Vaccine-Preventable Diseases

Pneumococcal

Streptococcus pneumoniae (pneumococcus) is the leading cause of invasive bacterial infections, meningitis, bacterial pneumonia and acute otitis media (AOM) in children. Invasive disease is most common in the very young, the elderly and certain specific groups at high risk, such as individuals with functional or anatomic asplenia and congenital or acquired immune deficiency, including those with AIDS. In Canada, there are an estimated 65 cases of meningitis, 700 cases of bacteremia, 2,200 cases of pneumonia requiring hospitalization, 9,000 cases of pneumonia not requiring hospitalization, and an average of 15 deaths per year due to S. pneumoniae infection in children < 5 years of age.

Pneumococcal Vaccine

It's Your Health - Pneumococcal Vaccine

Polysaccharide vaccine
The current polysaccharide pneumococcal vaccine, available since December 1983, contains 25 µg of capsular polysaccharide from each of 23 types of pneumococci: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F and 33F (Danish nomenclature). Approximately 90% of cases of pneumococcal bacteremia and meningitis are caused by these 23 types. The six serotypes that most often cause drug-resistant invasive pneumococcal infection are included in this vaccine. An earlier vaccine, which contained 50 µg of each of 14 types, was available between 1978 and 1983. Available vaccines include Pneumovax 23® (Merck Frosst Canada & Co.), Pneumo 23® (Aventis Pasteur) and Pnu-Immune® (Wyeth Ayerst Canada Inc.). They all contain the same serotype polysaccharides.

Conjugate vaccine
The first pneumococcal conjugate vaccine to be licensed in Canada for children < 9 years of age, Prevnar® (Wyeth Ayerst Canada Inc.), is composed of the purified polysaccharides of the capsular antigens of seven S. pneumoniae serotypes, individually conjugated to CRM197, a non-toxic mutant of diphtheria toxin. The vaccine is manufactured as a liquid suspension. Each 0.5 mL dose of vaccine is formulated to contain 2 µg of each polysaccharide for serotypes 4, 9V, 14, 18C, 19F and 23F, and 4 µg of serotype 6B per dose (16 µg total polysaccharide); approximately 20 µg of CRM197 carrier protein; and 0.125 mg of aluminum as aluminum phosphate adjuvant. The vaccine contains no thimerosal or other preservatives.

Efficacy and Immunogenicity

Polysaccharide vaccine
In healthy young adults, a single dose of polysaccharide vaccine stimulates an antibody response to each of the component capsular polysaccharides. The immunity conferred is type specific. Efficacy, as measured by serotype-specific protection against invasive bacteremic pneumococcal disease, can surpass 80% among healthy young adults (evidence from randomized controlled trials). It is in the range of 50% to 80% among the elderly and specific patient groups, such as those with diabetes mellitus, anatomic or physiologic asplenia, congestive heart failure or chronic pulmonary disease (evidence from case-control and retrospective cohort studies). Antibody response and clinical protection are decreased in certain groups at particularly high risk of pneumococcal infection. These include patients with renal failure, sickle-cell anemia or impaired immune responsiveness, including HIV infection. The response of children < 2 years of age to polysaccharide vaccine is irregular and unsatisfactory. Following polysaccharide pneumococcal immunization, serotype-specific antibody levels decline after 5 to 10 years and decrease more rapidly in some groups than others. The duration of immunity is not precisely known.

The results of economic analyses indicate that polysaccharide pneumococcal vaccine is cost-effective in the prevention of mortality and morbidity associated with invasive infections among people > 2 years of age at high risk and compares favourably with other standard preventive practices.

Conjugate vaccine
Infants immunized with a three-dose primary series beginning at 2 months of age, with doses separated by 4 to 8 weeks, develop a 3.4 to 20 fold increase in serum antibodies for the vaccine serotypes. Functional antibodies are induced in infants (as measured by opsonophagocytic assay and antibody avidity), together with strong and rapid anamnestic responses upon boosting with either conjugate or polysaccharide vaccines in the 6 to 12 months after the primary series. Serum antibody responses to some conjugate vaccine serotypes are substantial after one to two doses, whereas responses to others require completion of three doses. Approximately 97% of infants achieved protective antibody titres for all serotypes after the primary series (2, 4, 6 months). This correlates with an observed protective efficacy against invasive disease of 89% to 97%.

