Effectiveness of 7-valent pneumococcal conjugate vaccine: A meta-analysis of post-marketing studies

Abstract

AIM: To investigate the 7-valent pneumococcal conjugate vaccine (PCV7) effectiveness.

METHODS: A systematic literature review of studies which evaluated the effectiveness of PCV7 vaccine was performed searching the keyword “heptavalent pneumococcal conjugate vaccine” in PubMed and Scopus until March 16, 2013. The selection of potential eligible articles was done by two researchers independently on the basis of abstract and title and only post-marketing studies were included in the systematic review. Data extraction was carried out by two researchers with respect to invasive pneumococcal diseases due to both all and vaccine serotypes in pre-vaccine and post-vaccine periods in children less than 5 years. Results of studies which were considered suitable for meta-analysis were combined by means of relative risk (RR) with 95%CI. Vaccine effectiveness was calculated as (1-RR) × 100. Heterogeneity was assessed by I² and a random effects model was used to combine data in the case of heterogeneity. RevMan 5 was used to pool data.

RESULTS: On the whole, 757 eligible papers were identified from the literature search in PubMed and Scopus. Of them, 62 were finally considered in the systematic review and 38 were included in the meta-analysis. In all post-marketing studies included in the systematic review the incidence of invasive pneumococcal diseases due to vaccine serotypes declined significantly with the exception of few studies showing stability or a slight, but not significant, increase. Furthermore most of studies highlighted also a reduction in the incidence of invasive pneumococcal diseases due to all serotypes. With regards to meta-analysis, a random effects model was used to combine data because of the high heterogeneity. Data combination showed that the effectiveness of PCV7 in reducing invasive pneumococcal diseases due to vaccine serotypes and to all serotypes was 84% (95%CI: 74%-90%) and 53% (95%CI: 46%-59%) respectively. These results are confirmatory with respect to the efficacy of PCV7 against invasive pneumococcal diseases due to vaccine serotypes.

CONCLUSION: PCV7 implementation determines a significant decrease of invasive pneumococcal diseases.

Key Words: Streptococcus pneumoniae; Pneumococcal infections; Pneumococcal vaccines; Treatment outcome; Meta-analysis

Core tip: This systematic review and meta-analysis was performed with the aim to collect data from post-marketing studies on 7-valent pneumococcal conjugate vaccine (PCV7) and to provide evidence about the impact of the vaccine in the real world. Eligible articles were identified through a search on PubMed and Scopus. The meta-analysis showed that PCV7 is able to reduce invasive pneumococcal diseases due to both vaccine serotypes and to all serotypes. The effectiveness was 84% (95%CI: 74%-90%) and 53% (95%CI: 46%-59%) respectively. These data may be taken into consideration in order to foresee the impact under real conditions of PCV13 which has replaced PCV7 from 2010 onwards.

INTRODUCTION

Streptococcus pneumoniae (S. pneumoniae) is a leading cause of severe bacterial infectious disease and World Health Organization has estimated that this bacteria causes 1.4-1.6 million child deaths annually[1,2], in that around 11% of all deaths in children < 5 years[3]. More than 90 serotypes of S. pneumoniae exist. These strains may cause invasive pneumococcal disease (IPD). The highest incidence of IPD is seen in children < 2 years old. In order to prevent disease caused by S. pneumoniae, two types of vaccines, polysaccharide (PPV) and conjugate (PCV) exist, even though the PPV vaccine is ineffective in children < 2 years old[4].

The PCV vaccines consist of capsular PPVs bound to proteins which are highly immunogenic and enhance an immune response by recruiting type 2 helper T cells, which allows for immunoglobulin type switching and production of memory B cells. The main drawbacks of PCV vaccines are that they only provide protection against a subset of serotypes covered by the PPV vaccines[5-7]. In fact, PCV vaccines encompass the 7-valent vaccine (PCV7), the PCV10 and the PCV13. Currently, PCV13 is used in prevention campaigns. Its marketing authorization in the European Union goes back to December 2009[8]. PCV13 has replaced PCV7 from 2010 onward.

The PCV7, providing protection against serotypes 4, 6B, 9V, 14, 18C, 19F and 23F, was introduced into routine childhood immunization program in the United States in 2000 and was shown to reduce the incidence of IPD by all and vaccine-serotypes[9,10]. Notwithstanding, some studies have described significant rises in non-vaccine serotypes after the implementation of universal PCV7 programs[11-14]. Based on the favourable United States experience and the proof of vaccine efficacy[15] a number of countries have introduced PCV7[16]. Worldwide the vaccine has been provided with different schedules. In Europe both the 2 + 1 and 3 + 1 schedules have been used[16].

