Epidemiology of Gonoccoccal Subpopulations

描述(申请人提供)：淋病(GC)率居高不下。高度流行的核心群体被认为是持续传播的关键。核心群体是根据地理位置或通过反复淋病发病率等行为风险因素来定义的。在以前的工作中，我们已经开发并验证了一种基于porB外膜蛋白的GC分离物的分型方案，该方案既可以用于培养分离物，也可以用于从核酸诊断测试中获得的DNA。这一方案准确地将GC与其他奈瑟菌区分开来，并在抗菌素耐药性的爆发中展示了克隆性。我们认为，使用与流行病学特征相关联的分子标记来识别核心群体，porB分型可能是一种更有效的方法。在本R03中，我们提出了一系列概念验证实验。底物是从巴尔的摩重复项目获得的667个淋球菌分离株或淋球菌DNA材料的样本的集合，该项目是2004年的一项纵向干预措施，涉及在淋病患者首次诊断后3个月进行重新筛查。从临床摘要和问卷中获得的初始样本、重复样本以及相关的流行病学和行为数据均可获得。首先，我们将对分离株进行porB分型，并采用更快速的分型技术。最初的分型方法将通过先前验证的棋盘杂交分析进行，我们将把这些方法应用于实时聚合酶链式反应，这将更加快速。通过将分型结果与流行病学数据联系起来，我们将1)。确认GC感染的空间分布和与特定基因类型的联系，假设在地理范围内，分离株将是相似的。2)。确定在基线诊断的特定基因型别是否能预测重复感染。3)。通过链接行为数据，确定GC基因型是否与行为风险因素和性网络信息相关，假设分型可以作为行为变量的代理数据。我们认为，在实时或接近实时地进行基因分型，可能是一种有用的工具，可以识别哪些GC患者是高危性网络的成员，哪些患者是社区内传播的中心。这一进程反过来将引发集中努力进行密集的公共卫生干预。会比密集的面试技巧更快、更具成本效益。这一方法将为实施干预和控制方法提供框架

DESCRIPTION (provided by applicant): Gonorrhea (GC) rates remain stubbornly high. Hyperendemic core groups are believed essential for continued transmission. Core groups are defined geographically or through behavioral risk factors, such as repeated gonorrhea incidence. In previous work, we have developed and validated a typing scheme for GC isolates, based on the porB outer membrane proteins, that can be used on either culture isolates or DNA obtained from nucleic acid diagnostic testing. This scheme accurately differentiates GC from other Neisseriae, and has demonstrated clonality in outbreaks of antimicrobial resistance. We propose that porB typing may be a more efficient way to identify core groups using a molecular signature linked to epidemiological characteristics. In this R03, we propose a series of proof of concept experiments. The substrate is a collection of 667 samples of gonococcal isolates or gonococcal DNA material obtained from the Baltimore Repeaters Project, a longitudinal intervention in 2004 which involved re- screening patients with gonorrhea 3 months after their initial diagnosis. Initial samples, repeat samples, and linked epidemiological and behavioral data obtained from clinic abstraction and questionnaires are available. Initially we will perform porB typing on the isolates, and adapt the techniques for more rapid typing. Initial typing methods will be performed by previously validated checkerboard hybridization assays, and we will be adapting these methods to real-time PCR, which would be more rapid. By linking the typing results to the epidemiological data we will 1). Confirm spatial distribution of GC infection and linkage to specific genotypes, hypothesizing that within geographic confines, the isolates will be similar. 2). Determine if specific genotypes diagnosed at baseline predict repeat infection. 3). By linking behavioral data, determine whether GC genotypes are associated with behavioral risk factors and sexual network information, hypothesizing that typing can act as proxy data for behavioral variables. We propose that genotyping, performed in or close to real time, may be a useful tool to identify patients with GC who are members of high-risk sexual networks, and who are central to transmission within a community. This process would in turn trigger focused efforts for intensive public health interventions. would be much more rapid and cost effective than intensive interview techniques. This method would then provide the framework for implementing intervention and control approaches