Clinical Sequelae and Urogenital Viral Dynamics in Survivors of Ebola Virus Disease

 描述（由申请人提供）：埃博拉病毒病已成为国际关注的公共卫生威胁。该K23指导的以患者为导向的职业发展奖申请的目的是促进基本技能的发展，使主要研究者成为一名独立和富有成效的医生-科学家，并解决埃博拉幸存者的两个主要问题：a）埃博拉病毒的性传播潜力和B）埃博拉病毒感染的持续临床后遗症的存在。目前肆虐西非的埃博拉疫情已演变成一场前所未有的人道主义危机。在发现埃博拉病毒后的四十年里，由于与这种病毒相关的高死亡率，幸存者人数少，以及大多数疫情的严峻环境，我们能够了解的很少，这限制了在全球范围内进行研究的能力。 领域目前疫情的规模以及首席研究员和他的 导师Wohl博士已经到位，将使他们能够直接解决埃博拉病毒病（EVD）幸存者的上述问题。尽管从EVD中恢复，但活病毒继续脱落具有许多公共卫生影响，包括通过持续的病毒传播使流行病永久化的可能性。世界卫生组织和美国疾病控制和预防中心建议禁欲7周和3个月分别根据数据只有10个受试者。该提案的目的I包括通过PCR和培养在至少200名埃博拉病幸存者的精液和阴道液中进行埃博拉病毒存在的横断面研究，这些幸存者从恢复开始的时间范围（0- 3个月，3- 6个月，6- 9个月和9- 12个月）。然后，我们将纵向跟踪最近从ETU出院的幸存者组（0-3个月），以确定活病毒脱落的持续时间。因此，拟议的研究将提供一个彻底的特征，在泌尿生殖系统的良好的公共卫生政策和建议，可以根据病毒动力学。AIM II包括对幸存者的横截面和纵向研究方面的临床和心理社会评估。这一点，沿着血液收集用于评估免疫活化和炎症的血清学标志物，将为埃博拉病毒病的临床后遗症提供重要的见解，并探索正在进行的病毒复制，全身炎症和埃博拉后症状之间的潜在关联。最终，这项研究将确保世界为下一次流行病做好准备，通过提高对精液和阴道液中病毒脱落的理解，提高对埃博拉病毒病临床并发症的认识，以及将首席研究员培养为临床研究人员，使他不仅能够应对，而且能够同时作为医生和科学家学习和领导。

 DESCRIPTION (provided by applicant): Ebola virus disease has emerged as a public health threat of international concern. The objective of this K23 Mentored Patient-Oriented Career Development Award Application is to facilitate the development of essential skills that will allow the principal investigator to become an independent and productive physician-scientist and to address the two primary concerns of Ebola survivors: a) the potential for sexual transmission of the Ebola virus and b) the presence of ongoing clinical sequelae of Ebola virus infection. The Ebola epidemic currently devastating West Africa has evolved into an unprecedented humanitarian crisis. In the forty years since the discovery of the Ebola virus we have been able to learn very little due to the high mortality rates associated with this virus, the low number of survivors, and the austere settings of most outbreaks which limit the ability to do research in the field. The scale of current outbreak and the infrastructure that the principal investigator and his mentor, Dr. Wohl, have put in place will allow them to be able to directly address the concerns listed above by Ebola virus disease (EVD) survivors. The continued shedding of live virus despite recovery from EVD has a number of public health implications including the potential for perpetuation of the epidemic through on going viral transmission. The WHO and CDC recommend abstinence for 7 weeks and 3 months respectively based on data from only 10 subjects. AIM I of this proposal includes a cross sectional study of the presence of Ebola virus by PCR and culture in the semen and vaginal fluid from at least 200 Ebola disease survivors across the spectrum of time from recovery (0-3months, 3-6months, 6-9months, and 9-12months). We will then longitudinally follow the group of survivors most recently discharged from an ETU (0-3 months) to determine the duration of live viral shedding. The proposed studies will thus provide a thorough characterization of viral dynamics in urogenital compartments on which sound public health policies and recommendations can be based. AIM II includes a clinical and psychosocial assessment of survivors in both the cross-sectional and longitudinal aspects of the study. This, along with collection of blood for evaluation of serologic markers of immune activation and inflammation will provide important insight into the clinical sequelae of Ebola virus disease and explore potential associations between ongoing virus replication, systemic inflammation, and Post-Ebola symptoms. Ultimately this study will ensure that the world is prepared for the next epidemic through improved understanding of virus shedding in semen and vaginal fluid, heightened awareness of the clinical complications of Ebola virus disease and the development of the principal investigator as a clinical researcher so that he can not only respond but learn and lead at the same time as a physician and a scientist.