Streptococcus pneumoniae, resistance and disease in adults in the era of conjugate vaccines

Programa de Doctorat en Medicina i Recerca Translacional [eng] Streptococcus pneumoniae is an important human pathogen, being one of the main etiological agents of serious infectious diseases such as pneumonia or meningitis and other less serious like otitis media. S. pneumoniae adheres to the respiratory epithelium being part of the nasopharyngeal microbiome. This nasopharyngeal colonization is more frequent in young children (colonization percentages of around 27-65%) than in adults with a frequency of colonization around 10%. In recent years, the introduction of the pneumococcal conjugate vaccines (PCVs) for children has changed the epidemiology of pneumococcal diseases. Since vaccination by PCVs prevents the carrier status of those strains expressing serotypes included in the vaccine, their transmission is reduced and a beneficial group protection (“herd protection”) occurs in the non-vaccinated population. Three PCVs have been marketed in Spain: PCV7 (introduced in 2001), PCV10 (in 2009) and PCV13 (which replaced PCV7 in 2010). All of them were administered voluntarily until 2015, when PCV13 became part of the routine vaccination schedule for children and were subsidized by the government. The main objective of this thesis is to study the impact of the introduction of PCVs in children on invasive pneumococcal disease in adults (IPD). The works included in this thesis focus on describing the effects of the introduction of PCVs in Spain on the epidemiology of IPD in adults. Specifically, this thesis has studied the changes in the incidence of IPD, in the rates of antibiotic resistance, in the clones responsible for IPD and in the clinical characteristics of patients in the era of PCVs. The first part of this thesis shows how the introduction of PCV13 in Spain caused an early decrease in the incidence of adult IPD. The global incidence of IPD decreased by 33.9% from 2008-2009 to 2012-2013. These results were related to a decrease in the incidence of those serotypes included in PCV7 (decrease of 52.7%) and of those additional PCV13 (decrease of 55.0%), while disease caused by non-vaccine serotypes remained stable. The reduction in IPD rates was greater in the Community of Madrid, a community in which PCVs (PCV7 and later PCV13) were included in the routine childhood vaccination schedule in 2009. Regarding the additional PCV13 serotypes all decreased except serotype 3 which remained stable, possibly indicating a lower effectiveness of PCV13 in preventing I