Pneumococcal disease is caused by Streptococcus pneumoniae, a bacterium that has more than 100 serotypes. Most serotypes cause disease, but only a few produce the majority of invasive pneumococcal disease.
The disease is spread from person to person by droplets in the air. The pneumococci bacteria are common inhabitants of the human respiratory tract. They may be isolated from the nasopharynx of 5%–90% of healthy people.
There are two major clinical syndromes of invasive pneumococcal disease: bacteremia (blood stream infection), and meningitis (infection of the meninges that surround the brain). They are both caused by infection with the same bacteria, but produce different signs and symptoms.
Pneumococcal pneumonia is the most common disease caused by pneumococcal infection. An estimated 400,000 hospitalizations from pneumococcal pneumonia occur in the United States annually.
Pneumococcal pneumonia can occur in combination with bacteremia and/or meningitis (invasive pneumococcal pneumonia), or it can occur alone (non-invasive pneumococcal pneumonia). Non-invasive pneumococcal pneumonia can be severe. Symptoms include abrupt onset of fever, shaking chills or rigors, chest pain, cough, shortness of breath, rapid breathing and heart rate, and weakness. The fatality rate is 5%–7% and may be much higher in older adults. Pneumococcal bacteremia occurs in about 25%–30% of patients with pneumococcal pneumonia.
About 4,000 cases of pneumococcal bacteremia without pneumonia occur each year in the United States. Bacteremia is the most common clinical presentation among children less than two years, accounting for up to 70% of invasive disease in this age group.
Pneumococci cause 50% of all cases of bacterial meningitis in the United States. There are an estimated 2,000 cases of pneumococcal meningitis each year. Symptoms and signs may include headache, tiredness, vomiting, irritability, fever, seizures, and coma. The case-fatality rate of pneumococcal meningitis is about 8% among children and 22% among adults. Permanent neurological damage is common among survivors.
Pneumococcal disease is a serious disease that causes much sickness and death. CDC estimates that more than 150,000 hospitalizations from pneumococcal disease occur annually in the U.S. An estimated 30,300 cases and 3,250 deaths from invasive pneumococcal diseases (IPD-bacteremia and -meningitis) occurred in the United States in 2019 (see www.cdc.gov/abcs/downloads/SPN_Surveillance_Report_2019.pdf.). Children younger than age two years and adults age 50 years and older) have the highest incidence of serious disease. Case-fatality rates are highest for pneumococcal meningitis and bacteremia, and the highest mortality occurs among older adults and patients who have underlying medical conditions. The overall case-fatality rate for pneumococcal bacteremia is about 20%. Among older adults, this rate may be as high as 60%.
One pneumococcal polysaccharide vaccine (PPSV23, Pneumovax 23, Merck) and three pneumococcal conjugate vaccines [PCV13 (Prevnar 13, Pfizer), PCV15 (Vaxneuvance, Merck), and PCV20 (Prevnar 20, Pfizer)] are FDA-licensed and recommended by CDC for use in the United States.
PPSV23 is licensed for age 2 years and older. It was first licensed in 1983. It is recommended for children ages 2 years or older with specified risk factors for pneumococcal disease. It is recommended as an option, when used in series with PCV15, for adults 19 through 64 at increased risk for invasive pneumococcal disease due to behavioral or medical risk factors. A PCV15 + PPSV23 series also is recommended as an option for pneumococcal disease prevention in adults 65 years and older. Following the 2022 changes to the pneumococcal vaccination schedule for adults, PPSV23 is no longer recommended alone, however PPSV23 is recommended for adults after PCV13 or PCV15 vaccination. It is not recommended for people who have previously received a PCV20 vaccination.
PCV13 is licensed for people age 6 weeks and older and was first licensed in 2010. Following the 2022 changes to adult pneumococcal vaccination recommendations, it is only recommended for use in children through age 18 years. CDC recommends the use of PCV13 for the routine vaccination of children younger than 5 years of age (4-dose series at age 2 months, 4 months, 6 months, and 12–15 months) and children 6 years and older without prior PCV13 vaccination who have certain medical conditions that put them at high risk of invasive pneumococcal disease. It is no longer recommended for use in adults.
