Elsevier

Vaccine

Volume 32, Issue 18, 11 April 2014, Pages 2022-2026
Vaccine

Review
Can the success of pneumococcal conjugate vaccines for the prevention of pneumococcal diseases in children be extrapolated to adults?

https://doi.org/10.1016/j.vaccine.2014.02.008Get rights and content

Highlights

  • Diseases and mortality caused by Streptococcus pneumoniae are vaccine-preventable.

  • Children and adults do not have the same disease manifestations or risk factors.

  • Vaccinating children with PCV7 has reduced disease incidence in all ages.

  • PCV13 adult vaccination could reduce disease burden and contribute to stronger overall control.

Abstract

Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children.

As highlighted in this paper, differences exist between children and adults for PD manifestations (incidence, morbidity and mortality) and serotypes isolated in nasopharyngeal carriage and diseases, so benefits from adult vaccination must be considered in this light. PCV13 induces an immune response in adults that is non-inferior for all serotypes common with the 23-valent plain polysaccharide vaccine that is currently recommended for adults and even superior for many serotypes. Although there is no evidence that this immune response translates to clinical efficacy in adults as seen in children, the results from a randomised trial in The Netherlands, expected in 2014, should provide the missing evidence. This evidence and efficient surveillance systems should provide the necessary data, essential for policy makers in their decisions on adult pneumococcal vaccination policies.

Section snippets

Streptococcus pneumoniae

The diseases and mortality associated with some Streptococcus pneumoniae serotypes are largely vaccine-preventable. It was estimated that S. pneumoniae was responsible for 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis per year in the United States in the whole population, prior to the introduction of conjugate pneumococcal vaccines [1]. The age-specific incidences of pneumococcal disease show a U-shaped distribution with the highest incidences in the

Pneumococcal nasopharyngeal carriage

There is convincing evidence that pneumococcal nasopharyngeal (NP) carriage is an immediate and essential precursor for pneumococcal disease and also the source of pneumococcal transmission between people [2], [3]. Pneumococcal NP carriage rate is age-dependent, starting early in the first year of life and peaking at about 55% around three years, with a steady continual decline into adulthood [4]. Although the prevalence of NP carriage in the elderly is low, frequent acquisition was reported in

Pneumococcal serotypes associated with IPD

Prior to PCV7 introduction, serotype 14 was the most frequently found serotype in IPD in all age groups in the US and Germany although its relative frequency differed with age [9], [10]. It was reported to be 33.5% in children <2 years, 25.2% in children <16 years, 16.7% in adults ≥16 years and 15.2% in adults ≥65 years. The second and third most frequent serotypes in children <2 years were 23F (7.3%) and 6B (7.7%) whereas in adults ≥16 years serotypes 3 (8.3%) and 4 (7.0%) were the second and

Clinical presentations following pneumococcal infections prior to the introduction of PCV7

Pneumococcal disease (PD) can be non-invasive such as otitis media, sinusitis, mastoiditis and non-bacteraemic pneumonia, or invasive (IPD) such as bacteraemia, meningitis, and bacteraemic pneumonia. IPD is defined by the isolation of S. pneumoniae from a normally sterile site (e.g. blood or cerebrospinal fluid, but not sputum).

In the US, the main clinical manifestation was occult bacteraemia in the younger age groups and bacteraemic pneumonia in the older age groups [10]. The case fatality

Pneumococcal serotypes, invasive power and disease severity

Not all of the more than 90 pneumococcal serotypes that have been identified based on their capsular polysaccharide antigens cause disease [12]. Among those that cause disease, not all have the same invasive potential. Serotypes that are more heavily encapsulated, with a lower invasive power and higher carriage prevalence have been reported to cause more severe disease. Serotypes 3, 6A, 6B, 9N and 19F have been repeatedly reported to be associated with an increased 30-day mortality risk in

Risk factors for IPD

The frequency of IPD in patients with comorbidities aged ≥50 years in the US increased significantly from 1998–1999 to 2002–2003; in patients with diabetes (from 15.3% to 21.8%), chronic obstructive pulmonary disease (from 21.7% to 25.0%), receiving recent immunosuppressive treatment (from 6.6% to 9.1%), ≥1 immunocompromising condition (from 19.5% to 23.0%) and those with other co-morbid conditions (from 53.9% to 62.6%) [17]. In the US the percentage of children <5 years with IPD with ≥1

Pneumococcal vaccination in children: Direct and indirect effects

Conjugation of certain capsule polysaccharides to protein carriers provides a vaccine that enables children aged <2 years to mount a protective immune response against vaccine serotypes early in life. Since the introduction of a seven-valent conjugate vaccine, PCV7, containing serotypes 4, 6B, 9V, 14, 18C, 19F and 23F, in North America, Australia and many European countries, substantial reductions in the incidences of PCV7-VT IPD, and healthcare visits (hospitalization, emergency room and

Pneumococcal vaccination in adults

In many countries the licensed 23-valent plain polysaccharide vaccine (PPV23) is recommended for all adults ≥65 years who are unvaccinated or were vaccinated ≥5 years previously and for adults aged 19–64 years with high risk of IPD due to underlying conditions; the exact conditions vary between countries but often include congenital or acquired immunosuppression, asthma, diabetes, and several other chronic disorders. PPV23 contains 12 of the serotypes in PCV13 (not 6A) and 11 other serotypes:

