Pneumococcal Disease

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17

Streptococcus pneumoniae causes acute bacterial infections. 

The bacterium, also called pneumococcus, was first isolated 

by Louis Pasteur in 1881 from the saliva of a patient with 

rabies. The association between pneumococcus and lobar 

pneumonia was first described in 1883, but pneumococcal 

pneumonia was confused with other types of pneumonia 

until the development of the Gram stain in 1884. Between 

1915 and 1945, the chemical structure and antigenicity of 

the pneumococcal capsular polysaccharide, its association 

with virulence, and the role of bacterial polysaccharides in 

human disease were described. More than 80 serotypes of 

pneumococci had been described by 1940.

Efforts to develop effective pneumococcal vaccines began as 

early as 1911. However, with the advent of penicillin in the 

1940s, interest in pneumococcal vaccination declined until it 

was observed that many patients still died despite antibiotic 

treatment. By the late 1960s, efforts were again being made 

to develop a polyvalent pneumococcal vaccine. The first 

pneumococcal vaccine was licensed for use in the United States 

in 1977. The first conjugate pneumococcal vaccine was licensed 

in the United States in 2000.

Streptococcus pneumoniae

S. pneumoniae bacteria are lancet-shaped, gram-positive,

facultative anaerobic organisms. They are typically observed

in pairs (diplococci) but may also occur singularly or in short

chains. Most pneumococci are encapsulated, and their

surfaces are composed of complex polysaccharides. Capsular

polysaccharides are one determinant of the pathogenicity of

the organism. They are also antigenic and form the basis for

classifying pneumococci by serotypes. One hundred serotypes

were documented as of 2020, based on their reaction with

type-specific antisera. Type-specific antibody to capsular

polysaccharide is protective against disease caused by that

serotype. These antibodies and complement interact to

opsonize pneumococci, which facilitates phagocytosis and

clearance of the organism. Antibodies to some pneumococcal

capsular polysaccharides may cross-react with related types

as well as with other bacteria, providing protection against

additional serotypes.

Most S. pneumoniae serotypes have been shown to cause 

serious disease, but only a few serotypes cause most 

pneumococcal infections. The ranking and serotype prevalence 

differ by patient age group and geographic area. In the United 

States, prior to the widespread use of 7-valent pneumococcal 

conjugate vaccine (PCV7), the seven most common serotypes 

isolated from blood or cerebrospinal fluid (CSF) of children 

Ryan Gierke, MPH; A. Patricia Wodi, MD; and Miwako Kobayashi, MD, MPH

Pneumococcal Disease

● S. pneumoniae first isolated by

Pasteur in 1881

● Confused with other types of

pneumonia until discovery of

Gram stain in 1884

● More than 80 serotypes

described by 1940

● First pneumococcal vaccine

licensed in U.S. in 1977; first

conjugate pneumococcal

vaccine in 2000

Streptococcus pneumonia

● Facultative anaerobic grampositive organism

● 100 serotypes documented as

of 2020

● Most serotypes cause serious

disease, only a few cause most

pneumococcal infections

● Serotype prevalence differ by

age and geographic area

https://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html Aug 2021
256

Pneumococcal Disease

 17

younger than age 5 years accounted for 80% of infections; these 

seven serotypes accounted for about 50% of isolates from older 

children and adults.

The clinical spectrum of pneumococcal infections ranges from 

invasive disease (i.e., infection of normally sterile sites including 

osteomyelitis, bacteremia without focus of infection, pneumonia 

with bacteremia, septic arthritis, and meningitis) to non-invasive 

infections such as pneumonia without bacteremia, otitis media, 

and sinusitis. Pneumococci cause more than 50% of all cases 

of bacterial meningitis in the United States with approximately 

2,000 cases of pneumococcal meningitis occurring each year. 

Over 150,000 hospitalizations from pneumococcal pneumonia 

are estimated to occur annually in the United States and it 

has been demonstrated to complicate influenza infection. 

Pneumococci is the most common bacterial cause of childhood 

pneumonia, especially in children younger than age 5 years. 

In adults, pneumococci account for 10% to 30% of adult 

community-acquired pneumonia. 

Pathogenesis 

Pneumococci are common inhabitants of the respiratory tract 

and may be isolated from the nasopharynx of 5% to 90% of 

healthy persons. Rates of asymptomatic carriage vary with 

age, environment, and the presence of upper respiratory 

infections. Among school-age children, 20% to 60% may be 

colonized. Only 5% to 10% of adults without children are 

colonized, although on military installations, as many as 50% 

to 60% of service personnel may be colonized. The duration of 

carriage varies and is generally longer in children than adults. 

The relationship of carriage to the development of natural 

immunity is poorly understood.

Clinical Features

The major clinical syndromes of invasive pneumococcal disease 

are pneumonia, bacteremia, and meningitis. 

Pneumococcal Disease in Adults

Pneumococcal pneumonia is the most common clinical 

presentation of pneumococcal disease among adults. The 

incubation period of pneumococcal pneumonia is short, 

about 1 to 3 days. Symptoms generally include an abrupt 

onset of fever and chills or a single rigor. Repeated shaking 

chills are uncommon. Other common symptoms include 

pleuritic chest pain, cough productive of mucopurulent, rusty 

sputum, dyspnea, tachypnea, hypoxia, tachycardia, malaise, 

and weakness. Nausea, vomiting, and headaches occur less 

frequently. Complications of pneumococcal pneumonia include 

bacteremia, empyema (i.e., infection of the pleural space), 

pericarditis (inflammation of the sac surrounding the heart), and 

Pneumococcal Disease 

Pathogenesis

● Pneumococci commonly 

inhabit respiratory tract

● Asymptomatic carriage varies

■ School-age children 

20% to 60%

■ Adults 5% to 10%

● Relationship of carriage to 

development of natural 

immunity is poorly understood

Pneumococcal Disease 

Clinical Features

● Major clinical syndromes are 

pneumonia, bacteremia, 

and meningitis
Pneumococcal Disease

257

17

endobronchial obstruction, with atelectasis (partial collapse of 

lung tissue) and lung abscess formation. 

