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Title: Statistical epidemiology of gonorrhoea in the United Kingdom
Author: Whittles, Lilith K.
ISNI:       0000 0004 9356 6985
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Gonorrhoea is one of the most common sexually-transmitted bacterial infections in the UK. Almost half of the 44,000 cases recorded in 2017 occurred in men who have sex with men (MSM). The bacterium has developed resistance to each first-line antibiotic in turn, such that clinicians are running out of treatment options. We need to make informed decisions to combat antibiotic-resistant gonorrhoea, but are hampered by a lack of understanding in key areas, including: the dynamics of how resistance spreads, its relationship with antibiotic prescribing, and the potential impact of interventions, such as vaccination. To improve understanding of the fitness benefits and costs of antibiotic resistance to inform control policy and planning, I developed a mathematical model that captures the dynamics of cefixime resistance observed in the UK from 2008-2015. Cefixime was abandoned because of rising resistance, but I found that the fitness cost is such that resistance levels have since dropped, and reintroduction could be considered to treat a minority of cases. Both the dynamic forming and breaking of partnerships and heterogeneity in sexual behaviours affect how gonorrhoea outbreaks spread. To assess the implications of network structure on transmission dynamics, I developed a stochastic simulation framework that produces dynamic sexual networks calibrated to real-world data. I used the model to improve estimates of the generation-time and offspring distributions, and to predict the impact of a range of interventions, including vaccination. Vaccination against gonorrhoea could extend the useful life of our first-line therapies. Although no gonococcus-specific vaccine exists, there is evidence that a meningococcal vaccine, MeNZB, offers partial protection. I investigated how efficacious and long-lasting a vaccine would be needed to control antibiotic resistance, and found that even partially-effective vaccines show great promise. In particular, MeNZB could have a substantial impact on incidence, even if gonorrhoea becomes untreatable.
Supervisor: Didelot, Xavier ; White, Peter Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral