Epidemiology of Gonoccoccal Subpopulations

描述（由申请人提供）：淋病（GC）发病率居高不下。高流行核心人群被认为对持续传播至关重要。核心群体是根据地理或行为风险因素界定的，例如淋病的反复发病率。在之前的工作中，我们已经开发并验证了一种基于porB外膜蛋白的GC分离物分型方案，该方案可用于培养分离物或从核酸诊断测试中获得的DNA。该方案可准确地将GC与其他奈瑟菌区分开来，并在抗菌素耐药性暴发中证明了克隆性。我们提出，利用与流行病学特征相关的分子特征，porB分型可能是一种更有效的识别核心群体的方法。在本R03中，我们提出了一系列概念验证实验。底物收集了667份淋球菌分离物样本或淋球菌DNA材料，这些样本来自巴尔的摩中继器项目，该项目是2004年的一项纵向干预，涉及在初次诊断后3个月对淋病患者进行重新筛查。初始样本、重复样本以及从临床抽查和问卷调查中获得的相关流行病学和行为数据都是可用的。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。初始分型方法将通过先前验证的棋盘杂交分析进行，我们将使这些方法适应实时PCR，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型的联系，假设在地理范围内，分离株将是相似的。2）. 确定基线时诊断的特定基因型是否可预测重复感染。3)。通过连接行为数据，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。我们建议，实时或接近实时的基因分型可能是一种有用的工具，用于识别高危性网络成员中的GC患者，以及在社区内传播的核心人群。这一进程反过来又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省钱。这种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