PCV15 was licensed in 2021 for people age 18 years and older. CDC recommends it as an option for pneumococcal disease prevention in adults age 19 years or older who have not previously received a pneumococcal conjugate vaccine. It is always recommended to be used as part of a vaccination series with PPSV23 typically given 1 year later (a minimum interval of 8 weeks may be considered for certain high-risk individuals). PCV15 followed by PPSV23 is an option for adults 19 through 64 at increased risk for invasive pneumococcal disease due to behavioral or medical risk factors or for adults age 65 or older.
PCV20 was licensed in 2021 for people age 18 years and older. CDC recommends it as an option for pneumococcal disease prevention in adults age 19 years or older who have not previously received a pneumococcal conjugate vaccine. If PCV20 is given, no further pneumococcal vaccination is recommended. PCV20 is an option for adults 19 through 64 at increased risk for invasive pneumococcal disease due to behavioral or medical risk factors or for adults age 65 or older.
A polysaccharide vaccine is a type of vaccine that is composed of long chains of sugar molecules, called polysaccharides, that resemble the surface of certain serotypes of pneumococcal bacteria in order to help the immune system mount a response.
A conjugate vaccine is a type of vaccine that joins a protein to an antigen (in the case of pneumococcal vaccines, the protein is connected to unique polysaccharides from the surface of each of the pneumococcal serotypes). The protein helps improve the quality of the immune system response to the vaccine compared to the response to an unconjugated polysaccharide.
The polysaccharide vaccine includes the different polysaccharides (chains of complex sugars) from different serotypes as the antigen. The conjugate vaccines have the polysaccharides for different serotypes attached (or conjugated) to a CMR197 carrier protein. The immune response to the PPSV23 vaccine is a T-cell independent immune response, while the immune response to PCV vaccination is a T-cell dependent response that produces memory B-cells and reduces carriage of the bacteria in the respiratory track. The PPSV23 does not reduce bacterial carriage.
FDA licensed the first pneumococcal conjugate vaccine against seven serotypes (PCV7, Prevnar7, Pfizer) in 2000. A large clinical trial showed PCV7 reduced invasive disease caused by vaccine serotypes by 97%. Compared to unvaccinated children, children who received PCV7:
FDA licensed PCV13 based on studies comparing the serologic response of children who received PCV13 to those who received PCV7. Substantial evidence demonstrates that routine infant PCV7 and PCV13 vaccination reduces the carriage and transmission of vaccine serotypes.
Researchers conducted a randomized placebo-controlled trial (CAPiTA trial) in the Netherlands among approximately 85,000 adults 65 years or older from 2008 through 2013. This trial evaluated the clinical benefit of PCV13 in the prevention of pneumococcal pneumonia. The results of the CAPiTA trial demonstrated:
FDA licensed PCV15 and PCV20 in 2021 based on studies comparing the serologic response of adults who received either PCV15 or PCV20 to those who received PCV13. These studies showed PCV15 and PCV20 induced antibody levels comparable to those induced by PCV13 and shown to be protective against invasive disease.
According to CDC, more than 80% of healthy adults who receive PPSV23 develop antibodies against the serotypes contained in the vaccine that persist for at least 5 years. Older adults and people with some chronic illnesses or immunodeficiency may not respond as well and their antibody levels may decline more quickly.
Overall, the vaccine is 60% to 70% effective in preventing invasive pneumococcal disease caused by serotypes in the vaccine. PPSV23 shows less effectiveness among immunocompromised people; however, because of their increased risk of invasive pneumococcal disease, CDC recommends PPSV23 for people in these groups who receive PCV15. There has not been consensus regarding the ability of PPSV23 to prevent non-bacteremic pneumococcal pneumonia; however, recent observational studies reported 21%–46% effectiveness against PPSV23-type pneumococcal pneumonia when PPSV23 was given less than 5 years before illness onset.
Unlike conjugate vaccines, PPSV23 vaccination has not been shown to decrease nasal carriage of pneumococcal bacteria among those vaccinated.
The recommendations for pneumococcal vaccination of children and adults vary depending upon the specific vaccines available and the age and medical or behavioral risk factors of potential recipients. CDC has summarized all of its recommendations at this site: www.cdc.gov/vaccines/vpd/pneumo/hcp/recommendations.html.
S. pneumoniae bacteria are serotyped based on the polysaccharides in the outer capsule of the bacteria. Serotypes vary in how common they are and in what percentage of pneumococcal disease they cause.
