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Pneumococcal vaccination in adults
Author
Daniel M Musher, MD
Section Editor
John G Bartlett, MD
Deputy Editor
Anna R Thorner, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2016. | This topic last updated: Feb 24, 2016.
INTRODUCTION Pneumococcal infections, including pneumonia and invasive disease such as bacteremia and
meningitis, are important sources of morbidity and mortality in children <1 year of age, older adults, and persons with
conditions that affect their ability to make antibody to capsular polysaccharides. Asplenia greatly increases the risk for
overwhelming systemic infection, and cerebrospinal fluid leak or a cochlear implant greatly increases the risk for
meningitis. Pneumococcal vaccination is recommended for all children, for adults who have a condition that places
them at increased risk for pneumonia or invasive pneumococcal disease, and for all adults 65 years of age.
The highest incidence of invasive pneumococcal disease occurs in children <2 years of age, persons who have certain
underlying conditions such as HIV infection, and those 65 years of age (table 1). The highest mortality rates occur in
individuals 65 years of age, especially in those who have significant comorbidities. (See "Invasive pneumococcal
(Streptococcus pneumoniae) infections and bacteremia", section on 'Epidemiology' and "Invasive pneumococcal
(Streptococcus pneumoniae) infections and bacteremia", section on 'Prognosis'.)
The indications for, immunogenicity of, and efficacy and adverse reactions associated with pneumococcal vaccination in
adults will be presented here. Pneumococcal vaccination in children and specific groups of high-risk adults is discussed
in detail separately. (See "Pneumococcal (Streptococcus pneumoniae) conjugate vaccines in children" and
"Pneumococcal (Streptococcus pneumoniae) polysaccharide vaccines in children" and "Pneumococcal immunization in
HIV-infected adults" and "Prevention of sepsis in the asplenic patient", section on 'Pneumococcal vaccine' and
"Immunizations in solid organ transplant candidates and recipients", section on 'Pneumococcus' and "Immunizations in
hematopoietic cell transplant candidates and recipients", section on 'Pneumococcus' and "Immunizations in patients
with cancer", section on 'Pneumococcal vaccine' and "Immunizations for patients with chronic liver disease", section on
'Pneumococcal vaccine' and "Immunizations in patients with end-stage renal disease", section on 'Pneumococcal
vaccine'.)
The microbiology, pathogenesis, epidemiology, clinical manifestations, diagnosis, and treatment of pneumococcal
infections are also presented separately. (See "Microbiology and pathogenesis of Streptococcus pneumoniae" and
"Invasive pneumococcal (Streptococcus pneumoniae) infections and bacteremia" and "Pneumococcal pneumonia in
adults".)
APPROACH TO VACCINATION
Available vaccines The surface capsular polysaccharide of Streptococcus pneumoniae is the principal means by
which these organisms resist ingestion and killing by phagocytic cells. Antibody to capsule greatly facilitates
phagocytosis and killing. Capsular polysaccharide is the essential component of all pneumococcal vaccines that are
currently available. More than 90 different pneumococcal capsular serotypes have been identified (see "Microbiology
and pathogenesis of Streptococcus pneumoniae", section on 'Capsule'). Since it is not possible to include all of the
serotypes in a pneumococcal vaccine, available vaccines contain capsular polysaccharides from serotypes that are
most likely to cause invasive disease.
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Two types of pneumococcal vaccines are approved for use in the United States:
Pneumococcal polysaccharide vaccine (PPSV23; Pneumovax or Pnu-Immune) consists of capsular material from
23 pneumococcal types (table 2), which, in the past, caused approximately 85 to 90 percent of cases of
pneumococcal disease [1] but now cause only about 50 to 60 percent of such cases in adults [2]. PPSV23 has
been used in adults for decades but not in infants or toddlers under age two since polysaccharide antigens are
poorly immunogenic in such individuals.
