Pneumococcal vaccination in older persons: where are we today?
Van Buynder and Booy Pneumonia
Pneumococcal vaccination in older persons: where are we today?
Paul Van Buynder 0 1
Robert Booy 0 2
0 Immunisation Coalition , Melbourne, VIC , Australia
1 Griffith University , Southport, QLD , Australia
2 Sydney University , Sydney , Australia
Disease due to Streptococcus pneumoniae, the pneumococcus, remains a major source of illness in older persons. Globally, it remains the most important pathogen in respiratory infection deaths. Conjugated pneumococcal vaccines are used extensively in national pediatric programs, whereas a polysaccharide vaccine is used in all age groups, but mainly in the elderly and for high-risk groups. Recent data from the Netherlands led to the licensing in many countries of conjugated pneumococcal vaccines for older persons. There are substantial differences in recommendations from various national immunization technical advisory groups, which owe at least as much to differing assessments of available studies as to differences in local epidemiology. This review examines those differences and proposes a way forward.
Pneumococcus; Vaccination; Effectiveness; Elderly
Infections caused by Streptococcus pneumoniae, the
pneumococcus, may involve a normally sterile site; for
example, blood or joint fluid (known as invasive
pneumococcal disease (IPD)], or more commonly a local
mucosal infection; for example, community-acquired
non-bacteraemic pneumonia (CAP). Pneumococcal
infection remains a major source of illness in the elderly.
Globally, across all age groups, pneumococcus remains
the most important pathogen in deaths due to
respiratory infections [
]. Data on IPD cases are relatively
robust in many countries, but for CAP the magnitude of
the pneumococcus’ contribution is poorly understood.
Two types of vaccine are available and in widespread
use in many countries. Conjugated vaccines (PCVs),
covering 7 (Prevenar 7® Pfizer, 7vPCV), 10 (Synflorix®
GlaxoSmithKline), or 13 serotypes (Prevenar 13 Pfizer,
13vPCV), are used extensively in national pediatric
programs, whereas a polysaccharide vaccine containing
23 serotypes (Pneumovax23® Merck, 23vPPV) is used
mainly in the elderly and for high-risk groups.
Neither the 7-valent nor the 10-valent conjugated
vaccines are commonly used in current immunization
programs; therefore, these vaccines are not considered
further in this review. Both vaccines contain a subset of
serotypes in 13vPCV.
Recent data from the Netherlands
CommunityAcquired Pneumonia Immunisation Trial in Adults
(CAPiTA) led to the licensing in many countries of
conjugated vaccine for older persons and also assessment of
the role of both vaccines in this age group [
debate about the effectiveness of vaccines (particularly
against CAP), the duration of their effectiveness, the
presence of hypo-responsiveness when 23vPPV and a
PCV are given in sequence, and herd protection induced
by pediatric programs resulting in disease reduction in
older persons, has led to various vaccination program
There are substantial differences in the recommendations
from various national immunization technical advisory
groups (NITAGs), which the authors believe owes at least
as much to differing assessments of available studies as to
differences in local epidemiology.
This review examines those differences and proposes a
Burden of pneumococcal disease in the elderly
Assessing data for CAP of any cause and, more
specifically, pneumococcal CAP is challenging—there is often
no surveillance mechanism in place and published
studies have used various combinations of diagnostic
tests including blood culture, urinary antigen test, and
sputum culture. Additionally, some historical studies
used a pneumolysin test that no longer is regarded as
diagnostic due to its poor specificity [
A review of national databases from 2004 to 2012 and
of published studies in Australia set the pneumococcal
pneumonia hospitalization rate in those aged ≥65 years
at 274/100,000 population, or 20% of all CAP
hospitalisations. GP visits for pneumococcal CAP averaged 455
per 100,000 per year. Hospitalizations for IPD in 2012
were only found to be 19/100,000; thus pneumococcal
CAP hospitalization rates were 15-fold higher than for
IPD and the costs to the healthcare system were
determined to be around 30 fold higher [
Similarly, a three-year Canadian Serious Outcomes
Surveillance (SOS) Network review found 23% of
allcause pneumonia admissions to be due to
pneumococcus with a higher percentage in older patients and
patients with a higher disease burden and mortality [
The number of admissions due to pneumococcal CAP
was 13-fold higher than the rate of IPD admission.
Trends in the burden of disease
Is the vaccine- type IPD burden decreasing as a result of
An Australian review of IPD trends in non-indigenous
elderly people showed an ongoing substantial decrease
in IPD due to serotypes found in the 7 V conjugated
vaccine since its introduction in 2004. A similar trend was
evident after only about 3 years of use of 13vPCV
(against the additional 6 serotypes), and further decline
continues. Conversely, likely as a result of serotype
replacement, the IPD proportion attributable to 23v–
non13v serotypes is increasing, with a rise from 19% to
27% of IPD in Australia [
]. Studies in other countries
have confirmed the impact of pediatric conjugated
vaccine programs on vaccine-type (VT) IPD rates in
older persons [
A significant proportion of the residual 13vPCV IPD
currently seen is due to serotype 3; neither 13vPCV nor
23vPPV appear to have much effectiveness against this
serotype. Studies in many countries have shown both
poor vaccine effectiveness (VE) and no, or low, impact
on disease rates with this serotype [
]. In the Andrews
] of 23vPPV, the VE against serotype 3 was
−23% (95% CI, −85% to −19%).
