Prevention And Control Pneumococcal Vaccines

There are two types of pneumococcal vaccines: a 23-valent pneumococcal polysaccharide vaccine (PPV) and a 7-valent pneumococcal conjugate vaccine (PCV).

Pneumococcal Polysaccharide Vaccine

This is a polyvalent vaccine containing 25 |lg of purified capsular polysaccharide from each of 23 capsular types of pneumococci that together account for about 96% of the pneumococcal isolates causing serious infection in Great Britain (World Health Organization, 1999).

Most healthy adults develop a good antibody response to a single dose of the vaccine by the third week following immunisation. Protection is much less reliable in the immunocompromised and in children below the age of 2 years.

Pneumococcal Conjugate Vaccine

This vaccine contains polysaccharide antigens from seven common serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) conjugated to a protein carrier (currently CRM197 protein). The selected serotypes accounted for 65.6% of pneumococcal invasive infections in England and Wales in 2000 (82.3% in children <5 years) (World Health Organization, 1999). The main advantage of this vaccine is that it is protective in children over 2 months of age. Conjugation of polysaccharide antigen to a protein carrier has the effect of converting a T-independent immune response to a T-dependent one, hence achieving better immu-nogenicity.

Vaccine Effectiveness

Studies on the polysaccharide vaccine have produced variable results, but overall protective efficacy in preventing bacteraemic infection ranges from 50% to 70% (Mangtani, Cutts and Hall, 2003). The main drawbacks of this vaccine are its ineffectiveness at preventing nonbacteraemic pneumococcal pneumonia, otitis media and exacerbations of chronic bronchitis and inability to protect children below the age of 2 years and the immunocompromised. In addition, data from several Asian countries suggest that the 23 vaccine serotypes account for only 63% of infections, and serotype data from many parts of the world are scarce (Lee, Banks and Li, 1991).

The PCV has been shown to protect against meningitis, pneumonia, bacteraemia and otitis media in children vaccinated at 2, 4, 6 and 15 months of age. Serotype-specific efficacy was 94% after the first dose of vaccine and 97% after the fourth (Black etal., 2000).

The potential of pneumococcal proteins, such as pneumolysin, PspA and CbpA, as vaccine candidates is being examined. These antigens should circumvent the issues of serotype-specific immunity and low immunogenicity that hamper polysaccharide-based vaccines, but many factors require further study, including allelic variation and its effects on cross-reactivity.

Recommendations

Vaccination is recommended for all those in whom pneumococcal infection is likely to be common and/or serious, i.e.

1. all adults aged 65 and over;

2. asplenia and severe splenic dysfunction [ideally 4-6 weeks (no less than 2 weeks) before splenectomy. If not possible, vaccination should be delayed until after recovery. Vaccination against H. influenzae type b, influenza and Neisseria meningitidis group C is additionally recommended, together with antibiotic prophylaxis (usually with phenoxymethyl penicillin) until at least age 16 years];

3. chronic renal disease;

4. chronic heart disease;

5. chronic liver disease including cirrhosis;

6. diabetes mellitus;

7. immunodeficiency or immunosuppression [ideally 4-6 weeks (no less than 2 weeks) before chemotherapy or radiotherapy. If not given, vaccination should be delayed until at least 3 months after treatment];

8. HIV infection at all stages. A report of increased risk of pneumococcal disease in severely immunocompromised HIV-infected Ugandan adult vaccinees requires further confirmatory studies and additional studies to assess its relevance to the United Kingdom (French etal., 2000). However, current UK recommendations are to vaccinate all HIV-infected individuals;

9. patients with cochlear implants.

The vaccine routinely used is the 23-valent polysaccharide vaccine, the conjugate vaccine only being recommended in children belonging to the groups above, who are below the age of 2 years. These children should be subsequently vaccinated with the polysaccharide vaccine after they reach the age of 2 years, to broaden the spectrum of serotype coverage.

Dosage and Administration

The polysaccharide vaccine may be administered either subcutaneously or intramuscularly as a single dose. It may be given simultaneously with the influenza vaccine, at a different site. Revaccination is not routinely recommended, except at 5-yearly intervals in patients in whom antibody levels are more likely to have declined rapidly, such as those with nephrotic syndrome, asplenia or splenic dysfunction.

The conjugate vaccine is given intramuscularly. It may be administered at the same time as other childhood immunisations but must be given at a separate site in a separate limb. The dosage regimen varies depending on the age of the child (Table 3.8).

The polysaccharide vaccine should be administered at least 2 months following the last dose of conjugate vaccine.

Adverse Reactions

Both vaccines are generally well tolerated but have been associated with mild erythema and induration that last 1-3 days at the site of injection. Systemic reactions are rare.

A transient increase in viral load usually follows vaccination in HIV-infected patients, the clinical significance of which remains to be ascertained.

Table 3.8 Dosage regimen for pneumococcal conjugate vaccine

Age

Regimen

<6 months

Three doses separated by at least 1 month

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