Town, Katherine Jane;
(2019)
Exploring the application of whole genome sequencing to inform the control of Neisseria gonorrhoeae.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Background: Neisseria gonorrhoeae is a sexually transmitted infection that persists globally and is of concern because of the development of antimicrobial resistance (AMR). Novel methods for investigating how N. gonorrhoeae spreads within sexual networks, such as phylogenetic analysis of whole genome sequencing (WGS) data could support the public health response. The aim of my PhD was to explore the application of WGS to inform the control of N. gonorrhoeae and associated AMR. Methods: I conducted a systematic review to describe N. gonorrhoeae studies that combined molecular and epidemiological data. I created a novel WGS dataset using specimens that were broadly representative of gonorrhoea in England. I identified clusters of infection representing sexual networks and characterised these using epidemiological and phenotypic data. I explored the genetic markers of AMR and compared the sample with international WGS datasets. Results: In the systematic review, I found that there have been few N. gonorrhoeae WGS studies to date. In my phylogenetic analysis, I found clusters containing men reporting sex with men (MSM) as well as men who only report heterosexual sex, indicating there may be groups of heterosexual men who would benefit from further sexual health testing and prevention messages that would normally be targeted to MSM. The clustering also indicated extensive sexual mixing between HIV-positive and HIV-negative/unknown MSM and might inform methods to identify MSM at high risk of HIV infection. N. gonorrhoeae with reduced susceptibility appears to have emerged separately in different sexual networks in England. Distinct lineages of N. gonorrhoeae in England were related to cases in Europe and the USA indicating frequent transmission between countries. Conclusion: WGS data analysis provided new insights about the transmission of N. gonorrhoeae and AMR in sexual networks, which reveal the complexity of sexual mixing patterns and might inform clinical care and public health policy.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Exploring the application of whole genome sequencing to inform the control of Neisseria gonorrhoeae |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10071552 |
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