Both the ten-valent pneumococcal conjugate vaccine (PCV10) and the 13-valent pneumococcal conjugate vaccine (PCV13) have shown substantial effects and vaccine effectiveness against vaccine serotype and overall incidence of invasive pneumococcal disease in multiple studies.1, 2, 3 The effectiveness and impact of PCV13 on serotype 19A paediatric invasive pneumococcal disease is well described.2, 4, 5 Also vaccine effectiveness of PCV10 against serotype 19A invasive pneumococcal disease is reported.1, 2, 6, 7 Studies of short-term outcomes have shown evidence for the cross-protection of PCV10 against serotype 19A invasive pneumococcal disease,6, 7 but some studies published between 2017 and 2019 evaluating the impact of PCV10 for at least 3 years were not able to support this effect.1, 3, 8, 9 An increase in invasive pneumococcal disease caused by non-vaccine serotypes has been reported because of a serotype replacement phenomenon.3
In Belgium, seven-valent pneumococcal conjugate vaccine (PCV7) became available on the market in October, 2004 (estimated vaccine uptake of 42% in 2006).10 It was in 2007 that PCV7 was included in the nation's childhood vaccination programmes in a 2 + 1 schedule, rapidly achieving a coverage of more than 90%. The effect of the PCV7 introduction on the invasive pneumococcal disease epidemiology in Belgium has previously been described in detail.10 From 2011, PCV13 was used but replaced by PCV10 in July, 2015 (in Flanders), and May, 2016 (in Wallonia).
Research in context
Evidence before this study
We searched PubMed for articles in English on invasive pneumococcal disease using the terms “pneumococcal conjugate vaccine”, “impact”, “pneumococcal disease”, or “serotype replacement”. We searched for population-based studies published between Jan 1, 2000, and Sept 1, 2019, that studied the effect of both ten-valent and 13-valent pneumococcal conjugate vaccine (PCV) on serotype distribution and incidence. These vaccines are used worldwide and have shown substantial benefit in reducing the Streptococcus pneumoniae paediatric burden, especially by decreasing the incidence of invasive pneumococcal disease related to vaccine serotypes. For each country, the choice of using PCV10 or PCV13 depends on the targeted infections (invasive or non-invasive) and the expected effect on the S pneumoniae burden. In addition to immunogenicity studies, prediction of vaccine effects is based on careful assessment and follow-up of local S pneumoniae epidemiology and on experiences from other countries. The current literature mainly describes results from implementing a single PCV, but apart from one published study comparing the use of PCV13 and PCV10 among Swedish counties, there is no report of long-term follow-up after consecutive use of both PCV13 and PCV10 on a national scale.
Added value of this study
Our study describes the evolution of paediatric invasive pneumococcal disease epidemiology with the sequential use of the three conjugate vaccines PCV7, PCV13, and PCV10 in Belgium from 2007 to 2018. The significant decrease in paediatric invasive pneumococcal disease incidence that was observed during the PCV13 period was followed by an increase during the PCV10 period. This rise in invasive pneumococcal disease cases was significant already 2 years after the vaccine switch and mainly due to serotype 19A. Moreover, we observed a high genetic diversity among the serotype 19A circulating clones involved in invasive pneumococcal disease during the PCV10 period.
Implications of all the available evidence
This Article delivers the real word experience of a country with high vaccine coverage that switched from a higher-valent pneumococcal vaccine (PCV13) to a lower-valent pneumococcal vaccine (PCV10), and underlines the importance of a long-term follow-up of S pneumoniae dynamics to assess vaccine effects. This observation is important because it could guide policy makers when introducing either PCV13 or PCV10 in childhood vaccination programmes, while each country's own epidemiology and expectations also needs to be taken into account.
In general, in addition to financial requirements, the choice between vaccines depends on objectives (decrease of invasive or noninvasive diseases, such as acute otitis media), targeted groups (eg, children, older adults) and local epidemiology. Moreover, decision making is complicated by uncertainties about serotype cross-protection, serotype replacement phenomenon, interaction with other bacteria in the nasopharynx, and indirect effects.11 The switch from PCV13 to PCV10 in Belgium was decided following the equally effective rating of PCV10 and PCV13 published by the Belgian Superior Health Council in 2015.12
Thanks to the Belgian national prospective surveillance network, the epidemiology of invasive pneumococcal disease is monitored closely. Passive laboratory surveillance has been done for more than 20 years at the National Reference Centre for Streptococcus pneumoniae (NRC). A mean of 1632 invasive pneumococcal disease strains from 95 laboratories are sent yearly (appendix 3 p 2), making the surveillance representative for the roughly 11 million inhabitants. Based on the surveillance, changes in the incidence of paediatric invasive pneumococcal disease and serotype distribution were already observed in 2017, and it has been hypothesised that these changes resulted from the switch in vaccine schedule.13 The aim of the present study was to deeply assess the Belgian epidemiology of paediatric invasive pneumococcal disease before and after the switch in PCV. The vaccine coverage of more than 93% (2 + 1 schedule) and the easy access to health-care systems in Belgium provide an interesting model to examine the epidemiology of invasive pneumococcal disease.14, 15