Pneumococcal Vaccination in Adults

Pneumococcal vaccination in adults

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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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below. (See 'PCV13 and PPSV23' below and 'Revaccination' below.)
Adults with the following underlying conditions who are <65 years of age should receive PPSV23 alone:
● Cigarette smoking
● Chronic heart disease, including congestive heart failure and cardiomyopathy, but excluding hypertension
● Chronic lung disease, including asthma and chronic obstructive pulmonary disease (see "Management of infection
in exacerbations of chronic obstructive pulmonary disease")
● Diabetes mellitus
● Alcoholism
● Chronic liver disease (see "Immunizations for patients with chronic liver disease")
PCV13 and PPSV23 — The ACIP recommends that both PCV13 and PPSV23 be given sequentially to all adults
aged ≥65 years and to adults of any age who have the underlying conditions listed below (table 3) [6]. When possible,
PCV13 should be given first, followed by PPSV23 (table 4). The schedule for dual vaccination is discussed below.
(See 'Schedule for dual vaccination' below.)
Persons who should receive both PCV13 and PPV23 given sequentially include those with any of the following risk
factors:
● Age ≥65 years – The incidence of pneumococcal disease and the associated mortality are very low in adults
under the age of 50. Both the incidence of pneumococcal disease and the mortality rate increase after age 50
and more sharply after age 65 [9].
● Cerebrospinal fluid leak
● Cochlear implant
● Functional or anatomic asplenia, including sickle cell disease, other hemoglobinopathies, congenital asplenia, and
acquired asplenia – In the absence of antibody (most unvaccinated adults lack measurable antibody to most
pneumococcal capsular polysaccharides), the only clearance of pneumococci from the bloodstream is by the
spleen. Asplenic individuals are at risk for overwhelming pneumococcal sepsis that may occur even in the
absence of a focal infection such as pneumonia. (See "Clinical features and management of sepsis in the asplenic
patient", section on 'Role of the spleen in host defense' and "Prevention of sepsis in the asplenic patient".)
● Immunocompromise:
• Congenital or acquired immunodeficiency, including B or T lymphocyte deficiency, complement deficiencies
(particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous
disease)
• HIV infection (see "Pneumococcal immunization in HIV-infected adults", section on 'When to immunize')
• Chronic renal failure
• Nephrotic syndrome
• Leukemia
• Lymphoma
• Hodgkin disease
• Multiple myeloma
• Generalized malignancy

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• Iatrogenic immunosuppression, including glucocorticoids or radiation
• Solid organ transplant
As noted above, PCV13 is not recommended for healthy adults <65 years of age who do not have a specific risk
factor for pneumococcal infection. (See 'Indications' above.)
Although the ACIP has not made a recommendation about vaccinating any adult who has been diagnosed with invasive
pneumococcal disease, we suggest that all such individuals also receive PCV13 followed by PPSV23 even if they have
not been diagnosed with one of the conditions listed above because they have proven themselves to be susceptible,
and infection with one serotype does not provide protection against other serotypes.
Schedule for dual vaccination — Individuals who have an indication to receive both PCV13 and PPSV23 should
be vaccinated according to the following schedule (table 4) [6,7,10]:
● For immunocompromised adults or adults with functional or anatomic asplenia, a CSF leak, a cochlear implant, or
advanced kidney disease who are any age (including those ≥65 years of age) and who have not previously
received either PCV13 or PPSV23, a single dose of PCV13 should be given, followed by a dose of PPSV23 ≥8
weeks later.
● 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) [10]. In 2015, the recommended timing for administration of PPSV23
following PCV13 administration in immunocompetent adults ≥65 years of age was changed from 6-12 months to
≥1 year to simplify the administration schedule.
● For patients who have previously received one or more doses of PPSV23, a single dose of PCV13 should be
given ≥1 year after the last PPSV23 dose was received.
● For patients <65 years of age who require revaccination with PPSV23 (eg, immunocompromised patients), the
first such dose should be given at least eight weeks after PCV13 and at least 5 years after the most recent dose
of PPSV23 [6]. For patients ≥65 years of age, the first such dose of PPSV23 should be given at least 1 year
after PCV13 and at least 5 years after the most recent dose of PPSV23 [10]. (See 'Revaccination' below.)
Administration — Both pneumococcal vaccines are administered as a 0.5 mL dose. PCV13 should be given
intramuscularly, whereas PPSV23 can be given either intramuscularly or subcutaneously. Intradermal administration
can cause severe local reactions and should be avoided.
Administration with other vaccines — Either formulation of pneumococcal vaccine may be given concomitantly with
other vaccines [11,12]. When more than one vaccine is given, they should be administered with different syringes and
at different injection sites.
Concurrent administration of either PPSV23 or PCV13 with the inactivated influenza vaccine is safe and is unlikely to
reduce the effectiveness of either pneumococcal vaccine [13,14]. Some data suggest a modest suppression of
immunogenicity to PCV13 if PCV13 is administered on the same day as an inactivated influenza vaccine, even though
different arms were used for injection [14]. Nevertheless, the United States Centers for Disease Control and
Prevention (CDC) states that these vaccines can be coadministered [7].
Coadministration of PPSV23 and the zoster vaccine does not alter the antibody response to PPSV23 [15], although
such coadministration may reduce the immunogenicity of the zoster vaccine [11,15,16]. In order to avoid introducing
barriers to patients receiving indicated vaccines, the CDC recommends that PPSV23 and the zoster vaccine be
administered at the same visit if the patient is eligible for both vaccines [17-19].
With availability of vaccines at local pharmacies, it may not be inconvenient for people to receive two vaccines a few
weeks apart; this would be ideal in patients who are highly motivated and able to have two visits to receive two
different vaccines (PCV13 and influenza vaccine; PPSV23 and zoster vaccine). However, if there is any question of
decreased adherence, such that one vaccine would be given but the other one not given, we favor giving both at the
same time but in different arms.

