2008 Addendum
This notice updates the recommendation for use of 7-valent pneumococcal conjugate vaccine (PCV7) among children aged 24 to 59 months who are either unvaccinated or who have a lapse in PCV7 administration.* In February 2000, PCV7, marketed as Prevnar® and manufactured by Wyeth Vaccines (Collegeville, Pennsylvania), was approved by the Food and Drug Administration for use in infants and young children. At that time, the Advisory Committee on Immunization Practices (ACIP) recommended that children aged 24 to 59 months who have certain underlying medical conditions or are immunocompromised receive PCV7. In addition, ACIP recommended that PCV7 be considered for all other children aged 24 to 59 months, with priority given to those who are American Indian/Alaska Native or of African-American descent, and to children who attend group day care centers. The recommendation also provided schedules for administering PCV7 to children aged 24 to 59 months who were either unvaccinated or who had a lapse in PCV7 administration; these schedules included 1) 1 dose of PCV7 for healthy children, and 2) 2 doses of PCV7 >2 months apart for children with certain chronic diseases or immunosuppressive conditions.
ACIP's rationale for limiting the recommendation for routine vaccination to children aged 24 to 59 months who have certain underlying medical conditions or are immunocompromised was concern about limited vaccine supply and cost. Since September 2004, PCV7 has not been in short supply. Additionally, certain health-care providers have found the permissive recommendation for healthy children aged 24 to 59 months to be confusing. The ACIP Pneumococcal Vaccines Work Group reviewed data on safety and immunogenicity of PCV7 in children aged 24 to 59 months, current rates of PCV7-type invasive disease, vaccination coverage rates, and post-licensure vaccine effectiveness. In October 2007, on the basis of that review, ACIP approved the following revised recommendation for use of PCV7 in children aged 24 to 59 months**.
- For all healthy children aged 24 to 59 months who have not completed any recommended schedule for PCV7, administer 1 dose of PCV7.
- For all children with underlying medical conditions aged 24 to 59 months who have received 3 doses, administer 1 dose of PCV7.
- For all children with underlying medical conditions aged 24 to 59 months who have received <3 doses, administer 2 doses of PCV7 at least 8 weeks apart.
No changes were made to previously published recommendations regarding 1) the use of PCV7 in children aged 2 to 23 months, 2) the list of underlying medical or immunocompromising conditions, or 3) the use of 23-valent pneumococcal polysaccharide vaccine in children aged >2 years who have previously received PCV7.
*PCV7 is recommended for routine administration as a 4-dose series for infants at ages 2, 4, 6, and 12 to 15 months. Catch-up immunization is recommended for children aged <23 months, using fewer doses depending on age at the time of first vaccination.
**The minimum interval between all doses of PCV7 for children aged 24 to 59 months is 8 weeks.
2000 Guideline
The strength of evidence grading (A-C) is defined at the end of the "Major Recommendations" field.
Children for Whom 7-valent Pneumococcal Polysaccharide-Protein Conjugate Vaccine (PCV7) Is Recommended
Children Aged <23 Months
All children aged <23 months should be vaccinated with PCV7 (see Table 8 in the original guideline document). Infant vaccination provides the earliest possible protection, and children aged <23 months have the highest rates of pneumococcal infection. PCV7 is safe and highly efficacious in preventing invasive disease, and it is effective in preventing a portion of acute otitis media cases and pneumonia among healthy infants and young children (Strength of evidence: Children aged 2 to 6 months, A; children aged 7 to 23 months, B – see Table 9 in the original guideline document)
Vaccination Schedule. Infants receiving their first dose at age <6 months should receive three doses of PCV7 at intervals of approximately 2 months, followed by a fourth dose at age 12 to 15 months. Newborns should begin the schedule at age 2 months, although PCV7 can be administered as young as age 6 weeks. Prematurely born infants (i.e., <37 weeks gestation) should receive PCV7 at the recommended chronologic age concurrent with other routine vaccinations. For infants with prolonged nursery stays, initiation of vaccination should begin during discharge planning. Children aged >7 months not previously vaccinated should also be vaccinated according to the recommended schedule (see Table 10 in the original guideline document). The proposed vaccination schedule is the same for all children aged <23 months, regardless of the presence of underlying medical conditions (e.g., children with HIV infection, sickle cell disease or other asplenia, chronic disease, or who are otherwise immunocompromised). Interruption of the vaccination schedule does not require reinstitution of the entire series or the addition of extra doses (see Table 11 of the original guideline document).