Pneumococcal conjugate vaccine (PCV, initially marketed as a 7-valent vaccine, PCV7 [Prevnar or Prevnar 7],
now replaced by PCV13 [Prevnar 13]) consists of capsular polysaccharides from the 13 most common types that
cause disease, covalently linked to a nontoxic protein that is nearly identical to diphtheria toxin. This covalent
linking to a protein renders the polysaccharide antigenic in infants and toddlers. Pneumococcal conjugate
vaccines with different numbers of serotypes are produced in other parts of the world (table 2). Because of its
excellent immunogenicity in infants and toddlers, PCV7 was adopted for universal use in this age group beginning
in 2000; since 2010, PCV13 has been recommended for infants and children in its place. Starting in 2012, PCV13
began to be recommended for use in selected high-risk adults and, in 2014, PCV13 began to be recommended
for all adults 65 years of age (table 3).
In countries that have widespread childhood vaccination programs in place, PCV13 contains antigens that, in
2013, might have stimulated antibody to serotypes that cause 28 to 42 percent of adult pneumococcal infections
[3]. This percentage is rapidly declining, and experience with PCV7 showed a three- to four-year lag when
declines in invasive pneumococcal disease in adults were compared with those in children [4].
The use of pneumococcal vaccines in infants and children is discussed in detail separately. (See "Pneumococcal
(Streptococcus pneumoniae) conjugate vaccines in children" and "Pneumococcal (Streptococcus pneumoniae)
polysaccharide vaccines in children".)
Indications The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for many
years in the United States for all adults 65 years of age and in younger patients who have a condition that increases
the risk of invasive pneumococcal disease or pneumococcal pneumonia. Risk factors for invasive pneumococcal
disease and pneumococcal pneumonia are discussed in detail separately. (See "Invasive pneumococcal
(Streptococcus pneumoniae) infections and bacteremia", section on 'Risk factors for infection' and "Pneumococcal
pneumonia in adults", section on 'Risk factors'.)
In 2011, PCV13 was approved by the US Food and Drug Administration (FDA) for use in adults 50 years of age,
based on studies showing that PCV13 stimulates good antibody responses in adults in this age group [5].
In 2012, the United States Advisory Committee on Immunization Practices (ACIP) began recommending sequential
administration of both PCV13 and PPSV23 for individuals aged 19 or older with functional or anatomic asplenia, an
immunocompromising condition (eg, HIV infection, cancer), a cerebrospinal fluid leak, a cochlear implant, or advanced
kidney disease [6].
In 2014, the ACIP began recommending sequential administration of both PCV13 and PPSV23 for all adults 65 years
of age who have not previously received a pneumococcal vaccine [7]. The ACIP will reevaluate their recommendations
for adults 65 years of age in 2018 and will revise them as needed.
ACIP recommendations for use of one or both kinds of vaccines are summarized in the Table (table 3). Specific
recommendations for pneumococcal vaccination of hematopoietic cell transplant recipients are presented separately.
(See "Immunizations in hematopoietic cell transplant candidates and recipients", section on 'Pneumococcus'.)
To our knowledge, no other developed country has made an official recommendation for routine use of PCV13 in adults
65 years of age, but some countries recommend its use (followed by PPSV23) for immunocompromised patients.
PPSV23 In accordance with the ACIP, we recommend PPSV23 alone for persons aged 19 to 64 years who
have certain risk factors for pneumococcal infection and/or serious complications of pneumococcal infection (table 3)
[6,8]. Patients who should receive both PPSV23 and PCV13 as well as indications for revaccination are discussed
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In patients who require both PPSV23 and PCV13, the two vaccines should be given at different times as outlined
above; the schedule depends on which formulation was given first. (See 'Schedule for dual vaccination' above.)
Revaccination For immunocompromised patients and individuals with functional or anatomic asplenia who are <65
years of age, the ACIP recommends only one single revaccination with PPSV23 5 years after the first dose (table 3)
[6,8]. However, since asplenic patients are at particularly high risk for overwhelming pneumococcal infection, some
authorities recommend regular revaccination at six- to seven-year intervals [20,21]. (See "Prevention of sepsis in the
asplenic patient", section on 'Revaccination in children and adults'.)
