Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 18, Number 11—November 2012

Invasive Pneumococcal Disease and 7-Valent Pneumococcal Conjugate Vaccine, the Netherlands

Anna M.M. van Deursen1, Suzan P. van Mens1, Elisabeth A.M. Sanders, Bart J.M. Vlaminckx, Hester E. de Melker, Leo M. Schouls, Sabine C. de Greeff2, Arie van der Ende2Comments to Author , on behalf of the Invasive Pneumococcal Disease Sentinel Surveillance Laboratory Group
Author affiliations: University Medical Center, Utrecht, the Netherlands (A.M.M. van Deursen, S.P. van Mens, E.A.M. Sanders); Linnaeus Institute, Hoofddorp, the Netherlands (A.M.M. van Deursen); St Antonius Hospital, Nieuwegein, the Netherlands (S.P. van Mens, B.J.M. Vlaminckx); National Institute for Public Health and the Environment, Bilthoven, the Netherlands (H.E. de Melker, L.M. Schouls, S.C. de Greeff); Academic Medical Center, Amsterdam, the Netherlands (A. van der Ende); Netherlands Reference Laboratory for Bacterial Meningitis, Amsterdam (A. van der Ende)

Cite This Article


CME Logo

Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit.

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians.

Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at; (4) view/print certificate.

Release date: October 19, 2012; Expiration date: October 19, 2013

Learning Objectives

Upon completion of this activity, participants will be able to:

•     Analyze previous research into the effects of 7-valent pneumococcal conjugate vaccine (PCV7)

•     Compare the effects of PCV7 on different continents

•     Distinguish age groups most affected by PCV7

•     Evaluate the clinical presentation and outcomes of IPD after introduction of PCV7.

CME Editor

Claudia Chesley, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: Claudia Chesley has disclosed no relevant financial relationships.

CME Author

Charles P. Vega, MD, Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.


Disclosures: Anna M.M. van Deursen; Suzan P. van Mens, MD; Bart J.M. Vlaminckx, MD, PhD; Hester E. de Melker; Leo M. Schouls; and Sabine C. de Greeff, MSc, have disclosed no relevant financial relationships. Elisabeth A.M. Sanders, MD, PhD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Pfizer, GSK; received grants for clinical research from Pfizer, GSK. Arie van der Ende, PhD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Pfizer, GSK; received grants for clinical research from Pfizer, GSK.



In the Netherlands, the national immunization program includes 7-valent pneumococcal conjugate vaccine (PCV7) for all newborns born after April 1, 2006. We compared the incidence of invasive pneumococcal disease (IPD) and patient and disease characteristics before PCV7 introduction (June 2004–June 2006) with those after PCV7 introduction (June 2008–June 2010). Culture-confirmed IPD cases were identified by 9 sentinel laboratories covering ≈25% of the Dutch population. Significant declines in overall IPD incidence were observed in children <2 (60%) and in persons >65 (13%) years of age. A trend toward gradual increases in non–PCV7 serotype IPD infections was observed in all age groups; the largest increases were among persons 50–64 (37%) and >65 (25%) years of age. In adults, the proportion of immunocompromised persons increased among IPD patients. Overall, deaths from IPD decreased from 16% to 12% because of a lower case-fatality rate for persons with non–PCV7 serotype IPD.

Streptococcus pneumoniae is a major cause of severe invasive infections, such as meningitis, invasive pneumonia, and other bloodstream infections. The highest incidence rates for such infections are for infants and elderly persons (1).

Since 2001, many high-income countries included the 7-valent pneumococcal conjugate vaccine (PCV7; Prevenar; Pfizer Pharmaceuticals, Pearl River, NY, USA) in their national immunization programs for newborns (2). In general, within a few years after the introduction of PCV7, the age group targeted for vaccination and unvaccinated adults showed a dramatic decrease in invasive pneumococcal disease (IPD) caused by the 7 vaccine serotypes (25). However, at the same time, the incidence of non-PCV7 serotype IPD increased (3,4,6,7).

The overall benefit of PCV7 varies by country, perhaps as a result of differences in surveillance methods and the maturity of vaccination programs (8). For all age groups, the overall reduction in IPD incidence is greater in the United States than in European countries; the great reduction in the United States is a result of a decrease in PCV7-serotype IPD in adults and less replacement of PCV7-serotype by non–PCV7 serotype IPD in children and older adults (3,4,7). The United States began using PCV7 in 2000, but many European countries did not begin using the vaccine until after 2005–2006, and they have experienced less protection from indirect herd protection (herd immunity). Furthermore, not all European countries implemented a catch-up program for children <5 years of age; catch-up programs speed up eradication of vaccine serotypes. Geographic variations in circulation of PCV7 serotypes before the implementation of routine vaccination also caused differences in the relative proportion of IPD covered by the vaccine (7,8).

