The effect of pneumococcal conjugate vaccines on otitis media from 2005 to 2013 in children aged ≤5 years: a retrospective cohort study in two Swedish regions

Abstract

Seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to Sweden in 2009 and replaced by pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or 13-valent PCV (PCV13) from late 2009. A retrospective cohort study assessed the impact of PCVs on otitis media/acute otitis media (OM) in children aged ≤5 years (NCT02742753) living in Skåne (PCV7 then PHiD-CV) or Västra Götalandsregionen (PCV7 then PCV13) between 2005 and 2013 using linked regional and national databases. Time-series analyses described differences between pre-PCV and post-PCV eras. Adjusted age-period-cohort (APC) predictive models estimated vaccine effectiveness and OM incidence ratios between PCV cohorts. Time-to-first OM diagnosis was estimated in ≤2 year-olds by survival analysis using a Cox proportional hazards model. Descriptive interrupted time-series analyses showed OM incidence in ≤2 year-olds declined by 42% (Skåne) and 25% (Västra Götalandsregionen) after PHiD-CV/PCV13, respectively, versus pre-PCV, but baseline OM incidence and duration of PCV7 use differed between regions. In adjusted APC models, OM incidence decreased after PHiD-CV by 9.9% (95% confidence interval [CI]: 4.4; 15.1, p < .001) and PCV13 by 2.3% (95%CI: −3.2; 7.6, p = .401) compared with pre-PCV. Both PHiD-CV and PCV13 decreased the risk of first OM diagnosis: hazard ratio (95%CI) for PHiD-CV relative to pre-PCV 0.67 (0.65; 0.69); 0.87 (0.85; 0.89) for PCV13 relative to pre-PCV; p < .001 for both comparisons. Within the limitations of this study conducted in two large Swedish regions, descriptive time-series analyses showed that OM incidence rates declined following the introduction of PHiD-CV and PCV13; however, this reduction only reached statistical significance for PHiD-CV in the adjusted APC models.

Impact of pneumococcal conjugate vaccines on healthcare utilization and direct costs for otitis media in children ≤2 years of age in two Swedish regions

“…Antibiotic prescribing for OM showed strong annual seasonality and significant levels of autocorrelation in all ages and in each vaccine era (Figure S1), which mirrored OM incidence rates. 18 Before the introduction of PCV, antibiotic prescribing rates for OM in children aged ≤5 years were higher in Skåne than in VGR, particularly among children aged 1 year (Figure S1), also mirroring trends observed in OM incidence rates. 18 The interrupted time-series showed a decrease in antibiotic prescribing (events per 100,000 person-years) between the pre-PCV period and the PHiD-CV period that was statistically significant in 1 year-olds (−697, 95% CI: −1138; −255), 2 yearolds (−369, 95% CI: −655; −83), and ≤5 years (−314, 95% CI: −616; −13) (Table S3).…”

“…18 Before the introduction of PCV, antibiotic prescribing rates for OM in children aged ≤5 years were higher in Skåne than in VGR, particularly among children aged 1 year (Figure S1), also mirroring trends observed in OM incidence rates. 18 The interrupted time-series showed a decrease in antibiotic prescribing (events per 100,000 person-years) between the pre-PCV period and the PHiD-CV period that was statistically significant in 1 year-olds (−697, 95% CI: −1138; −255), 2 yearolds (−369, 95% CI: −655; −83), and ≤5 years (−314, 95% CI: −616; −13) (Table S3). In VGR, statistically significant decreases were observed in all age years, with an overall change in slope of −356 (95% CI: −531; −181) from the pre-PCV to the PCV13 period (Table S3).…”

“…As reported previously, there was no evidence of seasonality, autocorrelation, or systematic trends in the incidence of urinary tract infection observed in the time-series analysis. 18 To allow for the fact that within each calendar year children may have received different vaccinations, or no vaccination according to their age, separate analyses were performed by age category (≤2, 3-5 and ≤5 years).…”

“…Both PHiD-CV and PCV13 appeared to decrease the risk of first OM in young children. 18 Here, we report secondary study objectives, which were to assess trends over time in rates of OM-related antibiotic prescriptions, TTP, and OM-related healthcare resource utilization and associated costs before and after sequential use of PCVs in Skåne and VGR.…”

Comparing Watchful Waiting Approach vs. Antibiotic Therapy in Children with Nonsevere Acute Otitis Media: A Randomized Clinical Trial

“…Results of a study in Sweden showed that pneumococcal conjugate vaccines reduce the incidence of otitis media up to 26% and delay the first episode of otitis media in infants and young children [ 15 ]. This could be due to the reduced nasopharyngeal colonization of bacteria by PCVs [ 16 ].…”