All adults aged 65 years should receive a dose of PPSV23 even if they were vaccinated when they were <65 years
of age; however, a minimum interval of five years between PPSV23 doses should be maintained (algorithm 1) [6,8].
The ACIP does not recommend routine revaccination of immunocompetent adults with PPSV23 because data on the
efficacy of additional doses are insufficient.
Some studies have raised concern that repeated vaccination with pneumococcal polysaccharide vaccines may lead to
hyporesponsiveness [22], but this does not appear to be relevant if more than five years have passed since the
previous dose [23-25].
Some data have shown that injection site reactions are more common after revaccination than after primary
vaccination, but in most studies, such reactions were not severe, were self-limited, and tended to occur when the time
between vaccinations was less than five years [26-28]. (See 'Adverse reactions' below.)
At the present time, revaccination of adults with PCV13 is not recommended.
OVERVIEW OF BENEFITS AND LIMITATIONS Preventing pneumococcal disease in older adults and those with
certain underlying conditions is an important goal given the high burden of disease and associated morbidity and
mortality in these populations [8]. Many (but not all) studies of the pneumococcal polysaccharide vaccine have
demonstrated efficacy against invasive and noninvasive pneumococcal disease [29], such as bacteremia and
meningitis, but both immunogenicity and efficacy are lower in elderly patients and immunocompromised hosts (ie, the
ones who are most in need of the vaccine).
The development of pneumococcal conjugate vaccines represents a major advance, and the universal use of such
vaccines in infants has led to dramatic reductions in the incidence of pneumococcal disease. This decline is seen both
among children who are vaccinated and, because the vaccine effectively eradicates nasal colonization, also among
older, nonvaccinated children and adults. This phenomenon, called the herd effect, has resulted in greater than a 90
percent decline in pneumococcal disease due to serotypes contained in PCV7 in older children who did not receive the
vaccine, as well as in adults (figure 1) [30,31]. The universal use of PCV7 has also led to a substantial reduction in
hospitalizations for pneumonia in children and adults in the United States [32]. With widespread use of PCV, preliminary
data suggest that precisely the same decline in pneumonia due to vaccine serotypes is being observed, an observation
that raises serious question about the potential benefits of using PCV13 routinely in adults, despite Advisory
Committee on Immunization Practices (ACIP) recommendations for its use. (See "Pneumococcal (Streptococcus
pneumoniae) conjugate vaccines in children", section on 'Efficacy and effectiveness' and "Invasive pneumococcal
(Streptococcus pneumoniae) infections and bacteremia", section on 'Impact of childhood vaccination' and "Impact of
universal infant immunization with pneumococcal (Streptococcus pneumoniae) conjugate vaccines in the United
States".)
There are few data on the efficacy of pneumococcal conjugate vaccines in specific high-risk groups, such as various
immunocompromised populations. The most well-studied immunocompromised group has been HIV-infected patients in
Africa, in whom the polysaccharide vaccine was not effective but the conjugate vaccine was effective [33,34]. The
CAPiTA trial, a randomized placebo-controlled trial that included approximately 85,000 adults 65 years of age in the
Netherlands demonstrated the efficacy of PCV13 in this age group [35], but there was no comparison with PPSV23
and immunocompromised adults were excluded. Interestingly, in those persons who developed an
immunocompromising condition during the years of observation after they received PCV13, no protective effect was
observed. (See 'Efficacy' below and "Pneumococcal immunization in HIV-infected adults", section on 'Efficacy and
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number of events in studies) and the difficulty in accurately diagnosing pneumococcal pneumonia. In general, studies
with more specific endpoints (eg, invasive pneumococcal disease caused by vaccine serotypes) have been more likely
to demonstrate efficacy than studies with less specific endpoints (eg, nonbacteremic pneumococcal pneumonia,
all-cause pneumonia, all-cause mortality) [37].