In addition, the benefits of vaccination with PCV7 may have been biased, for example, by changes in the directive for blood culture after 2000, as in the United States (9,10), and by enhanced surveillance, as reported for England and Wales (4). Unlike studies in the United States, studies in Europe, particularly Dutch surveillance studies, have focused almost exclusively on patients requiring hospitalization for severe IPD and who often had other underlying illnesses (11,12). This difference in reporting leads to different baseline incidence rates and may affect the observed net benefit of vaccination (13). For example, compared with healthy persons of the same age, US adults with comorbid conditions benefited less from the indirect effects of PCV7 because of an increase in non–PCV7 serotype IPD after introduction of the vaccine (14). Differences in the directive for blood culture and patient populations under surveillance can partly explain the differences in results from use of PCV7.

The invasive disease potential of S. pneumoniae and the population at risk for IPD differs by serotype (12,13,15). Therefore, shifts in circulating serotypes may change the clinical manifestations of IPD, the population segment most at risk for infection, and the disease course and outcome. We investigated these issues and changes in IPD incidence in the Netherlands 4 years after a PCV7 vaccine program was implemented and compared our findings with those from the years just before introduction of the vaccine.


Pneumococcal Vaccination in the Netherlands

PCV7 was introduced into the Dutch national immunization program in June 2006 and was recommended for children born after April 1, 2006, at 2, 3, 4, and 11 months of age (16). Vaccination uptake is 94%–95% among Dutch infants (17). Use of the 23-valent pneumococcal polysaccharide vaccine is restricted to persons at high-risk for IPD (e.g., persons with asplenia or Hodgkin lymphoma); uptake in elderly persons is negligible (<1%) (18).

Surveillance Data

For this study, we registered all persons with a diagnosis of culture-confirmed IPD during June 1, 2008–May 31, 2010 (late post-implementation period) and all case-patients from previous Dutch IPD surveillance studies during June 1, 2004–May 31, 2006 (pre-implementation period) (1) and June 1, 2006–May 31, 2008 (post-implementation period) (11). All study procedures were the same as those used in the previous studies (11).

Nine sentinel laboratories identified IPD case-patients, which were defined as patients for whom S. pneumoniae was isolated from blood or cerebrospinal fluid (CSF) samples. The laboratories submitted all invasive pneumococcal isolates to the Netherlands Reference Laboratory for Bacterial Meningitis (NRLBM, Academic Medical Center, Amsterdam, the Netherlands) for typing and characterization. We selected the laboratories on the basis of their geographic distribution throughout the country and their reliability for submitting isolates (1,11). The laboratories were estimated to cover a representative cohort of ≈25% of the Dutch population (≈4.1 million inhabitants, including ≈0.6 million adults >65 years of age). In addition, ≈25% of the other meningitis-causing bacterial isolates that were submitted to NRLBM during the study period were submitted by the 9 sentinel laboratories.

At the NRLBM, co-agglutination was used to type the pneumococcal isolates and the capsular swelling method (Quellung reaction), using antisera (Statens Serum Institute, Copenhagen, Denmark), including serotype 6C, was used for serotyping. For isolates collected before June 2008, serotype 6C was determined by using PCR and antisera. The serotypes were grouped in either PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) or non–PCV7 serotypes (all other serotypes, including 6A).

Clinical Characteristics

Trained medical students, using a standardized data collection form, retrospectively extracted the following information for all case-patients from hospital records, as described (1,11): patient characteristics, clinical syndrome, comorbidity, and disease course and outcome. We subdivided comorbid conditions as immunocompromising or nonimmunocompromising and categorized clinical syndromes as meningitis, invasive pneumonia, bacteremia with other focus, and bacteremia without focus, as described (1). Information on disease course and outcome included the length of hospital stay, admission to an intensive care unit, and death (i.e., in-hospital death and/or death within 30 days after first reported blood/CSF culture positive for S. pneumoniae). Cases without clinical information were excluded from all analyses.

Statistical Analyses

National population coverage was ≈25% by the sentinel laboratories; thus, we estimated annual IPD incidence rates per 100,000 inhabitants by dividing the total number of IPD cases in a specific epidemiologic year by 25% of the total Dutch population. Epidemiologic years were defined as June 1st–May 31 of the succeeding year. We used the population on January 1 of each consecutive year as the population at risk for infection (StatLine,, assuming a stable population throughout the year.

We assessed the effect of vaccination by determining the incidence rate ratio. The assessment was done by comparing incidences in the late post-implementation period (2008–2010) with those in the pre-implementation period (2004–2006); we also determined 95% CIs.

