A multi-level genomic and spatial analysis of MRSA transmission

项目摘要（重写） 社区相关耐甲氧西林链球菌。金黄色葡萄球菌（CA-MRSA）是城市地区的主要问题， 吸毒、监禁、不稳定的住房和居住的地理区域，每一个都与CA相关- MRSA风险。使用基因组测序，我们以前已经证明，社区网络可能 促进MRSA在家庭以外的传播，以及流行病学暴露，包括居住在 被拘留者释放率高的地区，可作为被殖民或感染的个人之间的联系的基础， 基因相似的MRSA菌株监狱促进MRSA传播的程度， 对整个社会和整个社会的影响是未知的。我们的初步数据显示 的人进入监狱已经殖民与MRSA和监狱，然后提供了一个机会， 这可能会促进MRSA的进一步传播。由于城市监狱的特点是 营业额和高累犯率，我们推测监狱可能是MRSA传播的主要驱动力之一， 回到城市社区。尽管研究表明与社区环境相关的风险， MRSA的感染预防检查几乎完全在医院进行。不清楚是否 在社区中获得MRSA的传播动力学和风险因素与那些 在医院里传播。先前对性传播疾病的研究表明， 对城市监狱的干预可以对社区产生重大的下游效益， 有机会对难以接触到的往往得不到医疗服务的人群进行干预。我们认为 这种类型的干预可以扩展到MRSA，分子流行病学分析将有助于 设计并最大化社区干预的好处。要求提供资金， MRSA在城市社区的流行病学，并确定和表征MRSA传播的震中。 我们将使用2008-2018年现有的MRSA临床培养物，并整合这些分离株的基因组数据 地理编码，流行病学，被拘留者释放和美国人口普查数据，以测试是否有地理 MRSA传播风险最高的地区。我们将使用空间传播模型来确定MRSA的发病率， 在社区内和社区之间传播，并测试假设的干预措施。该提案 三个目标：（1）描述MRSA随时间的运动，以确定是否存在不同的传播风险 在不同的社区，（2）确定社区MRSA菌株是否与MRSA基因组相关 从监狱监禁的个人中分离的菌株，以及（3）确定MRSA在监狱中传播的热点 社区使用人口基因组学建模。这个创新的项目将是第一个跟踪传播的 MRSA在一个大的城市地区，结果突出的人口和社区地区，可能是最好的 预防工作的目标。因为这项研究将探索CA-MRSA的有据可查的差异， 调查结果将推广到其他得不到充分服务的人群，强调公共卫生的重要性。

Project Summary (REWRITTEN) Community-associated methicillin-resistant S. aureus (CA-MRSA) is a major problem in urban areas, with illicit drug use, incarceration, unstable housing, and geographic area of residence each being associated with CA- MRSA risk. Using genomic sequencing, we have previously demonstrated that community networks may facilitate the spread of MRSA outside of households, and epidemiologic exposures, including residence in a high detainee release area, may serve as the basis for linkages between individuals colonized or infected with genetically similar MRSA strains. The extent to which jails facilitate MRSA transmission, both during incarceration and to the community at large, is unknown. Our preliminary data demonstrate a high proportion of individuals enter the jail already colonized with MRSA and jails then provide an opportunity for at-risk individuals to intermingle which may promote further spread of MRSA. As urban jails are characterized by high turnover and high recidivism, we speculate the jails may be one of the major drivers of MRSA spread from and back into urban communities. Despite the demonstrated risk associated with community settings, studies examining infection prevention for MRSA have been conducted almost exclusively in hospitals. It is unknown if transmission dynamics and risk factors for acquisition of MRSA in the community are the same as those that drive transmission in hospitals. Prior studies of sexually transmitted diseases have demonstrated that interventions in urban jails can have significant downstream benefits in the community and provide an opportunity to intervene with a difficult-to-reach population that often lacks access to medical care. We believe this type of intervention could be extended to MRSA and that molecular epidemiologic analysis would help to design and maximize the benefits of a community intervention. Funds are requested to examine the genomic epidemiology of MRSA in an urban community and to identify and characterize epicenters for MRSA spread. We will use existing MRSA clinical cultures from 2008-2018 and integrate genomic data from these isolates with geocoding, epidemiologic, detainee release, and US census data to test whether there are geographic areas at highest risk for MRSA spread. We will use spatial transmission modeling to identify rates of MRSA transmission within and between community areas and to test hypothetical interventions. The proposal has three aims: (1) Characterize the movement of MRSA over time to identify if there is differential risk for spread in various community areas, (2) Determine if community MRSA strains are genomically related to MRSA strains isolated from individuals incarcerated at the jail, and (3) Identify hotspots of MRSA spread in the community using population genomics modeling. This innovative project will be the first to track the spread of MRSA in a large urban area, with results highlighting populations and community areas that may be the best targets for prevention efforts. Because the study will explore well-documented disparities with CA-MRSA, our findings will be generalizable to other underserved populations, underscoring the public health importance.