In the light of monitoring the health impact of technologies and policies, data from the real practice should be collected and analysed. Because of the recent introduction and implementation of PCV13, many data from real practice are only available for PCV7 even though evidence is being produced on PCV13 also[17-23]. Notwithstanding, this evidence should be considered early and is still scant in order to make a meta-analysis. Furthermore, it is mostly related to the transition period between the use of PCV7 and the introduction of PCV13 which took place from 2010 onward with different time schedules across countries. Based on this premises, the objective of this study was to perform a systematic review and a meta-analysis of post-marketing studies on the effectiveness of PCV7 in comparison with no vaccination in preventing IPD in children less than 5 years of age worldwide. The final aim was to provide evidence about PCV7 effectiveness under real conditions and to foresee the potential impact of PCV13 on the basis of results. The systematic review was performed according to PRISMA Statement published by Moher et al[24].

MATERIALS AND METHODS

Selection of articles

A literature search was conducted using PubMed and Scopus search engines. The following search strategy was used: “heptavalent pneumococcal PCV vaccine” (Substance Name) NOT [“Clinical Trial” (Publication Type) OR “Clinical Trials as Topic” (Mesh) OR “Controlled Clinical Trial” (Publication Type) OR “Clinical Trial, Phase IV” (Publication Type) OR “Clinical Trial, Phase III” (Publication Type) OR “Clinical Trial, Phase II” (Publication Type) OR “Clinical Trial, Phase I” (Publication Type)]. The search covered the period up to March 16, 2013, without starting date, and was limited to English-language publications.

The selection of potential eligible articles was done by two researchers independently on the basis of title and abstract. Full text of eligible articles was collected for the final judgment on inclusion. Disagreements were solved through consensus or the consultation of a third researcher.

We defined a priori criteria for the inclusion of studies in this meta-analysis, selecting studies dealing with the incidence of IPD in children less than 5 years of age in the period before and after the introduction of PCV7. Only articles releasing data on IPD incidence in pre- and post-vaccination periods were included in the quantitative assessment.

Data extraction

The following data were recorded from each study: first author, journal, published year, country, study population, IPD case definition, crude number or incidence of IPD before and after the introduction of PCV7. Data on IPD caused by all serotypes and due to vaccine serotypes, if available, were collected. Data extraction was performed by two researchers independently and disagreements were solved through consensus or the consultation of a third researcher.

Statistical analysis

Studies were included in the meta-analysis if they provided crude data or if it was possible to get them through computation.

The relative risk (RR) with 95%CI was used to combine data. Vaccine effectiveness was calculated as (1-RR) × 100. RevMan 5 was used to combine data and a fixed effects model was applied in the case of absence of heterogeneity (I² < 50%). On the other way around, a random effects model was used. Studies which were not considered in the meta-analysis were described qualitatively in Table 1. Finally, publication bias was assessed by means of funnel plots.

Table 1 Summary of studies characteristics and results.