Pneumococcal bacteremia can occur with or without 

pneumonia and lead to arthritis, meningitis, and endocarditis. 

The case fatality ratio of pneumonia with bacteremia is around 

10%. More than 5,000 cases of pneumococcal bacteremia 

without pneumonia occur each year. The overall case fatality 

ratio for bacteremia is about 12%. Patients with asplenia who 

develop bacteremia may experience a fulminant clinical course.

Some patients with pneumococcal meningitis also have 

pneumonia. The clinical symptoms, CSF profile, and neurologic 

complications of pneumococcal meningitis are similar to other 

forms of purulent bacterial meningitis. Symptoms may include 

headache, lethargy, vomiting, irritability, fever, nuchal rigidity, 

cranial nerve signs, seizures, and coma. The case fatality ratio 

of pneumococcal meningitis is about 14% among adults. 

Neurologic sequelae are common among survivors. 

Adults with certain medical conditions are at highest 

risk for invasive pneumococcal disease. For adults age 

18 through 64 years with hematologic cancer, the rate of 

invasive pneumococcal disease in 2013–2014 was 129 per 

100,000 population. Other conditions that place adults 

at highest risk for invasive pneumococcal disease include 

other immunosuppressive conditions from disease or drugs, 

functional or anatomic asplenia, and renal disease. Other 

conditions that increase the risk of invasive pneumococcal 

disease in adults include chronic heart disease, lung disease 

(including asthma), liver disease, smoking cigarettes, alcoholism, 

CSF leak, and having a cochlear implant.

Pneumococcal Disease in Children

Bacteremia without a known site of infection is the most 

common invasive clinical presentation of pneumococcal 

infection among children age 2 years or younger, accounting 

for approximately 40% of invasive disease in this age group. 

Bacteremic pneumonia accounts for 25% to 30% of invasive 

pneumococcal disease among children age 2 years or younger. 

With the decline of invasive Haemophilus influenzae type b 

(Hib) disease, S. pneumoniae has become the leading cause 

of bacterial meningitis among children younger than age 5 

years in the United States. Before routine use of pneumococcal 

conjugate vaccine, children younger than 1 year had the highest 

rates of pneumococcal meningitis, approximately 10 cases per 

100,000 population.

Pneumococci are a common cause of acute otitis media and 

are detected in 24% to 31% of middle ear aspirates. By age 

12 months, more than 60% of children have had at least 

one episode of acute otitis media. Middle ear infections 

Pneumococcal Disease 

in Adults

● Pneumococcal pneumonia

■ Most common clinical 

presentation

■ Incubation period 1 to 3 days

■ Symptoms: Fever, chills, 

pleuritic chest pain, cough, 

rusty sputum, dyspnea, 

tachypnea, hypoxia, 

tachycardia, malaise, 

weakness

● Pneumococcal bacteremia

■ Can lead to arthritis, 

meningitis, and endocarditis

■ 12% overall case fatality ratio

● Pneumococcal meningitis

■ Symptoms: Headache, 

lethargy, vomiting, irritability, 

fever, nuchal rigidity, cranial 

nerve signs, seizures, coma

■ 14% case fatality ratio

Pneumococcal Disease in Children

● Pneumococcal pneumonia

■ Accounts for 25% to 30% of 

invasive disease in children 

age 2 years or younger

● Pneumococcal bacteremia

■ Accounts for 40% of invasive 

disease in children age 2 years 

or younger

● Pneumococcal meningitis

■ S. pneumoniae leading cause 

of bacterial meningitis among 

children younger than age 

5 years

● Pneumococci common cause of 

acute otitis media
258

Pneumococcal Disease

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are a leading reason for pediatric office visits in the United 

States, resulting in more than 10 million visits annually. 

Complications of pneumococcal otitis media may include 

mastoiditis and meningitis.

Children with functional or anatomic asplenia, particularly 

those with sickle cell disease, and children with 

immunocompromising conditions are at very high risk for 

invasive disease, with rates in some studies more than 50 times 

higher than those among children of the same age without 

these conditions (i.e., incidence rates of 5,000 to 9,000 per 

100,000 population). Other conditions that increase the risk 

of invasive pneumococcal disease in children include chronic 

heart disease, lung disease (including asthma if treated with 

high-dose oral corticosteroid therapy), liver disease, CSF leak, 

and having a cochlear implant. Rates are also increased among 

children of certain racial and ethnic groups, including Alaska 

Natives, African Americans, and certain American Indian 

groups (Navajo and White Mountain Apache). The reason for 

this increased risk by race and ethnicity is not known with 

certainty but has also been noted for invasive Haemophilus 

influenzae infection (also an encapsulated bacterium). 

Attendance at a childcare center has also been shown to 

increase the risk of invasive pneumococcal disease and acute 

otitis media 2- or 3-fold among children younger than age 5 

years. Children with a cochlear implant are at increased risk for 

pneumococcal meningitis.

