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Rapport

Efficacy and effectiveness of pneumococcal vaccination in elderly – an update of the literature

This work is a collaboration between colleagues at the Norwegian, Swedish and Danish Public Health Institutes based on a common need for an updated knowledgebase to inform national guidelines for pneumococcal vaccination in medical risk groups and elderly.

Pneumococcal vaccines in elderly_OMSLAG_web.png

This work is a collaboration between colleagues at the Norwegian, Swedish and Danish Public Health Institutes based on a common need for an updated knowledgebase to inform national guidelines for pneumococcal vaccination in medical risk groups and elderly.


Hovedbudskap

  • S. pneumonia is a major cause of morbidity and mortality, specifically at the extremes of age and in individuals with immunocompromising medical conditions. Two different vaccines, a 23-valent polysaccharide vaccine (PPV23) and a 13-valent pneumococcal conjugate vaccine (PCV13) are available to prevent pneumococcal disease in adults.
  • No studies compare vaccine effectiveness of PPV23 and PCV13 head-to-head.
  • Direct comparison between the two vaccines are difficult due to differences in populations, time since vaccination and study designs.
  • Whereas the evidence for PCV13 is dominated by one large trial with overall healthy elderly, the evidence for PPV23 VE is based on several trials of moderate quality and several observational studies.
  • Results obtained from RCTs and those obtained from various observational designs are inconsistent, making it difficult to summarize available evidence into single quantitative measures.
  • Higher vaccine effectiveness seen in clinical trials may reflect shorter follow-up time compared with observational studies, where waning immunity is likely to play a role.
  • Both PPV23 and PCV13 are comparably effective for the prevention of all-type invasive pneumococcal disease (IPD) in the broader adult population, across study designs and settings.
  • PCV13 seems to provide better protection than PPV23 against vaccine type IPD (for serotypes common to PCV13 and PPV23).
  • The overall body of evidence shows PPV23 VE at a level comparable to PCV13.
  • Both vaccines showed generally lower VE with increasing age, but data are limited for PCV13.
  • Both vaccines showed generally lower VE in groups with comorbidities compared with groups without known risk.
  • With one exception from a case-control study with overall high VE estimates, both vaccines failed to show significant VE in immunocompromised groups.

Sammendrag

Norsk sammendrag

Introduksjon

Små barn, eldre og personer med svekket immunforsvar har høyest risiko for å få invasiv pneumokokksykdom og pneumokokkpneumoni. To ulike vaksiner er tilgjengelig for å forebygge pneumokokksykdom hos voksne; en 23-valent polysakkarid vaksine (PPV23) og en 13-valent konjugat vaksine (PKV13). Denne litteraturgjennomgangen vil brukes som grunnlag for oppdaterte nasjonale anbefalinger for bruk av pneumokokkvaksiner hos eldre i Norge, Sverige og Danmark.

Metode

Rapporten inkluderer publikasjoner om effekt av PKV13 og PPV23 fra 2000 til april 2019 fra randomiserte kontrollerte studier og observasjonsstudier. Utfall inkluderer invasiv pneumokokksykdom og pneumokokkpneumoni.

Resultater

Totalt 27 artikler er inkludert; 18 publikasjoner om effekt av PPV23 og ni publikasjoner om effekt av PKV13. Ingen studier har sammenlignet effekt av PKV13 og PPV23 direkte. Kunnskapsgrunnlaget for effekt av PKV13 hos eldre domineres av en stor randomisert studie med i hovedsak friske eldre. For PPV23 er kunnskapsgrunnlaget basert på randomiserte studier med moderat kvalitet og en rekke observasjonsstudier. Forskjell i studiepopulasjoner, studiedesign og tid siden vaksinasjon gjør det vanskelig å oppsummere effektestimat i entydige kvantitative mål.


