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

乌干达儿童和青少年原发 KSHV 感染的决定因素

• 批准号: 10684841
• 负责人: Jackson Orem
• 金额: $ 58.88万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-13 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10684841
• 关键词: Address; Adolescent; Africa South of the Sahara; Age; Antibodies; Behavior; Behavioral; Biological; Biological Factors; Biology; Blood; Blood specimen; Cancer Etiology; Characteristics; Child; Clinical; Cohort Studies; Cytomegalovirus; DNA-Directed DNA Polymerase; Development; Disease; Dose; Eating Utensils; Enrollment; Feasibility Studies; Food; Fred Hutchinson Cancer Research Center; Frequencies; Gender; Genotype; Goals; HIV; Herpesviridae; Herpesviridae Infections; Home visitation; Household; Human; Human Herpesvirus 4; Human Herpesvirus 6; Human Herpesvirus 8; Immune response; Immunity; Immunologics; Incidence; Individual; Infant; Infection; Kinetics; Learning; Lytic; Malaria; Malignant Neoplasms; Modeling; Mothers; Oral; Oral cavity; Oral mucous membrane structure; Oropharyngeal; Palate Kaposi' s Sarcoma; Polymerase Chain Reaction; Predisposition; Prevention strategy; Primary Infection; Risk; Risk Behaviors; Risk Factors; Route; Salivary; Sampling; Serology; Siblings; Simplexvirus; Source; Swab; Testing; Uganda; Viral; Viral Load result; Virus; Virus Shedding; Visit; associated symptom; chronic infection; co-infection; cohort; design; drinking; experience; human disease; human old age (65+); immunological status; immunosuppressed; infection risk; mathematical model; prevent; rational design; response; sample collection; seroconversion; transmission process

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.

项目摘要 /摘要 Kaposi肉瘤相关的疱疹病毒（KSHV）仍然是全球人类疾病的重要原因。 虽然KSHV最初是在大约25年前发现的，但有关您的许多基本问题仍然存在 获取的时间，传播途径，感染的危险因素，作为病毒学和免疫学。 解决这些问题的驱动因素对于预防策略的理性设计至关重要 并相信与KSHV相关的疾病。 我们的小组在弗雷德·哈钦森癌症研究中心（FHCRC）和乌干达癌症研究所（UCI）的小组 已经对乌干达儿童的原发性人类疱疹病毒感染进行了全面研究 我们的“ Phics”同类研究的一部分。 一年来，我们能够识别出多种疱疹病毒的事件发病率感染并表征动力学 在初次和慢性感染期间的口腔脱落。 婴儿中的KSHV感染，表明KSHV传播的动力学是独一无二的，可能较少 比其他人类疱疹病毒高效，可能会在年龄较大。 我们现在建议将PHICS研究的方法全面研究 定义原发性感染的时机，我们旨在解决对初始生物学的解雇 KSHV感染的步骤。 他们在乌干达的坎帕拉的孩子。 每周的口服拭子和每月的血液样本在18个月内。 通过聚合酶链反应（PCR）的DNA鉴定出入射儿童的入口KSHV感染， 在潜在家庭暴露中，青少年是kshv脱落的特征。 1）确定发病率并定义原发性KSHV的病毒，免疫学和临床特征 感染。 2）确定与原发性KSHV感染相关的生物和行为风险因素。 3）开发数学模型来表征KSHV动力学和所需的病毒驱动器 用于传输。