Pan-serotype Reduction in Progression of Streptococcus pneumoniae to Otitis Media After Rollout of Pneumococcal Conjugate Vaccines

Abstract

Background: Reductions in otitis media (OM) burden following rollout of pneumococcal conjugate vaccines (PCVs) have exceeded predictions of vaccine impact. In settings with active surveillance, reductions in OM caused by vaccine-targeted pneumococcal serotypes have co-occurred with reductions in OM caused by other pathogens carried in the upper-respiratory tract of children. To understand these changes, we investigated the progression of vaccine-targeted and non-vaccine pneumococcal serotypes from carriage to OM before and after vaccine rollout.

Methods: Nasopharyngeal carriage prevalence of pneumococcus was monitored in prospective studies of Bedouin and Jewish children <3 years old in southern Israel between 2004 and 2016. Incidence of OM necessitating middle-ear fluid culture (predominantly complex OM including recurrent, spontaneously-draining, non-responsive, and chronic cases) was monitored via prospective, population-based active surveillance. We estimated rates of pneumococcal serotype-specific progression from carriage to disease before and after rollout of PCV7/13, measured as OM incidence per carrier. We pooled serotype-specific estimates using Bayesian random-effects models.

Results: On average, rates of progression declined 92% (95% credible interval: 79-97%) and 80% (46-93%) for PCV7/13 serotypes among Bedouin and Jewish children <12 months old, respectively, and 32% (-58-71%) and 61% (-5-86%) among children aged 12-35m. For non-vaccine serotypes, rates of progression among Bedouin and Jewish children aged <12m declined 74% (55-85%) and 43% (4-68%), respectively.

Conclusions: Vaccine-targeted and non-vaccine pneumococcal serotypes showed lower rates of progression to complex OM after rollout of PCV7/13. Early-life OM episodes historically associated with vaccine-serotype pneumococci may impact the susceptibility of children to OM progression.

Keywords: complex otitis media; otitis media; pneumococcal conjugate vaccine; surveillance.

Figure 1.

Serotype-specific progression rate for otitis media (OM). We illustrate measures of serotype-specific progression rates (OM incidence per 1000 person-years at risk among children, divided by carriage prevalence) with 95% credible intervals in the pre-PCV era (black) and era of widespread PCV13 use (red). Pooled estimates from Bayesian random effects models are included to the right of serotype-specific measurements, including all PCV7 serotypes, the six additional serotypes included in PCV13, all PCV13 serotypes, and all non-vaccine serotypes. Pooled estimates of NVT progression rate include all NVTs as listed elsewhere (Table S6); the 15 NVTs plotted represent those with the highest prevalence in carriage. Serotype-specific estimates with varying precision contribute differentially to pooled posterior estimates from Bayesian random effects models. Abbreviations: NVT, Non-vaccine serotype; OM, otitis media; PCV, Pneumococcal conjugate vaccines; PYAR, Person-years at risk.

Figure 2.

Reduction in progression rate for PCV7 and PCV13 serotypes. Plots illustrate medians (points) and 95% credible intervals of estimated fold changes in serotype-specific progression rate for vaccine-targeted serotypes between the pre-PCV7 era and era of widespread PCV13 use, stratified by age and ethnicity of children, as calculated from estimates of absolute progression rate presented in Figure 1. Serotype-specific estimates with varying precision contribute differentially to pooled posterior estimates from Bayesian random effects models. Abbreviations: OM, otitis media; PCV, Pneumococcal conjugate vaccines.

Figure 3.

Reduction in progression rate for non-vaccine serotypes. Plots illustrate medians (points) and 95% credible intervals of estimated fold changes in serotype-specific progression rate for serotypes not targeted by PCVs between the pre-PCV7 era and era of widespread PCV13 use, stratified by age and ethnicity of children, as calculated from estimates of absolute progression rate presented in Figure 1. Pooled estimates of NVT progression rate include all NVTs as listed elsewhere (Table S6); the NVTs plotted represent those with the highest prevalence in carriage. Serotype-specific estimates with varying precision contribute differentially to pooled posterior estimates from Bayesian random effects models. Abbreviations: NVT, Non-vaccine serotype; OM, otitis media; PCV, Pneumococcal conjugate vaccines.