To evaluate any changes in population at risk, we compared the proportion of patients with comorbid conditions in the pre- and late post-implementation periods. We also determined changes in disease course (intensive care unit admission, median length of hospital stay, and death). Differences in percentages were compared by using the χ2 test, and differences in median length of hospital stay were compared by using the Mann-Whitney U test.

All analyses were stratified by age group (<2, 2–4, 5–17, 18–50, 50–64, and >65 years) and by serotype group (PCV7/non–PCV7). All p values <0.05 were considered statistically significant.



In the late post-implementation period (June 1, 2008–May 31, 2010), a total of 1,196 pneumococcal isolates from CSF and blood samples were submitted to the NRLBM by the 9 sentinel laboratories; this number compares with 1,297 and 1,352 isolates submitted during the pre- and early post-implementation periods, respectively. In the late post-implementation period, clinical characteristics were available for 1,144 (96%) case-patients, compared with 1,216 (94%) in the pre-implementation period and 1,304 (96%) in the early post-implementation period (Table 1).

IPD Incidence and Serotype Distribution

The overall incidence of IPD declined from 14.9 to 13.8 cases/100,000 persons during the pre- and late post-implementation periods, respectively (Table 1). A 60% decline in overall IPD incidence (from 35.0 to 14.1 cases/100,000 persons) was observed in children <2 years of age (i.e., children age-eligible for PCV7 vaccination). A similar but nonsignificant decline was seen in children 2–4 years of age. In the age group with the highest incidence rate, i.e., persons >65 years of age, the overall IPD incidence had a significant decline of 13% (from 57.7 to 49.9 cases/100,000 persons). IPD incidence rates remained unchanged in persons 5–64 years of age.


Thumbnail of Serotype distribution of invasive pneumococcal disease in the Netherlands before and after (early and late) introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The 7 vaccine serotypes and the most prevalent nonvaccine serotypes are shown. The cases represent case-patients included in the study (covering ≈25% of the Dutch population). Gray, pre-implementation period (June 2004–May 2006); white, early post-implementation period (June 2006–May 2008); black, late post-im

Figure. . . . . . Serotype distribution of invasive pneumococcal disease in the Netherlands before and after (early and late) introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). The 7 vaccine...

The overall decline of IPD incidences seen among persons <2 and >65 years of age from the pre- to the late post-implementation period resulted from declines in the incidence of PCV7-serotype IPD of 100% and 55%, respectively (Table 1); in children <2 years of age, no PCV7-serotype IPD cases were reported after June 1, 2008. Of 3 children (2–4 years of age) with PCV7-serotype IPD after June 1, 2008, 2 were born before April 1, 2006 and had not received PCV7. The third patient (2 years of age) experienced a vaccine failure; PCV7–serotype 19F IPD developed even though the child was fully vaccinated with 4 doses of PCV7. The child was previously healthy, without any comorbidity. Overall, infections with all PCV7 serotypes declined significantly, except for infection with serotype 18C, which was already low (Figure).

However, from the pre- to the late post-implementation period, the overall incidence of non–PCV7 serotype IPD increased by 33% (from 8.0 to 10.6 cases/100,000 persons) (Table 1). IPD incidence due to non–PCV7 serotypes showed an increasing trend in all age groups, and the increase was significant in patients 50–64 and >65 years of age. Non–PCV7 serotypes 1, 19A, 22F, and 23B increased significantly (Figure), although absolute numbers remained relatively small.

Clinical Characteristics

During all 3 study periods, surveillance data were primarily (97%–98%) for hospitalized IPD patients; the few exceptions were data for patients who visited a hospital emergency department and went home the same day. The distribution of clinical IPD manifestations among patients in different age groups did not change between the pre- and late post-implementation period (Table 2). In children <5 years of age, there was no decline in the incidence of meningitis because of an increase in non–PCV7 serotype meningitis in the late post-implementation period. In older children and adults, invasive pneumonia remained the most prevalent manifestation. The incidence of invasive pneumonia declined in the late post-implementation period in persons >65 years of age despite a significant increase in invasive pneumonia caused by non–PCV7 serotypes (Table 2).

Although the overall number of IPD cases declined from 1,216 in the pre-implementation period to 1,144 in the late post-implementation period, the number of IPD patients (all ages) with an immunocompromising condition increased from 216 to 255 (Table 3). This increase mainly occurred among persons >5 years of age, particularly among those >65 years of age. The number of PCV7-serotype IPD cases declined from 565 in the pre-implementation period to 268 in the late post-implementation period (all ages), and the number of patients with any comorbidity also showed a clear reduction. However, the number of immunocompromised persons with PCV7-serotype IPD declined only marginally (Table 3), indicating that persons with immunocompromising conditions may benefit less than others from herd immunity against PCV7-serotype IPD. This relatively marginal decline was seen for all PCV7 serotypes (data not shown). For non–PCV7 serotype IPD cases, there were similar increases in the number of infected immunocompromised patients and patients with any comorbidity. Moreover, at baseline a smaller proportion of immunocompromised (41%) than nonimmunocompromised (47%) persons had PCV7-serotype IPD (Table 4). Before and after introduction of PCV7, few children <5 years of age had a comorbid condition along with IPD (Technical Appendix Table).

