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Streptococcus pneumoniae in conjugate vaccine period: epidemiology and molecular characterization
Boek - Dissertatie
Vaccination of young children with pneumococcal conjugate vaccines is an importanttool to decrease the burden of pneumococcal disease.In the first chapter we investigated the evolution of invasive pneumococcal diseasein 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 oncoverage in Belgium was observed. Aft er a signifi cant decrease during the PCV13period, paediatric invasive pneumococcal disease incidence increased again duringthe PCV10 period. This observation resulted mainly from a fast resurgence of PCV13-only serotype invasive pneumococcal disease, which was mainly related to serotype19A, which became predominant in paediatric IPD. These observations together withrecent reports regarding the long-term impact of PCV10 on IPD suggest that the
cross-protecti on of PCV10 against serotype 19A based on immunogenicity studiesand short-term studies, may not be as effectivee as PCV13 in preventing serotype 19AIPD. The increase in IPD incidence due to an increase in serotype 19A IPD, a serotypeincluded in PCV13 but not in PCV10, resulted in the decision to switch back fromPCV10 to PCV13 in the Belgian childhood vaccinati on programmes in 2019.In the second chapter we investigated the carriage of S. pneumoniae on the nasopharynxof children attending day-care centres during and after the switch from PCV13to PCV10 (2016-2018). While the carriage rate of pneumococci in the nasopharynxof children attending day-care centres in Belgium was high and stable, a significant
change in the proportion of PCV13 only serotypes was detected during the 3-yearfollow-up period. The increase in the proportion of serotype 19A in carriage was concurrentwith the increase seen in IPD in children with the same age during the periodpost PCV13 to PCV10 switch. These concurrent evolutions of serotype 19A in IPDand carriage in the same age group are probably a result of the high invasive disease
potenti al of serotype 19A. In contrast to the increase of serotype 19A aft er the vaccineswitch, 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, weexplored the relation between S. pneumoniae strains that were carried by youngchildren attending day care centres and S. pneumoniae strains that caused IPD inchildren during and aft er the PCV13-to-PCV10 switch (2015-2018). Different serotypesdominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). Weobserved that the most invasive serotypes (12F, 1, 3, 24A/B/F, 33F, 19A, and 9N) werenot frequently carried. On the other hand, the predominant serotypes in carriage onlyinfrequently 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 needand the potential of new higher valent PCVs.Both in IPD and carriage an increase in serotype 19A post PCV13 to PCV10 switchwas observed. We developed a whole-genome sequencing protocol to characterizepneumococci. The sequencing of a total of 166 serotype 19A IPD isolates fromchildren and older adults, and carriage isolates from healthy children from thesame period after the vaccine switch (2017-2018) revealed presence of 24 diff erentsequence types. Two sequence types, ST416 and ST994, accounted together forthe 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 introductionof the 7-valent pneumococcal vaccine in Belgium (ST193 and ST276), which indicatesthat prediction of emerging strains cannot be completely based on historical strainsin childhood IPD. While both aft er PCV7 and PCV10 introducti on a rise in serotype19A was detected, the impact on the micro epidemiology of serotype 19A is differentthrough the emergence of diff erent clones. Despite their susceptible antibiotic profile,ST416 and ST994 clones expanded both in carriage and IPD during PCV10 use. Further
exploration of the characteristics of these strains and comparison of the Belgian strains
with serotype 19A strains from both PCV13 and PCV10 using countries is needed tobetter understand the emergence of the predominant clones during the use of PCV10in Belgium.Our study delivers important informati on for policy makers and underscores theimportance of good surveillance systems to closely follow-up the potential impactof changes in vaccination strategy. Deep characterization of pneumococci can helpto better understand changes in epidemiology. A better understanding of the emergence
of specific pneumococcal clones is needed to be able to better forecast serotypereplacement associated with changes in vaccination programmes and its impacton pneumococcal disease and carriage.
cross-protecti on of PCV10 against serotype 19A based on immunogenicity studiesand short-term studies, may not be as effectivee as PCV13 in preventing serotype 19AIPD. The increase in IPD incidence due to an increase in serotype 19A IPD, a serotypeincluded in PCV13 but not in PCV10, resulted in the decision to switch back fromPCV10 to PCV13 in the Belgian childhood vaccinati on programmes in 2019.In the second chapter we investigated the carriage of S. pneumoniae on the nasopharynxof children attending day-care centres during and after the switch from PCV13to PCV10 (2016-2018). While the carriage rate of pneumococci in the nasopharynxof children attending day-care centres in Belgium was high and stable, a significant
change in the proportion of PCV13 only serotypes was detected during the 3-yearfollow-up period. The increase in the proportion of serotype 19A in carriage was concurrentwith the increase seen in IPD in children with the same age during the periodpost PCV13 to PCV10 switch. These concurrent evolutions of serotype 19A in IPDand carriage in the same age group are probably a result of the high invasive disease
potenti al of serotype 19A. In contrast to the increase of serotype 19A aft er the vaccineswitch, 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, weexplored the relation between S. pneumoniae strains that were carried by youngchildren attending day care centres and S. pneumoniae strains that caused IPD inchildren during and aft er the PCV13-to-PCV10 switch (2015-2018). Different serotypesdominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). Weobserved that the most invasive serotypes (12F, 1, 3, 24A/B/F, 33F, 19A, and 9N) werenot frequently carried. On the other hand, the predominant serotypes in carriage onlyinfrequently 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 needand the potential of new higher valent PCVs.Both in IPD and carriage an increase in serotype 19A post PCV13 to PCV10 switchwas observed. We developed a whole-genome sequencing protocol to characterizepneumococci. The sequencing of a total of 166 serotype 19A IPD isolates fromchildren and older adults, and carriage isolates from healthy children from thesame period after the vaccine switch (2017-2018) revealed presence of 24 diff erentsequence types. Two sequence types, ST416 and ST994, accounted together forthe 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 introductionof the 7-valent pneumococcal vaccine in Belgium (ST193 and ST276), which indicatesthat prediction of emerging strains cannot be completely based on historical strainsin childhood IPD. While both aft er PCV7 and PCV10 introducti on a rise in serotype19A was detected, the impact on the micro epidemiology of serotype 19A is differentthrough the emergence of diff erent clones. Despite their susceptible antibiotic profile,ST416 and ST994 clones expanded both in carriage and IPD during PCV10 use. Further
exploration of the characteristics of these strains and comparison of the Belgian strains
with serotype 19A strains from both PCV13 and PCV10 using countries is needed tobetter understand the emergence of the predominant clones during the use of PCV10in Belgium.Our study delivers important informati on for policy makers and underscores theimportance of good surveillance systems to closely follow-up the potential impactof changes in vaccination strategy. Deep characterization of pneumococci can helpto better understand changes in epidemiology. A better understanding of the emergence
of specific pneumococcal clones is needed to be able to better forecast serotypereplacement associated with changes in vaccination programmes and its impacton pneumococcal disease and carriage.
Jaar van publicatie:2022
Toegankelijkheid:Closed