Laboratory Testing

A definitive diagnosis of infection with S. pneumoniae generally 

relies on isolation of the organism from blood or other normally 

sterile body sites (e.g., CSF, middle ear fluid, joint fluid, and 

peritoneal fluid). Tests are also available to detect capsular 

polysaccharide antigen in body fluids.

The appearance of lancet-shaped diplococci on Gram stain 

is suggestive of pneumococcal infection, but interpretation 

of stained sputum specimens may be difficult because of the 

presence of normal nasopharyngeal bacteria. The suggested 

criteria for obtaining a diagnosis of pneumococcal pneumonia 

using gram-stained sputum includes more than 25 white blood 

cells and fewer than 10 epithelial cells per low-power field, and 

a predominance of gram-positive diplococci.

A urinary antigen test based on an immunochromatographic 

membrane technique to detect the C-polysaccharide antigen of 

S. pneumoniae as a cause of community-acquired pneumonia 

among adults is commercially available and has been cleared 

by FDA. The test is rapid and simple to use, has a reasonable 

specificity in adults, and has the ability to detect pneumococcal 

pneumonia after antibiotic therapy has been started.
Pneumococcal Disease

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17

Antimicrobial Resistance

S. pneumoniae resistance to penicillin and other antibiotics 

was previously very common. Following introduction of PCV7, 

antibiotic resistance declined and then began to increase 

again. Then, in 2008, the definition of penicillin resistance was 

changed such that a much larger proportion of pneumococci 

were considered susceptible to penicillin. The revised 

susceptibility breakpoints for S. pneumoniae, published by the 

Clinical and Laboratory Standards Institute (CLSI) in January 

2008, were the result of a reevaluation that showed clinical 

response to penicillin was being preserved in clinical studies 

of pneumococcal infection, despite reduced susceptibility 

response in vitro. Since introduction of 13-valent pneumococcal 

conjugate vaccine (PCV13) in children in 2010, antibioticresistant pneumococcal infections declined significantly.

Epidemiology

Occurrence

Pneumococcal disease occurs throughout the world.

Reservoir

S. pneumoniae is a human pathogen. The reservoir for 

pneumococci is the nasopharynx of asymptomatic humans. 

There is no animal or insect vector.

Transmission

Transmission of S. pneumoniae occurs as the result of direct 

person-to-person contact via respiratory droplets or by 

autoinoculation in persons carrying the bacteria in their upper 

respiratory tract. Different pneumococcal serotypes have 

different propensities for causing asymptomatic colonization, 

otitis media, meningitis, and pneumonia. The spread of the 

organism within a family or household is influenced by such 

factors as household crowding and viral respiratory infections. 

Temporal Pattern

Pneumococcal infections are more common during the 

winter and in early spring when respiratory diseases are 

more prevalent.

Communicability

The period of communicability for pneumococcal disease is 

unknown, but presumably transmission can occur as long as the 

organism appears in respiratory secretions.

Pneumococcal Disease 

Epidemiology

● Reservoir

■ Humans

● Transmission

■ Person-to-person through 

respiratory droplets or by 

autoinoculation

● Temporal pattern

■ More common during winter 

and early spring

● Communicability

■ Presumably transmissible 

as long as organism is in 

respiratory secretions
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Pneumococcal Disease

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Secular Trends in the United States

Estimates of the incidence of pneumococcal disease have 

been made from a variety of population-based studies. 

More than 31,000 cases and more than 3,500 deaths from 

invasive pneumococcal disease (bacteremia and meningitis) 

are estimated to have occurred in the United States in 2017. 

More than half of these cases occurred in adults who had an 

indication for pneumococcal polysaccharide vaccine. 

Before routine use of pneumococcal conjugate vaccine in 

2000, the burden of pneumococcal disease among children 

younger than age 5 years was significant. An estimated 

17,000 cases of invasive disease occurred each year, of which 

13,000 were bacteremia without a known site of infection 

and about 700 were meningitis. An estimated 200 children 

died every year as a result of invasive pneumococcal disease. 

Although not considered invasive disease, an estimated 5 

million cases of acute otitis media occurred each year among 

children younger than 5 years of age. The widespread use of 

pneumococcal conjugate vaccines in children has resulted 

in a decrease in transmission of vaccine-type strains, thereby 

preventing pneumococcal disease among unvaccinated 

children and adults. 

Data from the Active Bacterial Core surveillance (ABCs) 

system indicate that in 2008, before PCV13 replaced PCV7 for 

routine use among children, approximately 61% of invasive 

pneumococcal disease cases among children younger than age 

5 years were attributable to the serotypes included in PCV13, 

with serotype 19A accounting for 43% of cases; PCV7 serotypes 

caused less than 2% of cases. 

ABCs data suggest that the use of pneumococcal conjugate 

vaccine has had a major impact on the incidence of invasive 

disease among young children. The reductions in overall 

incidence resulted from a 99% decrease in disease caused 

by the seven serotypes in PCV7 and serotype 6A, a serotype 

against which PCV7 provides some cross-protection. The 

decreases were offset partially by increases in invasive disease 

caused by serotypes not included in PCV7, in particular 19A. 

In 2010, PCV13 replaced PCV7 in the United States. PCV13 

contains the serotypes in PCV7, plus 6 additional serotypes, 

including 19A. Since PCV13 introduction, invasive disease 

caused by PCV13 serotypes has declined 90% in children. 

Declines have been sustained and have not been offset by 

increases in non-vaccine type disease.

