Transmission of KSHV/HHV-8 in South Africa

描述（由申请人提供）：卡波西肉瘤相关疱疹病毒（KSHV）是卡波西肉瘤的病毒病原体。在撒哈拉以南非洲，KSHV潜在地方性感染与艾滋病毒流行之间的灾难性交叉导致KS成为该地区许多国家成人中最常见的恶性肿瘤以及儿童癌症的日益增长的原因。尽管KSHV病毒学研究进展迅速，但对KSHV流行病学的了解却很少，特别是在撒哈拉以南非洲。已知的是，KSHV在非洲的感染最常发生在儿童时期，在青春期前达到成人水平的流行率（20-60%，取决于地区），唾液是最常携带KSHV的体液。目前尚不清楚KSHV是如何在非洲传播的，以及人口、行为和生物因素如何影响传播。这项研究的长期目标是开发干预措施，以阻止KSHV的传播，并最终预防KS。这项建议的具体目标是： (1)评估南非儿童及其照顾者中KSHV血清阳性的流行率和决定因素， (2)检查KSHV感染者唾液中KSHV脱落的决定因素， (3)在纵向研究中制定量化措施，以检查KSHV感染事件的决定因素，包括使儿童接触唾液的做法的作用、家庭内部关系和家庭特征; (4)确定南非儿童及其家庭成员纵向研究的可行性。 拟议的研究将利用巴特勒博士和她的导师以前在国内和非洲研究中收集的现有数据和生物标本，以及在南非收集的主要数据。这项工作的目的是提供必要的初步数据，随后确定的纵向研究KSHV在南非的儿童传播。拟议的培训将为巴特勒博士提供人口科学、与传染病有关的生物科学方面的必要技能，以及在资源贫乏的环境中进行研究所需的道德行为，以多学科方法研究影响资源贫乏国家儿童及其家庭的传染病。

DESCRIPTION (provided by applicant): Kaposi's sarcoma-associated herpes-virus (KSHV) is now known to be the viral etiologic agent of Kaposi's sarcoma. In sub-Saharan Africa, the catastrophic intersection between an underlying endemic infection with KSHV and the HIV epidemic has resulted in KS becoming the most common malignancy among adults in many countries in this region as well as a growing cause of cancer in children. Despite rapid advances in KSHV virology, less is understood about KSHV epidemiology, especially in sub-Saharan Africa. What is known is that KSHV infection in Africa most commonly occurs in childhood, reaching adult level prevalence before puberty (20-60% depending on region), and that saliva is the body fluid that most commonly harbors KSHV. What is not known is specifically how KSHV is spread in Africa and how demographic, behavioral, and biologic factors influence transmission. The long-term goal of this research is to develop interventions to halt the spread of KSHV and ultimately prevent KS. The specific aims of this proposal are to: (1) Evaluate the prevalence and determinants of KSHV seropositivity in South African children and their caregivers, (2) Examine determinants of the shedding of KSHV in saliva among KSHV-infected individuals, (3) Develop quantitative measures for examining the determinants of incident KSHV infection in a longitudinal study, including the role of practices that expose children to saliva, intra- household relationships, and household characteristics; and (4) Determine the feasibility of a longitudinal study of South African children and their household members. The proposed research will utilize existing data and biological specimens previously collected by Dr. Butler and her mentors in domestic and African studies, as well as primary data collection in South Africa. The work is designed to provide the requisite preliminary data for a subsequent definitive longitudinal study of KSHV transmission in children in South Africa. The proposed training will provide Dr. Butler with the necessary skills in the population sciences, the biological sciences related to infectious diseases, and the ethical conduct of research in resource-poor settings needed for a research career that takes a multidisciplinary approach to the study of infectious diseases that affect children and their families in resource-poor countries.