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）：抗生素耐药链球菌。金黄色葡萄球菌感染现在越来越多地在社区中遇到。这些以社区为基础的感染，特别是那些由于耐甲氧西林的S。金黄色葡萄球菌（MRSA），发生在没有通常的危险因素的群体中。人们对这些菌株如何传播并随后在社区内建立的了解很少。如果要设计干预措施以防止社区相关（CA）MRSA分离株的人群水平传播，这仍然是一个关键问题。本研究将探讨以下问题。1.什么压力是负责CA-MRSA在社区内传播的途径？将确定哥伦比亚大学医学中心集水区内CA-MRSA传播模式，该集水区是一个服务不足的移民人口。本研究将采用回顾性病例对照研究设计。有记录的CA-MRSA感染的索引病例和社区匹配的索引对照将提供关于他们自己和他们以自我为中心的网络成员的信息。网络信息将补充从社区内CA-MRSA潜在储存库收集的数据（例如，日托设施和学校）。将对这些研究中心的受试者进行匿名采样，以检测CA-MRSA定植/感染。结果将用于创建个人，网络和社区参数的传输概率的估计。然后将开发一个数学模型来模拟社区内的传播途径，并研究可能用于预防CA-MRSA传播的潜在干预策略。2. S.菌株。金黄色葡萄球菌在社区中进化，变得更适应环境？我们假设CA-MRSA菌株适应了它们的环境，并且随着它们的传播而变得更加生态“适合”。在群体的不同亚群中流行的选定菌株（例如，日托儿童）将使用比较总基因组测序进行遗传分析。将使用生长速率、对不同组织表面的粘附性和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。然后将对所有S进行“适应性”突变的筛选。金黄色葡萄球菌菌株从社区收集。该应用程序检查了CA-MRSA在市中心人群中的传播。我们最近完成的CDC研究表明，社区有兴趣并愿意参与这些类型的调查。与美国其他社区不同，CA-MRSA只是最近才开始在该社区成为一种突出的病原体，因此在CA-MRSA成为地方病之前，传播研究仍然是可能的。最后，这项调查是多种研究方法的创新整合，包括社会网络数据收集策略，分子流行病学，遗传菌株分析和数学建模，以解决这一紧迫的问题。最终的结果应该是更全面地了解CA-MRSA的传播和最有可能在社区环境中取得成功的干预策略。公共卫生相关性对于社区相关耐甲氧西林S。金黄色葡萄球菌（CA-MRSA）传播，随后在社区内建立。本研究的目的是 收件人：1）识别CA-MRSA感染受试者的社交网络接触以及接触的性质和CA-MRSA的潜在环境储存库; 2）开发预测社区内的传播途径和潜在干预策略的数学模型;和3）定义适应性遗传变化在CA-MRSA菌株的“适应性”中对传播的作用。