A 2013 systematic review and meta-analysis assessed the efficacy of PPSV for preventing invasive pneumococcal
disease, all-cause pneumonia, and all-cause mortality in adults in 16 randomized trials; some of the individual
meta-analyses included data from fewer than 16 trials [29]. The following results were observed:
PPSV substantially reduced the risk of invasive pneumococcal disease (odds ratio [OR] 0.26, 95% CI 0.14-0.45).
Among otherwise healthy individuals in low-income countries included in one trial, there was a significant
reduction in invasive pneumococcal disease (OR 0.14, 95% CI 0.03-0.61). This group is considered to be at
elevated risk of pneumococcal disease due to overcrowding and/or environmental factors.
Among otherwise healthy individuals in high-income countries (many of whom were elderly), there was a
significant reduction in invasive pneumococcal disease (OR 0.20, 95% CI 0.10-0.39).
The benefit of PPSV for preventing invasive pneumococcal disease was more pronounced when the analysis was
limited to trials that assessed the incidence of disease caused by serotypes included in the vaccine (OR 0.18,
95% CI 0.10-0.31).
PPSV was also associated with a substantial reduction in both invasive (OR 0.26, 95% CI 0.15-0.46) and
noninvasive pneumococcal pneumonia (OR 0.46, 95% CI 0.25-0.84).
There was efficacy against all-cause pneumonia among individuals in low-income countries (OR 0.54, 95% CI
0.43-0.67), presumably because S. pneumoniae remains the principal cause of pneumonia in such countries but
not among individuals in high-income countries in either the general population or in adults with chronic illness.
PPSV did not reduce all-cause mortality.
A 2009 systematic review graded randomized trials based on statistical criteria and retained only a few in their
meta-analysis [52]. When the analysis was limited to trials of highest methodologic quality, efficacy of vaccination was
not observed. However, their analysis gave disproportionate weight to two studies that relied on nonstandardized
serologic techniques to diagnose pneumococcal pneumonia [53,54]. These serologic tests have been shown to be of
questionable validity for diagnosing pneumococcal pneumonia [58].
As noted above, despite the fact that antibodies following PPSV23 administration decline over time, in a report from
the CDC, efficacy of the pneumococcal polysaccharide vaccine did not decline at seven or more years after
vaccination [41]. (See 'Immunogenicity' above.)
The immunogenicity and efficacy of PPSV23 in patients with a specific risk factor is discussed in detail separately.
(See "Pneumococcal immunization in HIV-infected adults", section on 'Efficacy and immunogenicity of pneumococcal
vaccination' and "Immunizations in solid organ transplant candidates and recipients", section on 'Pneumococcus' and
"Immunizations in patients with cancer", section on 'Pneumococcal vaccine' and "Immunizations in hematopoietic cell
transplant candidates and recipients", section on 'Pneumococcus' and "Management of infection in exacerbations of
chronic obstructive pulmonary disease", section on 'Vaccination' and "Immunizations in patients with end-stage renal
disease", section on 'Pneumococcal vaccine' and "Immunizations for patients with chronic liver disease", section on
'Pneumococcal vaccine'.)
Adverse reactions The most common adverse reactions to PPSV23 are injection site pain or tenderness (in 60
percent of vaccinees), swelling or induration (in 20 percent), and erythema (in 16 percent) [11]. These reactions usually
persist for less than 72 hours. Moderate systemic reactions (eg, fever and myalgias) and more severe local reactions
(eg, local induration) occur less commonly. (See "Pneumococcal polysaccharide vaccine (23-valent): Drug
information".)
As noted above, some studies have suggested that injection site reactions are more common after revaccination than
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after primary vaccination, but in most studies, such reactions were mild and self-limited [26-28]. One retrospective
study showed no increase in medically attended adverse events among individuals who received three or more doses
of PPSV23 compared with those who received one dose [59].
