GAS-III

气体-III

• 批准号: 7380997
• 负责人: GULIZ ERDEM
• 金额: $ 5.31万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380997
• 关键词: GAS; III

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Group A streptococci (GAS) cause a wide spectrum of diseases and certain GAS M protein sequence types (emm types) have been associated with such sequelae as acute rheumatic fever (ARF). While the incidence of ARF has declined in industrialized countries, it remains high in Hawaii particularly among Samoans. The objectives of the proposed research are to identify GAS types responsible for clinical disease, particularly ARF in Samoans, and to determine the serologic responses to these specific infections. Our central hypothesis is that the GAS emm types associated with sequelae in Samoans in Hawaii originate from circular migration of Samoans, thus resulting in the high incidence of ARF in Hawaii. The secondary hypothesis is that the antibody responses to GAS infections are different in Samoans. We base these hypotheses on our preliminary studies which indicate that GAS emm types, which are uncommonly found on the continental US and not classically associated with ARF, are frequently identified among Hawaiian patients with GAS infections and ARF; and that asymptomatic children and ARF patients of Samoan ethnicity have higher prevalence rates of GAS infections due to these uncommon emm types. The proposed study will address these specific aims: Specific aim 1. Determine the GAS types circulating among Samoan children in Hawaii and American Samoa: a. Prospectively collect GAS isolates from throats of asymptomatic school-aged children, patients with mild throat and skin infections, patients with invasive infections and with ARF in American Samoa and Hawaii, b. Perform emm gene sequencing, T agglutination typing, opacity factor typing of these GAS isolates, c. Analyze the differences among GAS emm types isolated in American Samoa and Hawaii. Specific aim 2. Determine the GAS types and anti-streptococcal antibody responses in cohorts of Samoans: a. Establish two cohorts of 50 Samoan children each from Hawaii and American Samoa to include patients with ARF, pharyngitis, skin infection, invasive GAS infection and asymptomatic school-aged children with GAS colonization and repeat throat swabs of these cohorts 3 times within an 18-month study period, b. Prospectively determine the anti-streptococcal antibody responses [antistreptolysin O and anti-DNase B titers] in the two cohorts. The study results will provide new knowledge about GAS epidemiology associated with human migration and will yield comprehensive data to address the means by which different populations are affected differently by a wide variety of GAS types. Also, these studies will provide much-needed information about the transmission dynamics of GAS and exert an impact on tailoring candidate GAS vaccines for these vulnerable populations.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。 A组链球菌（气体）引起广泛的疾病，某些气体M蛋白序列类型（EMM类型）与诸如急性风湿热（ARF）等后遗症有关。尽管工业化国家的ARF发生率下降，但夏威夷尤其是萨摩亚人的发病率仍然很高。拟议研究的目标是确定导致临床疾病的气体类型，尤其是萨摩亚人的ARF，并确定对这些特定感染的血清学反应。我们的中心假设是，夏威夷萨摩亚人与后遗症有关的气体EMM类型源自萨摩亚人的圆形迁移，从而导致夏威夷ARF的高发病率。次要假设是萨摩亚人对气体感染的抗体反应不同。我们将这些假设以我们的初步研究为基础，这些研究表明，在美国大陆上发现的气体EMM类型在夏威夷气体感染和ARF的患者中经常被发现。萨摩亚种族的无症状儿童和ARF患者由于这些不常见的EMM类型而导致气体感染的患病率更高。拟议的研究将解决以下特定目的：具体目标1。确定夏威夷萨摩亚儿童和美国萨摩亚儿童循环的气体类型：前瞻性地从无症状的学校儿童，轻度喉咙和皮肤感染的患者，侵入性感染的患者以及ARF中的ARF中，从无症状的学龄儿童的喉咙中收集气体分离株。执行EMM基因测序，t凝集键入，这些气体分离株的不透明度因子键入，c。分析美国萨摩亚和夏威夷分离的气体EMM类型之间的差异。 具体目标2。确定萨摩亚人群中的气体类型和抗链球菌抗体反应：建立两个来自夏威夷和美国萨摩亚的50名萨摩亚儿童的队列，包括ARF患者，咽炎，皮肤感染，侵入性气体感染和无症状的校生气体殖民儿童，并在18个月内重复进行这些同类拭子3次学习期，b。前瞻性确定两个队列中的抗链球菌抗体反应[抗抑制素O和抗DNase B滴度]。 该研究结果将提供有关与人类迁移相关的气体流行病学的新知识，并将产生全面的数据，以解决不同种群受到多种气体类型的不同影响的手段。此外，这些研究将提供有关气体传输动态的急需信息，并对这些脆弱人群的调整候选气体疫苗产生影响。