Modeling of S. aureus Transmission in Northern Manhattan.

描述(由调查人员提供)：现在社区中越来越多地遇到抗药性金黄色葡萄球菌感染。这些以社区为基础的感染，特别是那些由耐甲氧西林金黄色葡萄球菌(MRSA)引起的感染，是在没有常见危险因素的群体中发生的。对于这些毒株是如何传播并随后在社区内形成的了解很少。如果要设计干预措施以防止社区相关(CA)-MRSA分离株在人群一级传播，这仍然是一个关键问题。这项研究将解决以下问题。1.CA-MRSA在社区内的传播途径是什么压力造成的？将确定CA-MRSA在哥伦比亚大学医疗中心集水区内的传播模式，该地区基本上是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感染和社区匹配指数控制的索引病例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。网络信息将与从社区内潜在的CA-MRSA储存库(例如，日托设施和学校)收集的数据相补充。这些地点的受试者将被匿名抽样进行定居/感染CA-MRSA。结果将用于创建个人、网络和社区参数的传输概率估计。然后将开发一个数学模型来模拟社区内的传播路径，并调查可能用于防止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菌株适应它们的环境，并随着它们的传播变得更适合生态。在种群的不同亚群中流行的选定菌株(例如，托儿所的儿童)将使用比较的全基因组测序进行遗传分析。将使用生长速度、对不同组织表面的粘附力和在环境表面的存活率等参数来筛选可能增强适应性的突变。然后，将对从该社区收集的所有金黄色葡萄球菌菌株进行“适合”突变的筛查。这个应用程序检查CA-MRSA在市中心人群中的传播情况。我们最近完成的疾病控制与预防中心的研究表明，社会有兴趣并愿意参与这类调查。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成为地方性疾病之前，传播研究仍然是可能的。最后，这项调查是对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成功的干预策略。公共卫生相关性对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形成了解甚少。这项研究的目标是 为了：1)确定CA-MRSA感染者的社会网络接触以及接触的性质和CA-MRSA潜在的环境宿主；2)建立一个数学模型，预测社区内的传播途径和潜在的干预策略；以及3)确定适应性基因变化在CA-MRSA菌株在传播过程中的“适合度”中的作用。

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.