Healthcare providers should report suspected adverse events to the Vaccine Adverse Event Reporting System
(VAERS). VAERS can be contacted via the VAERS website or by telephone at 800-822-7967.
Contraindications A severe allergic reaction (eg, anaphylaxis) to PPSV23, an exceedingly rare event, is an
absolute contraindication to revaccination with PPSV23 [12]. (See "Pneumococcal polysaccharide vaccine (23-valent):
Drug information".)
PNEUMOCOCCAL CONJUGATE VACCINES Pneumococcal protein-conjugate polysaccharide vaccines have a
number of beneficial properties that polysaccharide vaccines lack (table 5). Children <2 years of age respond poorly to
polysaccharide antigens. However, when a polysaccharide is covalently conjugated to a carrier protein, the resulting
antigen is recognized as T celldependent, stimulating a good serum antibody response, mucosal immunity, and
immunologic memory in children (including those <2 years) and adults.
As a result of inducing a mucosal immune response and reducing nasopharyngeal colonization, pneumococcal
conjugate vaccines cause herd protection, reducing rates of disease not only in vaccinated individuals but also in those
who were not vaccinated, especially siblings and playmates, but also parents and other unvaccinated adults. With the
widespread use of PCV7 in children, the implementation of universal vaccination of infants in the United States with a
pneumococcal conjugate vaccine beginning in 2000 has resulted in a dramatic decrease in invasive pneumococcal
disease in both children and adults (figure 1). The incidence of pneumonia requiring hospitalization in all age groups has
declined, and this decline has been largely attributed to the widespread use of PCV [32]. (See "Pneumococcal
(Streptococcus pneumoniae) conjugate vaccines in children", section on 'Efficacy and effectiveness'.)
A 7-valent pneumococcal conjugate vaccine, PCV7, which contained protein-conjugated capsular polysaccharides from
the seven pneumococcal serotypes that most commonly infected children, was recommended for universal use in
infants and toddlers in the United States beginning in 2000. This recommendation was followed by a dramatic
decrease in invasive pneumococcal disease in both children and adults (figure 1). In 2010, a 13-valent pneumococcal
conjugate vaccine, PCV13, which contains four additional common serotypes plus types 1 and 5 (table 2) that are of
major significance in underdeveloped countries, was recommended in place of PCV7. Some European countries have
used a 10-valent vaccine, and a 15-valent vaccine is in development.
From January to June 2012, 29 percent of cases of invasive pneumococcal disease in adults in the United States were
caused by PCV13 serotypes [60]. In 2012, PCV13 began to be recommended for use in selected high-risk adults. In
2014, the ACIP began recommending PCV13 for all adults 65 years of age [7]. (See 'Approach to vaccination' above
and 'Available vaccines' above.)
Immunogenicity The data from various studies comparing pneumococcal conjugate vaccines (PCV) with the
23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults show that the conjugate vaccines are at least as
immunogenic as PPSV23 for the serotypes covered. A careful review of all studies published until 2011 found no
definitive or consistent advantage of either vaccine [36]. In a subsequent large study, antibody levels and opsonizing
activity were greater for the first month after vaccination with PCV13 than after vaccination with PPSV23, but, by one
year, no difference was apparent [61].
A trial showed that PCV7 elicited an increase in serotype-specific memory B cell responses, whereas PPSV23
resulted in a decrease in memory B cell frequency, supporting the hypothesis that pneumococcal conjugate vaccines
(but not polysaccharide vaccines) induce a T celldependent memory B cell response [62]. While, in theory, it might
have seemed likely that pneumococcal conjugate vaccines induce a more persistent immune response than PPSV23,
the only published data on this subject show that 12 months after vaccination, antibody activity in serum was identical
in subjects who received PCV13 when compared with PPSV23 [61].