Among children born during 2016–2017, 91.6% had received at 

least 3 doses of PCV, and 81.7% had received at least 4 doses, 

by age 24 months. In 2017, 69.0% of persons age 65 years or 

older had ever received a pneumococcal vaccine. Vaccination 

coverage levels in 2017 were 24.5% among persons age 19 

through 64 years at increased risk for pneumococcal disease. 

Pneumococcal Disease Secular 

Trends in the United States

● In 2017, more than 31,000 cases 

and 3,500 deaths from invasive 

pneumococcal disease; more 

than 50% occurred in adults

● Before routine use of 

pneumococcal conjugate 

vaccine, annual burden in 

children younger than age 5 

years was significant:

■ 17,000 cases of invasive 

disease 

■ 200 deaths from invasive 

pneumococcal disease

■ 5 million cases of acute 

otitis media

● Since use of pneumococcal 

conjugate vaccine in children, 

invasive disease caused by 

serotypes in PCV7 declined 99% 

in children

● Since introduction of PCV13, 

invasive disease caused by 

PCV13 serotypes declined 90% 

in children
Pneumococcal Disease

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17

Opportunities to vaccinate persons at increased risk of 

pneumococcal disease are missed both at the time of hospital 

discharge and during visits to clinicians’ offices. Effective 

programs for vaccine delivery are needed, including offering 

the vaccine in hospitals at discharge and in clinicians’ offices, 

nursing homes, and other long-term care facilities.

More than 65% of persons hospitalized with severe 

pneumococcal disease had been admitted to a hospital in the 

preceding 3 to 5 years, yet few had received pneumococcal 

vaccine. In addition, persons who frequently visit physicians and 

who have chronic conditions are more likely to be at increased 

risk of pneumococcal infection than those who require 

infrequent visits. Screening and subsequent immunization of 

hospitalized persons found to be at increased risk could have 

a significant impact on reducing complications and death 

associated with pneumococcal disease.

Pneumococcal Vaccines

The first pneumococcal polysaccharide vaccine was licensed for 

use in the United States in 1977. It contained purified capsular 

polysaccharide antigen from 14 different types of pneumococci. 

In 1983, a 23-valent polysaccharide vaccine (PPSV23, 

Pneumovax 23) was licensed and replaced the 14-valent 

vaccine, which is no longer produced. 

The first pneumococcal conjugate vaccine (Prevnar 7, PCV7) was 

licensed for use in the United States in 2000. It included purified 

capsular polysaccharide of seven serotypes of S. pneumoniae. 

In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13, 

Prevnar 13) was licensed in the United States. It contains the 

same 7 serotypes of S. pneumoniae as PCV7 plus serotypes 1, 3, 

5, 6A, 7F, and 19A. 

In 2008, the serotypes covered in PCV13 caused 53%, 49%, and 

44% of invasive pneumococcal disease cases among persons 

age 18 through 49 years, 50 through 64 years, and 65 years or 

older, respectively; serotypes covered in PPSV23 caused 78%, 

76%, and 66% of IPD cases among persons in these age groups.

Characteristics

Pneumococcal Polysaccharide Vaccine

PPSV23 is composed of purified preparations of pneumococcal 

capsular polysaccharide from 23 types of pneumococci. The 

serotypes are: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 

17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F. PPSV23 is administered 

by either intramuscular or subcutaneous injection. Each dose 

of PPSV23 contains phenol as a preservative. It contains no 

adjuvant or antibiotic. 

Pneumococcal Vaccine 

Characteristics

● PPSV23

■ Administered by 

intramuscular or 

subcutaneous injection

■ Contains phenol as a 

preservative

● PCV13

■ Administered by 

intramuscular injection

■ Contains aluminum 

phosphate as an adjuvant

Pneumococcal Vaccines

● PPSV23 (Pneumovax 23)

● PCV13 (Prevnar 13)
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Pneumococcal Disease

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Pneumococcal Conjugate Vaccine

PCV13 contains 13 serotypes of S. pneumoniae (1, 3, 4, 5, 6A, 

6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) conjugated to a nontoxic 

variant of diphtheria toxin known as CRM197. PCV13 is 

administered by intramuscular injection. Each dose of PCV13 

contains aluminum phosphate as an adjuvant. It contains no 

antibiotic or preservative.

Vaccination Schedule and Use

All children age 2 through 59 months should routinely 

receive PCV13, and all adults age 65 years or older should 

receive PPSV23. In addition, persons age 2 years or older with 

certain conditions (see table “Conditions with Pneumococcal 

Vaccination Indications” below) should receive both PCV13 

and PPSV23, or PPSV23 alone. PPSV23 is not recommended for 

children younger than age 2 years. Children and adults who 

have a condition for which PCV13 is indicated should receive 

PCV13 first, followed by PPSV23 at least 8 weeks later. Adults 

age 65 years or older, who do not have any conditions for 

PCV13 indication (see table “Conditions with Pneumococcal 

Vaccination Indications” below), can discuss with their clinician 

and decide whether to receive PCV13 (shared clinical decision 

making). If the decision is made to receive PCV13 based on 

shared clinical decision making, it should be given at least 1 year 

before PPSV23.

