Epidemiology, mathematical modelling and economics of Streptococcus pneumoniae : assessing the potential impact of vaccination
This thesis explores aspects of Streptococcus pneumoniae (pneumococcus) epidemiology and control, in view of the possible widespread introduction of conjugate vaccines in England and Wales. A review and analysis of a range of different epidemiological data sources showed that the burden of pneumococcal disease in England and Wales is high and remains mostly a condition of the very young and the elderly. A meta-analysis demonstrated the effectiveness of the polysaccharide vaccine against invasive pneumococcal disease among healthy elderly, to whom vaccination was not recommended at the start of this work. Using this result, a costeffectiveness analysis assessed the economic acceptability of such a programme, from the public health perspective. A better understanding of pneumococcal carriage and transmission is required to assess the effectiveness and cost-effectiveness of mass vaccination strategies with the pneumococcal conjugate vaccine. A novel model framework was developed and fitted to a longitudinal dataset of carriage in UK families. The results demonstrated an inverse relationship between duration of carriage and age and highlighted the importance of both family size and composition for persistence in a household. Great dissimilarities were estimated among the specific serotypes in terms of transmissibility, duration of carriage and level of competition. Realistic age structured dynamic models were developed and used to investigate the impact of a range of vaccine strategies. The importance of serotype replacement, as a consequence of vaccination, was demonstrated. The economic acceptability of alternative interventions with the conjugate vaccine depended on the magnitude of its indirect effects. Herd immunity had a considerable impact on the overall cost-effectiveness of the programmes since it may substantially reduce the burden of disease in older age groups. However, serotype replacement may counterbalance this reduction and lead to a non cost-effective result.