Epidemiology of Gonoccoccal Subpopulations

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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