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

 描述(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。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，使首席研究员能够成为一名独立和富有成效的内科科学家，并解决埃博拉幸存者的两个主要关切：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经演变成一场史无前例的人道主义危机。在埃博拉病毒被发现后的40年里，由于与这种病毒相关的高死亡率、低幸存者数量以及大多数疫情的严峻背景限制了对埃博拉病毒的研究能力，我们对此了解很少。 菲尔德。目前疫情的规模和首席调查员及其 Mentor、Wohl博士所采取的措施将使他们能够直接解决埃博拉病毒病(EVD)幸存者的上述关切。尽管埃博拉病毒病已痊愈，但活病毒仍在继续传播，这对公共卫生产生了一些影响，包括通过病毒传播使这一流行病永久存在的可能性。世界卫生组织和疾控中心仅根据10名受试者的数据，分别建议禁食7周和3个月。这项建议的目的一包括通过聚合酶链式反应和精液和阴道液培养对至少200名埃博拉病毒幸存者在康复期间(0-3个月、3-6个月、6-9个月和9-12个月)进行的埃博拉病毒存在的横断面研究。然后，我们将纵向跟踪最近从ETU出院的幸存者群体(0-3个月)，以确定活病毒脱落的持续时间。因此，拟议的研究将彻底描述泌尿生殖系统内的病毒动态，作为制定合理的公共卫生政策和建议的依据。AIM II从横向和纵向两个方面对幸存者进行了临床和心理社会评估。这一点，以及用于评估免疫激活和炎症的血清学标志的血液采集，将为了解埃博拉病毒疾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联系。最终，这项研究将通过提高对精液和阴道液中病毒传播的了解，提高对埃博拉病毒疾病临床并发症的认识，以及培养首席研究员成为临床研究人员，从而确保世界为下一次疫情做好准备，这样他不仅可以做出反应，而且作为一名医生和科学家，他可以同时学习和领导。

 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.