New Recommendations for Pneumococcal Vaccine
By Robert Baltimore, MD, FAAP
The latest summary of recommendations from the Advisory Committee on Immunization Practices (ACIP) of the Centers of Disease Control updates the previous recommendations concerning the use of pneumococcal polysaccharide vaccines.1
Since the licensing of the first pneumococcal (14-valent) vaccine in 1977, the CDC has periodically updated its recommendations for use of the vaccine in the United States. In this paper, the ACIP updates the last recommendation for the 23-valent vaccine, which was published in 1989.2 The 23 pneumococcal serotypes that are included in the currently used vaccine include about 90% of the serotypes that are associated with invasive human disease and also include the six serotypes that are most frequently involved in antibiotic-resistant pneumococcal infections. The new recommendations are based upon data indicating a decline in serum antibody concentrations after immunization, especially among the elderly. Current evidence strongly supports the effectiveness of pneumococcal vaccines in preventing invasive pneumococcal diseaseespecially bacteremia. The evidence that the vaccine prevents other kinds of pneumococcal infections such as pneumonia and otitis media is not as clear.
As in the previous recommendations, the vaccine is not recommended for children younger than 2 years old because they have a poor antibody response to pneumococcal polysaccharides. It should be pointed out that even after 2 years of age, the immunologic response may be suboptimal. A recent study of a large group of 5-year-old children with sickle cell anemia who had received the pneumococcal vaccine at 2 years of age showed that their levels of circulating pneumococcal antibodies were not different from a control group of normal 5 year olds who had never been vaccinated. Further, no anamnestic, "booster" antibody increase was seen in the sickle cell anemia children after the second immunization.3 The reason for the non-reactivity of young children to polysaccharide antigens is not completely clear, but there is clearly an inability of the immune system of the infant and young child to mount an antibody response to many polysaccharide antigens, including those of Streptococcus pneumoniae, Hemophilus influenzae (type b), and the meningococcus.
Table
Indications for pneumococcal vaccination
Older than 2 years with:
· functional or anatomic asplenia*
· immunocompromise or immunosuppression (congenital or acquiredincluding **)
· HIV infection
· malignancies (i.e., leukemia, lymphoma, Hodgkin disease, or other generalized malignancies)
· Chronic renal failure, hemodialysis, nephrotic syndrome · Chronic cardiovascular or pulmonary disease
· Alaskan natives, American Indians
Revaccination:
· If patient is 65 years, consider revaccination five years after previous dose.
*If a patient with asplenia is older than 10 years of age, consider a single revaccination five years after previous dose.
**Consider a single revaccination five years after the first dose. If patient is 10 years of age, consider revaccination three years after previous dose.
When cancer chemotherapy or other immunosuppressive therapy is being considered, the interval between vaccination and initiation of immunosuppressive therapy should be at least two weeks. When possible, vaccination should be performed at least two weeks before elective splenectomy. Vaccination during chemotherapy or radiation therapy should be avoided.
Revaccination is not recommended at this time for other indications for pneumococcal vaccine.
The target group of children older than 2 years for whom pneumococcal vaccine immunization is recommended includes those who have chronic cardiovascular or pulmonary diseases, diabetes mellitus, asplenia, as well as immunocompromised children and children from certain populations know to be at high risk for invasive pneumococcal infections such as Alaskan natives and American Indians. (See Table.) The largest group of children at risk include those with major sickle cell diseases (Hb SS, Hb SC, and Hb S B-thalassemia diseases) who develop a state of functional hyposplenism in early life.4
For the first time, the CDC recommendations give specific recommendations concerning revaccination or "booster" immunizations with the pneumococcal polysaccharide vaccine.
Revaccination of children with chronic cardiovascular or pulmonary disorders, diabetes, or for the special ethnic populations at risk is not recommended.
The recommendations for "boosters" are based upon the continuing high risk as well as a concern about possible declines in antibody levels over time below a protective level. In healthy adults, antibody levels persist for at least five years after vaccination but may then decrease to prevaccination levels in 10 years. This decline may be more rapid in the elderly, in splenectomized individuals, in immunocompromised patients (including those on hemodialysis), and those with HIV infections.
These factors formed the basis for the recommendations of the ACIP for reimmunization. However, the statement clearly notes that proof of the efficacy of revaccination is lacking, compared with strong evidence for efficacy of primary vaccination in the above-indicated groups of individuals. For individuals who meet the criteria for vaccination but whose previous vaccination status is unknown, vaccination is encouraged. The consequences of inadvertent revaccination (chiefly fever and local reactions) are considered to be much smaller than the risk of not vaccinating a susceptible individual who actually never received the vaccine.
Healthy children attending day care and children with recurrent upper respiratory diseases including otitis media and sinusitis are not at this time considered candidates for routine immunization with the current pneumococcal vaccine. It should be pointed out that conjugate pneumococcal vaccines, in which the pneumoccocal polysaccharide antigens are combined with a protein antigen such as pertussis, will presumably be as effective as the current H. influenzae type b conjugate vaccines. The conjugate pneumococcal vaccines are currently under development and testing. If they are shown to be effective in both normal and high-risk children, they may be licensed and become available for clinical use. When this will occur is not yet clear.
When cancer chemotherapy or other immunosuppressive therapy is being considered, the interval between vaccination and initiation of immunosuppressive therapy should be at least two weeks. When possible, vaccination should be performed at least two weeks before elective splenectomy. Vaccination during chemotherapy or radiation therapy should be avoided. (Dr. Baltimore is Professor of Pediatrics and Epidemiology and Public Health at Yale University School of Medicine.)
References
1. Centers for Disease Control and Prevention. Prevention of polysaccharide disease: Recommendations of the Advisory Committee on Immunization Practice (ACIP). MMWR Morb Mortal Wkly Rep 1997;46: (NoRR-8)124.
2. Centers for Disease Control and Prevention. Recommendations of Immunization Practices Advisory Committee. Pneumopolysaccaride vaccine. MMWR Morb Mortal Wkly Rep 1989;38:64-68,73-76.
3. Bjornson AB, et al. Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: Effects of continued penicillin prophylaxis. J Pediatr 1996;129: 828-835.
4. Pearson HA, et al. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediatrics 1985;76: 392-397.
Pneumococcal vaccine:
a. contains 14 serotypes.
b. is predictably immunogenic in children younger than 2 years of age.
c. is indicated for children with frequent attacks of otitis media.
d. should not be given during cancer chemotherapy or immunotherapy.
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