Abstract
After administering the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D–conjugated vaccine (PHiD-CV) to children aged 2–18 months, we observed a reduction in vaccine-type nasopharyngeal carriage, resulting in a reduction of overall pneumococcal nasopharyngeal carriage, which may be important for indirect vaccine effects. We noted a trend toward reduction of acute otitis media.BackgroundThis trial (ClinicalTrials.gov identifier NCT00839254), nested within a cluster-randomized double-blind invasive pneumococcal disease effectiveness study in Finland (ClinicalTrials.gov identifier NCT00861380), assessed the effectiveness of the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D–conjugated vaccine (PHiD-CV or PCV10) against bacterial nasopharyngeal carriage and acute otitis media (AOM).MethodsInfants (aged 6 weeks to 6 months) received the PHiD-CV or a control vaccine (hepatitis B) (schedule 3+1 or 2+1). Nasopharyngeal swabs were collected at 4 time points post-vaccination from all of the infants and at pre-vaccination from a subset. Parent-reported physician-diagnosed AOM was assessed from first vaccination until last contact (mean follow-up, 18 months). Vaccine effectiveness (VE) was derived as (1 – relative risk)*100, accounting for cluster design in AOM analysis. Significant VE was assessed descriptively (positive lower limit of the non-adjusted 95% confidence interval [CI]).ResultsThe vaccinated cohort included 5093 infants for carriage assessment and 4117 infants for AOM assessment. Both schedules decreased vaccine-serotype carriage, with a trend toward a lesser effect from the 2+1 schedule ( VE across timpoints 19%–56% [3+1] and 1%–38% [2+1]). Trends toward reduced pneumococcal carriage (predominantly vaccine serotypes 6B, 14, 19F, and 23F), decreased carriage of vaccine-related serotype 19A, and small increases at later time points (ages 14–15 months) in non–vaccine-serotype carriage were observed. No effects on nontypeable Haemophilus influenzae, Staphylococcus aureus, or Moraxella catarrhalis carriage were observed. There were non-significant trends toward a reduction in the number of infants reporting AOM episodes (VE 3+1: 6.1% [95% CI, −2.7% to 14.1%] and 2+1: 7.4% [−2.8% to 16.6%]) and all AOM episodes (VE 3+1: 2.8% [−9.5% to 13.9%] and 2+1: 10.2% [−4.1% to 22.9%]). PHiD-CV was immunogenic and had an acceptable safety profile.ConclusionsWe observed reduced vaccine-type pneumococcal carriage, a limited increase in non–vaccine-type carriage, and a trend toward AOM reduction.
Highlights
Streptococcus pneumoniae is a leading cause of respiratory tract infections and bacterial invasive disease [1]
acute otitis media (AOM) analyses were performed for the total vaccinated cohort (TVC) for AOM effectiveness
These misrandomized infants were reallocated to the groups corresponding to the vaccination they received for the TVC for carriage/safety and immunogenicity according-to-protocol cohort but were excluded from the TVC for AOM effectiveness, which substantially affected the 2+1 PHiD-CV group for AOM assessment (371 misrandomized children) [14]
Summary
Streptococcus pneumoniae is a leading cause of respiratory tract infections and bacterial invasive disease [1]. Bacterial nasopharyngeal carriage precedes infection, and various studies have pointed toward a causal link between carriage and disease [2]. Children younger than 5 years are a population vulnerable to pneumococcal disease, and they form a reservoir for other age groups. S pneumoniae is one of the main bacterial pathogens in acute otitis media (AOM). Clinical trials have shown efficacy of pneumococcal conjugate vaccines (PCVs) against vaccine-type AOM, but they have generally shown little or no efficacy against all-cause AOM (vaccine efficacy range, 1%–7%) [5,6,7,8,9]; except for one study showing efficacy of 34% for an 11-valent pneumococcal protein D–conjugated vaccine in children [10]
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