Ophthalmic Disease and Laboratory Surveillance in a Viral Hemorrhagic Fever Zone

病毒性出血热地区眼科疾病及实验室监测

• 批准号: 10470503
• 负责人: JESSICA Shantha
• 金额: $ 24.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470503
• 关键词: Adult; Africa; African; Anti-Inflammatory Agents; Aqueous Humor; Asia; Attention; Autoimmune; Autopsy; Blindness; Caring; Cataract; Cataract Extraction; Cessation of life; Child Health; Child Mortality; Childhood; Cicatrix; Clinical; Clinical Management; Clinical Research; Clinical Skills; Collaborations; Communicable Diseases; Competence; Complication; Control Groups; Cystoid Macular Edema; Cytomegalovirus; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Outbreaks; Disease Surveillance; Ebola Hemorrhagic Fever; Ebola virus; Emerging Communicable Diseases; Epidemic; Epidemiologic Methods; Epidemiology; Etiology; Event; Eye; Eye Development; Eye diseases; Foundational Skills; Foundations; Future; Glaucoma; Goals; Government; Guidelines; Health; Health Personnel; Health Policy; Hospitals; Immune; Incidence; Individual; Inflammation; Inflammatory; Infrastructure; International; Investigation; K-Series Research Career Programs; Knowledge; Laboratories; Lassa Fever; Lassa virus; Lead; Liberia; Liberian; Liquid substance; Marburgvirus; Medical Records; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Methods; Morbidity - disease rate; Neuraxis; Organ; Outcome; Pathogen detection; Pharmaceutical Preparations; Phenotype; Policies; Prevalence; Prevention; Prospective cohort study; Public Health; Quality of life; Readiness; Recording of previous events; Recurrence; Reporting; Research; Research Project Grants; Resources; Retina; Retrospective cohort; Risk; Risk Factors; Sampling; Scientist; Security; Seminal fluid; Series; Sierra Leone; Site; Structure; Survivors; Symptoms; Syndrome; System; Techniques; Testing; Time; Time Factors; Tissue Sample; Tissues; Toxoplasmosis; Training; United States; United States National Institutes of Health; Universities; Uveitis; Viral; Viral Hemorrhagic Fevers; Vision; Visual; Visual Acuity; Visual impairment; World Health Organization; Zika Virus; acute infection; antimicrobial; body system; career; career development; clinical care; cohort; design; detection method; disease diagnosis; education research; emerging pathogen; epidemiology study; global health; hearing impairment; infectious disease model; meetings; minimally invasive; molecular diagnostics; mortality; multidisciplinary; novel; pathogen; prevent; research clinical testing; screening; skills; success; surveillance network; surveillance study; symposium; tool; transmission process

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.

项目概要 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 卫生组织已确定可能导致严重和迫在眉睫的疫情爆发的病原体，其中包括 埃博拉病毒（EBOV）和拉沙热病毒，所有这些都需要研究中的紧急关注。西非埃博拉病毒 2013 年至 2016 年爆发的埃博拉病毒病 (EVD) 疫情是历史上最具破坏性的埃博拉病毒疫情，共有超过 28,600 人感染， 11,300 人死亡。迄今为止，仍然存在发病率和死亡率很高的孤立疫情。有 大约 17,000 名埃博拉病毒病幸存者面临埃博拉病毒后疾病综合症（最近描述的一种疾病）的风险， 其中包括全身性疾病、眼部疾病和病毒在免疫特权部位（房水、房水、 精液和中枢神经系统）。鉴于埃博拉病毒的引发，病毒持续存在对公共卫生具有重要意义 传播事件及其与终末器官损伤的关联。 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，发生在 西非约 13-34% 的埃博拉病毒病幸存者。我们已经描述了由于眼部并发症导致的视力丧失 塞拉利昂和利比里亚的回顾性队列。具体来说，利比里亚埃博拉病毒病幸存者患有葡萄膜炎 60% 的 EVD 患者出现视力障碍，约 40% 的患者出现失明（视力低于 20/400） 幸存者。目前，我们对埃博拉病毒病相关葡萄膜炎的病程了解不够，长期 视力结果，以及对这种威胁视力的疾病的适当治疗。除了我们最近的相关研究之外 埃博拉病毒病幸存者的临床葡萄膜炎，我们最近对埃博拉病毒持续性的调查提出了关于埃博拉病毒感染的潜力的问题 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 是其他具有公共卫生意义的新出现病原体的地方病。 本研究的目的是 1. 确定葡萄膜炎的患病率、随时间推移发生的视力丧失以及风险因素 埃博拉病毒病幸存者葡萄膜炎的发展 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，采用眼液取样作为传染病监测检测方法 和死亡预防监测研究。 此 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. 获得眼液分子诊断在感染性病原体诊断中的能力 3. 继续 培养国际环境中临床研究的技能 4. 进一步接受统计和流行病学方法方面的培训 临床研究成功所必需的。为了实现这些目标，我设计了一个培训计划，其中包括 课程作业、国际领导人的指导、出席地方和国家研究并进行演讲 会议/会议以及定向实践培训。这个 K23 指导的职业发展奖将是 成为一名成功的独立临床科学家所需技能的基础。