Satisfactory safety and immunogenicity of conjugate pneumococcal vaccines have been demonstrated in children with sickle cell disease and HIV infection. Protection against development of AOM ranges from 6% against an episode from any cause to a 25% reduction in pneumococcal-associated AOM and a 56% reduction in AOM due to the serotypes included in the vaccine. A 20% reduction in tympanostomy tube placement has also been observed with use of the vaccine.

The long-term efficacy of the conjugate pneumococcal vaccines is not known, but immunologic memory has been demonstrated 18 months after two to three doses in infancy and up to 20 months after one dose in children 2 to 3 years of age. In Canada, 80% of the most common serotypes isolated from the blood or cerebrospinal fluid (CSF) of children, 95% of serotypes isolated with high level penicillin resistance, and 73% of those with intermediate level resistance are included in Prevnar®. There may be populations or communities, such as Aboriginal children in northern communities, with different distributions of serotypes.

Recommended Usage

Conjugate pneumococcal vaccine is recommended for routine administration to all children <= 23 months of age. Conjugate pneumococcal vaccine is also recommended for children 24 to 59 months of age who are at higher risk for invasive pneumococcal infections. These include children with sickle cell disease and other sickle cell hemoglobinopathies, other types of functional or anatomic asplenia, HIV infection, immunocompromising conditions (e.g., primary immunodeficiencies, malignancies, immunosuppressive therapy, solid organ transplant, long-term systemic corticosteroids, nephrotic syndrome) and chronic medical conditions (e.g., chronic cardiac and pulmonary disease such as bronchopulmonary dysplasia, diabetes mellitus or CSF leak). The conjugate vaccine should be considered for all other children in this age group, especially those who attend child care or Aboriginal children living in isolated communities.

Polysaccharide pneumococcal vaccine is not recommended for children < 2 years of age as it is relatively ineffective and the conjugate vaccine is superior. Children from 2 to 5 years of age may receive polysaccharide vaccine, but the conjugate vaccine is generally preferred because of the age-dependent response. Polysaccharide vaccine may be used both as a booster dose in this age group and to increase the serotype coverage.

Polysaccharide pneumococcal vaccine is recommended for all individuals >= 65 years of age. Pneumococcal polysaccharide vaccine may be administered simultaneously with influenza vaccine, at a separate anatomic site. Individuals with unknown immunization histories should receive the vaccine.

Polysaccharide vaccine should be given to all individuals > 5 years of age with asplenia, splenic dysfunction or sickle cell disease if not previously immunized. In addition, those > 5 years of age with the following conditions should receive the polysaccharide vaccine: chronic cardiorespiratory disease (except asthma), cirrhosis, alcoholism, chronic renal disease, nephrotic syndrome, diabetes mellitus, chronic CSF leak, HIV infection and other conditions associated with immunosuppression (Hodgkin's disease, lymphoma, multiple myeloma, induced immunosuppression for organ transplantation). When circumstances permit, the conjugate vaccine may be given as the initial dose followed by the polysaccharide vaccine to provide additional serotype coverage and as a booster. Polysaccharide vaccine should be given to smokers, since they are at increased risk.

Immunologic abnormalities may decrease both the antibody response to and protection by either type of vaccine. When possible, vaccine should be given at least 10 to 14 days before splenectomy or initiation of immunosuppression therapy and early in the course of HIV infection. Because of variable vaccine efficacy in certain groups, those at highest risk (and their families) should be counselled regarding the risk of fulminant pneumococcal sepsis, which may occur despite immunization. In these highest risk patients, some authorities recommend continuous antimicrobial prophylaxis.

