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: 8390495
• 负责人: FRANKLIN D LOWY
• 金额: $ 53.59万
• 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 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8390495
• 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; Research Design; Research Methodology; 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; social; transmission process

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 proposal 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.

抗生素抗性S.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，特别是那些由于耐甲氧西林S。金黄色葡萄球菌（MRSA），发生在 没有通常的危险因素。人们对这些菌株如何传播的了解很少， 后来在社区内建立起来。这仍然是一个关键问题， 旨在预防社区相关（CA）MRSA分离株的人群水平传播。本研究 将回答以下问题。1.什么样的压力是CA-MRSA传播途径的原因 在社区内？哥伦比亚大学医学中心CA-MRSA传播模式 将确定服务不足的移民人口的集水区。该研究将使用 回顾性病例对照研究设计。有记录的CA-MRSA感染和社区的索引病例 匹配的索引控件将提供关于它们自己和它们的以自我为中心的网络成员的信息。 网络信息将补充从CA-MRSA的潜在储库收集的数据， 社区（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， CA-MRSA定植/感染。结果将用于创建传输概率的估计 个人、网络和社区参数。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 用于预防CA-MRSA传播。2.做S.金黄色葡萄球菌在群落中进化， 更适应环境？我们假设CA-MRSA菌株适应了它们的环境， 随着它们的传播变得更加“适合”生态环境。在不同的社区中流行的选定菌株 群体的子群体（例如，儿童在日托）将进行遗传分析，使用比较总 基因组测序可能增强适应性的突变将使用生长等参数进行筛选 速率、对不同组织表面的粘附性和在环境表面上的存活率。屏幕上的“健身” 所有的突变都将在S上进行。金黄色葡萄球菌菌株从社区收集。 该提案研究了CA-MRSA在市中心人群中的传播。我们最近完成的疾病控制中心 研究结果显示，市民有兴趣及愿意参与这类调查。 与美国其他社区不同，CA-MRSA最近才开始成为一个突出的社区。 因此，在CA-MRSA成为 地方病最后，本研究创新性地整合了社会学等多种研究方法， 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 来解决这个紧迫的问题。最终的结果应该是对CA-MRSA有更全面的了解 传播和干预战略，最有可能在社区环境中取得成功。

项目成果

Molecular characterization of Staphylococcus aureus from outpatients in the Caribbean reveals the presence of pandemic clones.

来自加勒比海门诊病人的金黄色葡萄球菌的分子表征揭示了大流行克隆的存在。

• DOI: 10.1007/s10096-011-1339-2
• 发表时间: 2012-04
• 期刊: EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES
• 影响因子: 4.5
• 作者: Uhlemann, A-C;Dumortier, C.;Hafer, C.;Taylor, B. S.;Sanchez E, J.;Rodriguez-Taveras, C.;Leon, P.;Rojas, R.;Olive, C.;Lowy, F. D.
• 通讯作者: Lowy, F. D.

Staphylococcus aureus infections: transmission within households and the community.

• DOI: 10.1016/j.tim.2015.03.007
• 发表时间: 2015-07
• 期刊: TRENDS IN MICROBIOLOGY
• 影响因子: 15.9
• 作者: Knox, Justin;Uhlemannl, Anne-Catrin;Lowy, Franklin D.
• 通讯作者: Lowy, Franklin D.

Community-associated methicillin-resistant Staphylococcus aureus transmission in households of infected cases: a pooled analysis of primary data from three studies across international settings.

• DOI: 10.1017/s0950268814000983
• 发表时间: 2015-01
• 期刊: Epidemiology and infection
• 影响因子: 4.2
• 作者: Knox J;Van Rijen M;Uhlemann AC;Miller M;Hafer C;Vavagiakis P;Shi Q;Johnson PD;Coombs G;Kluytmans-Van Den Bergh M;Kluytmans J;Bennett CM;Lowy FD
• 通讯作者: Lowy FD

Toward an understanding of the evolution of Staphylococcus aureus strain USA300 during colonization in community households.

• DOI: 10.1093/gbe/evs094
• 发表时间: 2012
• 期刊: Genome biology and evolution
• 影响因子: 3.3
• 作者: Uhlemann AC;Kennedy AD;Martens C;Porcella SF;Deleo FR;Lowy FD
• 通讯作者: Lowy FD

Environmental contamination as a risk factor for intra-household Staphylococcus aureus transmission.

• DOI: 10.1371/journal.pone.0049900
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Knox J;Uhlemann AC;Miller M;Hafer C;Vasquez G;Vavagiakis P;Shi Q;Lowy FD
• 通讯作者: Lowy FD