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

项目概要/摘要 卡波西肉瘤相关疱疹病毒（KSHV）仍然是世界范围内人类疾病的重要原因。 虽然KSHV是在近25年前首次发现的，但关于KSHV的许多基本问题仍然没有答案。 获得时间、传播途径、感染的危险因素以及病毒学和免疫学 传输的驱动程序。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 我们在弗雷德哈钦森癌症研究中心（FHCRC）和乌干达癌症研究所（UCI）的小组 对乌干达儿童中的原发性人类疱疹病毒感染进行了全面研究， 我们的“PHICS”队列研究的一部分。通过深入跟踪乌干达的母亲和幼儿家庭， 在一年的时间里，我们能够识别多种疱疹病毒的偶发感染，并描述其动力学特征 每种病毒在原发性和慢性感染期间的口腔脱落。重要的是，我们没有观察到任何事件 婴儿中KSHV感染，表明KSHV传播的动力学是独特的， 比其他人类疱疹病毒更有效，并且可能发生在老年。 我们现在建议扩展PHICS的研究方法，全面研究KSHV。通过精确 定义原发性感染的时间，我们的目标是解决几个假设有关的生物学的初始感染， KSHV感染的步骤为了完成这些研究，我们将招募80名KSHV感染的母亲， 他们的孩子在乌干达的坎帕拉。我们将每周进行一次家访，记录风险行为， 在18个月的时间内每周进行口腔拭子和每月进行血液样本。将对样本进行KSHV检测 通过聚合酶链反应（PCR）进行DNA检测，以识别易感儿童中发生的KSHV感染， 青少年以及表征KSHV脱落在潜在的家庭暴露。我们的具体目标是： 1)确定原发性KSHV的发病率并确定其病毒、免疫学和临床特征 感染 2)确定与原发性KSHV感染相关的生物学和行为学危险因素。 3)开发表征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.