Pneumococcal disease is caused by Streptococcus pneumoniae, a bacterium that has more than 90 serotypes. Most pneumococci are encapsulated in a complex polysaccharide (sugar) that forms the basis for classification of serotypes. Serotype-specific antibody to capsular polysaccharide is protective against disease. Most serotypes cause disease, but only a few produce the majority of invasive pneumococcal disease.
The first pneumococcal polysaccharide vaccine was licensed in the United States in 1977 and consisted of purified polysaccharide antigen from 14 pneumococcal serotypes. In 1983, this vaccine was replaced with a vaccine that contained capsular polysaccharide antigen from 23 pneumococcal serotypes (PPSV23, Pneumovax 23, Merck).
Pure polysaccharide vaccines generally do not work well in children younger than 2 years of age, induce only short-term immunity, do not eliminate pharyngeal colonization, and multiple doses do not boost immunity. A conjugate vaccine contains purified bacterial capsular polysaccharides that are attached to a protein. A conjugate vaccine avoids many of the shortcomings associated with polysaccharide vaccines.
In 2000, the first conjugated pneumococcal vaccine was licensed in the United States (PCV7, Prevnar, Wyeth). This vaccine consisted of purified capsular polysaccharide from seven serotypes conjugated to a naturally occurring, nontoxic variant of diphtheria toxin (CRM197). Following widespread use of PCV7, rates of invasive pneumococcal disease (including pneumonia, meningitis, bacteremia and other infections of normally sterile sites) due to the seven vaccine serotypes demonstrated a remarkable decline among children and adults.
Data from the Centers for Disease Control and Prevention indicated that by 2008, less than 2% of pneumococcal disease among children younger than 5 years of age was caused by serotypes contained in PCV7, demonstrating the extraordinary benefit of this vaccine. While the overall rates of invasive pneumococcal disease declined following PCV7 use, serotype replacement by nonvaccine serotypes (particularly 19A) became a more common cause of pharyngeal colonization and invasive disease.
In 2010, PCV13 (Prevnar 13, Pfizer) replaced PCV7. PCV13 included the seven serotypes in the first-generation vaccine as well as six additional serotypes, including 19A, conjugated to the carrier protein (CRM197). Because one of the serotypes (6A) in the original PCV7 vaccine conferred cross protection against one of the six additional serotypes in PCV13 (6B), the second-generation vaccine added coverage for five additional serotypes.
Are the following statements true or false?
a) A dose of PPSV23 should be administered every five years to a patient with functional or anatomic asplenia.
b) Administration of PCV13 is recommended for all children starting at 2 months of age followed by booster doses at 4, 6 and 12 through 15 months of age.
c) PCV13 is not routinely administered to unvaccinated healthy children ages 5 years and older.
d) Serotype replacement refers to a population-based change in serotype distribution, often involving serotypes that were in circulation before vaccine introduction.
Answer: a is false; b, c and d are true
PPSV23 vaccine is not routinely recommended for healthy children. No more than two doses of PPSV23 are recommended for people younger than 65 years of age, including severely immunocompromised patients such as those without a spleen. When indicated, the two doses of PPSV23 should be administered five years apart.
A pattern of antibody response termed hyporesponsiveness is observed after administration of more than two doses of the pure polysaccharide vaccine. A second dose of PPSV23 is recommended five years after the first dose for people at increased risk of disease, but multiple revaccination (more than two doses) with PPSV23 is not recommended because of concerns regarding benefit and safety.
Unvaccinated children 7 months of age and older do not require four doses of PCV13. For example, previously unvaccinated healthy children 24 through 59 months of age are recommended to receive a single dose of PCV13. Routine use of PCV13 among healthy children 5 years of age and older is not recommended.
A single dose of PCV13 is recommended for children 6 years through 18 years of age who were not previously vaccinated and are at increased risk of invasive pneumococcal disease because of conditions such as functional or anatomic asplenia, immunocompromising conditions, cochlear implants or cerebrospinal fluid leak.
If elective splenectomy or cochlear implant is being considered, PPSV23 (as well as the PCV13 series) should be administered at least two weeks in advance. If vaccination prior to the procedure is not possible, the vaccines should be administered as soon as possible thereafter to minimize the risk of pneumococcal disease caused by the five serotypes unique to PPSV23.
For patients in whom PPSV23 or PCV13 is recommend and a documented vaccination history is not readily obtainable, the vaccine should be administered as recommended since extra doses do not increase the risk of an adverse event.
Dr. Meissner is professor of pediatrics at Floating Hospital for Children, Tufts Medical Center. He also is an ex officio member of the AAP Committee on Infectious Diseases and associate editor of the AAP Visual Red Book.