Effekt av PPV23 for forebygging av invasiv pneumokokksykdom er på linje med tidligere systematiske litteraturgjennomganger, og i samsvar med PKV13 effekt-estimater. Effekt-estimater var konsistente på tvers av observasjonelle studier og økologiske studier med overvåkingsdata for den generelle eldre befolkningen. PKV13 ser ut til å gi bedre beskyttelse enn PPV23 for serotyper som inngår i begge vaksinene. Vi fant at både PPV23 og PKV13 er effektive i å forebygge pneumokokkpneumoni hos eldre på sammenlignbare nivå. Effekt-estimater for PPV23 var høyere i kontrollerte studier enn i observasjonsstudier, noe som muligens reflekterer kortere oppfølgingstid og dermed mindre betydning av fallende immunitet. Både PPV23 og PKV13 viste generelt lavere effekt med økende alder for alle utfall og hos personer med immunsvekkende tilstander. I hovedsak ble det ikke vist signifikant vaksineeffekt hos personer med immunsvekkelse.

Konklusjon

Rapporten viser at både PKV13 og PPV23 beskytter mot invasiv pneumokokksykdom og pneumokokkpneumoni hos eldre. Det totale kunnskapsgrunnlaget viser at effekt av PPV23 er på sammenlignbart nivå som PKV13. Dette er av stor betydning for folkehelsen på grunn av den høye sykdomsbyrden knyttet til pneumokokkpneumoni. Det er viktig å legge seortypefordeling i bærerskap og sykdom til grunn for å vurdere nytten av vaksinasjon. Den lave andelen pasienter som i dag blir syke med serotyper som inngår i PKV13 antyder begrenset potensiale for forebygging fra PKV13 vaksinasjon hos voksne.  Vel-designede og serotype-spesifikke randomiserte kontrollerte studier er nødvendige for å forbedre kunnskapsgrunnlaget.

 

English summary

Introduction

Young children, elderly and persons with weakened immune systems are at high risk of acquiring invasive pneumococcal disease and pneumococcal pneumonia. Two different vaccines are available for the prevention of pneumococcal disease in adults; a 23-valent polysaccharide vaccine (PPV23), and a 13-valent conjugated vaccine (PCV13). The updated review will serve as a bases to inform national recommendations for use of pneumococcal vaccines in elderly in Norway, Sweden and Denmark.

Methods

The report covers publications on PCV13 and PPV23 efficacy and effectiveness from 2000 until April 2019 from randomized controlled trials and observational studies. Outcomes include invasive pneumococcal disease and pneumococcal pneumonia.

Results

A total of 27 publications are included; 18 publications on PPV23 effectiveness and nine publications on PCV13 effectiveness. No study compared the effectiveness of PPV23 and PCV13 directly. One large trial with overall healthy elderly dominates the evidence for PCV13 efficacy and effectiveness. The evidence for PPV23 vaccine effectiveness, on the other hand, is based on trials of moderate quality and several observational studies. Differences in populations, study designs and time since vaccination makes it difficult to summarize available evidence into single quantitativemeasures.

The vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease was consistent with past systematic reviews and similar to the estimates that have been reported for PCV13 efficacy and effectiveness. Consistent effects were reported across observational studies and ecological studies of surveillance data for the general elderly population. PCV13 seems to provide better protection than PPV23 against vaccine-type invasive pneumococcal disease (for serotypes common to PCV13 and PPV23).

We found both PPV23 and PCV13 to be effective in preventing pneumococcal pneumonia in elderly at comparable levels. The PPV23 vaccine effectiveness was higher in clinical trials than observational studies, possibly reflecting a shorter follow-up time and a more limited impact of waning immunity.

Both PPV23 and PCV13 showed generally lower effectiveness with increasing age for all outcomes and in groups with immunocompromising conditions. Overall, significant VE was not shown for immunocompromised groups.

Conclusion

This report shows that both PCV13 and PPV23 provide prevention for invasive disease and pneumococcal pneumonia in the elderly. The overall body of evidence shows PPV23 effectiveness at a level comparable to PCV13. This finding is of paramount importance for public health due to the high pneumococcal pneumonia disease burden. The serotype distribution in carriage and disease is important to consider for the impact of vaccination. The currently low proportion of patients falling ill with serotypes included in PCV13 suggests limited potential for prevention from adult PCV13 vaccination. Well-designed and serotype specific randomized controlled trials are important to improve evidence.

Referanser

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    Om rapporten

  • Utgitt: 12/2019
  • Av: Folkehelseinstituttet
  • Forfattere: Winje BA, Berild JD, Vestrheim DF, Denison E, Lepp T, Roth A, Valentiner-Branth P, Slotved HC, Storsæter J .
  • ISBN elektronisk: 978-82-8406-053-8