Modeling of S. aureus Transmission in Northern Manhattan.

曼哈顿北部金黄色葡萄球菌传播模型。

• 批准号: 7744696
• 负责人: FRANKLIN D LOWY
• 金额: $ 63.44万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-15 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7744696
• 关键词: Academic Medical Centers; Accounting; Address; Adherence; Antibiotic Resistance; Athletic; Case-Control Studies; Catchment Area; Cell Survival; Centers for Disease Control and Prevention (U.S.); Child; Clinic; Communities; Community Networks; Controlled Study; Data; Data Collection; Disease; Disease Outbreaks; Environment; Epidemic; Epidemiologic Methods; Epidemiology; Epithelial Cells; Fibronectins; Goals; Growth; Healthcare; Immigrant; Individual; Infection; Information Networks; Intervention; Invaded; Investigation; Keratin; Life; Link; Measures; Methicillin Resistance; Military Personnel; Mobile Genetic Elements; Modeling; Molecular; Molecular Epidemiology; Mutation; Native Americans; Nature; Pathway interactions; Pattern; Population; Prevalence; Prisons; Probability; Recruitment Activity; Research Design; Research Methodology; Research Personnel; Risk; Risk Factors; Role; Sampling; Schools; Sexually Transmitted Diseases; Simulate; Site; Site-Directed Mutagenesis; Social Network; Sports; Staphylococcus aureus; Subgroup; Surface; Tissues; United States; base; community setting; comparative; defined contribution; design; fitness; genetic analysis; genetic strain; genome sequencing; in vitro Assay; indexing; inner city; innovation; interest; mathematical model; member; methicillin resistant Staphylococcus aureus; pathogen; pressure; prevent; public health relevance; social; transmission process

DESCRIPTION (provided by investigator): Antibiotic-resistant S. aureus infections are now increasingly encountered in the community. These community-based infections, especially those due to methicillin-resistant S. aureus (MRSA), have occurred in groups without the usual risk factors. There is minimal understanding of how these strains spread and subsequently become established within communities. This remains a critical issue if interventions are to be designed to prevent population level dissemination of community-associated (CA)-MRSA isolates. This study will address the following questions. 1. What pressures are responsible for the pathways of CA-MRSA spread within the community? Patterns of CA-MRSA transmission within the Columbia University Medical Center catchment area, a largely underserved immigrant population, will be identified. The study will use a retrospective, case control study design. lndex cases with a documented CA-MRSA infection and community matched index controls will provide information on both themselves and their egocentric network members. Network information will be supplemented with data collected from potential reservoirs of CA-MRSA within the community (e.g., daycare facilities and schools). Subjects at these sites will be anonymously sampled for colonization/infection with CA-MRSA. The results will be used to create estimates of transmission probabilities for individual, network and community parameters. A mathematical model will then be developed to simulate transmission pathways within the community, as well as investigate potential intervention strategies that might be used to prevent CA-MRSA transmission. 2. Do strains of S. aureus evolve in the community and become more adapted to the environment? We hypothesize that CA-MRSA strains adapt to their environment and become more ecologically "fit" as they spread. Selected strains prevalent in the community among different subgroups of the population (e.g., children at daycare) will undergo genetic analysis using comparative total genome sequencing. Mutations that might enhance fitness will be screened using parameters such as growth rate, adherence to different tissue surfaces and survival on environmental surfaces. Screens for the "fitness" mutations will then be carried out on all S. aureus strains collected from the community. This application examines the spread of CA-MRSA in an inner city population. Our recently completed CDC study demonstrated that the community is interested and willing to participate in these types of investigations. Unlike other communities in the United States, CA-MRSA has only recently begun to emerge as a prominent pathogen in this community so that transmission studies are still possible, before CA-MRSA becomes endemic. Finally, this investigation is an innovative integration of diverse research methods including social network data collection strategies, molecular epidemiology, genetic strain analysis and mathematical modeling to address this pressing issue. The end result should be a more comprehensive understanding of CA-MRSA transmission and the intervention strategies that are most likely to be successful in a community setting. PUBLIC HEALTH RELEVANCE There is minimal understanding of how community-associated methicillin-resistant S. aureus (CA-MRSA) spreads and subsequently become established within communities. The goals of this study are to: 1) identify the social network contacts as well as the nature of contacts of CA-MRSA infected subjects and the potential environmental reservoirs of CA-MRSA; 2) develop a mathematical model that predicts transmission pathways and potential intervention strategies within the community; and 3) define the role of adaptive genetic changes in "fitness" of CA-MRSA strains on transmission.

描述（由研究者提供）：现在社区中越来越多地遇到抗生素耐药性金黄色葡萄球菌感染。这些社区感染，特别是由耐甲氧西林金黄色葡萄球菌 (MRSA) 引起的感染，发生在没有常见危险因素的群体中。人们对这些菌株如何传播并随后在社区内扎根的了解甚少。如果要设计干预措施来防止社区相关 (CA)-MRSA 菌株在人群中传播，这仍然是一个关键问题。本研究将解决以下问题。 1. CA-MRSA 在社区内传播的途径有哪些压力？将确定哥伦比亚大学医学中心服务范围内的 CA-MRSA 传播模式，该区域主要是服务不足的移民人群。该研究将采用回顾性病例对照研究设计。具有记录的 CA-MRSA 感染和社区匹配索引控制的索引案例将提供有关其自身及其以自我为中心的网络成员的信息。网络信息将得到从社区内 CA-MRSA 潜在储存库（例如日托设施和学校）收集的数据的补充。这些地点的受试者将被匿名采样以检测 CA-MRSA 的定植/感染。结果将用于估计个人、网络和社区参数的传播概率。然后将开发一个数学模型来模拟社区内的传播途径，并研究可用于预防 CA-MRSA 传播的潜在干预策略。 2. 金黄色葡萄球菌菌株是否在群落中进化并变得更适应环境？我们假设 CA-MRSA 菌株适应其环境，并在传播时变得更加“适合”生态。将使用比较全基因组测序对社区中不同人群（例如日托儿童）中流行的选定菌株进行遗传分析。将使用生长速率、对不同组织表面的粘附性以及在环境表面上的存活率等参数来筛选可能增强适应性的突变。然后将对从社区收集的所有金黄色葡萄球菌菌株进行“适应性”突变筛选。该应用程序检查了 CA-MRSA 在市中心人口中的传播情况。我们最近完成的疾病预防控制中心研究表明，社区有兴趣并愿意参与此类调查。与美国其他社区不同，CA-MRSA 最近才开始成为该社区的一种重要病原体，因此在 CA-MRSA 流行之前，传播研究仍然是可能的。最后，这项研究是多种研究方法的创新整合，包括社交网络数据收集策略、分子流行病学、遗传菌株分析和数学建模，以解决这一紧迫问题。最终结果应该是对 CA-MRSA 传播和最有可能在社区环境中成功的干预策略有更全面的了解。公共卫生相关性 对于社区相关的耐甲氧西林金黄色葡萄球菌 (CA-MRSA) 如何传播并随后在社区内定植的了解甚少。本研究的目标是 1) 识别 CA-MRSA 感染者的社交网络联系人以及接触者的性质以及 CA-MRSA 的潜在环境储存库； 2）开发一个数学模型来预测社区内的传播途径和潜在的干预策略； 3) 定义适应性遗传变化在 CA-MRSA 菌株“适应性”传播中的作用。