Despite the relative increase in immunocompromised patients with IPD, the overall death rate for IPD decreased significantly from 2.4 to 1.6 cases/100,000 persons. This decline in IPD-related deaths appears to be the result of 1) an overall decrease in the incidence of PCV7-serotype IPD and 2) a lower case-fatality rate among persons with non–PCV7 serotype IPD (Table 3). The lower death rate was seen in all age groups, but the decrease was significant only for patients >65 years of age. Moreover, a decrease in the case-fatality rate for non–PCV7 serotype cases was seen not only among otherwise healthy persons (decrease from 10% to 4%; p = 0.02), but also among immunocompromised persons (from 27% to 16%; p = 0.03) and/or persons with other comorbidities (from 19% to 14%; p = 0.03). Likewise, the median length of hospital stay for children >5 years of age and adults was significantly lower during the post-implementation period than in the pre-implementation period (Technical Appendix Table).


Our findings show that 4 years after introduction of PCV7 in the Netherlands, the overall annual incidence of IPD decreased by 60% (from 35.0 to 14.1 cases/100,000 persons) among children <2 years of age, the age group targeted for vaccination; the decrease was a result of virtually complete eradication of PCV7 serotypes. In children 2–4 years of age, a 48% reduction was seen in IPD cases overall. A significant decline of 13% was also observed in persons >65 years of age. No significant decline in overall IPD was seen in persons 5–64 years of age because the decline in PCV7-serotype IPD was offset by a similar increase in non–PCV7 serotype IPD. The proportion of immunocompromised patients within PCV7-serotype IPD also increased. Despite these findings, the length of hospital stay and case-fatality rates declined over the last years. Our findings indicate that use of PCV7 in the Netherlands resulted in a major decrease in PCV7-serotype IPD among all age groups.

Our results for children are in line with those in England and Wales (4). However, among persons 5–65 years of age, the effect of herd immunity was less pronounced in the Netherlands than in England and Wales (4), where PCV7 was introduced around the same time as in the Netherlands (summer 2006), or in the United States 4 years after the introduction of PCV7 in 2000 (14). This difference can be partly explained by the absence of a catch-up campaign for children <2 years of age in the Netherlands. Young children are a primary reservoir for carriage and transmission of pneumococci because of prolonged colonization episodes related to their immature immune systems. Vaccination of toddlers in addition to newborns has a major effect on the speed of onset of herd immunity in the population. Therefore, by continuing surveillance in the Netherlands, we will likely see more reduction of PCV7-serotype IPD in the years after 2010. A major issue will be the rise in non–PCV7 serotypes, which is estimated by Choi et al. (19) to be ≈90% in England and Wales. Despite this large increase in non–PCV7 serotype IPD, it is expected that this will not offset the decrease in PCV7-serotype IPD in infants and elderly persons.

The decline of IPD cases among persons with immunocompromising conditions was limited compared with the decline among nonimmunocompromised persons. This result may be biased because the number of PCV7-serotype IPD cases in this group was relatively small before introduction of PCV7. However, the case-fatality rate for non–PCV7 serotype IPD in the post-implementation period declined among otherwise healthy persons and among those with comorbid conditions, suggesting a less severe course of disease, even in patients with serious immunocompromising conditions. Thus, even if the incidence of IPD decreased less in immunocompromised persons than in the general population, persons with immunocompromising conditions still appear to benefit from the vaccination program because of a reduction in case-fatality rates.

The reduced case-fatality rate for non–PCV7 serotype IPD since the introduction of PCV7 can be partly explained by a large increase in serotype 1 IPD. This invasive serotype is associated with a low case-fatality rate (12,15,20), which remained low (6%–8%) in the Netherlands during the study period. Case-fatality rates for the other individual serotypes also did not change significantly after introduction of PCV7. In line with a lower case-fatality rate, we also found a reduced length of hospital stay for patients with PCV7-serotype IPD and those with non–PCV7 serotype IPD. However, in the Netherlands, there has been a tendency toward shorter hospital stays, which along with other factors (e.g., improved hospital efficiency) may affect the finding of a reduced length of hospital stay for patients with IPD (21). For example, in 2006 a new financial system was introduced in the Netherlands that encourages shortening of the length of hospital stay.

