of EVD survivors in West Africa. We have described vision loss due to ocular complications in retrospective cohorts in both Sierra Leone and Liberia. Specifically, within Liberian EVD survivors with uveitis developed vision impairment was noted in 60% and blindness (vision worse than 20/400) in approximately 40% of EVD survivors. Currently, we have insufficient knowledge about the disease course of EVD-associated uveitis, long-term visual acuity outcomes, and appropriate treatment for this sight-threatening disease. Besides our recent studies related to clinical uveitis in EVD survivors, our recent investigation of EBOV persistence raises questions about the potential for the eye to serve as a novel tissue site for infectious disease surveillance, particularly in a viral hemorrhagic fever zone endemic for other emerging pathogens of public health significance. The objectives of this study are to 1. Determine the prevalence of uveitis, incident vision loss over time, and risk factors for uveitis development in EVD survivors 2. Explore ophthalmic manifestation in Lassa fever virus survivors 3. Validate ocular fluid sampling as method for detection for surveillance of infectious diseases in collaboration with the Child Health and Mortality Prevention Surveillance study. The career development aims for this K-23 proposal are to 1. Obtain methodological skills in disease surveillance systems 2. Gain competency in molecular diagnostics of ocular fluid in the diagnosis of infectious pathogens 3. Continue to develop skills in clinical research in international settings 4. Further my training in statistical and epidemiology methods necessary for success in clinical studies. To accomplish these goals, I have designed a training plan that includes coursework, mentorship with international leaders, attendance and presentation at local and national research meetings/conferences, and directed, hands-on training. This K23 mentored career development award will be the foundation for the skills necessary to become a successful independent clinician scientist.