Streptococcus pneumoniae in conjugate vaccine period: epidemiology and molecular characterization

Vaccination of young children with pneumococcal conjugate vaccines is an important
tool to decrease the burden of pneumococcal disease.
In the first chapter we investigated the evolution of invasive pneumococcal disease
in Belgium during the sequential use of different pneumococcal conjugate vaccines
(2007-2018) with a focus on the period aft er the switch from PCV13 to PCV10 (2016-
2018). During the study period, a stable IPD surveillance and stable high vaccinati on
coverage in Belgium was observed. Aft er a signifi cant decrease during the PCV13
period, paediatric invasive pneumococcal disease incidence increased again during
the PCV10 period. This observation resulted mainly from a fast resurgence of PCV13-
only serotype invasive pneumococcal disease, which was mainly related to serotype
19A, which became predominant in paediatric IPD. These observations together with
recent reports regarding the long-term impact of PCV10 on IPD suggest that thecross-protecti on of PCV10 against serotype 19A based on immunogenicity studies
and short-term studies, may not be as effectivee as PCV13 in preventing serotype 19A
IPD. The increase in IPD incidence due to an increase in serotype 19A IPD, a serotype
included in PCV13 but not in PCV10, resulted in the decision to switch back from
PCV10 to PCV13 in the Belgian childhood vaccinati on programmes in 2019.
In the second chapter we investigated the carriage of S. pneumoniae on the nasopharynx
of children attending day-care centres during and after the switch from PCV13
to PCV10 (2016-2018). While the carriage rate of pneumococci in the nasopharynx
of children attending day-care centres in Belgium was high and stable, a significantchange in the proportion of PCV13 only serotypes was detected during the 3-year
follow-up period. The increase in the proportion of serotype 19A in carriage was concurrent
with the increase seen in IPD in children with the same age during the period
post PCV13 to PCV10 switch. These concurrent evolutions of serotype 19A in IPD
and carriage in the same age group are probably a result of the high invasive diseasepotenti al of serotype 19A. In contrast to the increase of serotype 19A aft er the vaccine
switch, the rate of the other two PCV13-non-PCV10 serotypes, i.e. serotype 3 and 6A,
remained low and stable both in carriage and IPD in children.
Based on the parallel design of the IPD surveillance and the carriage study, we
explored the relation between S. pneumoniae strains that were carried by young
children attending day care centres and S. pneumoniae strains that caused IPD in
children during and aft er the PCV13-to-PCV10 switch (2015-2018). Different serotypes
dominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). We
observed that the most invasive serotypes (12F, 1, 3, 24A/B/F, 33F, 19A, and 9N) were
not frequently carried. On the other hand, the predominant serotypes in carriage only
infrequently caused IPD, which is mainly in accordance with observations from other studies. Only some of the serotypes with high invasive disease potenti al (serotype 1,
3, 19A) in Belgium are included in PCV10 and/or PCV13, which underscores the need
and the potential of new higher valent PCVs.
Both in IPD and carriage an increase in serotype 19A post PCV13 to PCV10 switch
was observed. We developed a whole-genome sequencing protocol to characterize
pneumococci. The sequencing of a total of 166 serotype 19A IPD isolates from
children and older adults, and carriage isolates from healthy children from the
same period after the vaccine switch (2017-2018) revealed presence of 24 diff erent
sequence types. Two sequence types, ST416 and ST994, accounted together for
the majority of serotype 19A strains both in IPD in children and adults and carriage.
These STs differed from the predominant 19A IPD STs in children after introduction
of the 7-valent pneumococcal vaccine in Belgium (ST193 and ST276), which indicates
that prediction of emerging strains cannot be completely based on historical strains
in childhood IPD. While both aft er PCV7 and PCV10 introducti on a rise in serotype
19A was detected, the impact on the micro epidemiology of serotype 19A is different
through the emergence of diff erent clones. Despite their susceptible antibiotic profile,
ST416 and ST994 clones expanded both in carriage and IPD during PCV10 use. Furtherexploration of the characteristics of these strains and comparison of the Belgian strainswith serotype 19A strains from both PCV13 and PCV10 using countries is needed to
better understand the emergence of the predominant clones during the use of PCV10
in Belgium.
Our study delivers important informati on for policy makers and underscores the
importance of good surveillance systems to closely follow-up the potential impact
of changes in vaccination strategy. Deep characterization of pneumococci can help
to better understand changes in epidemiology. A better understanding of the emergenceof specific pneumococcal clones is needed to be able to better forecast serotype
replacement associated with changes in vaccination programmes and its impact
on pneumococcal disease and carriage.