Molecular epidemiology of HIV and Neisseria gonorrhoeae in the context of drug resistance

点击翻译按钮获取中文摘要

Abstract Neisseria gonorrhoeae (NG) infection is a potential driver of HIV acquisition and transmission. The dynamic structure of transmission networks governs the spread of infection and can inform public health control efforts. HIV and NG transmission networks may overlap and the overlap can help identify at-risk HIV uninfected individuals. The structure of the NG transmission network can be used as a tool for HIV network inference and potential changes in the network over time. Over the past 75 years, NG infections have become increasingly resistant to antimicrobial therapy. Cephalosporins in combination with azithromycin are a last line treatment option for NG infection and cases of reduced susceptibility to these agents have already been documented. The U.S. Centers for Disease Control and Prevention (CDC) has identified drug-resistant NG as one of the top three urgent infectious threats. Antiretroviral resistant HIV is also an important public health problem that is associated with poorer treatment outcomes and reduced virologic suppression that could lead to increased risk of transmission. The impact of antibiotic resistant NG on HIV transmission is unknown, however, drug resistant HIV and NG may uniquely impact the transmission networks. This project will support my development as an independent researcher with expertise in molecular epidemiology by providing me with intensive training in scientific areas that are critical for understanding the global health threat of HIV and NG, including molecular epidemiology and genetic sequence analysis. The proposed project will use genetic sequence data from HIV and NG to understand the spread and potential transmission dynamics of these infections in Tijuana, Mexico and San Diego, California, an important border region. The data generated through the proposed work will strengthen local HIV and NG prevention and control efforts, enhance surveillance data for antibiotic resistant NG, and inform targeted prevention and intervention efforts in this busy border region. Through determination of the structure of HIV and NG transmission networks and an understanding of the factors that drive the transmission of these pathogens, screening, contact tracing and prevention can be appropriately targeted to maximally disrupt HIV and NG transmission networks. This project will build on my background in global health epidemiology and facilitate expertise in HIV and NG molecular epidemiology and antibiotic resistance. The specific training foci will be: 1) genetic sequence analysis of HIV and NG, 2) inference of transmission networks; 3) ethical conduct of prevention, diagnosis and phylogenetic analysis research of HIV and NG; and 4) skills for a successful academic career. I will receive my training from experienced mentors with outstanding track records in molecular genetics research. Each mentor has complementary areas of expertise relevant to my training needs. This proposal builds on previous NIH funded research and complements current NIH funded projects lead by my mentoring team.