Clinical efficacy of conjugate pneumococcal vaccines in adults

Clinical efficacy data for PCVs in adults are sparse. In HIV-infected adults who had recovered from documented IPD, PCV7 has been reported to prevent recurrent pneumococcal infections due to PCV7-types and serotype 6A [55]. However, there is a wealth of immunological bridging data suggesting that since PCVs induce similar antibody levels in adults as those seen in children (although children need more doses), similar clinical efficacy can be expected, but direct evidence is now needed. The

Acknowledgements

The authors would like to thank Margaret Haugh (MediCom Consult) for writing and editorial assistance, funded by Pfizer International Operations, Paris, France, in the preparation of this manuscript. The authors received no financial support for the preparation of this manuscript.

References (56)

  • E. Miller et al.

    Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine

    Vaccine

    (2011)
  • D.R. Feikin et al.

    Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults

    Vaccine

    (2001)
  • S.B. Gordon et al.

    Pneumococcal conjugate vaccine is immunogenic in lung fluid of HIV-infected and immunocompetent adults

    J Allergy Clin Immunol

    (2007)
  • Centres for Disease Control and Prevention

    Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP)

    MMWR Recomm Rep

    (1997)
  • B. Simell et al.

    The fundamental link between pneumococcal carriage and disease

    Expert Rev Vaccines

    (2012)
  • C. Weil-Olivier et al.

    Prevention of pneumococcal diseases in the post-seven valent vaccine era: a European perspective

    BMC Infect Dis

    (2012)
  • J. Flamaing et al.

    Pneumococcal colonization in older persons in a nonoutbreak setting

    J Am Geriatr Soc

    (2010)
  • A. Melegaro et al.

    Estimating the transmission parameters of pneumococcal carriage in households

    Epidemiol Infect

    (2004)
  • G. Regev-Yochay et al.

    Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings

    Clin Infect Dis

    (2004)
  • D. Goldblatt et al.

    Antibody responses to nasopharyngeal carriage of Streptococcus pneumoniae in adults: a longitudinal household study

    J Infect Dis

    (2005)
  • M. Imohl et al.

    Association of serotypes of Streptococcus pneumoniae with age in invasive pneumococcal disease

    J Clin Microbiol

    (2010)
  • K.A. Robinson et al.

    Epidemiology of invasive Streptococcus pneumoniae infections in the United States, 1995–1998: opportunities for prevention in the conjugate vaccine era

    JAMA

    (2001)
  • A.G. Jansen et al.

    Invasive pneumococcal disease among adults: associations among serotypes, disease characteristics, and outcome

    Clin Infect Dis

    (2009)
  • D.S. Shouval et al.

    Site-specific disease potential of individual Streptococcus pneumoniae serotypes in pediatric invasive disease, acute otitis media and acute conjunctivitis

    Pediatr Infect Dis J

    (2006)
  • M. Weinberger Daniel et al.

    Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis

    Clin Infect Dis

    (2010)
  • Z.B. Harboe et al.

    Pneumococcal serotypes and mortality following invasive pneumococcal disease: a population-based cohort study

    PLoS Med

    (2009)
  • K. Sjostrom et al.

    Clonal and capsular types decide whether pneumococci will act as a primary or opportunistic pathogen

    Clin Infect Dis

    (2006)
  • A.J. van Hoek et al.

    Effect of serotype on focus and mortality of invasive pneumococcal disease: coverage of different vaccines and insight into non-vaccine serotypes

    PLoS One

    (2012)
  • Cited by (21)

    • Serotype distribution of invasive Streptococcus pneumoniae in adults 65 years of age and over after the introduction of childhood 13-valent pneumococcal conjugate vaccination programs in Canada, 2010–2016

      2018, Vaccine
      Citation Excerpt :

      Adult vaccines for pneumococcal disease include the 23-valent pneumococcal polysaccharide vaccine (PPV23), which has been available since 1996 with efficacy in preventing invasive disease but has limited effectiveness with respiratory disease [7,20,21]. PPV23 is not licenced for routine use in young children and has little efficacy on carriage, an important reservoir for the transmission and spread of invasive disease [5,22–24]. PPV23 has also had little effect on IPD prevalence rates of constituent serotypes in adults, possibly due to low coverage, or due to the lower effectiveness of a non-conjugated polysaccharide vaccine [22,25–27].

    • Risk and outcomes of invasive pneumococcal disease in adults with underlying conditions in the post-PCV7 era, The Netherlands

      2016, Vaccine
      Citation Excerpt :

      Quantification of the risk of IPD and outcomes in persons with underlying conditions and elderly can be useful for policy makers to decide about preventive strategies. Since the European population is ageing [36] the burden of pneumococcal disease is likely to increase and vaccination of elderly or risk groups with a pneumococcal conjugate vaccine could be an effective strategy [11,13]. However, herd effects after PCV7 introduction in children already resulted in a substantial decrease in PCV7-type IPD and replacement disease with non-PCV7-type IPD in both elderly ≥65 years and other non-vaccinated adults (with and without underlying conditions) [1].

    View all citing articles on Scopus
    1

    Tel.: +33 450 636 320.

    View full text