Children Aged 24 to 59 Months Who Are at High Risk for Pneumococcal Infection
Children aged 24 to 59 months should receive PCV7 vaccination if they are at high risk for pneumococcal infection caused by an underlying medical condition. This recommendation applies to the following groups:
- Children with sickle cell disease and other sickle cell hemoglobinopathies, including hemoglobin SS, hemoglobin S-C, or hemoglobin S-beta-thalassemia, or children who are functionally or anatomically asplenic
- Children with HIV infection
- Children who have chronic disease, including chronic cardiac and pulmonary disease (excluding asthma), diabetes mellitus, or cerebral spinal fluid leak
- Children with immunocompromising conditions, including (a) malignancies (e.g., leukemia, lymphoma, Hodgkin's disease); (b) chronic renal failure or nephrotic syndrome; (c) those children receiving immunosuppressive chemotherapy, including long-term systemic corticosteroids; and (d) those children who have received a solid organ transplant.*
*Note: This recommendation excludes children who have received a bone marrow transplant (BMT). Children who undergo bone marrow transplantation have impaired humoral immune system responses for months or years after the procedure and are at increased risk for serious pneumococcal infection. Because studies among this population are not complete, the ACIP is currently unable to make recommendations regarding use of PCV7 among bone marrow transplant patients. PCV7 might produce superior antibody responses compared with 23-valent polysaccharide vaccine (PPV23) among bone marrow transplant patients. However, pending results of studies of PCV7 among bone marrow transplant patients, health-care providers should vaccinate this population with PPV23 vaccine at 12 and 24 months after bone marrow transplant, as recommended by an expert panel (Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Recommendations of the Centers for Disease Control and Prevention [CDC], the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR Morb Mortal Wkly Rep 2000 Oct 20;49[RR-10]:1-125).
Immunogenicity and safety studies have been conducted using PCV7 among children with sickle cell disease and a 5-valent conjugate vaccine among children with HIV infection (Strength of evidence: B). The efficacy of PCV7 among children with chronic disease or who are immunocompromised has not been evaluated, but effectiveness is anticipated on the basis of studies conducted in other groups (Strength of evidence: C).
Vaccination Schedule. For children aged 24 to 59 months with underlying medical conditions (see Table 8 of the original guideline document), the ACIP recommends two doses of PCV7, administered 2 months apart, followed by one dose of PPV23 administered >2 months after the second dose of PCV7 (see Tables 10 and 12 of the original guideline document). The recommendation for two PCV7 doses is based on results of an immunogenicity study conducted among sickle cell disease patients. That study reported that a nonstatistically significant antibody response to serotype 6B after one dose of PCV7 increased statistically significantly after a second dose of PCV7. Serotype 6B is one of the most common pneumococcal serotypes colonizing or causing invasive disease among sickle cell disease patients and healthy children.
Penicillin prophylaxis should be continued for children with sickle cell disease to age >5 years, regardless of vaccination with PCV7. Protective efficacy of PCV7 for children with sickle cell disease has not been studied, and the vaccine does not protect against all serotypes causing disease. However, penicillin prophylaxis substantially reduces the risk for invasive pneumococcal infections among sickle cell disease patients.
Other Children Who Might Benefit from Vaccination with PCV7
The ACIP recommends that health-care providers consider PCV7 vaccination for all other children aged 24 to 59 months, with priority given to the following populations:
This recommendation is made on the basis of the moderate risk for pneumococcal disease, including antibiotic-resistant infections, among these populations and on potential cost-benefit. Data regarding efficacy and immunogenicity of PCV7 are limited for these specific risk and age groups. However, the vaccine is safe and immunogenic among all healthy children aged 24 to 59 months. Also, immunogenicity data are available regarding use of another pneumococcal conjugate vaccine among Apache, Navajo, and Alaska Native children, and efficacy data for children aged <23 months probably are relevant for healthy children aged 24 to 59 months (Strength of Evidence: B).
PPV23 is licensed for use among children aged >2 years who are at high risk for pneumococcal infections (e.g., those with sickle cell disease or HIV infection). However, the conjugate vaccine has advantages over PPV23, which include induction of immune system memory (possibly resulting in longer duration of protection), reduction in carriage, probable higher efficacy against serotypes causing most invasive disease, and probable effectiveness against noninvasive syndromes (e.g., nonbacteremic pneumonia and acute otitis media). If pneumococcal vaccine is to be used among healthy children aged 24-59 months, the ACIP recommends that PCV7 be used.
Vaccination Schedules. The ACIP recommends that one dose of PCV7 be considered for Alaska Native and American Indian children aged 24 to 59 months. Previously, the ACIP recommended PPV23 for Alaska Natives and certain American Indian populations aged >2 years. However, use of PCV7 among these children offers multiple potential advantages over PPV23 as previously discussed. In contrast, PPV23 offers potentially broader serotype coverage. Recent studies demonstrate that only 68% and 57% of invasive infections among Alaska Natives and American Indians in the U.S. Southwest aged 24 to 59 months, respectively, were caused by serotypes included in the 7-valent conjugate vaccine, lower proportions than among non-Alaska Native/non-American Indian populations. Therefore, vaccination program personnel and other health-care providers might consider whether Alaska Native and American Indian children aged 24 to 59 months would benefit by the additional coverage provided by the 23-valent polysaccharide vaccine. Data are limited regarding safety and immunogenicity of PPV23 after PCV7. If additional serotype coverage is desired by parents and health-care providers, PPV23 should be administered >2 months after PCV7 (Strength of evidence: C). A community-randomized trial to evaluate the efficacy of PCV7 among Navajo and Apache children in preventing pneumococcal disease is underway. Future recommendations for use of PCV7 among Alaska Native and American Indian populations might be modified on the basis of that trial.