In children, the increase in non–PCV7 serotype disease was most pronounced among patients with meningitis. Although the numbers were too small to yield significant differences, these data indicate that surveillance should be continued and special attention should be paid to patient characteristics and the evolution of serotype circulation over time.

The incidence of IPD caused by nonvaccine– S. pneumoniae serotypes 1, 19A, 22F, and 23B increased significantly after introduction of PCV7 in the Netherlands. The increase in serotype 19A has been consistently reported worldwide, especially increased carriage among children (22,23) and increased cases of serotype 19A–associated invasive disease (24) and otitis media (2527). The role of PCV7 in promoting serotype 19A carriage in vaccinated children compared with unvaccinated controls has been shown (22,28). In many countries, the increase in serotype 19A disease is associated with high levels of penicillin resistance (24). In the Netherlands, only 1.8% of pneumococcal strains are reported to be resistant (29). The increase in serotype 22F was also seen in the United States and in England and Wales (3,4). The occurrence of serotype 1 was also shown to fluctuate and decline in presence of PCV7 (4). We did not see an increase in IPD caused by serotypes 6C and 15B/C, although increases have been reported elsewhere (3,4). On May 1, 2011, the Dutch government switched from the 7-valent to the 10-valent pneumococcal conjugate vaccine, which includes serotypes 1, 5, and 7F in addition to those in PCV7 (30). The 13-valent pneumococcal conjugate vaccine, which has not been introduced in the Netherlands, adds protection against serotypes 3, 6A, and 19A.

Surveillance artifacts resulting from enhanced surveillance and increased awareness after the introduction of the vaccine should be considered when evaluating the effects of the PCV7 vaccination program (4). However, adjustments for these artifacts can introduce new biases leading to over- and underestimation of the true effects of the vaccine. We believe there are no indications for enhanced surveillance and increased awareness in our study. The laboratory-based surveillance system remained unchanged during the study period, 2004–2010. Unlike the situation in England and Wales (4), the number of pneumococcal isolates obtained from CSF samples in the Netherlands remained stable during the years before PCV7 was introduced (Technical Appendix Figure 1). Moreover, the incidences of IPD caused by a great majority of non–PCV7 serotypes remained stable during the entire study period; the exceptions were for IPD caused by serotypes 1, 19A, 22F, and 23B (Technical Appendix Figure 2). If enhanced surveillance had taken place, one would expect an increase in the reported number of IPD cases caused by any of these serotypes. Thus, we made no corrections for increased case ascertainment or awareness in this study.

Our study does have limitations. First, the study periods before and after implementation of the vaccine program were relatively short; this may have caused an overestimation or underestimation of our results. To account for a proper transition period, we did not include June 2006–May 2008 in our comparisons because no clear conclusions could be drawn from this period. Second, changes in IPD epidemiology could have been influenced by variations in the seasonal influenza and the influenza A(H1N1)pdm09 virus epidemics in 2009 (31,32). Last, no data were available on the national prevalence of comorbidities/diseases. Thus, we could not evaluate IPD incidence rate ratios for the 3 patient groups in our study: otherwise healthy persons, persons with any comorbidity, and persons with immunocompromising conditions.

The results of this study show that PCV7 use has reduced the number of IPD cases and deaths in children <2 years of age (the age group targeted for vaccination) and in persons >65 years of age. However, after introduction of PCV7, cases of IPD caused by non–PCV7 serotypes increased significantly among elderly persons, and the proportion of immunocompromised persons with IPD increased. Despite these increases, the overall IPD case-fatality rate among patients >65 years of age decreased, which seems to be a positive consequence of shifts in circulating serotypes after introduction of a pneumococcal conjugate vaccine for infants.

Ms van Deursen is a doctoral candidate at Utrecht University; this manuscript was part of her doctoral research project. Her research interests include the effectiveness of pneumococcal conjugate vaccinations on invasive pneumococcal disease and more common respiratory infections in vaccinated and unvaccinated populations.



We thank all involved medical students for making data collection possible and all participating hospitals and sentinel laboratories for their cooperation.

This study was supported by an unrestricted research grant from Pfizer Pharmaceuticals. The sponsor played no role in the study design, data-analyses, and preparation, review, or approval of the manuscript.

E.A.M.S. has received grant support from Pfizer and GlaxoSmithKline for research on pneumococcal infections for pneumococcal vaccine studies; grant support from Baxter for research on immunodeficiency disease; consulting fees from Pfizer and GlaxoSmithKline; and lecturing fees from Pfizer and GlaxoSmithKline. E.A.M.S. is involved in Independent data monitoring committees for Pfizer and GlaxoSmithKline vaccine studies. A.v.d.E. has received grants from Pfizer for research on pneumococcal infections.