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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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immunogenicity of pneumococcal vaccination'.)
An untoward effect of the widespread use of pneumococcal conjugate vaccines has been the emergence of
"replacement strains," a term used to describe nonvaccine pneumococcal serotypes that have appeared as colonizers
of the nasopharynx and as a cause of pneumococcal disease [36]. Reduction in nasal carriage of PCV serotypes
appears to create an ecologic niche for nonvaccine serotypes [37]. As an example, S. pneumoniae type 19A (not
included in PCV7, but included in PCV13) emerged as the most common cause of pneumococcal disease in children
and adults a few years after universal vaccination with PCV7 began in the United States (figure 1) [30,38]. (See
"Impact of universal infant immunization with pneumococcal (Streptococcus pneumoniae) conjugate vaccines in the
United States".)
The recommendation to give both PPSV23 and PCV13 to high-risk adults is far more costly than recommending
PPSV23 alone. In addition, adherence to a two-vaccine regimen is likely to be poorer than adherence to a one-vaccine
regimen. Despite the strength of the current United States Centers for Disease Control and Prevention
recommendation, data supporting this approach are meager.
A comparison of the properties of pneumococcal polysaccharide and conjugate vaccines is reviewed in the Table (table
5).
PNEUMOCOCCAL POLYSACCHARIDE VACCINES — Pneumococcal polysaccharide vaccine (PPSV23; Pneumovax
23, Pnu-Immune) includes 23 purified capsular polysaccharide antigens (table 2). These serotypes were initially
chosen because they represented 85 to 90 percent of the serotypes that cause invasive disease in the United States.
In 2009, 60 to 76 percent of cases of invasive pneumococcal disease in adults in the United States were caused by
PPSV23 serotypes [39].
Immunogenicity — Successful vaccination is indicated by antigen-specific antibody responses or enhanced in vitro
opsonic activity of serum for type-specific pneumococci within two to three weeks; the responses may not be
consistent among all serotypes in PPSV23 and vary from one individual to another. Although important for
epidemiologic studies, checking antibody responses after vaccination is rarely performed in clinical practice. (See
"Assessing the immunologic response to vaccination".)
The serum concentration of antibody that correlates with protection against pneumococcal disease has not been
clearly defined, although a level of 0.35 micrograms/mL has been set for children [40]. After healthy adults >50 years
of age are vaccinated, antibody declines rapidly over a one- to two-year period, persisting at low levels for 10 or more
years [23,26,28,36]. Despite these observations, in one report from the United States Centers for Disease Control and
Prevention (CDC), efficacy of the pneumococcal polysaccharide vaccine did not decline at seven or more years after
vaccination [41].
Revaccination with PPSV23 induces persistent functional antibody response in healthy middle-aged and older adults
[24,26]. Some studies have shown an inverse association between circulating antibody concentrations just before
primary vaccination or revaccination and subsequent increase, consistent with other observations suggesting that it
may be detrimental to revaccinate patients too soon following initial vaccination [28]. (See 'Revaccination' above.)
Efficacy — Several case-control studies, randomized trials, and meta-analyses have shown that the pneumococcal
polysaccharide vaccine (PPSV) prevents pneumococcal disease. The bulk of evidence suggests that PPSV protects
against invasive pneumococcal infection (defined as pneumococcal disease with isolation of the infecting organisms
from a normally sterile body site) and noninvasive pneumococcal infection [29]. Some investigators, however, have
concluded that vaccine recipients are protected against invasive but not against noninvasive (ie, nonbacteremic)
pneumococcal pneumonia [37,42-52]. Other published studies have failed to demonstrate efficacy for preventing
invasive or noninvasive disease [46,47,52-55] or for reducing mortality [29,56]. A population-based case control study
showed that PPSV was 85 to 90 percent effective in preventing invasive pneumococcal disease in adults <55 years of
age, but that the efficacy of PPSV declined as age increased, as did the duration of any observed effect [44]. The
avidity of antibody for pneumococcal polysaccharide may diminish with age [57].
Possible reasons for the conflicting results include the rarity of the outcomes being assessed (leading to a small

