Mathematical, statistical and economic modelling of infection, immunity and vaccination of sexually transmissible infections

Sexually transmissible infections (STIs) are responsible for considerable morbidity and even mortality. In 2012, STIs resulted in 100 million lost disability-adjusted life years and human immunodeficiency syndrome (HIV) was the sixth leading cause of death in the world. In this thesis, mathematical models are applied to Chlamydia, gonorrhoea and HIV at in-host, population and global levels to understand pathogen and immune system interaction, spread of infection through populations, and effectiveness of control strategies.At the in-host level, a mathematical model tracking cell and chlamydiae counts in mice predicts that the chlamydial load at equilibrium is independent of the inoculum. Experimental data are shown to be consistent with this prediction. The model is used to identify the rate of replenishment of healthy cells as having a large impact on the equilibrium level, highlighting the importance of cell availability to Chlamydia dynamics.At the population level, a mathematical model of gonorrhoea is used to simulate the potential impact of vaccines. A vaccine of 50% efficacy that is protective for 20 years, administered before sexual debut, is predicted to reduce gonorrhoea prevalence in the population by over 90% after 20 years. A novel mathematical model is developed to simulate Chlamydia in declining koala populations, and is used to predict that it would be most effective to vaccinate females aged 1-2 years. Targeting these koalas and vaccinating around 10% of the population each year using a vaccine of 75% average efficacy is expected to reverse population decline in 5 years.At the global level, public health strategies are often informed by model-based costeffectiveness analyses. A systematic review is conducted of the cost-effectiveness literature for HIV interventions in regions with concentrated epidemics. Interventions that target key affected populations are found to be most cost-effective. Data on HIV spending for twelve countries shows that in eight more than 30% of spending goes to general population and non-targeted programs, suggesting that HIV resource allocation is not consistent with cost-effectiveness evidence.The findings in this thesis, from the in-host scale to the global scale, will inform vaccine development and resource allocation for STIs