Schedule and Dosage

The dose of both the polysaccharide and the conjugate vaccine for all age groups is 0.5 mL.

The recommended schedule for infants is four doses of the conjugate vaccine administered at 2, 4, 6 and 12 to 15 months of age. Children <= 6 months should receive the first three doses at intervals of approximately 2 months (6 to 8 weeks) apart followed by one dose at 12 to 15 months of age. The first dose should be given no earlier than 6 weeks of age. Infants of very low birth weight (< 1500 grams) should be given their first dose at a chronological age of 6 to 8 weeks, regardless of their calculated gestational age. Children 7 to 11 months old who have not previously been immunized against pneumococcus should receive two doses at least 6 to 8 weeks apart followed by the third dose at 12 to 15 months of age or at least 6 to 8 weeks after the second dose. Children aged 12 to 23 months who were not previously immunized should receive two doses at least 6 to 8 weeks apart. After 24 months of age one dose is sufficient.

When used after administration of the conjugate vaccine, the polysaccharide vaccine should ideally be given no earlier than 8 weeks after the conjugate vaccine. The minimal acceptable time interval is 4 weeks.

Route of Administration

The polysaccharide vaccine may be given by either intramuscular or subcutaneous injection. The conjugate vaccine is given only as an intramuscular injection.

Booster Doses and Re-immunization

Results from serologic and case studies indicate that polysaccharide vaccine-induced immunity decreases over time. Data are not yet available concerning a decline in immunity following the use of conjugate pneumococcal vaccine in infancy. At present, routine re-immunization is not recommended but should be considered for those of any age at highest risk of invasive infection, as detailed below. Experience with re-immunization is still limited, and there are no data on the relative effectiveness of a second dose.

People for whom re-immunization should be considered include those with functional or anatomic asplenia or sickle cell disease; hepatic cirrhosis; chronic renal failure or nephrotic syndrome; HIV infection; and immunosuppression related to disease or therapy. A single re-immunization is recommended after 5 years in those aged > 10 years and after 3 years in those aged <= 10 years. Either conjugate vaccine or polysaccharide vaccine may be used for re-immunization. Any need for further subsequent re-immunization remains to be determined.

Serologic Testing

Serologic testing, either pre- or post-immunization, is not recommended.

Storage Requirements

Both the polysaccharide vaccines and the conjugate vaccine should be stored refrigerated at a temperature of 2o C to 8o C (36o F to 46o F) as per the manufacturer's package insert. Freezing must be avoided.

Simultaneous Administration with Other Vaccines

On the basis of expert opinion, it is recommended that, if necessary or convenient, Prevnar® may be safely given with PentacelTM or QuadracelTM, or hepatitis B, measles, mumps and rubella vaccines, at separate sites and with separate syringes at a single visit. The polysaccharide vaccines may be given simultaneously with influenza, Hib conjugate and/or meningococcal vaccines, at a separate location and using a separate syringe.

Adverse Reactions

Polysaccharide vaccine
Reactions to the polysaccharide vaccine are usually mild. Local soreness and erythema are quite common. Occasionally, slight fever may occur. Studies involving immunocompetent individuals have shown that re-immunization less than 2 years after the initial dose of polysaccharide vaccine increased local and systemic reactions. Local reactions of the Arthus type have been rarely observed but may be severe. When re-immunization is carried out after an interval of 3 years or greater, the rate of adverse reactions is similar to that after a first dose.

Conjugate vaccine
The conjugated pneumococcal vaccines are generally well tolerated when administered at the same time as other childhood vaccines. Fever has been reported more frequently among children receiving their primary immunization series when conjugate pneumococcal vaccine was included. Few serious side effects have been reported. Children are subjected to an additional injection, and redness, swelling and tenderness at the injection site may occur. The severity or frequency of these reactions has not been found to increase with subsequent doses in the primary series or with booster doses.

Contraindications and Precautions

Anaphylactic reaction to polysaccharide pneumococcal vaccine or to conjugate pneumococcal vaccine is a contraindication to re-immunization with that product. Neither pregnancy nor breast-feeding is a contraindication to either the polysaccharide or the conjugate pneumococcal vaccine.