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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 cell–dependent, 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 cell–dependent 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.
REFERENCES
1. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR Recomm Rep 1997; 46:1.
2. Kobayashi M. Intervals between PCV13 and PPSV23 vaccines: Evidence supporting currently recommended
intervals and proposed changes. Advisory Committee on Immunization Practices, June 25, 2015.
http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2015-06/pneumo-02-kobayashi.pdf (Accessed on
August 03, 2015).
3. Moore MR, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal conjugate vaccine in
children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite,
population-based surveillance. Lancet Infect Dis 2015; 15:301.
4. Feikin DR, Kagucia EW, Loo JD, et al. Serotype-specific changes in invasive pneumococcal disease after
pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med 2013;
10:e1001517.
5. Centers for Disease Control and Prevention (CDC). Licensure of 13-valent pneumococcal conjugate vaccine for
adults aged 50 years and older. MMWR Morb Mortal Wkly Rep 2012; 61:394.
6. Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and
23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions:
recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep
2012; 61:816.
7. Tomczyk S, Bennett NM, Stoecker C, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent
pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory
Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2014; 63:822.
8. Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices. Updated
recommendations for prevention of invasive pneumococcal disease among adults using the 23-valent
pneumococcal polysaccharide vaccine (PPSV23). MMWR Morb Mortal Wkly Rep 2010; 59:1102.
9. Centers for Disease Control and Prevention — 2011. Active Bacterial Core Surveillance (ABCs) report, Emerging
Infections Program Network Streptococcus pneumoniae, 2010. http://www.cdc.gov/abcs/reports-findings
/survreports/spneu10-orig.pdf (Accessed on March 21, 2013).
10. Kobayashi M, Bennett NM, Gierke R, et al. Intervals Between PCV13 and PPSV23 Vaccines: Recommendations
of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2015; 64:944.
11. PNEUMOVAX 23 (pneumococcal vaccine polyvalent) sterile, liquid vaccine for intramuscular or subcutaneous
injection - prescribing information. http://www.merck.com/product/usa/pi_circulars/p/pneumovax_23
/pneumovax_pi.pdf (Accessed on October 24, 2013).
12. Prevnar 13 prescribing information. http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines
/approvedproducts/ucm201669.pdf (Accessed on January 08, 2013).
13. Honkanen PO, Keistinen T, Kivelä SL. Reactions following administration of influenza vaccine alone or with
pneumococcal vaccine to the elderly. Arch Intern Med 1996; 156:205.
14. Schwarz TF, Flamaing J, Rümke HC, et al. A randomized, double-blind trial to evaluate immunogenicity and
safety of 13-valent pneumococcal conjugate vaccine given concomitantly with trivalent influenza vaccine in adults
aged ≥65 years. Vaccine 2011; 29:5195.
15. MacIntyre CR, Egerton T, McCaughey M, et al. Concomitant administration of zoster and pneumococcal

