Characterizing determinants of primary KSHV infection among children and adolescents in Uganda

项目摘要/摘要 卡波西肉瘤相关疱疹病毒(KSHV)仍然是全球人类疾病的重要原因。 虽然KSHV在近25年前首次被发现，但关于KSHV的许多基本问题仍未得到解答 感染的时间、传播途径、感染的危险因素以及病毒学和免疫学 变速箱的驱动力。解决这些问题对于合理设计预防战略至关重要。 治疗KSHV相关疾病。 我们弗雷德·哈钦森癌症研究中心(FHCRC)和乌干达癌症研究所(UCI)的团队 已经对乌干达儿童中的主要人类疱疹病毒感染进行了全面的研究， 这是我们“PHICS”队列研究的一部分。通过密集跟踪乌干达母亲和幼儿的家庭 在一年的时间里，我们能够识别多种疱疹病毒的偶发感染并表征动力学。 在每种病毒的原发和慢性感染期间口腔脱落的可能性。重要的是，我们没有观察到任何事件 KSHV在婴儿中的感染，表明KSHV的传播动力学是独特的，可能较少 比其他人类疱疹病毒更有效，而且很可能发生在较年长的年龄。 我们现在建议扩展PHICS的研究方法，以全面研究KSHV。准确地说 定义初次感染的时间，我们的目标是解决与最初感染的生物学相关的几个假说 KSHV感染的步骤。为了完成这些研究，我们将招募80名感染KSHV的母亲和 他们的孩子在乌干达的坎帕拉。我们将每周进行家访，以记录危险行为并获得 每周口腔拭子和每月血样，为期18个月。样本将进行KSHV检测 用聚合酶链式反应(PCR)检测易感儿童中KSHV感染情况 以及在潜在的家庭暴露中表现出KSHV脱落的特征。我们的具体目标是： 1)确定原发KSHV的发病率和病毒、免疫学和临床特征 感染。 2)明确与原发KSHV感染相关的生物学和行为危险因素。 3)开发描述KSHV脱落动力学和所需病毒学驱动因素的数学模型 用于传输。

PROJECT SUMMARY / ABSTRACT Kaposi sarcoma-associated herpesvirus (KSHV) remains an important cause of human disease worldwide. While KSHV was first discovered nearly 25 years ago, many basic questions remain unanswered regarding the timing of acquisition, route of transmission, risk factors for infection, as well as the virologic and immunologic drivers of transmission. Addressing these questions is essential to the rational design of strategies to prevent and treat KSHV-related disease. Our group at the Fred Hutchinson Cancer Research Center (FHCRC) and the Uganda Cancer Institute (UCI) has conducted comprehensive studies of primary human herpesvirus infections among children in Uganda as part of our “PHICS” cohort study. By intensively following households of mothers and young children in Uganda for one year, we were able to identify incident infections for multiple herpesviruses and to characterize kinetics of oral shedding during primary and chronic infection for each virus. Importantly, we did not observe any incident KSHV infection among infants, suggesting that the dynamics of KSHV transmission are unique, may be less efficient than other human herpesviruses, and are likely to occur at an older age. We now propose to extend the PHICS study approaches to comprehensively study KSHV. By precisely defining the timing of primary infection, we aim to address several hypotheses related to the biology of the initial steps of KSHV infection. To complete these studies, we will enroll a cohort of 80 KSHV-infected mothers and their children in Kampala, Uganda. We will perform weekly home visits to document risk behaviors and to obtain weekly oral swabs and monthly blood samples over a period of 18 months. Samples will be tested for KSHV DNA by polymerase chain reaction (PCR) to identify incident KSHV infection in susceptible children and adolescents as well as to characterize KSHV shedding in potential household exposures. Our specific aims are: 1) To determine the incidence and to define the viral, immunologic, and clinical features of primary KSHV infection. 2) To identify the biologic and behavioral risk factors associated with primary KSHV infection. 3) To develop mathematical models that characterize KSHV shedding dynamics and virologic drivers required for transmission.