Among the PCV vaccines, PCV13 includes serotypes: 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F. PCV15 includes all PCV13 serotypes plus 22F and 33F. PCV20 includes all PCV15 serotypes plus 8, 10A, 11A, 12F, and 15B. PPSV23 vaccine does not contain serotype 6A or 19A, but contains 19 other serotypes present in PCV20, plus serotypes 2, 9N, 17F, and 20.
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PCV vaccines are recommended to be given first because this sequence provides the best immune response to both PCV and PPSV23 vaccines. An evaluation of immune response after a second pneumococcal vaccination administered 1 year after an initial dose showed that subjects who received PPSV23 as the initial dose had lower antibody responses after subsequent administration of PCV13 than those who had received PCV13 as the initial dose followed by a dose of PPSV23.
In 2000, the first pneumococcal conjugate vaccine (PCV) was licensed in the U.S. This vaccine contained seven serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) of Streptococcus pneumoniae and became known as PCV7 (Prevnar by Wyeth, now Pfizer). Ten years later in February 2010, a new 13-valent product was licensed — PCV13 (Prevnar 13, Pfizer) — which added 6 new serotypes (1, 3, 5, 6A, 7F, and 19A). Together, these 13 serotypes account for the majority of invasive pneumococcal disease (IPD) in the U.S., including serotype 19A, which is the most common IPD-causing serotype in young children. In February 2010 ACIP recommended that healthcare providers transition from use of PCV7 to use of PCV13 for routine vaccination of children.
PCV7 was initially recommended for routine use in infants and children ages 2 through 59 months. The recommendations were expanded with the licensure of PCV13 to include vaccination of children age 60 through 71 months with underlying medical conditions, and also vaccination of older children, ages 6 through 18 years, with medical conditions placing them at increased risk of invasive pneumococcal disease.
All infants should be given a primary series of PCV13, at ages 2, 4, and 6 months with a booster at age 12 to 15 months. Children who fall behind should be given catch-up vaccination through age 59 months, if otherwise healthy, or through age 71 months if they have certain underlying medical conditions.
For pneumococcal vaccination of children ages 2 through 5 years, see the CDC summary here: www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html#children-2-5.
A single dose of PCV13 should be given to children ages 6 –18 years who have not received PCV13 before and have anatomic or functional asplenia (including sickle cell disease), immunocompromising conditions (such as HIV infection), cochlear implant, or cerebrospinal fluid (CSF) leaks. Routine use of PCV13 is not recommended for healthy children 5 years of age or older.
When elective splenectomy, immunocompromising therapy, or cochlear implant placement is being planned, PCV13 and/or PPSV23 vaccination (as needed) should be completed at least 2 weeks before surgery or initiation of therapy. For people not vaccinated 2 weeks prior, vaccinate as soon as possible.
For a complete explanation of pneumococcal vaccination recommendations for ages 6 through 18 years, CDC has summarized the recommendations here: www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html#children-6-18.
All children should receive routine vaccination with PCV13 as age-appropriate. A child age 2 through 18 years should receive PPSV23 at least 8 weeks following the last recommended dose of PCV13 if they have any of the following conditions:
All children 2-18 years who are at highest risk for serious pneumococcal infection (see categories 9 through 16 in related answer) should first be assessed and age-appropriately vaccinated with PCV13, if indicated. At least 8 weeks following completion of PCV13 vaccination, these children should get the first of 2 doses of PPSV23, spaced five years apart. Children with risk factors 1 through 8 above should get one dose of PPSV23.
ACIP does not recommend routine PCV13 vaccination of healthy children 60 months of age or older. If there is a school requirement, the simplest solution is to give the child one dose of PCV13. However, health insurance may not pay for this dose. For more information on the ACIP recommendations for pneumococcal vaccination of children, go to CDC’s summary of pneumococcal vaccine recommendations: www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html.
No. Currently no data exist to indicate that people younger than 19 who smoke are at increased risk of pneumococcal disease.
PPSV23 is not effective in children less than 24 months of age. PPSV23 given to children younger than 2 years old should not be considered part of the pneumococcal vaccination series. PCV13 should be administered as soon as the error is discovered. Any time the wrong vaccine is given, the parent/patient should be notified.