2/27/2016 2:59 PM

Pneumococcal vaccination in adults

13 of 15

http://www.uptodate.com/contents/pneumococcal-vaccination-in-adults?t...

vaccines in adults ≥60 years old. Hum Vaccin 2010; 6:894.
16. ZOSTAVAX (zoster vaccine live) - highlights of prescribing information. http://www.merck.com/product
/usa/pi_circulars/z/zostavax/zostavax_pi2.pdf (Accessed on October 24, 2013).
17. Wyman MJ, Stabi KL. Concomitant administration of pneumococcal-23 and zoster vaccines provides adequate
herpes zoster coverage. Ann Pharmacother 2013; 47:1064.
18. Centers for Disease Control and Prevention. Herpes zoster vaccination - information for health care
professionals. http://www.cdc.gov/vaccines/vpd-vac/shingles/hcp-vaccination.htm (Accessed on October 24,
2013).
19. Tseng HF, Smith N, Sy LS, Jacobsen SJ. Evaluation of the incidence of herpes zoster after concomitant
administration of zoster vaccine and polysaccharide pneumococcal vaccine. Vaccine 2011; 29:3628.
20. Musher DM. Streptococcus pneumoniae. In: Principles and Practice of Infectious Diseases, Seventh Edition,
Mandell GL, Bennett JE, Dolin R (Eds), Churchill Livingstone Elsevier, Philadelphia 2010. p.2623.
21. Mourtzoukou EG, Pappas G, Peppas G, Falagas ME. Vaccination of asplenic or hyposplenic adults. Br J Surg
2008; 95:273.
22. O'Brien KL, Hochman M, Goldblatt D. Combined schedules of pneumococcal conjugate and polysaccharide
vaccines: is hyporesponsiveness an issue? Lancet Infect Dis 2007; 7:597.
23. Musher DM, Manoff SB, McFetridge RD, et al. Antibody persistence ten years after first and second doses of
23-valent pneumococcal polysaccharide vaccine, and immunogenicity and safety of second and third doses in
older adults. Hum Vaccin 2011; 7:919.
24. Manoff SB, Liss C, Caulfield MJ, et al. Revaccination with a 23-valent pneumococcal polysaccharide vaccine
induces elevated and persistent functional antibody responses in adults aged 65 > or = years. J Infect Dis 2010;
201:525.
25. Hammitt LL, Bulkow LR, Singleton RJ, et al. Repeat revaccination with 23-valent pneumococcal polysaccharide
vaccine among adults aged 55-74 years living in Alaska: no evidence of hyporesponsiveness. Vaccine 2011;
29:2287.
26. Musher DM, Manof SB, Liss C, et al. Safety and antibody response, including antibody persistence for 5 years,
after primary vaccination or revaccination with pneumococcal polysaccharide vaccine in middle-aged and older
adults. J Infect Dis 2010; 201:516.
27. Jackson LA, Benson P, Sneller VP, et al. Safety of revaccination with pneumococcal polysaccharide vaccine.
JAMA 1999; 281:243.
28. Grabenstein JD, Manoff SB. Pneumococcal polysaccharide 23-valent vaccine: long-term persistence of
circulating antibody and immunogenicity and safety after revaccination in adults. Vaccine 2012; 30:4435.
29. Moberley S, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults.
Cochrane Database Syst Rev 2013; 1:CD000422.
30. Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive pneumococcal disease in the era of
conjugate vaccine. J Infect Dis 2010; 201:32.
31. Musher DM. Editorial commentary: should 13-valent protein-conjugate pneumococcal vaccine be used routinely in
adults? Clin Infect Dis 2012; 55:265.
32. Griffin MR, Zhu Y, Moore MR, et al. U.S. hospitalizations for pneumonia after a decade of pneumococcal
vaccination. N Engl J Med 2013; 369:155.
33. French N, Nakiyingi J, Carpenter LM, et al. 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected
Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet 2000; 355:2106.
34. French N, Gordon SB, Mwalukomo T, et al. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected
adults. N Engl J Med 2010; 362:812.
35. Bonten MJ, Huijts SM, Bolkenbaas M, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia
in adults. N Engl J Med 2015; 372:1114.
36. Musher DM, Sampath R, Rodriguez-Barradas MC. The potential role for protein-conjugate pneumococcal
vaccine in adults: what is the supporting evidence? Clin Infect Dis 2011; 52:633.
37. Musher DM. How effective is vaccination in preventing pneumococcal disease? Infect Dis Clin North Am 2013;
27:229.
38. Kaplan SL, Barson WJ, Lin PL, et al. Serotype 19A Is the most common serotype causing invasive

