Elsevier

Vaccine

Volume 37, Issue 43, 8 October 2019, Pages 6558-6565
Vaccine

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease

https://doi.org/10.1016/j.vaccine.2019.08.025Get rights and content

Abstract

Introduction

In 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes.

Methods

Pneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype.

Results

Compared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016–2018 in children <5 years (69%), 18–49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016–2018 declined in children <5 years (RR:0.68, 95%CI:0.42–1.11), 5–17 year olds (RR:0.58, 95%CI:0.29–1.14) and 18–49 year olds (RR:0.72, 95%CI:0.57–0.90), but not in 50–64 year olds (RR:0.94, 95%CI:0.81–1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93–1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70–0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96–1.36).

Conclusion

Twelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes.

Introduction

Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality worldwide [1], [2]. IPD is defined as an infection of a normally sterile body fluid, typically blood or cerebrospinal fluid (CSF), by the gram-positive bacterium Streptococcus pneumoniae, with clinical syndromes including septicaemia, invasive pneumonia or meningitis.

Currently available vaccines are the 10- and 13-valent pneumococcal conjugate vaccines (PCV) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). As of September 2018, 145 countries worldwide have implemented PCV in their national immunisation programme for infants [3], [4]. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006, and was replaced by PCV10 in 2011. PCV coverage in children at age 2 years has been 93–95% since the introduction of PCV7 [5]. Up to 2018, PPV23 has been recommended only for those at high risk for IPD, and PPV23 use has been very low in the Netherlands (<0.5% of persons ≥65 years in 2017) [6], [7].

Four years after the introduction of PCV7, the overall IPD incidence in Dutch children under two years had decreased by 57% and, due to indirect protection, by 22% in adults ≥65 years [8]. Three years after the switch to PCV10, a further reduction in IPD incidence of 30% was observed in children under 2 years. In adults ≥65 years, a decline in IPD caused by the additional PCV10 serotypes 1, 5 and 7F of 25% was observed, but the overall IPD incidence plateaued; this was attributed to a steady rise of non-PCV10 serotypes [8], [9]. In England and Wales, replacement disease from non-PCV13 serotypes, in particular serotypes 8, 12F and 9N, has progressively eroded the IPD reduction in older adults; in 2016–2017 almost no net benefit was observed from the PCV7 to PCV13 switch [10].

The aim of the current study was to describe the overall impact since PCV7 introduction in 2006, and in particular the impact of the switch from PCV7 to PCV10 in 2011 on IPD incidence, clinical syndromes and patient outcomes in the Netherlands.

Section snippets

Study population and data collection

Since 2004, national IPD surveillance in the Netherlands is based on data from nine sentinel clinical microbiological laboratories which submit pneumococcal isolates to the Netherlands Reference Laboratory for Bacterial Meningitis for serotyping by agglutination and subtyping by the Quellung method [11]. IPD was defined as identification of S. pneumoniae isolated from the patient’s blood or CSF. The sentinel laboratories cover ∼25% of the Dutch population and coverage has not changed since 2004

IPD incidence (June 2004 to May 2018)

A total of 8865 IPD patients were identified between June 2004 and May 2018. Compared with the pre-PCV period, the overall incidence of IPD in 2016–2018 across all age groups had not declined significantly (RR: 0.94, 95%CI: 0.87–1.02) (Table 1, Fig. 1). There was, however, a statistically significant decline in IPD incidence in children <5 years (69%), in 18–49 year olds (31%) and in persons ≥65 years (19%). After the switch from PCV7 to PCV10, a continuous decline in overall IPD incidence was

Discussion

Since the introduction of PCV in the Dutch national immunisation programme in 2006, the incidence of IPD has declined, particularly among children under 5 years, with 69% reduction, and adults ≥65 years and older, with 19%. After the switch to PCV10 in 2011, a further 30% reduction in overall IPD was observed in those under 50 years of age, but no reduction was seen in those aged 50–64 years and ≥65 years. In these older age groups, the ongoing decline in vaccine serotypes was countered by the

Conclusions

Although we still observe a net benefit of introduction of PCV on IPD incidence in children and elderly, and on the CFR of IPD in the Netherlands, IPD incidence could rebound in the near future as vaccines have nearly reached their maximum effect, serotype replacement is ongoing, and the population is aging. New vaccines, either with broader serotype coverage or focused on the pneumococcus as a whole, might be needed to reduce the burden of IPD in the future. Ongoing monitoring of IPD serotype

CRediT authorship contribution statement

Stefan M.T. Vestjens: Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing - original draft. Elisabeth A.M. Sanders: Conceptualization, Formal analysis, Funding acquisition, Investigation, Writing - review & editing. Bart J. Vlaminckx: Conceptualization, Writing - review & editing. Hester E. de Melker: Conceptualization, Writing - review & editing. Arie van der Ende: Conceptualization, data curation, Project administration, Resources, Writing - review &

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

EAMS has received grant support from Pfizer and GlaxoSmithKline for research on vaccine studies (fees paid to University Medical Center Utrecht before 2015). AE has received a grant from Pfizer for research on pneumococcal infections (Investigator Initiated project: “Epidemiology of invasive pneumococcal disease” IIR WI173197) and participated in Advisory Boards

Acknowledgements

We thank all participating hospitals and sentinel laboratories for their cooperation. We thank the medical students who collected data from the health records.

Funding

This work was supported by the European Centre for Disease Prevention and Control (SpIDnet project) and the European Comission (Horizon 2020, I-MOVE+).

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