  1. Jansen  AG, Rodenburg  GD, de Greeff  SC, Hak  E, Veenhoven  RH, Spanjaard  L, Invasive pneumococcal disease in the Netherlands: syndromes, outcome and potential vaccine benefits. Vaccine. 2009;27:2394401. DOIPubMedGoogle Scholar
  2. Arguedas  A, Soley  C, Abdelnour  A. Prevenar experience. Vaccine. 2011;29(Suppl 3):C2634. DOIPubMedGoogle Scholar
  3. Pilishvili  T, Lexau  C, Farley  MM, Hadler  J, Harrison  LH, Bennett  NM, Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis. 2010;201:3241. DOIPubMedGoogle Scholar
  4. Miller  E, Andrews  NJ, Waight  PA, Slack  MP, George  RC. Herd immunity and serotype replacement 4 years after seven-valent pneumococcal conjugate vaccination in England and Wales: an observational cohort study. Lancet Infect Dis. 2011;11:7608. DOIPubMedGoogle Scholar
  5. Hammitt  LL, Bruden  DL, Butler  JC, Baggett  HC, Hurlburt  DA, Reasonover  A, Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease. J Infect Dis. 2006;193:148794. DOIPubMedGoogle Scholar
  6. Pelton  SI, Huot  H, Finkelstein  JA, Bishop  CJ, Hsu  KK, Kellenberg  J, Emergence of 19A as virulent and multidrug resistant pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine. Pediatr Infect Dis J. 2007;26:46872. DOIPubMedGoogle Scholar
  7. Weinberger  DM, Malley  R, Lipsitch  M. Serotype replacement in disease after pneumococcal vaccination. Lancet. 2011;378:196273. DOIPubMedGoogle Scholar
  8. Rozenbaum  MH, Boersma  C, Postma  MJ, Hak  E. Observed differences in invasive pneumococcal disease epidemiology after routine infant vaccination. Expert Rev Vaccines. 2011;10:18799. DOIPubMedGoogle Scholar
  9. Weatherholtz  R, Millar  EV, Moulton  LH, Reid  R, Rudolph  K, Santosham  M, Invasive pneumococcal disease a decade after pneumococcal conjugate vaccine use in an American Indian population at high risk for disease. Clin Infect Dis. 2010;50:123846. DOIPubMedGoogle Scholar
  10. Lacapa  R, Bliss  SJ, Larzelere-Hinton  F, Eagle  KJ, McGinty  DJ, Parkinson  AJ, Changing epidemiology of invasive pneumococcal disease among White Mountain Apache persons in the era of the pneumococcal conjugate vaccine. Clin Infect Dis. 2008;47:47684. DOIPubMedGoogle Scholar
  11. Rodenburg  GD, de Greeff  SC, Jansen  AG, de Melker  HE, Schouls  LM, Hak  E, Effects of pneumococcal conjugate vaccine 2 years after its introduction, the Netherlands. Emerg Infect Dis. 2010;16:81623. DOIPubMedGoogle Scholar
  12. Jansen  AG, Rodenburg  GD, van der Ende  A, van Alphen  L, Veenhoven  RH, Spanjaard  L, Invasive pneumococcal disease among adults: associations among serotypes, disease characteristics, and outcome. Clin Infect Dis. 2009;49:e239. DOIPubMedGoogle Scholar
  13. Brueggemann  AB, Peto  TE, Crook  DW, Butler  JC, Kristinsson  KG, Spratt  BG. Temporal and geographic stability of the serogroup-specific invasive disease potential of Streptococcus pneumoniae in children. J Infect Dis. 2004;190:120311. DOIPubMedGoogle Scholar
  14. Lexau  CA, Lynfield  R, Danila  R, Pilishvili  T, Facklam  R, Farley  MM, Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine. JAMA. 2005;294:204351. DOIPubMedGoogle Scholar
  15. Weinberger  DM, Harboe  ZB, Sanders  EA, Ndiritu  M, Klugman  KP, Ruckinger  S, Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis. Clin Infect Dis. 2010;51:6929. DOIPubMedGoogle Scholar
  16. van Oosten  M, de Greeff  SC, Spanjaard  L, Schouls  LM. Introduction of pneumococcal conjugate vaccine into the Dutch national immunisation programme. Euro Surveill. 2006;11:E060608.2.PubMedGoogle Scholar
  17. van Lier  EA, Oomen  PJ, Oostenbrug  MWM, Zwakhals  SLN, Drijfhout  IH, de Hoogh  PAAM, Vaccinatiegraad rijksvaccinatie programma Nederland; Verslagjaar 2009 [cited 2012 Jan 5].