The ACIP recommends that physicians consider administering one dose of PCV7 to their African-American pediatric patients aged 24-59 months because of their increased risk for pneumococcal infection. The proportion of invasive pneumococcal disease among African-American children that is caused by PCV7 serotypes does not differ from whites in the United States, and rates of invasive disease decline with age. Therefore, no additional vaccination with PPV23 is recommended (Strength of evidence: B). Additionally, because of increased risk for invasive pneumococcal disease, colonization with antibiotic-resistant pneumococcal strains, and acute otitis media, health-care providers should consider administering one dose of PCV7 to previously unvaccinated children aged 24-59 months who attend group day care centers.
Children Aged >5 Years and Adults Who Are At High Risk for Pneumococcal Infection
Data are limited regarding efficacy of PCV7 among children aged >5 years and adults. However, limited studies report that (a) 5-valent pneumococcal conjugate vaccine is immunogenic among HIV-infected children aged 2-9 years; (b) PCV7 is immunogenic among children aged 2-13 years with recurrent respiratory infections; and (c) PCV7 is immunogenic among older children and adults aged 4 to 30 years with sickle cell disease. Administering PCV7 to older children with high-risk conditions is not contraindicated.
Studies among healthy adults aged >50 years and among HIV-infected adults aged 18-65 years did not demonstrate substantially greater enzyme-linked immunosorbant assay (ELISA) antibody concentrations after administration of 5-valent pneumococcal conjugate vaccine compared with PPV23. Also, the proportion of invasive pneumococcal isolates covered by PCV7 is only 50% to 60% among older children and adults, in contrast with 80% to 90% coverage by PPV23 among this older group. Therefore, current data do not support a recommendation to replace PPV23 with PCV7 among older children and adults.
Recommendations for Use of PCV7 Among Children Previously Vaccinated with PPV23
Children aged 24 to 59 months who are at high risk for pneumococcal disease and who have already received PPV23 (i.e., children with sickle cell disease, HIV infection, or who have other immunocompromising illnesses or chronic diseases) could benefit from the immunologic priming and T-cell-dependent immune system response induced by PCV7. Thus, among children in these groups at high risk, sequential use of the two pneumococcal vaccines can provide additional protection. Health-care providers should vaccinate children aged 24 to 59 months at high risk who have not previously received PCV7 but who have already received PPV23 with two doses of PCV7 administered >2 months apart. Vaccination with PCV7 should be initiated >2 months after vaccination with PPV23. Providers should be aware that minimal safety data are available regarding this vaccine sequence.
Recommendations for Use of PPV23 Among Children Previously Vaccinated with PCV7
Administration of PCV7 Followed by PPV23 Among Children at High Risk for Pneumococcal Disease
Children who have completed the PCV7 vaccination series before age 2 years and who are among risk groups for which PPV23 is already recommended should receive one dose of PPV23 at age 2 years (>2 months after the last dose of PCV7). These groups at high risk include children with sickle cell disease, children with functional or anatomic asplenia, children who are HIV-infected, and children who have immunocompromising or chronic diseases (see Table 8 in the original guideline document). Although data regarding safety of PPV23 administered after PCV7 are limited, the opportunity to provide additional serotype coverage among these children at very high risk justifies use of the vaccines sequentially. For children of Alaska Native or American Indian descent, addition of PPV23 after PCV7 can be considered.
Revaccination with PPV23
Immunocompromised children or children with sickle cell disease or functional or anatomic asplenia should be revaccinated with PPV23 as previously recommended (see Table 12 in the original guideline document). If the child is aged <10 years, one revaccination should be considered 3 to 5 years after the previous dose of PPV23. Data are limited regarding adverse events related to a second dose of PPV23 administered after PCV7. Health-care providers should not administer a second dose of PPV23 any earlier than 3 years after the initial dose of PPV23.
Definitions:
Strength of Evidence Rating Scheme
- Strong evidence, including results of efficacy studies, supports vaccine use.
- Moderate evidence, including immunogenicity data but not efficacy data, supports vaccine use.
- No efficacy or immunogenicity studies are available regarding this population, but protection is anticipated on the basis of such studies among other groups; vaccination is supported by respected authorities.
