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 世卫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年的埃博拉病毒病（EVD）爆发是历史上最具破坏性的EBOV爆发，超过28，600人感染， 11,300人死亡迄今为止，仍有孤立的暴发，发病率和死亡率很高。有 大约17，000名EVD幸存者，他们有患埃博拉病毒后疾病综合征的风险，这是一种最近描述的疾病， 其包括全身性病症、眼部疾病和免疫豁免部位（眼房水， 精液和中枢神经系统）。病毒持续存在具有公共卫生重要性，因为它是EBOV的起源。 传播事件及其与终末器官损伤的关系。 葡萄膜炎是一种可能致盲的炎症性眼病，是最常见的眼部并发症，发生于 西非约13-34%的EVD幸存者。我们已经描述了视力丧失由于眼部并发症， 塞拉利昂和利比里亚的回顾性队列研究。具体而言，在患有葡萄膜炎的利比里亚EVD幸存者中， 在60%的EVD患者中观察到发展性视力损害，在约40%的EVD患者中观察到失明（视力差于20/400） 幸存者目前，我们对EVD相关性葡萄膜炎的病程、长期 视力结果，以及对这种威胁视力的疾病的适当治疗。除了我们最近的研究， 在EVD幸存者的临床葡萄膜炎中，我们最近对EBOV持续性的调查提出了关于EBOV持续性的潜在问题。 眼睛作为传染病监测的新组织部位，特别是在病毒性出血热地区 其他新出现的具有公共卫生意义的病原体的流行。 本研究的目的是1。确定葡萄膜炎的患病率、随时间发生的视力丧失和风险因素 EVD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 与儿童健康部合作，将眼液取样作为监测传染病的检测方法 和死亡率预防监测研究。 这个K-23提案的职业发展目标是1。获得疾病监测系统的方法技能 2.获得在感染性病原体的诊断中眼液的分子诊断能力3.继续 在国际环境中发展临床研究技能4.继续我在统计学和流行病学方法方面的训练 在临床研究中取得成功所必需的。为了实现这些目标，我设计了一个培训计划，其中包括 课程，与国际领导人的导师，出席和介绍在当地和国家的研究 会议/大会，以及有指导的实际操作培训。这个K23指导职业发展奖将是 成为一名成功的独立临床科学家所需技能的基础。

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.