Pneumococcal Vaccination Schedule

● PCV13

■ 3-dose primary series at age 

2, 4, and 6 months

■ Booster at age 12 through 15 

months

■ Minimum age for dose 1 is 6 

weeks

■ Minimum interval for doses 

before age 1 year is 4 weeks 

and age 1 year or older is 8 

weeks

■ Unvaccinated children age 7 

months or older require fewer 

doses

■ Shared clinical decision 

making for age 65 years or 

older 

● PPSV23

■ 1 dose for all adults age 65 

years or older

● Schedule for PCV13 and PPSV23 

varies by medical condition
Pneumococcal Disease

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Conditions with Pneumococcal Vaccination Indications

Conditions

PCV13 indicated 

for 2 through 

71 Months*

PCV13 indicated 

for 6 through 

18 Years*

PCV13 indicated 

for 19 Years 

or Older

PPSV23 indicated 

for 2 through 

64 Years

Chronic heart or lung disease† Yes No No Yes

Diabetes Yes No No Yes

Chronic liver disease,

 including cirrhosis

Yes No No Yes

Cigarette smoking (in adults) Yes No No Yes

Alcoholism (in adults) Yes No No Yes

Cerebrospinal Fluid (CSF) leak Yes Yes Yes Yes

Cochlear implant Yes Yes Yes Yes

Functional or anatomic asplenia, 

including sickle cell disease

Yes Yes Yes Yes

Immunocompromising conditions§ Yes Yes Yes Yes

Persons living in special environments 

or social settings¶

No No No Consider

*PCV13 only recommended if child is unvaccinated or received incomplete vaccine schedule.

†

Includes congestive heart failure, cardiomyopathies, chronic obstructive pulmonary disease, emphysema, and asthma. Asthma only 

included for children (through age 18 years) if treated with high-dose oral corticosteroid therapy.

§

Includes congenital or acquired immunodeficiencies, Hodgkin’s Disease, lymphoma, leukemia, multiple myeloma, generalized 

malignancy, and other cancers if on immunosuppressive therapy; HIV infection; chronic renal failure; nephrotic syndrome; organ 

transplant; and immunosuppressive medications, including chemotherapy and high-dose corticosteroid treatment.

¶

Includes Alaska Native, Navajo, and White Mountain Apache populations.

Children Age 2 Through 23 Months

Children should routinely receive a 3-dose primary series 

of PCV13 at age 2, 4, and 6 months, and dose 4 (booster) at 

age 12 through 15 months. Dose 1 can be administered as 

early as 6 weeks. For doses given before the 1st birthday, the 

minimum interval between doses is 4 weeks; doses given 

at age 12 months or older should be separated by at least 8 

weeks. PCV13 can be administered at the same time as other 

routine immunizations.

Unvaccinated children age 7 months or older do not require 

a full series of four doses. The number of doses depends on 

the child’s current age and the age at which the first dose of 

PCV13 was administered. If the child’s current age is 7 through 

11 months, the recommended series is 2 doses at least 4 weeks 

apart, and a booster dose at age 12 through 15 months. If the 

vaccination series is initiated at age 7 through 11 months, and 

the next dose is administered after the 1st birthday, another 

dose should be administered 8 weeks later. If the child’s current 

age is 12 through 23 months, the recommended series is 2 

doses at least 8 weeks apart.

Healthy Children Age 24 through 59 Months

Healthy children age 24 through 59 months should receive 

1 dose of PCV13 if child is unvaccinated or received 

any incomplete schedule. Routine use of PCV13 is not 

recommended for healthy children age 5 years or older.
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Pneumococcal Disease

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Children Age 24 through 71 Months, with Certain 

Medical Conditions

Children age 24 through 71 months with certain conditions (see 

table “Conditions with Pneumococcal Vaccination Indications” 

above) should receive 2 doses of PCV13 separated by 8 weeks if 

they are unvaccinated or received any incomplete schedule of 

less than 3 doses. Children with any incomplete schedule of 3 

doses should receive 1 dose of PCV13 at least 8 weeks after the 

most recent dose. 

These children should receive a dose of PPSV23 at least 8 

weeks after the final dose of PCV13. Additionally, if they 

are immunocompromised (see table “Conditions with 

Pneumococcal Vaccination Indications” above for list of 

conditions) or have functional or anatomic asplenia, they should 

receive a second dose of PPSV23 five years after the first. 

Children and Adolescents Age 6 through 18 Years, 

with Certain Medical Conditions

Unvaccinated children and adolescents age 6 through 18 years 

with certain medical conditions (see table “Conditions with 

Pneumococcal Vaccination Indications” above) should receive 

both PCV13 and PPSV23. A single dose of PCV13 should be 

given followed by a dose of PPSV23 at least 8 weeks later. A 

second dose of PPSV23 is recommended 5 years after the first 

PPSV23 dose for children with anatomic or functional asplenia, 

or other immunocompromising conditions (see footnote in 

table “Conditions with Pneumococcal Vaccination Indications” 

above for complete list of conditions). 

If a complete schedule of PCV13 has been given, no 

additional PCV13 doses are required. If PCV13 has not been 

given, and two doses of PPSV23 have already been given, 

a dose of PCV13 should be given at least 8 weeks after 

the most recent dose of PPSV23. PCV13 may also be given 

between two doses of PPSV23.