  18. de Greeff  SC, Sanders  EA, de Melker  HE, van der Ende  A, Vermeer  PE, Schouls  LM. Two pneumococcal vaccines: the 7-valent conjugate vaccine (Prevenar) for children up to the age of 5 years and the 23-valent polysaccharide vaccine (pneumo 23) for the elderly and specific groups at risk. Ned Tijdschr Geneeskd. 2007;151:14547.PubMedGoogle Scholar
  19. Choi  YH, Jit  M, Gay  N, Andrews  N, Waight  PA, Melegaro  A, 7-valent pneumococcal conjugate vaccination in England and Wales: is it still beneficial despite high levels of serotype replacement? PLoS ONE. 2011;6:e26190. DOIPubMedGoogle Scholar
  20. Harboe  ZB, Thomsen  RW, Riis  A, Valentiner-Branth  P, Christensen  JJ, Lambertsen  L, Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study. PLoS Med. 2009;6:e1000081. DOIPubMedGoogle Scholar
  21. Borghans  I, Heijink  R, Kool  T, Lagoe  RJ, Westert  GP. Benchmarking and reducing length of stay in Dutch hospitals. BMC Health Serv Res. 2008;8:220. DOIPubMedGoogle Scholar
  22. Spijkerman  J, van Gils  EJ, Veenhoven  RH, Hak  E, Yzerman  EP, van der Ende  A, Carriage of Streptococcus pneumoniae 3 years after start of vaccination program, the Netherlands. Emerg Infect Dis. 2011;17:58491.PubMedGoogle Scholar
  23. Dunais  B, Bruno-Bazureault  P, Carsenti-Dellamonica  H, Touboul  P, Pradier  C. A decade-long surveillance of nasopharyngeal colonisation with Streptococcus pneumoniae among children attending day-care centres in south-eastern France: 1999–2008. Eur J Clin Microbiol Infect Dis. 2011;30:83743. DOIPubMedGoogle Scholar
  24. Reinert  R, Jacobs  MR, Kaplan  SL. Pneumococcal disease caused by serotype 19A: review of the literature and implications for future vaccine development. Vaccine. 2010;28:424959. DOIPubMedGoogle Scholar
  25. Stamboulidis  K, Chatzaki  D, Poulakou  G, Ioannidou  S, Lebessi  E, Katsarolis  I, The impact of the heptavalent pneumococcal conjugate vaccine on the epidemiology of acute otitis media complicated by otorrhea. Pediatr Infect Dis J. 2011;30:5515. DOIPubMedGoogle Scholar
  26. Hoberman  A, Paradise  JL, Shaikh  N, Greenberg  DP, Kearney  DH, Colborn  DK, Pneumococcal resistance and serotype 19A in Pittsburgh-area children with acute otitis media before and after introduction of 7-valent pneumococcal polysaccharide vaccine. Clin Pediatr (Phila). 2011;50:11420. DOIPubMedGoogle Scholar
  27. Fenoll  A, Aguilar  L, Vicioso  MD, Gimenez  MJ, Robledo  O, Granizo  JJ. Increase in serotype 19A prevalence and amoxicillin non-susceptibility among paediatric Streptococcus pneumoniae isolates from middle ear fluid in a passive laboratory-based surveillance in Spain, 1997–2009. BMC Infect Dis. 2011;11:239. DOIPubMedGoogle Scholar
  28. van Gils  EJ, Veenhoven  RH, Hak  E, Rodenburg  GD, Keijzers  WC, Bogaert  D, Pneumococcal conjugate vaccination and nasopharyngeal acquisition of pneumococcal serotype 19A strains. JAMA. 2010;304:1099106. DOIPubMedGoogle Scholar
  29. SWAB. the Dutch Foundation of the Working Party on Antibiotic Policy. NethMap 2011: consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria in the Netherlands [cited 2012 Jan 5].$FILE/NethMap2011.pdf
  30. National Institute for Public Health and the Environment. Invoering pneumokokkenvaccin Synflorix. Bilthoven (the Netherlands): the Institute; 2011.
  31. Martin-Loeches  I, Sanchez-Corral  A, Diaz  E, Granada  RM, Zaragoza  R, Villavicencio  C, Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus. Chest. 2011;139:55562. DOIPubMedGoogle Scholar
  32. Wielders  CC, van Lier  EA, van ’t Klooster  TM, van Gageldonk-Lafeber  AB, van den Wijngaard  CC, Haagsma  JA, The burden of 2009 pandemic influenza A(H1N1) in the Netherlands. Eur J Public Health. 2012;22:1507. DOIPubMedGoogle Scholar