Immunologic priming Since pneumococcal conjugate vaccines stimulate memory B cells [62], it is possible that
administration of such a vaccine may prime the immune system for an improved secondary immune response to a
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pneumococcal polysaccharide vaccine (PPSV) [37,63,64]. However, several trials failed to show that a prime-boost
regimen with a pneumococcal conjugate vaccine followed by a pneumococcal polysaccharide vaccine enhances
immunogenicity [65-69]. Two large studies showed that PCV13 followed one year later by PPSV23 led to higher
antibody activity one month after PPSV23 administration [61,64]. In a smaller study, conjugate vaccine followed by
PPSV23 booster led to better antibody levels at one month but, by six months after receipt of PPSV23, antibody levels
in booster recipients had fallen to their baseline [67]. In an open-label randomized trial, administration of the 23-valent
pneumococcal polysaccharide vaccine (PPSV23) six months prior to the 7-valent pneumococcal conjugate vaccine
(PCV7) resulted in attenuated antibody concentrations compared with PCV7 alone [68].
After considering these data, the United States Advisory Committee on Immunization Practices (ACIP) recommended
that patients with an indication for both vaccines should generally receive the conjugate vaccine first, followed a
minimum of 8 weeks later by the polysaccharide vaccine, and patients who have already received polysaccharide
vaccine first should wait 1 year before receiving conjugate vaccine. (See 'Schedule for dual vaccination' above.)
Efficacy The largest trial to assess the efficacy of PCV13 in adults was the CAPiTA trial; this trial compared
PCV13 to placebo in approximately 85,000 immunocompetent adults 65 years of age in the Netherlands who were
enrolled between 2008 and 2010 and who had not received a pneumococcal vaccine previously or who had a prior
history of pneumococcal disease [35]. The trial demonstrated 46 percent efficacy (95% CI 22 to 63 percent) of PCV13
against vaccine-type pneumococcal pneumonia, 45 percent efficacy (95% CI 14 to 65 percent) against vaccine-type
nonbacteremic pneumococcal pneumonia, and 75 percent efficacy (95% CI 41 to 91 percent) against vaccine-type
invasive pneumococcal disease. Efficacy persisted for the duration of the trial (mean follow-up four years).
However, since this trial began before PCV13 was used routinely in infants in the Netherlands, it does not answer the
question of whether it will prove efficacious in countries that routinely administer this vaccine to infants [31]. Given the
dramatic reduction in invasive pneumococcal disease observed in adults following the routine use of PCV in children in
the United States due to the herd effect (figure 1), it is possible that vaccination of adults 65 years of age in the
United States with conjugate vaccine will not provide measurable additional benefit. (See 'Overview of benefits and
limitations' above.)
An additional limitation of the CAPiTA trial is that it did not have a comparative group that received PPV23, so it did not
address the question of whether PCV13 provides better protection than PPSV23 against the 13 serotypes contained
within it [31].
A further problem in extrapolating from the CAPiTA trial to the current United States recommendations is that the trial
specifically excluded subjects who were regarded as immunocompromised [35]. Importantly, among subjects who
developed an immunocompromising condition or who were placed on some immunosuppressive therapy during the
period of the study, PCV13 exhibited no protective effect (22 cases of pneumococcal disease in vaccine recipients
versus 24 cases in placebo recipients).
As noted above, pneumococcal conjugate vaccines have proven to be highly effective in children. (See "Pneumococcal
(Streptococcus pneumoniae) conjugate vaccines in children", section on 'Efficacy and effectiveness'.)
Adverse reactions As with PPSV, the most common adverse reactions with PCV13 include local reactions, such as
erythema, swelling, pain at the injection site, and limitation of movement of the arm in which the injection was given, as
well as systemic reactions, such as fatigue, headache, chills, anorexia, myalgias, and arthralgias [7,12,35]. (See
"Pneumococcal conjugate vaccine (13-valent): Drug information".)
Healthcare providers should report suspected adverse events to the Vaccine Adverse Event Reporting System
(VAERS). VAERS can be contacted via the VAERS website or by telephone at 800-822-7967.