Ref.	Country	Study period	Invasive pneumococcal disease definition	Main results
Albrich et al[25]	United States	1997-2004	Isolation of S. pneumoniae from sterile body fluid	1
Ampofo et al[26]	United States	1997-2010	Isolation of S. pneumoniae from sterile body fluid	The proportion of children younger than 2 yr with IPD decreased (54% vs 43% with respect to all serotypes and 56% vs 43% for vaccine serotypes), while the proportion of disease among children aged 2-4 slightly increased (27% vs 29% with respect to all and vaccine serotypes)
Aristegui et al[27]	Spain	1998-2003	Isolation of S. pneumoniae from sterile body fluid	1
Barricarte et al[28]	Spain	2001-2005	Isolation of S. pneumoniae from sterile body fluid	The overall effectiveness in reducing IPD was 31% (OR = 0.69, 95%CI: 0.37-1.27) and 88% (OR = 0.12, 95%CI: 0.02-0.91) for all serotypes and vaccine serotypes respectively
Benito-Fernández et al[29]	Spain	2000-2005	Isolation of S. pneumoniae from sterile body fluid	1
Ben-Shimol et al[30]	Israel	1989-2010	Isolation of S. pneumoniae from sterile body fluid	In 2009 and 2010, IPD incidence (due to vaccine serotypes) were 15.9 per 100000 and 5.4, per 100000 respectively (a 43% and 81% decrease compared to 2003-2007)
Bjornson et al[31]	Canada	2001-2005	Isolation of S. pneumoniae from sterile body fluid	1
Calbo et al[32]	Spain	1999-2004	Isolation of S. pneumoniae from sterile body fluid	The IPD incidence significantly decreased from 96.9 cases per 100000 person-years to 90.6 cases per 100000 person-years (7% reduction)
Carstairs et al[33]	United States	2000-2002	Isolation of S. pneumoniae from sterile body fluid	1
Casado-Flores et al[34]	Spain	2001-2006	Isolation of S. pneumoniae from sterile body fluid	1
CDC[35]	United States	1998-2005	Isolation of S. pneumoniae from sterile body fluid	1
De Serres et al[36]	United States	2001-2009	Isolation of S. pneumoniae from sterile body fluid	Effectiveness of PCV7 against IPD due to vaccine serotypes was 97% (95%CI: 92%-98%) among healthy children and 88% (95%CI: 78%-94%) among children with comorbid conditions. The incidence of IPD due to non-vaccine serotypes increased from 6.8 per 100000 (1998-1999) to 10.3 per 100000 in 2007 (51% increase)
De Wals et al[37]	Canada	2007-2010	Isolation of S. pneumoniae from sterile body fluid	A decrease in the frequency of IPD caused by vaccine serotypes was observed
Dias et al[38]	Portugal	1999-2004	Isolation of S. pneumoniae from sterile body fluid	1
Vestrheim et al[39]	Norway	2004-2008	Isolation of S. pneumoniae from sterile body fluid	1
Dubos et al[40]	France	2000-2005	Isolation of S. pneumoniae from sterile body fluid	A decrease of 82% (95%CI: 52%-95%) of cases was observed (from 8.9 cases per 100000 in 2001 to 1.8 per 100000 in 2005) in children < 2 yr
Fenoll et al[41]	Spain	1996-2001 2005-2006	Isolation of S. pneumoniae from sterile body fluid	A decrease of the incidence of IPD due to vaccine serotypes from 5.2 per 100000 in 1996-2001 to 2.4 per 100000 in 2005-2006 was observed
Flannery et al[42]	United States	1998-2002	Isolation of S. pneumoniae from sterile body fluid	1
Giele et al[43]	Australia	1996-2005	Isolation of S. pneumoniae from sterile body fluid	1
Schutze et al[44]	Arkansas	1998-2003	Isolation of S. pneumoniae from sterile body fluid	A decrease of IPD from 44.2 per 100000 person-years to 8.30 per 100000 person-years was observed in children < 2 yr
Guevara et al[45]	Spain	2001-2007	Isolation of S. pneumoniae from sterile body fluid	1
Haddy et al[46]	United States	1999-2002	Isolation of S. pneumoniae from sterile body fluid	1
Hanna et al[47]	Queensland	1999-2007	Isolation of S. pneumoniae from sterile body fluid	1
Hanquet et al[48]	Belgium	2002-2008	Isolation of S. pneumoniae from sterile body fluid	1
Harboe et al[49]	Denmark	2000-2008	Isolation of S. pneumoniae from sterile body fluid	In children < 2 yr, the overall incidence decreased from 54 to 23 cases per 100000 (IRR = 0.43, 95%CI: 0.29-0.62) and from 36.7 to 7.7 (IRR = 0.20, 95%CI: 0.09-0.38) for vaccine serotypes. A non-significant increase was observed in children aged 2-4 yr
Hennessy et al[50]	United States	1995-2003	Isolation of S. pneumoniae from sterile body fluid	1
CDC[51]	United States	1998-2003	Isolation of S. pneumoniae from sterile body fluid	A decrease of IPD due to vaccine serotypes from 80 cases per 100000 to 4.6 per 100000 was observed (decrease of 94% (95%CI: 92%-96%) from 1998-1999 to 2003
Hsu et al[52]	United States	1998-2005	Isolation of S. pneumoniae from sterile body fluid	1
Hsu et al[53]	United States	1990-1991 2001-2003	Isolation of S. pneumoniae from sterile body fluid	1