Some children and adolescents in this age group with certain 

conditions should only receive one dose of PPSV23, if they 

have not already.
Pneumococcal Disease

265

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Pneumococcal Vaccination Schedule for Children and Adolescents Age 6 through 18 years with 

Certain Chronic or Immunocompromising Conditions

Condition(s) Prior Pneumococcal 

Doses Recommendation

Chronic heart disease, chronic lung disease, 

diabetes, chronic liver disease 

(including cirrhosis)

PPSV23 (or PPSV23 

& PCV13)

No pneumococcal vaccine needed

None, or if PCV13 only • PPSV23 at least 8 weeks after previous PCV13

Cerebrospinal fluid leak, cochlear implant

None • PCV13

• PPSV23 at least 8 weeks after PCV13

PCV13 (No PPSV23) • PPSV23 at least 8 weeks after previous PCV13

PPSV23 (No PCV13) • PCV13 at least 8 weeks after previous PPSV23

Functional and/or anatomic asplenia 

(including sickle cell disease), 

immunocompromising conditions*

None • PCV13

• PPSV23 at least 8 weeks after PCV13

• PPSV23 at least 5 years after previous PPSV23

PCV13 (No PPSV23) • PPSV23 at least 8 weeks after previous PCV13 

• PPSV23 at least 5 years after 1st PPSV23

PPSV23 (No PCV13) • PCV13 at least 8 weeks after previous PPSV23 

• PPSV23 at least 8 weeks after PCV13 and at 

least 5 years after previous PPSV23

*Includes congenital or acquired immunodeficiencies, Hodgkin’s Disease, lymphoma, leukemia, multiple myeloma, generalized 

malignancy, and other cancers if on immunosuppressive therapy; HIV Infection; chronic renal failure; nephrotic syndrome; organ 

transplant; and immunosuppressive medications, including chemotherapy and high-dose corticosteroid treatment.

Adults Age 19 through 64 Years, with Certain 

Chronic or Immunocompromising Conditions

Routine use of PCV13 or PPSV23 is not recommended 

for healthy adults age19 through 64 years. Unvaccinated 

persons age 19 through 64 years with certain chronic 

conditions (see table “Conditions with Pneumococcal 

Vaccination Indications” above) should receive one dose of 

PPSV23 if they have not already.

Unvaccinated persons age 19 years or older with certain 

immunocompromising conditions, cerebrospinal fluid leak, or 

cochlear implant (see table “Conditions with Pneumococcal 

Vaccination Indications”, above) should receive a single dose of 

PCV13 followed by a dose of PPSV23 at least 8 weeks later. If a 

dose of PPSV23 was given first, PCV13 should be administered 

at least 1 year later. A second dose of PPSV23 is recommended 

5 years after the first PPSV23 dose for adults with anatomic or 

functional asplenia, or other immunocompromising conditions. 
266

Pneumococcal Disease

 17

Conditions for Administration of PCV13 and PPSV23 in Adults

Medical Condition(s)

PCV 13 

indicated for 

age 19 years or 

older

PSV23 

indicated for 

age 19 through 

64 years

PPSV23 

revaccination 

indicated for 

age 19 through 

64 years

PCV13 

indicated for 

age 65 years 

or older

PPSV23 indicated 

for age 65 years 

or older

None

No No No Based on 

shared clinical 

decisionmaking

Yes

If PCV13 has been 

given, then give 

PPSV23 at least 

1 year after PCV13

Chronic heart disease, chronic 

lung disease, diabetes, 

alcoholism, chronic liver disease 

(including cirrhosis), current 

cigarette smoking, asthma

No Yes No Based on 

shared clinical 

decisionmaking

Yes

If PCV13 has been 

given, then give 

PPSV23 at least 1 

year after PCV13 

and at least 5 years 

after any PPSV23 

given at less than 

age 65 years

Cerebrospinal fluid leak, 

cochlear implant

Yes Yes

At least 8 weeks 

after PCV 13

No Yes

If no previous 

PCV13 

vaccination

Yes

At least 8 weeks 

after PCV13 and at 

least 5 years after 

any PPSV23 given 

at less than age 

65 years

Functional or anatomic asplenia 

(including sickle cell disease/other 

hemoglobinopathies)

Yes Yes

At least 8 weeks 

after PCV13

Yes

At least 5 years 

after first dose 

of PPSV23

Yes

If no previous 

PCV13 

vaccination

Yes

At least 8 weeks 

after PCV13 and at 

least 5 years after 

any PPSV23 given 

at less than age 

65 years

Immunocompromising 

conditions*

Yes Yes

At least 8 weeks 

after PCV13

Yes

At least 5 years 

after first dose 

of PPSV23

Yes

If no previous 

PCV13 

vaccination

Yes

At least 8 weeks 

after PCV13 and at 

least 5 years after 

any PPSV23 given 

at less than age 

65 years

*Includes congenital or acquired immunodeficiencies, Hodgkin’s Disease, lymphoma, leukemia, multiple myeloma, generalized 

malignancy, and other cancers if on immunosuppressive therapy; HIV infection; chronic renal failure; nephrotic syndrome; organ 

transplant; and immunosuppressive medications, including chemotherapy and high-dose corticosteroid treatment.

Adults Age 65 Years or Older, without 

Immunocompromising Conditions, Cerebrospinal 

fluid leak, or Cochlear Implant

A single dose of PPSV23 is recommended for all adults age 65 

years or older, regardless of previous pneumococcal vaccination 

history. If any PPSV23 dose(s) were given before age 65 years, a 

single, final dose of PPSV23 should be given at age 65 or at least 

5 years after the last PPSV23 dose. If PPSV23 was administered 

at age 65 years or later, no additional doses are needed. 

Adults age 65 years or older without immunocompromising 

conditions (see table “Conditions with Pneumococcal 

Vaccination Indications” above) may discuss with their clinician 

and decide whether to receive PCV13 if a dose was not received 
Pneumococcal Disease

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17

before (i.e., shared clinical decision making). If a decision is

made to receive PCV13, a dose of PCV13 should be given first,

followed by a dose of PPSV23 at least one year later.