2/27/2016 2:59 PM

Pneumococcal vaccination in adults

14 of 15

http://www.uptodate.com/contents/pneumococcal-vaccination-in-adults?t...

pneumococcal infections in children. Pediatrics 2010; 125:429.
39. Muhammad RD, Oza-Frank R, Zell E, et al. Epidemiology of invasive pneumococcal disease among high-risk
adults since the introduction of pneumococcal conjugate vaccine for children. Clin Infect Dis 2013; 56:e59.
40. Siber GR, Chang I, Baker S, et al. Estimating the protective concentration of anti-pneumococcal capsular
polysaccharide antibodies. Vaccine 2007; 25:3816.
41. Butler JC, Breiman RF, Campbell JF, et al. Pneumococcal polysaccharide vaccine efficacy. An evaluation of
current recommendations. JAMA 1993; 270:1826.
42. Bolan G, Broome CV, Facklam RR, et al. Pneumococcal vaccine efficacy in selected populations in the United
States. Ann Intern Med 1986; 104:1.
43. Sims RV, Steinmann WC, McConville JH, et al. The clinical effectiveness of pneumococcal vaccine in the elderly.
Ann Intern Med 1988; 108:653.
44. Shapiro ED, Berg AT, Austrian R, et al. The protective efficacy of polyvalent pneumococcal polysaccharide
vaccine. N Engl J Med 1991; 325:1453.
45. Farr BM, Johnston BL, Cobb DK, et al. Preventing pneumococcal bacteremia in patients at risk. Results of a
matched case-control study. Arch Intern Med 1995; 155:2336.
46. Jackson LA, Neuzil KM, Yu O, et al. Effectiveness of pneumococcal polysaccharide vaccine in older adults. N
Engl J Med 2003; 348:1747.
47. Musher DM, Rueda-Jaimes AM, Graviss EA, Rodriguez-Barradas MC. Effect of pneumococcal vaccination: a
comparison of vaccination rates in patients with bacteremic and nonbacteremic pneumococcal pneumonia. Clin
Infect Dis 2006; 43:1004.
48. Austrian R, Douglas RM, Schiffman G, et al. Prevention of pneumococcal pneumonia by vaccination. Trans
Assoc Am Physicians 1976; 89:184.
49. Bentley DW, Ha K, Mamot K, et al. Pneumococcal vaccine in the institutionalized elderly: design of a
nonrandomized trial and preliminary results. Rev Infect Dis 1981; 3 Suppl:S71.
50. Gaillat J, Zmirou D, Mallaret MR, et al. [Clinical trial of an antipneumococcal vaccine in elderly subjects living in
institutions]. Rev Epidemiol Sante Publique 1985; 33:437.
51. Jackson LA, Janoff EN. Pneumococcal vaccination of elderly adults: new paradigms for protection. Clin Infect
Dis 2008; 47:1328.
52. Huss A, Scott P, Stuck AE, et al. Efficacy of pneumococcal vaccination in adults: a meta-analysis. CMAJ 2009;
180:48.
53. Koivula I, Stén M, Leinonen M, Mäkelä PH. Clinical efficacy of pneumococcal vaccine in the elderly: a
randomized, single-blind population-based trial. Am J Med 1997; 103:281.
54. Ortqvist A, Hedlund J, Burman LA, et al. Randomised trial of 23-valent pneumococcal capsular polysaccharide
vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study
Group. Lancet 1998; 351:399.
55. Simberkoff MS, Cross AP, Al-Ibrahim M, et al. Efficacy of pneumococcal vaccine in high-risk patients. Results of
a Veterans Administration Cooperative Study. N Engl J Med 1986; 315:1318.
56. Maruyama T, Taguchi O, Niederman MS, et al. Efficacy of 23-valent pneumococcal vaccine in preventing
pneumonia and improving survival in nursing home residents: double blind, randomised and placebo controlled
trial. BMJ 2010; 340:c1004.
57. Romero-Steiner S, Musher DM, Cetron MS, et al. Reduction in functional antibody activity against Streptococcus
pneumoniae in vaccinated elderly individuals highly correlates with decreased IgG antibody avidity. Clin Infect Dis
1999; 29:281.
58. Musher DM, Mediwala R, Phan HM, et al. Nonspecificity of assaying for IgG antibody to pneumolysin in
circulating immune complexes as a means to diagnose pneumococcal pneumonia. Clin Infect Dis 2001; 32:534.
59. Walker FJ, Singleton RJ, Bulkow LR, et al. Reactions after 3 or more doses of pneumococcal polysaccharide
vaccine in adults in Alaska. Clin Infect Dis 2005; 40:1730.
60. Kim L, Taylor T, Pondo T, et al. Impact of 13-valent pneumococcal conjugate vaccine (PCV13) on invasive
pneumococcal disease (IPD) among adults in the U.S. Pneumonia 2014; 3:175. Abstract ISPPD-0466.
61. Jackson LA, Gurtman A, van Cleeff M, et al. Immunogenicity and safety of a 13-valent pneumococcal conjugate
vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults.