Hsu et al[54]	United States	2001-2007	Isolation of S. pneumoniae from sterile body fluid	IPD incidence was stable during the 6 yr period, although IPD due to vaccine serotypes decreased
Ingels et al[55]	Denmark	2000-2010	Isolation of S. pneumoniae from sterile body fluid	1
Wenger et al[56]	United States, Alaska	1986-2007	Isolation of S. pneumoniae from sterile body fluid	1
Johnson et al[57]	South Australia	2002-2009	Isolation of S. pneumoniae from sterile body fluid	1
Kellner et al[58]	Canada	1998-2007	Isolation of S. pneumoniae from sterile body fluid	1
Kyaw et al[59]	United States	1996-2004	Isolation of S. pneumoniae from sterile body fluid	1
Leal et al[60]	Alberta	1998-2010	Isolation of S. pneumoniae from sterile body fluid	1
Liao et al[61]	Taiwan	2000-2008	Isolation of S. pneumoniae from sterile body fluid	The overall incidence of IPD decreased by 33% (95%CI: 0%-72.2%)
Messina et al[62]	United States	1999-2001 2003-2005	Isolation of S. pneumoniae from sterile body fluid	1
Muñoz-Almagro et al[63]	Spain	1997-2006	Isolation of S. pneumoniae from sterile body fluid	1
Patrzalek et al[64]	Poland	2005-2010	Isolation of S. pneumoniae from sterile body fluid	1
Pérez et al[65]	Spain	1998-2008	Isolation of S. pneumoniae from sterile body fluid	1
Pérez-Trallero et al[66]	Spain	1996-2007	Isolation of S. pneumoniae from sterile body fluid	1
Pilishvili et al[67]	United States	1998-2007	Isolation of S. pneumoniae from sterile body fluid	1
Poehling et al[68]	United States	1997-2004	Isolation of S. pneumoniae from sterile body fluid	1
[69]	Canada	2002-2005	Isolation of S. pneumoniae from sterile body fluid	1
Ramani et al[70]	United States	1994-2001	Hospital discharges for IPD	A significant decrease was observed only for children aged < 1 yr (from 40 per 100000 to 23 per 100000 person years). All other age groups did not show a significant change in discharge rates for IPD
Rendi-Wagner et al[71]	Austria	2001-2007	Isolation of S. pneumoniae from sterile body fluid	1
Rodenburg et al[72]	Netherlands	2004-2008	Isolation of S. pneumoniae from sterile body fluid	1
Rückinger et al[73]	Germany	1997-2003 2007-2008	Isolation of S. pneumoniae from sterile body fluid	1
de Sevilla et al[74]	Spain	2007-2009	Isolation of S. pneumoniae from sterile body fluid	An increase of 44% of IPD (95%CI: 10%-89%) was shown
Shafinoori et al[75]	United States	1998-2004	Isolation of S. pneumoniae from sterile body fluid	A significant 68% and 70% decrease of IPD in children < 2 yr and aged 2 to 4 yr respectively was observed
Shah et al[76]	United States	1999-2003	Hospital discharges for IPD	A significant decrease from 12.03 per 100000 person-years in 1999 to 5.60 per 100000 person-years in 2003 was shown
Techasaensiri et al[77]	United States	1999-2008	Isolation of S. pneumoniae from sterile body fluid	The incidence of IPD significantly decreased in children < 2 yr
Tsai et al[78]	United States	1994-1999 2001-2004	Hospital discharges for pneumococcal meningitis	The average annualized rates of hospitalizations decreased from 7.7 per 100000 to 2.6 per 100000 in children < 2 yr and from 0.9 per 100000 to 0.5 per 100000 in children aged 2-4 (a reduction of 66%, 95%CI: 56.3%-73.5% and of 51.5%, 95%CI: 28.9%-66.9% respectively)
Tsigrelis et al[79]	United States	1995-2007	Isolation of S. pneumoniae from sterile body fluid	1
Tyrrell et al[80]	Canada	2000-2006	Isolation of S. pneumoniae from sterile body fluid	IPD due to vaccine serotypes decreased of 61% in children < 2 yr (from 96.7 per 100000 person-years to 25.8 per 100000 person-years) and of 57% in children from 2 to 4 yr (from 24.5 per 100000 person-years to 10.6 per 100000 person-years)
Van der Linden et al[81]	Germany	1997-2010	Isolation of S. pneumoniae from sterile body fluid	IPD incidence decreased from 2.4 per 100000 to 0.3 per 100000
Vestrheim et al[82]	Norway	2002-2007	Isolation of S. pneumoniae from sterile body fluid	1
Weatherholtz et al[83]	United States	1995-2006	Isolation of S. pneumoniae from sterile body fluid	Rates of IPD due to vaccine serotypes among children aged < 1 yr, 1-2 yr, and 2-5 yr decreased from 210, 263, and 51 cases per 100000 respectively in to 0 case per 100000
Whitney et al[84]	United States	1998-2001	Isolation of S. pneumoniae from sterile body fluid	1
Winters et al[85]	Canada	2002-2005	Isolation of S. pneumoniae from sterile body fluid	The incidence of IPD decreased from 54 per 100000 person-years to 16 per 100000 person-years (decrease of 70%). An even stronger decrease was observed in children < 1 yr, where the incidence decreased from 135 per 100000 to 15 per 100000 person-years (decrease of 89%)
Yildirim et al[86]	United States	2007-2010	Isolation of S. pneumoniae from sterile body fluid	IPD cases due to vaccine serotypes decreased