Additional Scheduling and Timing Considerations 

Additional information on the timing of pneumococcal

vaccination for adults and children can be found at

https://www.cdc.gov/vaccines/vpd/pneumo/hcp/

recommendations.html. PCV13 and PPSV23 should not

be administered simultaneously (i.e., on the same clinic

day). Studies evaluating immune responses to PCV13 and

PPSV23 administered in series showed the immune response

was better when PCV13 was given first. The minimum

interval between PCV13 and PPSV23 is 8 weeks for adults

with immunocompromising conditions and 1 year for

immunocompetent adults. However, in adults, if they are

administered simultaneously or at an interval less than 8 weeks,

neither dose needs to be repeated. In children, if they are

administered simultaneously, PCV13 should be repeated at least 

8 weeks later. 

The target groups for pneumococcal vaccines and influenza vaccines 

overlap. Either pneumococcal vaccine may be given at the same time 

as influenza vaccine, if indicated, but at different anatomical sites. Most 

healthy adults age 65 years or older need only a single lifetime dose of 

PPSV23 and may be administered PCV13 on or after the 65th birthday 

based on shared clinical decision making.
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While for most other vaccines health care providers should only 

accept written, dated records as evidence of vaccination, selfreported doses of adult PPSV23 (but not PCV13) are acceptable. 

Persons with uncertain or unknown vaccination status should 

be vaccinated. 

When elective splenectomy, immunocompromising therapy, 

or cochlear implant placement is being planned, providers 

should choose the vaccines appropriate to the level of risk for 

invasive pneumococcal disease which would exist after the 

surgery or treatment. For example, a person who will undergo 

splenectomy should be considered asplenic when applying 

these vaccine recommendations. The choice of vaccine also 

depends on past history of pneumococcal vaccination. If PCV13 

and PPSV23 are both recommended, they both need to be 

administered, preferably before treatment or surgery. PCV13 

should be administered first, and PPSV23 at least 8 weeks later. 

PPSV23 should be given at least 2 weeks before the treatment 

or surgery. If treatment or surgery cannot be delayed, providers 

can consider administering pneumococcal vaccines afterward. 

Following vaccination with PPSV23, antibody levels decline 

after 5 to 10 years and decrease more rapidly in some groups 

than others. However, the relationship between antibody 

titer and protection from invasive disease is not certain for 

adults, so the ability to define the need for revaccination 

based only on serology is limited. In addition, currently 

available pneumococcal polysaccharide vaccine elicits a T-cellindependent response, and does not produce a sustained 

increase (“boost”) in antibody titers. Available data do not 

indicate a substantial increase in antibody level in the majority 

of revaccinated persons.

Immunogenicity and Vaccine Efficacy

Pneumococcal Polysaccharide Vaccine

More than 80% of healthy adults who receive PPSV23 develop 

antibodies against the serotypes contained in the vaccine, 

usually within 2 to 3 weeks after vaccination. Older adults and 

persons with some chronic illnesses or immunodeficiency 

may not respond as well, if at all. Elevated antibody levels 

following vaccination persist for at least 5 years in healthy adults 

but decline more quickly in persons with certain underlying 

illnesses. In children younger than age 2 years, antibody 

response to PPSV23 is generally poor.

PPSV23 vaccine efficacy studies have resulted in various 

estimates of clinical effectiveness. Overall, the vaccine is 

60% to 70% effective in preventing invasive disease caused 

by serotypes included in the vaccine. Despite the vaccine’s 

reduced effectiveness among immunocompromised persons, 

Pneumococcal Vaccine Efficacy

● PPSV23

■ 60-70% effective in

preventing invasive disease

caused by serotypes in

vaccine

● PCV13

■ Induces levels of antibodies

comparable to those induced

by PCV7, which was shown

to reduce invasive disease

caused by vaccine serotypes

by 97% in children

■ 45.6% efficacy against

vaccine-type pneumococcal

pneumonia, 45.0%

efficacy against vaccinetype nonbacteremic

pneumococcal pneumonia,

75.0% efficacy against

vaccine-type IPD in adults
Pneumococcal Disease

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PPSV23 is still recommended for such persons because they 

are at increased risk of developing severe disease. There is 

no consensus regarding the ability of PPSV23 to prevent 

non-bacteremic pneumococcal pneumonia. For this reason, 

providers should avoid referring to PPSV23 as a 

“pneumonia vaccine.”

Studies comparing patterns of pneumococcal carriage before 

and after PPSV23 vaccination have not shown clinically 

significant decreases in carriage rates among vaccine recipients. 

Pneumococcal Conjugate Vaccine

In a large clinical trial, PCV7 was shown to reduce invasive 

disease caused by vaccine serotypes by 97%. Children 

who received PCV7 had 20% fewer episodes of chest X-ray 

confirmed pneumonia, 7% fewer episodes of acute otitis 

media, and underwent 20% fewer tympanostomy tube 

placements than did unvaccinated children. There is evidence 

that PCV7 reduced nasopharyngeal carriage among children of 

pneumococcal serotypes included in the vaccine.

PCV13 was licensed in the United States based upon studies 

that compared the serologic response of children who received 

PCV13 to those who received PCV7. These studies showed that 

PCV13 induced levels of antibodies that were comparable to 

those induced by PCV7 and shown to be protective against 

invasive disease. 

In another study of PCV13, children age 7 through 11 months, 

12 through 23 months, and 24 through 71 months who 

had not received pneumococcal conjugate vaccine doses 

previously were administered 1, 2, or 3 doses of PCV13 

according to age-appropriate immunization schedules. These 

schedules resulted in antibody responses to each of the 13 

serotypes that were comparable to those achieved after 

the 3-dose infant PCV13 series in the U.S. immunogenicity 

trial, except for serotype 1, for which IgG geometric mean 

concentration (GMC) was lower among children age 24 

through 71 months. 