Follow Up

Earning CME Credit

To obtain credit, you should first read the journal article. After reading the article, you should be able to answer the following, related, multiple-choice questions. To complete the questions (with a minimum 70% passing score) and earn continuing medical education (CME) credit, please go to Credit cannot be obtained for tests completed on paper, although you may use the worksheet below to keep a record of your answers. You must be a registered user on If you are not registered on, please click on the New Users: Free Registration link on the left hand side of the website to register. Only one answer is correct for each question. Once you successfully answer all post-test questions you will be able to view and/or print your certificate. For questions regarding the content of this activity, contact the accredited provider, For technical assistance, contact American Medical Association’s Physician’s Recognition Award (AMA PRA) credits are accepted in the US as evidence of participation in CME activities. For further information on this award, please refer to The AMA has determined that physicians not licensed in the US who participate in this CME activity are eligible for AMA PRA Category 1 Credits™. Through agreements that the AMA has made with agencies in some countries, AMA PRA credit may be acceptable as evidence of participation in CME activities. If you are not licensed in the US, please complete the questions online, print the certificate and present it to your national medical association for review.

Article Title:
Invasive Pneumococcal Disease and 7-Valent Pneumococcal Conjugate Vaccine, the Netherlands

CME Questions

1. You are seeing a 2-month-old infant whose parents have multiple questions regarding the effects of the 7-valent pneumococcal conjugate vaccine (PCV7). What does previous research demonstrate regarding the efficacy of PCV7?

A.         PCV7 primarily reduces the risk of otitis media among children

B.         PCV7 has no effect on the rate of invasive pneumococcal disease (IPD) among adults

C.        PCV7 has no effect on the rate of IPD among young children

D.        The rate of non-PCV7-serotype IPD increased after introduction of PCV7

2. What else should you consider as you discuss PCV7 with these parents?

A.         IPD incidence has declined to a greater degree in Europe vs the United States

B.         Catch-up vaccination programs for children under 5 have sped up eradication of vaccine serotypes

C.        The greatest indirect benefit of PCV7 is found among older adults with comorbid conditions

D.        PCV7 contains serotype 1, which is the most common serotype implicated in IPD

3. As you continue your conversation regarding PCV7, which age groups from the current study can you tell these parents experienced the greatest decline in the incidence of IPD?

A.         2 to 4 years of age and 5 to 12 years of age

B.         0 to 2 years of age and middle-aged adults

C.        0 to 2 years of age and 65 years or older

D.        21 to 35 years of age and 50 to 64 years of age

4. What can you tell these parents regarding characteristics of IPD in the current study?

A.         IPD incidence due to non–PCV7-serotypes increased among young children but fell among adults

B.         Pneumonia was the most common infection related to IPD among children less than 5 years of age

C.        PCV-7 appeared particularly effective in reducing IPD among immunocompromised individuals

D.        The overall mortality rate associated with IPD declined during the study period

Activity Evaluation

1. The activity supported the learning objectives.

Strongly Disagree

Strongly Agree






2. The material was organized clearly for learning to occur.

Strongly Disagree

Strongly Agree






3. The content learned from this activity will impact my practice.

Strongly Disagree

Strongly Agree






4. The activity was presented objectively and free of commercial bias.

Strongly Disagree

Strongly Agree







Cite This Article

DOI: 10.3201/eid1811.120329

1These authors contributed equally to this article.

2These authors contributed equally to this article.

3Additional members of the Invasive Pneumococcal Disease Sentinel Surveillance Laboratory Group are listed at the end of this article.

Members of the Invasive Pneumococcal Disease Sentinel Surveillance Laboratory Group: Karola Waar, Izore, Centre for Infectious Diseases Friesland, Leeuwarden, the Netherlands; Bert Mulder, Laboratory of Medical Microbiology Twente Achterhoek, Enschede, the Netherlands; Caroline Swanink, Department of Medical Microbiology and Medical Immunology Hospital Rijnstate, Arnhem, the Netherlands; Bram Diederen, Regional Laboratory of Public Health, Haarlem, the Netherlands; Niek Arents, Laboratory for Pathology and Medical Microbiology, Veldhoven, the Netherlands; Ine Frénay, Regional Laboratory for Medical Microbiology and Infectious Diseases, Dordrecht–Gorinchem, the Netherlands; Hans Wagenvoort, Atrium Medical Center, Heerlen, the Netherlands; Bartelt de Jongh, St. Antonius Hospital, Nieuwegein, the Netherlands; Lodewijk Spanjaard, Academic Medical Center, Amsterdam, the Netherlands

Related Links

Table of Contents – Volume 18, Number 11—November 2012

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Arie M.M. van der Ende, Department of Medical Microbiology, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, the Netherlands

Send To

10000 character(s) remaining.


Page created: October 16, 2012
Page updated: October 16, 2012
Page reviewed: October 16, 2012
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.