¹Studies included in the meta-analysis. IPD: Invasive pneumococcal disease; CDC: Centers for Disease Control and Prevention; IRR: Incidence rate ratio; PCV7: 7-valent pneumococcal conjugate vaccine; S. pneumoniae: Streptococcus pneumoniae.

RESULTS

On the whole, 556 articles were yielded from PubMed and 388 from Scopus but 187 papers were shared by the two databases for a total of 757 papers. Of them, 62 were finally considered in the systematic review (Figure 1)[25-86]. Their characteristics and results are shown in Table 1.

Figure 1 Flow-chart of studies selection.

With respect to meta-analysis, 38 articles provided data on IPD due to all serotypes while 22 allowed the collection of data on IPD due to vaccine serotypes. Data combination showed a vaccine effectiveness of 84% for IPD due to vaccine serotypes (RR = 0.16, 95%CI: 0.10%-0.26; I² = 95%, Figure 2) and 53% (RR = 0.47, 95%CI: 0.41-0.54; I² = 95%, Figure 3) for IPD related to all serotypes. Publication bias could not be excluded with respect to the assessment of effectiveness against IPD due to vaccine serotypes while may be excluded as regards IPD due to all serotypes (Figures 4 and 5).

Figure 2 Data combination for invasive pneumococcal disease due to vaccine serotypes. ¹Data available not for the entire age group < 5 years. CDC: Centers for Disease Control and Prevention.

Figure 3 Data combination for invasive pneumococcal disease due to all serotypes. ¹Data available not for the entire age group < 5 years. CDC: Centers for Disease Control and Prevention.

Figure 4 Funnel plot of studies on invasive pneumococcal disease due to vaccine serotypes. RR: Relative risk.

Figure 5 Funnel plot of studies on invasive pneumococcal disease due to all serotypes. RR: Relative risk.

DISCUSSION

Our study aimed to review and combine data of post-marketing studies on PCV7 worldwide.

The analysis and data combination allowed us to investigate the effectiveness of PCV7 and its impact in terms of public health. Results are indeed useful for supporting decision-makers in the field of vaccinations. In particular, findings of the meta-analysis showed that the effectiveness of PCV7 in reducing IPD due to vaccine serotypes is 84%. The effectiveness is estimated to be 53% with respect to IPD due to all serotypes.

The results of our study are aligned with the evidence on the efficacy of PCV7 demonstrated in randomized clinical trials (RCT). In fact, a meta-analysis of RCT conducted by Pavia et al[15] showed an efficacy of 89% in preventing IPD due to vaccine serotypes, and of 63%-74% in preventing IPD due to all serotypes. Indeed, as IPD due to vaccine serotypes, effectiveness data have confirmed efficacy data. With this respect it is important to point out that the assessment of efficacy of interventions is critical in order to decide upon their adoption and is addressed through explanatory clinical trials[87]. Notwithstanding, the proof of efficacy is not always sufficient because it is also important to have evidence about how interventions work under more natural field conditions rather than in controlled clinical trials[87,88]. Indeed, overall effectiveness of interventions should be assessed by different study designs able to maximize external validity[87].