A meta-analysis of the indirect effects of conjugated
vaccines found the mean time taken to attain a 90%
reduction in VT IPD due to 7vPCV serotypes was 8.9 years,
and 9.5 years for the additional serotypes in 13vPCV, but
not in 7vPCV [
Is the vaccine-type CAP burden decreasing as a result of
While data are more limited and somewhat inconsistent
for CAP, a decline in VT 13vPCV CAP is also expected
from the childhood program and has already been seen
in unvaccinated young adults and older persons in some
A cohort study of non-bacteremic pneumococcal
pneumonia cases in adults in Nottingham described a
30% reduction of the proportion of 13vPCV serotypes
within 3 years of the switch from 7vPCV to 13vPCV in
the childhood program, having already seen an 88%
decrease in CAP due to serotypes in 7vPCV [
]. A Dutch
review demonstrated a decline in pneumococcal CAP
due to 7vPCV serotypes over a 5-year period, from 28%
of cases to 7% of cases [
]. In the United States (US),
an assessment of the impact of childhood 7vPCV, using
the Nationwide Inpatient Sample database, found an
annual reduction in pneumonia hospitalisations of 168,000,
with the majority of these in older persons [
Both invasive and non-invasive disease rates due to
serotypes covered in the childhood 13vPCV program
are declining in older persons.
Vaccine effectiveness against community-acquired pneumonia
Published estimates place the burden of disease due to
CAP (based on hospitalizations) as at least an order of
magnitude greater than that due to IPD. Thus the
effectiveness of both vaccine groups against CAP is important
in the comparative assessment of the two vaccines, even
if the burden of disease is decreasing due to serotypes in
VE data against CAP with 13vPCV is available from
the CAPITA study, which was a randomised controlled
trial (RCT). The study found a VE of 45% against VT
pneumococcal CAP, 22% against all-type pneumococcal
CAP and 5% against all-cause CAP [
Reviews of available studies, including RCTs and
observational studies, have come to differing conclusions
about 23vPPV effectiveness against pneumococcal CAP.
The variation occurs in both the estimated VE and the
duration of effectiveness. The differences in outcomes of
these meta-analyses are due to important variations in
study inclusion criteria and variations in the quality and
focus of the studies reviewed.
Two of the studies [
] included in some analyses
only measured all-cause CAP, thus biasing the observed
VE towards no effect. Additionally, in the study by Ortqvist
et al.  (VE of −18%) the diagnosis of pneumococcal
pneumonia was made on the detection of serum antibodies
against pneumolysin using poorly validated in-house
enzyme-linked immunosorbent assay (ELISA) methods,
which was later shown to have poor specificity.
Clinical studies and review documents have variously
ascribed impacts of 23vPPV against pneumococcal
CAP from no effect through to around 50% in many
studies. While the studies are beset with
methodological challenges and difficult to compare,
the weight of evidence from the ‘better’ studies suggests
that the attributable VE is non-zero and somewhere in
this range. Protection against all cause CAP with both
conjugate and polysaccharide vaccine types is similar
and low, around 5%.
The observational studies in favour of 23vPPV being
effective against VT CAP include a multi-centre
Japanese prospective cohort study, which found 33% VE
against VT CAP, 27% against all pneumococcal CAP and
2% against all CAP [
]; and a Spanish cohort study that
analysed for receipt of vaccine in the last 5 years and
found higher VE rates, namely, 48% against
pneumococcal CAP and 25% against all cause CAP [
prospective RCT that analysed receipt of 23vPPV in
high-risk residents of Japanese nursing homes also found
a significant reduction in both pneumococcal
pneumonia and all-cause CAP [
Supporting a duration of protection with 23vPPV
against CAP out to 5 years, Vila-Corcoles found a VE of
46% for pneumococcal CAP analysing subjects who were
vaccinated up to 5 years previously [
reviews in favour of 23vPPV effectiveness include a
German study [
] allocating a VE against pneumococcal
CAP of 64% in clinical trials with follow up of 2.5 years,
and 48% in cohort studies followed up to 5 years. A
Portuguese review [
] found the range of VE against
pneumococcal CAP hospitalisations to be between 32%
and 51%, with lower protection if vaccination was given
more than 5 years previously. The derived VE against
all-cause CAP hospitalisation was 10.2%. A Canadian
review focussing on all-cause CAP derived a VE of 4% for
trials, 17% for cohort studies and 7% for case control
studies and described it as similar to the results from
CAPITA, which assessed 13vPCV [
The 2013 Cochrane review of 23vPPV vaccine
effectiveness against pneumococcal pneumonia derived
a pooled VE of 54% (CI 16–75%) but this review
included some older PPV formulations with higher
antigen contents per serotype [
]. The studies also
included many young adults who have stronger
immune responses. No benefit was found against
CAP for adults in developed countries. The Cochrane
review is currently under revision.
