Invasive Pneumococcal Disease 3 Years after Introduction of 10-Valent Pneumococcal Conjugate Vaccine, the Netherlands

Three years after a 7-valent pneumococcal conjugate vaccine was replaced by a 10-valent pneumococcal conjugate vaccine in the Netherlands, we observed a decrease in incidence of invasive pneumococcal disease caused by Streptococcus pneumoniae serotypes 1, 5, and 7F. Our data do not support or exclude cross-protection against serotype 19A.

not change in the 2 years after PCV10 introduction, but in the third year, incidence decreased by 42% and 47% for persons 18-49 years of age and 50-64 years of age, respectively; a 25% decrease was observed for persons >65 years of age (Figure 2 panel C; Table 1). Non-PCV10 IPD incidence increased for most age groups in the 2 years after PCV10 introduction (overall CIR 1.25, 95% CI 1. 13 Table 1).

Conclusions
We observed a decrease in PCV7-type IPD >8 years after PCV7 introduction for all age groups. However, this decrease was lessened by an increase in non-vaccine-type IPD, a finding similar to that reported in other countries (6,7). There was an overall 80% decrease in IPD incidence for children <5 years of age and a 25% decrease for persons >65 years of age.
PCV10 introduction caused a decrease in PCV10-7 IPD incidence in PCV10-eligible children, providing evidence  for a direct effect from PCV10. Potential cross-protection of PCV10 against serotype 19A, as corroborated by a case-control study showing 82% effectiveness against 19A IPD (5), is still debated. In our study, the incidence rate for 19A IPD was lower in the PCV10-eligible cohort than the PCV7-eligible cohort, but the decrease in 19A IPD was not different from the decrease in PCV10unrelated IPD, which precludes drawing conclusions about cross-protection against 19A IPD. In addition, 19A carriage had already decreased in toddlers before PCV10 introduction (8).
We observed a decrease in non-PCV10 IPD in the PCV10-eligible cohort but have no indication that surveillance sensitivity changed over time. The decrease might be caused by natural fluctuations or different viral seasons (9). A study in Canada reported lower incidence rates for 19A IPD and other non-vaccine-type IPD in a PCV10-eligible cohort (4). It was hypothesized that lower antibody levels induced by PCV10 (10,11) might lead to smaller disturbances of the nasopharyngeal niche and replacement by new serotypes against which there is no immunity, which might result in a lower incidence of non-PCV10 IPD. However, a randomized controlled trial showed similar carriage rates for non-PCV10 serotypes, including 19A, for infants vaccinated with PCV7 and those vaccinated with PCV10 (12).
In the third year after PCV10 introduction, PCV10-7 IPD incidence also decreased in nonvaccinated age groups, which might indicate herd effects. After PCV7 introduction, herd effects appeared after 3 years (13). Non-PCV10 IPD incidence did not increase in the second and third years after PCV10 introduction, which was partially caused by a reduction in 19A IPD. Longer follow-up times are needed to distinguish whether these observations were caused by cross-protection against 19A in children through herd effects of PCV10, reduced nonvaccine serotype replacement by PCV10, or temporal fluctuations.
We used data from a stable surveillance system with constant coverage over time; age and serotype data were nearly complete (99.9%). However, a limitation of our study was the ecologic design. Thus, one should be cautious in interpreting findings as causally related to vaccination. Also, we have limited data on IPD before PCV7 introduction and after the switch to PCV10.
In conclusion, PCV10 introduction in 2011 decreased vaccine-type IPD incidence in targeted birth cohorts. Three years after introduction, herd effects became apparent. Stabilization of non-PCV10 IPD in the second and third years after PCV10 introduction might indicate reduced serotype replacement by PCV10 or cross-protection against 19A. However, we cannot make firm conclusions on crossprotection of PCV10 against serotype 19A. Continued surveillance of serotype-specific IPD is crucial for evaluating long-term effects of pneumococcal conjugate vaccines in human populations.
Dr. Knol is a senior epidemiologist at the Center for Infectious Disease Control of the National Institute of Public Health, Bilthoven, the Netherlands. Her research interests are epidemiology and surveillance of vaccine-preventable diseases, in particular IPD.