Contraindications Severe allergic reaction (eg, anaphylaxis) to any component of PCV13 or any diphtheria toxoid
containing vaccine is a contraindication to receiving PCV13 [12]. (See "Pneumococcal conjugate vaccine (13-valent):
Drug information".)
COST-EFFECTIVENESS A cost-effectiveness analysis has suggested that the use of PCV13 in adults using the
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existing indications (ie, vaccination at age 65 years and at younger ages if comorbidities are present) would be more
cost-effective than PPSV23, provided that the effectiveness of PCV13 at preventing nonbacteremic pneumococcal
pneumonia is high ($28,900 versus $34,600 per quality-adjusted-life-year [QALY] gained, respectively) [70]. A major
limitation of this study is that the authors relied on the meta-analysis of Huss et al [52], which appeared to show that
PPSV23 provides no protection against noninvasive pneumococcal infection rather than on that of Moberley et al [29],
which showed equivalent protection against invasive and noninvasive disease. Furthermore, if the herd effect of PCV13
is as large as has been shown for PCV7 (and results to date in the United States, United Kingdom, and France
suggest that it appears to be [71,72]), infection in adults due to strains contained in PCV13 will largely be eliminated,
which will render the use of PCV in adults irrelevant and will greatly increase the cost per QALY. A more recent cost
analysis from the United Kingdom [73] recognized the herd effect of conjugate vaccine, concluding that use of PCV13
in groups at risk for pneumococcal was not likely to be cost effective.
INVESTIGATIONAL APPROACHES Existing pneumococcal vaccines utilize capsular polysaccharides as antigens.
Vaccines cannot include all serotypes, replacement strains appear, and pneumococci readily acquire DNA from other
microorganisms by transformation, giving them the ability to switch capsular serotypes. These facts have led to
attempts to develop vaccines based on highly conserved proteins (eg, pneumolysin, histidine triad protein D, surface
proteins A and C), some of which are surface expressed and one of which (pneumolysin) contributes substantially to
the pathogenesis of pneumococcal disease. Several such vaccines are in development [31,37,74]. Data suggest that
the best approach for new vaccines might be to target virulence factors other than the pneumococcal capsule [75].
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and
"Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given condition. These articles are
best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to
12th grade reading level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics
to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info"
and the keyword(s) of interest.)
Basics topics (see "Patient information: Vaccines for adults (The Basics)" and "Patient information: Vaccines (The
Basics)")
Beyond the Basics topic (see "Patient information: Pneumonia prevention in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Pneumococcal infections, including pneumonia and invasive disease such as bacteremia and meningitis, remain
an important source of morbidity and mortality in adults, especially among older adults (table 1) and those with
certain conditions, including immunocompromising conditions and asplenia. (See 'Introduction' above.)
Two types of pneumococcal vaccines are approved for use in the United States:
A pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23, Pnu-Immune) that includes 23 purified
capsular polysaccharide antigens
A pneumococcal protein-conjugate vaccine (PCV13; Prevnar 13) that includes capsular polysaccharide
antigens covalently linked to a nontoxic protein that is nearly identical to diphtheria toxin (see 'Available
vaccines' above)
PPSV23 has been used in adults for decades in the United States but is not recommended for infants or toddlers
under age two because it is poorly immunogenic in this age group. (See 'Available vaccines' above.)
A 7-valent pneumococcal conjugate vaccine, PCV7, was recommended for universal use in infants and toddlers
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beginning in 2000; since 2010, a 13-valent pneumococcal conjugate vaccine, PCV13, has been recommended for
infants and children in its place.
Vaccination of infants and toddlers has led to a remarkable decrease in disease due to vaccine recipients (98
percent for PCV7 and >90 percent for PCV13).
