Characteristics of the 24-month-old children of all five studies.

<p>Characteristics of the 24-month-old children of all five studies.</p

IPD incidence in children <5 years and adults >65 years.

<p>PCV7 serotypes include serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. PHiD-CV10 shows the additional serotypes 1, 5 and 7F. PCV13 shows the additional serotypes 3, 6A and 19A. The incidence of IPD was calculated per two epidemiological years. The first bar (June 2004 –June 2006) depicts the IPD incidence in the years before implementation of PCV. The following five bars depict IPD incidence as observed after introduction of pneumococcal vaccination; respectively 1 year after PCV7 implementation (June 2006 –June 2008), 3 years after PCV7 implementation (June 2008 –June 2010), 5 years after PCV7 implementation (June 2010 –June 2012), 2 years after PHiD-CV10 implementation (June 2012 –June 2014) and 4 years after PHiD-CV10 implementation (June 2014 –June 2016).</p

Serotype distribution in 24-month-old children carrying <i>S</i>. <i>pneumoniae</i>.

<p>The first bar (2005) depicts carriage prevalence before implementation of PCV. The following four bars depict carriage prevalence as observed during the follow-up studies; respectively 3 years after PCV7 implementation (2009), 4.5 years after PCV7 implementation and immediately before introduction of PHiD-CV10 (2010/2011), 1.5 years after PHiD-CV10 implementation (2012/2013) and 4.5 years after PHiD-CV10 implementation (2015/2016).</p

Odds ratios for invasive disease potential of serotypes were calculated using nationwide IPD data (children <5 years) and carriage data (24-month-old children) from 2004–2016.

<p>Odds ratios for invasive disease potential of serotypes were calculated using nationwide IPD data (children <5 years) and carriage data (24-month-old children) from 2004–2016.</p

Seroprotection rate of the antibody concentrations against 13 pneumococcal serotypes for the PCV10 group and the PCV13 group with p-values for differences between the groups.

<p><b>*</b> Fisher Exact test</p><p>Seroprotection rate of the antibody concentrations against 13 pneumococcal serotypes for the PCV10 group and the PCV13 group with p-values for differences between the groups.</p

Characteristics of children and their parents before, 3 and 4.5 years after implementation of PCV-7 in the Netherlands.

<p>Note. PCV-7; 7-valent pneumococcal conjugate vaccine. SD; standard deviation. ^aDefined as more than 4 hours per week with at least 1 child from a different household. ^bDefined as passive tobacco smoke exposure indoors at least ≥1 cigar or cigarette during ≥5 days/week. ^cThe presence of symptoms of an upper respiratory tract infection (URTI) and/or acute otitis media (OMA) as defined by evaluation of parents. ^dDefined as use of oral or intravenous antibiotics within 1 month before sample was taken.</p

Frequencies of nasopharyngeal carriage and (adjusted) odds ratios of <i>S. pneumoniae, S. aureus, H. influenzae</i> and <i>M. catarrhalis</i> in children and parents before, 3 and 4.5 years after PCV-7 implementation.

<p>Note. PCV-7; all serotypes included in 7-valent pneumococcal conjugate vaccine. Non-PCV-7; all other serotypes not included in 7-valent pneumococcal conjugate vaccine. OR; odds ratio.CI; confidence interval. aOR; adjusted odds ratio. All (a)OR-values are based on comparison with cohort as indicated. ^aIn children, OR-values were adjusted by multivariate analysis for sex, months of sampling, presence of siblings <5yr in the household, day care attendance, antibiotic use, passive smoke exposure and the presence of URTI and/or OMA using binary logistic regression with backward LR. ^bIn parents, OR-values were adjusted by multivariate analysis for sex, months of sampling, antibiotic use, active smoking, presence of siblings <5yr other than participating child and day care attendance of their participating child.</p

Characteristics of the participants.

<p>a At 12 months of age</p><p>Characteristics of the participants.</p

Seroprotection rate (%) for diphtheria, tetanus, pertussis, and Hib antigens for the PCV10 group and the PCV13 group with p-values for differences between the groups.

<p>*Fisher Exact test</p><p>**N = 29 for PCV13</p><p>***N = 65 for PCV10</p><p>Seroprotection rate (%) for diphtheria, tetanus, pertussis, and Hib antigens for the PCV10 group and the PCV13 group with p-values for differences between the groups.</p

Enrollment and Study Participation.

<p>PCV10 indicates 10-valent pneumococcal conjugate vaccine, Synflorix; PCV13 indicates 13-valent pneumococcal conjugate vaccine, Prevenar-13. * When the enrolment target was reached, further children were considered redundant, and their parents’ informed consent procedures were cancelled. ** Plasma cell and memory B-cell analysis published by van Westen et al.[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0144739#pone.0144739.ref027" target="_blank">27</a>].</p