Modelling the ecology and epidemiology of Streptococcus pneumoniae and their impact on conjugate vaccination

• Main Author: Flasche, Stefan
• Published: University of Strathclyde 2012
• Subjects: 510
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576313

In September 2006 a 7-valent conjugate vaccine protective against pneumococcal carriage and disease was introduced into the national immunisation programme in the UK. This thesis assists with the assessment of the population impact of this vaccine and its 13-valent successor. The thesis links the observations in pneumococcal disease epidemiology to changes in carriage and assists with the understanding of the ecology of the pneumococcal serotypes. Statistical models are employed to analyse the changes in post vaccination epidemiology in the UK in both carriage and invasive disease and to correct for possible ascertainment biases. Established mathematical models are analysed for their ability to reflect the pneumococcal ecology and are employed to describe the changes in post vaccination invasive disease. An individual based model is developed to account for the diversity of penumococcal serotypes and to study the likely mechanisms causing the distinct pneumococcal ecolog y, i.e. competition and coexistence. Conjugate vaccination led to a decline in invasive disease associated with the targeted types and a consecutive increase of the non vaccine serotypes. Overall disease incidence declined while carriage rates stayed constant. This implies that the invasiveness of the replacing serotypes has been the main determinant for the impact of vaccination and that carriage data is essential to understand vaccine induced changes in disease. Only one of the established models which describe competition amongst two pneumococcal serotype groups was found to commonly result in coexistence. This model could not fit the age patterns of Scottish post vaccination epidemiology, where serotype replacement amongst isolates of invasive disease was mostly confined to the elderly population. The individual-based model shows that serotype specific immunity can permit stable coexistence of a range of pneumococcal serotypes and that increasing the valency of a vaccine does not necessarily improve public health.