Other Considerations: Strategies to Improve Vaccine Utilization

Immunization is a safe and effective means of preventing invasive pneumococcal infection among individuals in groups at increased risk of serious illness or death. It offers a partial solution to the emerging problem of disease caused by strains with antibiotic resistance. However, recent surveys show that less than 5% of the population (> 2 years of age) at increased risk have received this vaccine. Several provinces have initiated programs to make the polysaccharide pneumococcal vaccine more readily available to target populations.

Recommended strategies for delivering pneumococcal vaccine to individuals at higher risk of invasive disease include the following:

• Ensuring that all recipients of influenza vaccine are also immunized with pneumococcal vaccine, if appropriate. Providers should have both vaccines available to facilitate their concurrent administration.
• Implementing standing orders for pneumococcal immunization of residents for whom there are indications for use of these vaccines on admission to long-term care facilities.
• Implementing standing orders in hospitals for pneumococcal immunization of patients in high-risk groups to be immunized on discharge or during ambulatory visits.
• Delivering pneumococcal vaccine in adult day care and community centres to people at risk.
• Promoting pneumococcal and influenza immunization programs concurrently to both consumers and providers.

Selected References

American Academy of Pediatrics. Policy statement: recommendations for the prevention of pneumococcal infections, including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal polysaccharide vaccine, and antibiotic prophylaxis. Pediatrics 2000;106:362-66.

American Academy of Pediatrics. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis. Pediatrics 2000;106:367-76.

Black S, Shinefield H, Fireman B et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19:87-95.

Butler JC, Breiman RF, Campbell JF et al. Pneumococcal polysaccharide vaccine efficacy: an evaluation of current recommendations. JAMA 1993; 270:1826-31.

Eskola J, Anttila M. Pneumococcal conjugate vaccines. Pediatr Infect Dis J 1999;18:543-51.

Eskola J, Kilpi T, Palmu A et al. Efficacy of a pneumococcal conjugate vaccine against acute otitis media . N Engl J Med 2001;344:403-09.

Fedson DS. Clinical practice and public policy for influenza and pneumococcal vaccination of the elderly . Clin Geriatr Med 1992;8:183-99.

Fine MJ, Smith MA, Carson CA et al. Efficacy of pneumococcal vaccination in adults: a meta-analysis of randomized clinical trials. Arch Intern Med 1994;154:2666-77.

Fine MF, Smith MA, Carson CA et al. Prognosis and outcome of patients with communityacquired pneumonia. A meta-analysis. JAMA 1996;275:134-41.

Gable CB, Holzer SS, Engelhart L et al. Pneumococcal vaccine: efficacy and associated cost savings. JAMA 1990;264:2910-15.

Marrie TJ, Durant H, Yates L. Community-acquired pneumonia requiring hospitalization: 5-year prospective study . Rev Infect Dis 1989;11:586-99.

National Advisory Committee on Immunization (NACI). Statement on recommended use of pneumococcal conjugate vaccine. CCDR 2002;28(ACS-2):1-32. 

Rodriguez R. Safety of pneumococcal revaccination. J Gen Intern Med 1995;10:511-2.

Scheifele D, Halperin S, Pelletier L et al. Invasive pneumococcal infection in Canadian children 1991-1998: implications for new vaccination strategies. Clin Infect Dis 2000;31:58-64. 

Shapiro ED, Berg AT, Austrian R et al. The protective efficacy of polyvalent pneumococcal polysaccharide vaccine. N Engl J Med 1991;325:1453-60.

Shinefield HR, Black S, Ray P et al. Safety and immunogenicity of heptavalent pneumococcal CRM197 conjugate vaccine in infants and toddlers. Pediatr Infect Dis J 1999;18:757-63.

Snow R, Babish JD, McBean AM. Is there any connection between a second pneumonia shot and hospitalization among Medicare beneficiaries? Public Health Rep 1995;110:720-25.