GAS-III

气体-III

• 批准号: 7960426
• 负责人: GULIZ ERDEM
• 金额: $ 1.42万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960426
• 关键词: Acute; Address; Affect; Agglutination; American Samoa; Amino Acid Sequence; Antibody Formation; Antistreptolysin O; Child; Clinical; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Data; Developed Countries; Disease; Epidemiology; Ethnic Origin; Funding; Genes; Grant; Hawaii; Hawaiian population; High Prevalence; Incidence; Infection; Infectious Skin Diseases; Institution; Knowledge; Patients; Peptide Sequence Determination; Pharyngeal structure; Pharyngitis; Population; Research; Research Infrastructure; Research Personnel; Resources; Rheumatic Fever; Samoan; School-Age Population; Serological; Source; Streptococcal Infections; Streptococcus pyogenes; Streptococcus vaccine; Swab; Time; United States National Institutes of Health; Vulnerable Populations; base; cohort; deoxyribonuclease B; human migration; migration; multiple myeloma M Protein; opacity factor; response; transmission process

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 A 族链球菌 (GAS) 引起多种疾病，某些 GAS M 蛋白序列类型（emm 类型）与急性风湿热 (ARF) 等后遗症有关。 尽管 ARF 的发病率在工业化国家有所下降，但在夏威夷，尤其是萨摩亚人中，发病率仍然很高。 拟议研究的目的是确定导致临床疾病的 GAS 类型，特别是萨摩亚人的 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，与夏威夷萨摩亚人后遗症相关的GAS emm类型源于萨摩亚人的循环迁移，从而导致夏威夷ARF的高发病率。 第二个假设是萨摩亚人对 GAS 感染的抗体反应不同。 我们的这些假设基于我们的初步研究，这些研究表明，GAS emm 类型在美国大陆并不常见，并且通常与 ARF 无关，但在患有 GAS 感染和 ARF 的夏威夷患者中经常被发现；由于这些不常见的 emm 类型，萨摩亚族的无症状儿童和 ARF 患者的 GAS 感染患病率较高。 拟议的研究将解决这些具体目标： 具体目标 1. 确定在夏威夷和美属萨摩亚的萨摩亚儿童中传播的气体类型：前瞻性地从美属萨摩亚和夏威夷无症状学龄儿童、轻度咽喉和皮肤感染患者、侵袭性感染和 ARF 患者的咽喉中收集 GAS 分离物，b．对这些 GAS 分离株进行 emm 基因测序、T 凝集分型、不透明因子分型，c．分析美属萨摩亚和夏威夷分离出的 GAS emm 类型之间的差异。 具体目标 2. 确定萨摩亚人群中的 GAS 类型和抗链球菌抗体反应：建立两个队列，每组 50 名来自夏威夷和美属萨摩亚的萨摩亚儿童，其中包括患有 ARF、咽炎、皮肤感染、侵袭性 GAS 感染的患者以及有 GAS 定植的无症状学龄儿童，并在 18 个月内对这些队列重复咽拭子 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 [抗链球菌溶血素 O 和抗 DNase B 滴度]。 研究结果将提供有关与人类迁徙相关的 GAS 流行病学的新知识，并将产生全面的数据，以解决不同人群受到各种 GAS 类型不同影响的方式。 此外，这些研究还将提供有关 GAS 传播动态的急需信息，并对为这些弱势群体定制候选 GAS 疫苗产生影响。