Pneumococcal disease and the impact of pneumococcal conjugate vaccines

Abstract

This thesis addresses various aspects on pneumococcal disease, pneumococcal conjugate vaccines (PCVs) and the societal impact of PCV implementation in children. Implementation of 7-valent pneumococcal conjugate vaccine (PCV7) in the Dutch national immunization program for infants led to a shift from vaccine to non-vaccine serotypes (i.e. replacement disease) in invasive pneumococcal disease (IPD). This shift was observed in all age groups, including non-vaccinated persons, due to indirect effects.Indirect were caused by a reduction in nasopharyngeal colonization of vaccine serotypes in children and subsequent transmission (i.e. herd effects). Also after PCV7 was replaced by a 10-valent pneumococcal conjugate vaccine (PCV10) we observed herd effects for extra serotypes covered by PCV10.Replacement disease following PCVs was primarily caused by expansion of pre-existing non-vaccine serotypes (NVT) rather than capsular switch variants.Despite replacement disease IPD incidence has decreased dramatically in children <5 year old. Also in elderly aged 65 and older net IPD incidence decreased. The magnitude of herd effects and extent of disease caused by NVT strains was different between sexes in particular among 20–39 year-olds. Though these differences were subtle gender is an epidemiological factor to consider in the surveillance of IPD. Shifts in serotypes coincided with changes in clinical syndromes in IPD (i.e. increase in empyema incidence) and outcomes (i.e. decreased IPD case-fatality) for the post-PCV7 period. Also we showed that despite herd effects underlying conditions such as chronic lung or cardiovascular disease and HIV/AIDS persist as important risk factors for IPD in the post-PCV7 period. In addition, the long-term mortality after pneumococcal pneumonia remained high. The impact of PCVs on the microbiological aetiology of community-acquired pneumonia (CAP) in hospitalised adults for other pathogens than S. pneumoniae was unchanged. Potential disturbances of PCVs on the nasopharyngeal microbiome therefore do not seem to translate into a higher proportion of other pathogens in the aetiology of CAP. At last, we vaccinated former pneumococcal CAP patients and former CAP patients infected by another other identified pathogen. In both groups 13-valent pneumococcal conjugate vaccine (PCV13) was immunogenic.