Ten-valent and 13-valent pneumococcal conjugate vaccines (PCVs) have shown important benefits by decreasing invasive pneumococcal disease caused by vaccine serotypes. Belgium had an uncommon situation with sequential use of PCV7, PCV13, and PCV10 in the childhood vaccination programmes between 2007 and 2018. We aimed to analyse the changes in incidence of invasive pneumococcal disease and serotype distribution in children throughout this period.
Streptococcus pneumoniae isolates were obtained from patients with invasive pneumococcal disease in Belgium between 2007 and 2018 by the national laboratory-based surveillance. Paediatric invasive pneumococcal disease incidence, serotype distribution, and antimicrobial susceptibility were analysed in periods during which PCV7 (2009-10), PCV13 (2013-14), both PCV13 and PCV10 (2015-16), and PCV10 (2017-18) were used. Incidence rates and trends were compared. Vaccination status was collected. For a subset of serotype 19A isolates, multilocus sequence type was identified.
After a decrease in PCV7 serotype invasive pneumococcal disease was observed during the PCV7 period, total paediatric invasive pneumococcal disease incidence significantly declined during the PCV13 period (-2·6% monthly, p<0·0001). During the PCV13-PCV10 period (2015-16), the lowest mean in paediatric invasive pneumococcal disease incidence was achieved, but the incidence increased again during the PCV10 period (2017-18), especially in children younger than 2 years (+1·7% monthly; p=0·028). This increase was mainly due to a significant rise in serotype 19A invasive pneumococcal disease incidence in the PCV10 period compared with the PCV13 period (p<0·0001), making serotype 19A the predominant serotype in paediatric invasive pneumococcal disease in the PCV10 period. Genetic diversity within the 2017-18 serotype 19A collection was seen, with two predominant clones, ST416 and ST994, that were infrequently observed before PCV10 introduction. In 2018, among children younger than 5 years with invasive pneumococcal disease who were correctly vaccinated, 37% (37 of 100) had PCV13 serotype invasive pneumococcal disease, all caused by serotype 19A and serotype 3.
After a significant decrease during the PCV13 period, paediatric invasive pneumococcal disease incidence increased again during the PCV10 period. This observation mainly resulted from a significant increase of serotype 19A cases. During the PCV10 period, dominant serotype 19A clones differed from those detected during previous vaccine periods. Whether changes in epidemiology resulted from the vaccine switch or also from natural evolution remains to be further elucidated.
The Belgian National Reference is funded by the Belgian National Institute for Health and Disability Insurance and the whole genome sequencing by an investigator-initiated research grant from Pfizer.

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