Pneumococcal Vaccine

Part A             Illness, Risk Factors and prevention

1          Etiology:

Streptococcus pneumoniae (pneumococcus) is the leading cause of invasive

bacterial infections, meningitis, bacterial pneumonia and acute otitis media (AOM) in children.

11        Indication

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.

111     Prevention

                                                            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.

                                                             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.

Part B             Vaccine

There are 2 vaccines available in Canada.

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.

Pneumovax, a polysaccharide vaccine is for adults and children 9 and up.

1          Composition and efficacy

Pneumovax                                                               

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.

Prevnar vaccine is formulated to contain 2 μg of each polysaccharide for 7 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.

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.

The current polysaccharide pneumococcal vaccine, Pneumovax, 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.

11        Contraindications

Anaphylactic reaction to polysaccharide pneumococcal vaccine or to conjugate

pneumococcal vaccine is a contraindication to re-immunization with that product.

111     Precautions (pregnancy, nursing mothers, special conditions)

Neither pregnancy nor breast-feeding is a contraindication to either the polysaccharide or the conjugate pneumococcal vaccine.

1V       Drug interactions

V         Adverse reactions

                                                Polysaccharide vaccine (Pneumovax)

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 (Prevnar)

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.

Part C Administration

1          Dose (amount & schedule, booster)

            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  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.

Summary schedule for Pneumococcal Conjugate Vaccine in           Previously  Unvaccinated Children

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.

11        Route

Route of Administration

The polysaccharide vaccine (Pneumovax) may be given by either intramuscular or subcutaneous injection.

The conjugate vaccine (Prevnar) is given only as an intramuscular injection.

111     Post immunization care

References: Canadian Immunization Guide Edition 2002