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Increase of serotypes 15A and 23B in IPD in Germany in the PCV13 vaccination era
Mark van der Linden1, Stephanie Perniciaro2, Matthias Imöhl3
1Institute for Medical Microbiology, German National Reference Center for Streptococci, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. mlinden@ukaachen.de.
Insights
Invasive pneumococcal disease (IPD) caused by non-vaccine serotypes 15A and 23B has significantly increased in Germany following childhood pneumococcal conjugate vaccination. These serotypes exhibit high penicillin non-susceptibility.
Area of Science:
- Microbiology
- Epidemiology
- Vaccinology
Background:
- Analysis of invasive pneumococcal disease (IPD) isolates in Germany before and after the introduction of pneumococcal conjugate vaccines (PCVs).
- Focus on serogroups 15 and 23 isolates, examining trends following PCV7, PCV10, and PCV13 vaccine introductions.
- Surveillance data spans from July 1992 to June 2014, encompassing pre- and post-vaccination periods.
Purpose of the Study:
- To analyze the impact of childhood pneumococcal conjugate vaccination on the prevalence of specific Streptococcus pneumoniae serotypes in invasive pneumococcal disease (IPD).
- To identify shifts in serotype distribution and assess antibiotic susceptibility patterns, particularly for non-PCV13 serotypes.
- To evaluate the emergence and characteristics of serotypes 15A and 23B in the context of vaccination programs.
Main Methods:
- Utilized data from the German National Reference Center for Streptococci (GNRCS) surveillance of IPD isolates (n=23,957) from 1992 to 2014.
- Serotyped isolates and performed antibiotic susceptibility testing.
- Employed multilocus sequence typing (MLST) for molecular characterization of selected isolates.
Main Results:
- A significant increase in non-PCV13 serotypes was observed in the late PCV13 vaccination period (2010-2014).
- Serotypes 15A and 23B showed the most significant increases, rising from 0.5% to 2.4% and 2.8% respectively.
- High penicillin non-susceptibility rates were noted for serotype 15A (47.4%) and 23B (46.5%).
- MLST analysis revealed specific clonal complexes associated with serotype 23B (CC439, CC338) and serotype 15A (CC63).
Conclusions:
- The prevalence of non-PCV13 serotypes, particularly 15A and 23B, has significantly increased in Germany post-vaccination introduction.
- These emerging serotypes demonstrate substantial penicillin non-susceptibility, posing a potential public health challenge.
- Continued surveillance and characterization of IPD pathogens are crucial for monitoring vaccine effectiveness and guiding antimicrobial strategies.
Background:
This study presents an analysis of 1,491 serogroup 23 and 762 serogroup 15 isolates from invasive pneumococcal disease (IPD) in children and adults before and after the general recommendation for childhood pneumococcal conjugate vaccination in Germany in July 2006. Vaccination formulations used were PCV7 (from July 2006), PCV10 (from April 2009) and PCV13 (from December 2009, replacing PCV7).
Methods:
The German National Reference Center for Streptococci (GNRCS) has conducted surveillance of IPD since 1992. Isolates were serotyped and tested for antibiotic susceptibility. Selected isolates were characterized using MLST.
Results:
In an analysis of 23,957 isolates from IPD in children and adults sent to the GNRCS between July 1992 and June 2014, we found a strongly significant increase of non-PCV13 serotypes in the late vaccination (PCV13) period (2010-2014). Among these, the proportions of serotypes 15A and 23B were the most strongly significantly increasing. After the recommendation for pneumococcal conjugate childhood vaccination in 2006 and the introduction of higher-valent vaccines in 2009, the proportion of 15A increased significantly from 0.5% in the early vaccination period (2007-2010) to 2.4% in the late vaccination period (2010-2014, p=3.14 x 10(-22)). The proportion of serotype 23B increased from 0.5% to 2.8% in the same period (p=1.55 x 10(-29)). Penicillin non-susceptibility levels of the serotype 15A (47.4%) and serotype 23B (46.5%) isolates were high, with MIC values ranging from 0.12-2 μg/ml (15A) and 0.12-0.5 μg/ml (23B). MLSTs of serotype 23B isolates grouped in two clonal complexes (CC): CC439, with sequence type (ST) 439 as the main representative and CC338 (linked to CC156), with ST1349 as most prevalent clone. Both CCs have been present over almost the whole surveillance period. All penicillin non-susceptible isolates occurred in CC338. Serotype 15A isolates appeared to be more diverse. Six CCs, one group of three STs and two singletons were found among 20 isolates. Most prevalent was CC63, with ST63 as most prominent representative (n=5). Most penicillin non-susceptible isolates were found among CC63 isolates.
Conclusions:
The prevalence of non-PCV13 serotypes in Germany has increased significantly between July 2007 and June 2014, with 15A and 23B being the most strongly increasing serotypes of all. Both serotypes show a high proportion of penicillin non-susceptibility.