Other studies have found no effect of 23vPPV on
pneumonia rates. A recent very large study in 152,000
healthy adults demonstrated no vaccine effect on
pneumonia incidence [
]. However, this study was
conducted over a very short time frame and found no cases
at all of pneumococcal CAP. Another retrospective study
also concluded that 23vPPv did not affect pneumonia
hospitalization rates in the elderly [
The assessment of the cost effectiveness of
pneumococcal vaccines in older persons is critically affected by: 1)
the estimate used for herd protection produced by the
conjugated childhood program against CAP; 2) the
estimate used of VE for 23vPPVagainst pneumococcal
pneumonia; 3) the VE for all-cause CAP (for each
vaccine); and 4) the duration of effectiveness allocated to
A British review, influenced heavily by the herd
protection estimates, suggested that for 13vPCV to be cost
effective the vaccine price needed to be negative [
Germany, the decision made by their NITAG to not
recommend 13vPCV and to continue using 23vPPV was
based on the recent systematic review and meta-analysis
by Falconhurst et al. [
], and the cost effectiveness
review by Kuhlmann [
]. Again, herd protection was a
critical factor, with the 23vPPV effectiveness on
pneumococcal CAP a major source of uncertainty. The
National Advisory Committee on Immunization in
Canada also did not recommend the use of 13vPCV in
persons ≥65 years of age.
When making the decision in the US to use both
conjugate and polysaccharide vaccines sequentially for
3 years and then review the use of 13vPCV in 2018 [
the Advisory Committee on Immunization Practices
(ACIP) relied in part on a preliminary analysis using a
probabilistic model involving a single cohort of persons
aged 65 years. This demonstrated that “adding a dose of
13vPCV to the current 23vPPSV recommendations for
adults aged ≥65 years would prevent approximately
12,000 cases of CAP over the lifetime of a single cohort
of persons aged 65 years … [but] the expected benefits
of 13vPCV use among this cohort will likely soon
decline to an annually estimated 4,500 cases of CAP
averted among persons aged ≥65 years” [
A review of the evidence assessed in making this
decision highlighted the changing epidemiology of
pneumococcal disease and the need to evaluate the
utility and effectiveness of the new strategy [
The way forward
The burden of pneumococcal infections remains
significant and more effective prevention could be achieved.
Both conjugated and polysaccharide vaccines appear to
be equally ineffective (around 4–5% VE) against
allcause CAP, in part because of a low contribution of
pneumococcal CAP to all-cause CAP but also the
increase in non-VT pneumococcal disease being seen.
While some data exists to suggest that 23vPCV is not
effective against pneumococcal CAP, enough recent
studies suggest that VE with 23vPCV could even be as
high as 50% and the duration of effectiveness may
stretch to 5 years. There is no case to cease 23vPPV
programs in older persons and, despite some
hyporesponsiveness concerns, a case can be made for
revaccination of older persons with chronic conditions every
5 years. Disease rates increase with increasing age and
revaccination is likely to produce long-term antibody
levels consistent with primary vaccination [
5year interval minimises the increase in self-limiting
adverse events seen with revaccination [
The case for the additional use of 13vPCV is harder to
make on a cost basis. Strong data supports the very
significant reduction in VT disease due to 13vPCV in
older persons after pediatric conjugate vaccine programs,
thereby reducing the cost effectiveness of 13vPCV use for
the elderly. An opportunity exists now to await the
upcoming US review of using both vaccines sequentially to
clarify some of the uncertainties.
Current coverage rates of 23vPPV in older person
programs need to be increased. It is likely that the
increase in disease in the elderly due to the 11 serotypes
contained in 23vPPV (but not in 13vPCV) relates not
only to replacement infection but also inadequate
coverage rates with 23vPPV.
Where governments can afford to use both vaccines
for the elderly (as the US has done), better disease
prevention may be achieved. Most importantly, vaccines
with a broader coverage and duration of protection are
Most national advisory bodies have recommended
continuation of a polysaccharide program for older persons
without the addition of a conjugated vaccine to their
program. Monitoring of the burden of disease in
different countries over the next few years will be important
in providing better data for decision making.
The authors thank the members of the Immunisation Coalition Scientific
Advisory Committee for comments and discussions about the manuscript.
No funding was received for this editorial.
Availability of data and materials
Both authors contributed equally to the drafting, critical review and writing
of this manuscript. Both authors read and approved the final manuscript.
Ethics approval and consent to participate
Consent for publication
The authors declare that they hold non-remunerated positions as Chairman
(PVB) and a Director (RB) of the Immunisation Coalition, a not-for-profit
immunisation advocacy group. The Immunisation Coalition has received
funding support for education, workshops and marketing purposes from all
the companies with pneumococcal vaccines in Australia; GSK, Seqirus and
Springer Nature remains neutral with regard to jurisdictional claims in
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