As far as PCV7 is concerned, all post-marketing studies showed that the incidence of IPD due to vaccine serotypes declined significantly after the implementation of vaccination, with the exception of few studies[36,27,49,63,65] showing a stability or a slight increase. As a consequence, the implementation of vaccination has definitively contributed in consistently preventing IPD in children up to 5 years of age with a strong impact on population health and costs due to hospitalizations[89,90]. In fact, a relevant reduction of IPD due to all serotypes was also shown by the meta-analysis even though, comparing with IPD due to vaccine serotypes, more studies highlighted a stability or an increase in the overall incidence of IPD[26,32,38,45,48,52,63,65,66,70-72,74,79]. In particular two studies[64,75] showed a significant increase although due to non-vaccine serotypes and in a context of low vaccination coverage. The increase in the incidence of non-vaccine serotypes is a well-known phenomenon which may be counteracted by the extension of serotypes coverage. In this view the availability and the implementation of PCV13 is useful in order to further reduce the incidence of IPD. In fact, the post-licensure assessment already carried out by Andrews et al[23] estimated that the effectiveness of at least 2 doses of PVC13 before 12 mo of age or of 1 dose from 12 mo onwards was 90% (95%CI: 34%-98%) against PCV7 serotypes. This result is aligned with data from our and Pavia et al[15] meta-analyses. Furthermore, PCV13 was shown to have an effectiveness of 73% (95%CI: 55%-84%) against the additional serotypes included in the vaccine[23]. PCV13 may indeed provide an added value in comparison to PCV7. In fact, already available population-based studies showed that IPD decreased of a percentage from 18% to 42% when PCV13 era is compared to PCV7 one[18,20,21]. The decline is more important in children less than 2 years of age in which the decrease in all IPD varies from 50% to 60%[18,20,21].

This study presents some limitations. The research was limited to only two specialized searching engines and, consequently, selection bias may be not excluded. Papers included in the review were heterogeneous with respect to countries and study design as also highlighted by the test of heterogeneity. Crude data were not obtainable from all the papers selected and only children < 5 years of age, independently by their health status, were considered in the analysis. Furthermore, neither a quality assessment nor stratified analyses in order to investigate heterogeneity were performed.

Strengths of this study are represented by the objective itself, because we focused on effectiveness instead of efficacy, and the large number of papers included in the analysis.

The consistent decrease of IPD due to vaccine serotypes after the PCV7 implementation is important as the new PCV13 is being implemented. In fact, it is expected that it will have the same effectiveness in preventing IPD due PCV7 vaccine serotypes and it will also have an important impact on cases due to new vaccine serotypes[91,92].

COMMENTS

Background

Streptococcus pneumoniae (S. pneumoniae) is a leading cause of severe bacterial infectious disease, causing 1.4-1.6 million child deaths annually, in that around 11% of all deaths in children < 5 years. Two types of vaccines against S. pneumoniae exist, polysaccharide (PPV) and conjugate (PCV), even though the PPV vaccine is ineffective in children < 2 years old. PCV vaccines encompass the 7-valent vaccine (PCV7), the PCV10 and the PCV13. Currently, PCV13 is used in prevention campaigns. Its marketing authorization in the European Union goes back to December 2009 and it has replaced PCV7 from 2010 onward. Because of the recent introduction and implementation of PCV13, consistent data from real practice are only available for PCV7 and their assessment is of utmost importance in order to monitor the health impact of the vaccine.

Research frontiers

The monitoring of the overall health impact of technologies and policies is a key issue in medicine. It is mainly based on post-marketing studies on the effectiveness of interventions carried out through the collection and analysis of data from the real practice. In this context, the objective of the authors study was to perform a systematic review and a meta-analysis of post-marketing studies on the effectiveness of PCV7 worldwide.

Innovations and breakthroughs

The authors’ findings showed that the effectiveness of PCV7 in reducing invasive pneumococcal disease (IPD) is 84% with respect to IPD due to vaccine serotypes and 53% with respect to IPD due to all serotypes. Concerning IPD due to vaccine serotypes, effectiveness data have confirmed efficacy data previously reported in a meta-analysis of randomized clinical trial conducted by Pavia et al. However, with this respect, it is important to emphasize that efficacy trials test the expected results of an intervention under ideal circumstances whereas effectiveness studies measure the beneficial effects under “real world” clinical settings. Indeed, the results of their meta-analysis represent and advance in the knowledge of PCV7 impact.

Applications

Given the consistent decrease of IPD due to vaccine serotypes after the PCV7 implementation, results of their systematic review and meta-analysis allow forecasting that the new PCV13, which is being implemented, will further decrease the number of IPD. In fact PCV13 effectiveness is expected to be the same as PCV7 in preventing IPD due to both PCV7 vaccine serotypes and new vaccine serotypes.

Terminology

IPD is defined as the isolation of S. pneumoniae from a sterile site/body fluid.

Peer-review

The authors performed an interesting and well-written meta-analysis on a highly relevant topic.