Because PCV eliminates nasal carriage, young children, who traditionally have served as the source of spread of
infection to adults, no longer carry pneumococcal serotypes contained within the vaccine. As a result (the "herd
effect"), disease in adults due to PCV7 serotypes has decreased by >90 percent, and disease due to PCV13
serotypes is rapidly decreasing.
In 2012, PCV13 began to be recommended for use in selected high-risk adults and, in 2014, PCV13 began to be
recommended for all adults 65 years of age. (See 'Available vaccines' above.)
The indications (table 3) and schedule (table 4) for vaccination depend upon age and risk factors for
pneumococcal disease; our recommendations are in accordance with those of the United States Advisory
Committee on Immunization Practices (ACIP) (see 'Indications' above):
For adults 19 to 64 years of age at intermediate risk of pneumococcal disease (ie, cigarette smokers;
patients with chronic heart disease, chronic lung disease, diabetes mellitus, alcoholism, or chronic liver
disease), we recommend pneumococcal vaccination (Grade 1B). Such patients should receive PPSV23
alone.
For adults aged 19 or older who are at high risk of pneumococcal disease (ie, patients with functional or
anatomic asplenia, an immunocompromising condition [eg, HIV infection, cancer], a cerebrospinal fluid leak,
a cochlear implant, advanced kidney disease), we recommend pneumococcal vaccination (Grade 1B). The
ACIP recommends that such patients receive PCV13 followed at least eight weeks later by PPSV23. In
patients who have already received PPSV23, at least one year should elapse before they are given PCV13.
For all adults 65 years of age, we recommend pneumococcal vaccination (Grade 1B). For individuals 65
years of age without any of the conditions described in the previous bullet, PPSV23 should be given 1 year
following PCV13 (algorithm 1). In those who have already received PPSV23, at least one year should
elapse before they are given PCV13.
A single revaccination with PPSV23 is recommended in adults 65 years of age if they were vaccinated
more than five years previously at a time when they were less than 65 years of age and, in
immunocompromised patients, five years or more after the first dose. Some experts continue to
recommend administration of PPSV23 every six to seven years for asplenic individuals. Revaccination with
PCV13 is not recommended. (See 'Revaccination' above.)
PCV13 is not recommended for healthy adults <65 years of age who do not have a specific risk factor for
pneumococcal infection.
PPSV23 and PCV13 are administered intramuscularly as a 0.5 mL dose. They may be administered concurrently
with other vaccines, such as the influenza vaccine, but at a separate site. However, PPSV23 and PCV13 should
be administered at different times as outlined above. (See 'Administration' above and 'Schedule for dual
vaccination' above.)
The trend for vaccine strains to disappear from the population following universal immunization of infants may
substantially reduce the potential benefit of PCV13 use in adults. The ACIP has stated that they will reconsider
the recommendations for the use of PCV13 in adults in 2018. (See 'Indications' above and 'Overview of benefits
and limitations' above and 'Efficacy' above.)
Indirect evidence for a possible benefit of PCV over PPSV23 in immunocompromised adults comes from
randomized trials in HIV-infected individuals in Africa, which demonstrated a reduction in invasive pneumococcal
disease among individuals who received PCV7 but no reduction in recipients of PPSV23. These trials were not,
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however, entirely comparable. In a large placebo-controlled trial of individuals 65 years of age in the
Netherlands, PCV13 was efficacious at preventing vaccine-type pneumococcal pneumonia, vaccine-type
nonbacteremic pneumococcal pneumonia, and vaccine-type invasive pneumococcal disease; this trial did not
include a group that received PPSV23. (See 'Efficacy' above.)
ACKNOWLEDGMENT The editorial staff at UpToDate Inc. would like to acknowledge Dr. Elaine Tuomanen and Dr.
Patricia Hibberd, who contributed to earlier versions of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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Disclosures
Disclosures: Daniel M Musher, MD Nothing to disclose. John G Bartlett, MD Nothing to disclose. Anna R Thorner, MD Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a
multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is
required of all authors and must conform to UpToDate standards of evidence.
Conflict of interest policy
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