2/27/2016 2:59 PM

Pneumococcal vaccination in adults

15 of 15

http://www.uptodate.com/contents/pneumococcal-vaccination-in-adults?t...

Vaccine 2013; 31:3577.
62. Clutterbuck EA, Lazarus R, Yu LM, et al. Pneumococcal conjugate and plain polysaccharide vaccines have
divergent effects on antigen-specific B cells. J Infect Dis 2012; 205:1408.
63. Jackson LA, Gurtman A, van Cleeff M, et al. Influence of initial vaccination with 13-valent pneumococcal
conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following
subsequent pneumococcal vaccination in adults 50 years and older. Vaccine 2013; 31:3594.
64. Greenberg RN, Gurtman A, Frenck RW, et al. Sequential administration of 13-valent pneumococcal conjugate
vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naïve adults 60-64 years
of age. Vaccine 2014; 32:2364.
65. Goldblatt D, Southern J, Andrews N, et al. The immunogenicity of 7-valent pneumococcal conjugate vaccine
versus 23-valent polysaccharide vaccine in adults aged 50-80 years. Clin Infect Dis 2009; 49:1318.
66. O'Brien KL. Pneumococcal conjugate vaccine, polysaccharide vaccine, or both for adults? We're not there yet.
Clin Infect Dis 2009; 49:1326.
67. Musher DM, Rueda AM, Nahm MH, et al. Initial and subsequent response to pneumococcal polysaccharide and
protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal
pneumonia. J Infect Dis 2008; 198:1019.
68. Lazarus R, Clutterbuck E, Yu LM, et al. A randomized study comparing combined pneumococcal conjugate and
polysaccharide vaccination schedules in adults. Clin Infect Dis 2011; 52:736.
69. Miernyk KM, Butler JC, Bulkow LR, et al. Immunogenicity and reactogenicity of pneumococcal polysaccharide
and conjugate vaccines in alaska native adults 55-70 years of age. Clin Infect Dis 2009; 49:241.
70. Smith KJ, Wateska AR, Nowalk MP, et al. Cost-effectiveness of adult vaccination strategies using pneumococcal
conjugate vaccine compared with pneumococcal polysaccharide vaccine. JAMA 2012; 307:804.
71. Ladhani SN, Andrews NJ, Waight P, et al. Invasive pneumococcal disease, comorbidities, and polysaccharide
vaccine use in children aged 5-15 years in England and Wales. Clin Infect Dis 2014; 58:517.
72. Angoulvant F, Levy C, Grimprel E, et al. Early impact of 13-valent pneumococcal conjugate vaccine on
community-acquired pneumonia in children. Clin Infect Dis 2014; 58:918.
73. Rozenbaum MH, van Hoek AJ, Fleming D, et al. Vaccination of risk groups in England using the 13 valent
pneumococcal conjugate vaccine: economic analysis. BMJ 2012; 345:e6879.
74. Moffitt KL, Malley R. Next generation pneumococcal vaccines. Curr Opin Immunol 2011; 23:407.
75. Browall S, Norman M, Tångrot J, et al. Intraclonal variations among Streptococcus pneumoniae isolates influence
the likelihood of invasive disease in children. J Infect Dis 2014; 209:377.
Topic 7021 Version 51.0

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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