Licensure of PCV13 for adults age 50 years or older was based 

on serologic studies comparing immune response of PCV13 

recipients to immune response following a dose of PPSV23. 

In two randomized, multicenter immunogenicity studies 

conducted in the United States and Europe, immunocompetent 

adults age 50 years or older received a single dose of PCV13 

or PPSV23. In adults age 60 through 64 years and age 70 years 

or older, PCV13 elicited opsonophagocytic activity geometric 

mean antibody titers that were comparable with, or higher than, 

responses elicited by PPSV23. Persons who received PPSV23 as 

the initial study dose had lower opsonophagocytic antibody 
270

Pneumococcal Disease

 17

responses after subsequent administration of a PCV13 dose 1 

year later than those who had received PCV13 as the initial dose. 

Since introduction of PCV13 in children in 2010, invasive disease 

caused by PCV13 serotypes has declined over 60% among 

adults age 65 years or older through PCV13 indirect effects. 

A randomized placebo-controlled trial was conducted in the 

Netherlands among approximately 85,000 adults age 65 years 

or older during 2008–2013 to evaluate the clinical benefit of 

PCV13 in the prevention of pneumococcal pneumonia. The 

results of this trial demonstrated 45.6% efficacy of PCV13 

against vaccine-type pneumococcal pneumonia, 45.0% efficacy 

against vaccine-type nonbacteremic pneumococcal pneumonia, 

and 75.0% efficacy of PCV13 against vaccine-type IPD.

Contraindications and Precautions 

to Vaccination

As with other vaccines, a history of a severe allergic reaction 

(anaphylaxis) to a vaccine component or following a prior 

dose is a contraindication to further doses. Moderate or severe 

acute illness (with or without fever) in a patient is considered a 

precaution to vaccination, although persons with minor illness 

may be vaccinated. 

Vaccine Safety

Studies support the safety of PCV13 and PPSV23 in children 

and adults.

Pneumococcal Polysaccharide Vaccine

In pre-licensure PPSV23 studies, the most common adverse 

reactions reported were local reactions (pain, soreness, 

tenderness, injection-site swelling, and induration), headache, 

fatigue, and muscle pain. These reactions usually resolved 

within 48 hours. In study participants age 65 years or older, 

systemic adverse reactions that were related to the vaccine were 

more frequent following the second dose than the first dose. 

Results from studies done after PPSV23 was licensed have 

been consistent with the safety findings in the pre-licensure 

studies. A transient increase in viral replication among 

HIV-positive persons has been reported following PPSV23 

vaccine. No clinical or immunologic deterioration has been 

reported in these persons.

Pneumococcal Conjugate Vaccine

In the pre-licensure studies, the common adverse reactions 

reported were local reactions (pain, tenderness, swelling and 

erythema), decreased appetite, fatigue, headache, muscle pain, 

irritability, and fever. Increased and decreased sleep was also 

commonly reported in infants and toddlers. 

Pneumococcal Vaccine 

Contraindications and Precautions

● Contraindication

■ Severe allergic reaction 

to vaccine component or 

following prior dose

● Precaution

■ Moderate or severe 

acute illness

Pneumococcal Vaccine Safety

● PPSV23

■ Pain, soreness, tenderness, 

injection site swelling, 

induration, headache, fatigue, 

muscle pain

● PSV13

■ Pain, tenderness, swelling, 

erythema, decreased 

appetite, fatigue, headache, 

muscle pain, irritability, fever

■ Simultaneous administration 

of PCV13 and inactivated 

influenza vaccine associated 

with an increased risk of 

febrile seizures
Pneumococcal Disease

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In young children, studies done after PCV13 was licensed 

showed simultaneous PCV13 and inactivated influenza vaccine 

was associated with an increased risk of febrile seizures during 

some influenza seasons. Febrile seizures can be concerning to 

caregivers, but they are brief and are not associated with any 

long-term complications. A review of adverse events reported 

to the Vaccine Adverse Event Reporting System after PCV13 

vaccination in children age 6 weeks through 59 months was 

consistent with the pre-licensure studies.

Vaccination in Pregnancy

ACIP recommendations for use of PCV13 during pregnancy 

do not exist.

The safety of PPSV23 vaccine for pregnant women has not 

been studied, although no adverse consequences have been 

reported among newborns whose mothers were inadvertently 

vaccinated during pregnancy. Women who are at increased 

risk of pneumococcal disease and who are candidates 

for pneumococcal vaccine should be vaccinated before 

pregnancy, if possible.

Vaccine Storage and Handling

PCV13 and PPSV23 should be maintained at refrigerator 

temperature between 2°C and 8°C (36°F and 46°F). 

Manufacturer package inserts contain additional 

information. For complete information on best practices and 

recommendations for vaccine storage and handling, please 

refer to CDC’s Vaccine Storage and Handling Toolkit, www.cdc.

gov/vaccines/hcp/admin/storage/toolkit/storage-handlingtoolkit.pdf. 

Surveillance and Reporting of 

Pneumococcal Disease

Invasive pneumococcal disease is a notifiable condition in 

most states. For information on guidance for state and local 

health department staff who are involved in surveillance 

activities for vaccine-preventable diseases, please consult the 

Manual for the Surveillance of Vaccine-Preventable Diseases, 

www.cdc.gov/vaccines/pubs/surv-manual/chapters.html.
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Acknowledgements

The editors would like to acknowledge Tamara Pilishvili and 

Ginger Redmon for their contributions to this chapter.

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NOTES