Modeling of S. aureus Transmission in Northern Manhattan.

描述（由研究者提供）：耐抗生素金黄色葡萄球菌感染现在越来越多地在社区中遇到。这些社区感染，特别是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人群中。对于这些菌株如何传播并随后在社区中扎根，人们知之甚少。如果要设计干预措施以防止社区相关(CA)-MRSA分离株在人群水平的传播，这仍然是一个关键问题。本研究将解决以下问题。1. 什么压力导致CA-MRSA在社区内的传播途径？在哥伦比亚大学医疗中心集水区，一个很大程度上服务不足的移民人口，CA-MRSA传播模式将被确定。本研究将采用回顾性病例对照研究设计。有CA-MRSA感染记录的索引病例和社区匹配的索引对照将提供他们自己和他们以自我为中心的网络成员的信息。从社区内（如日托设施和学校）的CA-MRSA潜在宿主收集的数据将补充网络信息。这些地点的受试者将匿名取样以检测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输概率。然后将开发一个数学模型来模拟社区内的传播途径，以及调查可能用于防止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菌株适应其环境，并在传播过程中变得更加生态“适应”。将使用比较全基因组测序对社区中不同亚群（如日托儿童）中流行的选定菌株进行遗传分析。可能增强适应性的突变将通过诸如生长速度、对不同组织表面的粘附以及在环境表面的存活等参数进行筛选。然后将对从该社区收集的所有金黄色葡萄球菌菌株进行“适应性”突变筛选。本应用程序检查CA-MRSA在市中心人群中的传播。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这些类型的调查。与美国其他社区不同，CA-MRSA最近才开始在该社区作为一种突出的病原体出现，因此在CA-MRSA成为地方病之前，传播研究仍然是可能的。最后，本研究创新性地整合了多种研究方法，包括社会网络数据收集策略、分子流行病学、遗传品系分析和数学建模，以解决这一紧迫问题。最终的结果应该是对CA-MRSA的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。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建立的了解很少。本研究的目的是

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.