Invasive Disease Potential of Pneumococcal Serotypes in Children After PCV13 Implementation.

We aimed to assess the invasive disease potential of non-PCV13 serotypes after the implementation of this vaccine. Most non-PCV13 serotypes had low invasive disease potential. Among serotypes with the highest invasive disease potential (12F, 24F, 38, 8, 33F, 22F, and 10A), all but 24F and 38 were included in PCV20.

Intraclonal variations among Streptococcus pneumoniae isolates influence the likelihood of invasive disease in children.

BACKGROUND: Pneumococcal serotypes are represented by a varying number of clonal lineages with different genetic contents, potentially affecting invasiveness. However, genetic variation within the same genetic lineage may be larger than anticipated. METHODS: A total of 715 invasive and carriage isolates from children in the same region and during the same period were compared using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. Bacterial genome sequencing, functional assays, and in vivo virulence mice studies were performed. RESULTS: Clonal types of the same serotype but also intraclonal variants within clonal complexes (CCs) showed differences in invasive-disease potential. CC138, a common CC, was divided into several PFGE patterns, partly explained by number, location, and type of temperate bacteriophages. Whole-genome sequencing of 4 CC138 isolates representing PFGE clones with different invasive-disease potentials revealed intraclonal sequence variations of the virulence-associated proteins pneumococcal surface protein A (PspA) and pneumococcal choline-binding protein C (PspC). A carrier isolate lacking PcpA exhibited decreased virulence in mice, and there was a differential binding of human factor H, depending on invasiveness. CONCLUSIONS: Pneumococcal clonal types but also intraclonal variants exhibited different invasive-disease potentials in children. Intraclonal variants, reflecting different prophage contents, showed differences in major surface antigens. This suggests ongoing immune selection, such as that due to PspC-mediated complement resistance through varied human factor H binding, that may affect invasiveness in children.

Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area, southern Mozambique.

BACKGROUND: Invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4 months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction. METHODS: We used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged <5 years in Manhiҫa, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI > 1 indicated high invasive disease potential and OR and 95% CI < 1 indicated low invasive disease potential. RESULTS: In the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5]). CONCLUSION: The number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period.

The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: A systematic review and meta-analysis.

OBJECTIVES: Burden of pneumococcal disease depends on the prevalence and invasive disease potential of serotypes. We aimed to estimate the invasive disease potential of serotypes in children under 5 years of age by combining data from different settings with routine immunisation with pneumococcal conjugate vaccines (PCV). METHODS: We conducted a systematic review, supplemented by unpublished data, to identify data on the frequency of pneumococcal serotypes in carriage and invasive pneumococcal disease (IPD). We estimated the invasive disease potential of serotypes as the ratio of IPD in relation to carriage (odds ratio and 95%CI) compared with 19A (reference serotype) by meta-analysis. We report results based on a random effects model for children aged 0-23, 24-29, and 0-59 months and by invasive clinical syndromes. RESULTS: In comparison with 19A, serotypes 1, 7F, and 12F had a significantly higher invasive disease potential in children aged 0-23 and 0-59 months for all IPD and clinical syndromes (OR > 5). Several non-vaccine types (NVTs) (6C, 15A, 15BC, 16F, 23B, in these two age groups) had a lower invasive disease potential than 19A (OR 0.1-0.3). NVTs 8, 12F, 24F, and 33F were at the upper end of the invasiveness spectrum. CONCLUSIONS: There is substantial variation among pneumococcal serotypes in their potential to cause IPD and disease presentation, which is influenced by age and time after PCV introduction. Surveillance of IPD and carriage is critical to understand the expected effectiveness of current PCVs (in the longer term) and guide the development of future vaccines.

Surveillance of pneumococcal colonization and invasive pneumococcal disease reveals shift in prevalent carriage serotypes in Massachusetts' children to relatively low invasiveness.

BACKGROUND: Following the introduction of pneumococcal conjugate vaccines (PCV), overall nasopharyngeal colonization rates have not changed significantly, however a dramatic and sustained decline in invasive pneumococcal disease (IPD) in children was observed in every setting where the PCVs were implemented. We aimed to describe the differences in invasive disease potential of serotypes that are common colonizers in pre- and post-vaccine eras in order to provide further insight in our understanding of dynamic epidemiology of pneumococcal diseases. METHODS: Using data from surveillance of nasopharyngeal carriage and enhanced surveillance for IPD, a serotype specific "invasive capacity (IC)" was computed by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children <7years of age in Massachusetts. We have evaluated the serotype specific invasive capacity in two periods; pre-PCV13 (2001/02, 2003/04, 2006/07, 2008/09) and post-PCV13 (2010/11 and 2013/14), and by age groups; <24monthsvs. ≥24months. RESULTS: An approximate 50-fold variation in the point estimate was observed between the serotypes having the highest (7F, 38, 19A, 3, 33F) and the lowest (6C, 35B, 21, 11A, 23B and 23A) computed serotype specific invasive disease potential. In the post-PCV13 era (6C, 35B, 11A, 23B and 23A), 5 of the 7 most common serotypes colonizing the nasopharynx were serotypes with the lowest invasive capacity. Serotype specific invasive capacity trended down in older children for majority of the serotypes, and serotypes 3, 10A and 19A had significantly lower invasive capacity in children older than 24months of age compared to younger children. CONCLUSION: Invasive capacity differs among serotypes and likely by age. Point estimates of IC for most of the common serotypes colonizing children in Massachusetts in post-PCV13 era were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes.

Invasive disease potential of pneumococci before and after the 13-valent pneumococcal conjugate vaccine implementation in children.

BACKGROUND: Changes in serotype distribution have been induced after pneumococcal conjugate vaccines (PCV) implementation, and non-vaccine serotypes are now circulating. Among these latter serotypes, we aimed to distinguish those with high invasive disease potential before (2008-2009) and after PCV13 implementation (2012-2013). METHODS: Invasive pneumococcal disease (IPD) serotypes isolated from children 6 to 24 months were compared with nasopharyngeal-colonizing serotypes in healthy children. To assess the invasive potential of a given serotype, odds ratios (ORs) were calculated. For each serotype, OR >1 indicated increased probability of association with IPD and OR <1 decreased probability. RESULTS: In 2008/2009 and 2012/2013, 355 pneumococci were isolated from 1212 healthy children and from 569 IPD, including 166 meningitis, 114 pneumonia, and 289 other IPDs. In period 1, serotypes 7F, 3, 1, 24F, and 19A showed highly significant invasive disease potential whereas in period 2, only serotype 24F was associated with a significant high OR (6.6 [95% CI 2.6; 16.2]). Of note, for serotype 12F, OR could not be calculated because of no carrier recorded, however, if there had been a single 12F carrier, the OR would be among the highest, in period 2, 15.7 [95% 3.4; 73.0]). Only two serotypes appeared negatively associated with IPD, 11A and 23B in the period 2 as compared with nine in period 1. In the second period, pneumococcal penicillin non-susceptible isolates were mostly represented by serotypes 19A, 15A, 19F, 35B and 24F both in carriers and IPD. Only one strain was resistant to penicillin with MIC=4 µg/ml (serotype 19A) during the first period. CONCLUSION: In children <2 years old, compared to the previous period, the number of serotypes having a high disease potential decreased after PCV13 implementation, only two non-vaccine serotypes, 24F and 12F, had high invasive disease potential.