Invasive pneumococcal disease (bacteraemic pneumonia, bacteraemia and meningitis) is a major cause of morbidity and mortality, especially among the very young, the elderly, those with an absent or nonfunctioning spleen and those with other causes of impaired immunity. The pneumococcus is the commonest cause of community acquired pneumonia.1 Pneumococcal pneumonia is estimated to affect 1/1000 adults each year and to have a mortality of 10-20%.2 The pneumococcus is also one of the most frequently reported causes of bacteraemia and meningitis. During 2000, 4744 laboratory isolates from blood, CSF or other normally sterile sites were reported to the Public Health Laboratory Service (PHLS) (now part of the Health Protection Agency) from laboratories in England and Wales.3 Recurrent infections may occur associated with abnormalities such as fractures of the skull.
Streptococcus pneumoniae is an encapsulated gram positive coccus. Ninety capsular types have been characterised, of which only eight to ten cause two thirds of the serious infections in adults and about 80% of infections in children.4 Immunity to infection is complicated, but depends greatly on type specific anti-capsular antibodies. However, the level of antibody required for protection is not currently known. Antimicrobial resistance among S.pneumoniae is increasing, both in the UK and worldwide and susceptibility to penicillin, cephalosporin and macrolide antimicrobials can no longer be assumed.
An increase in pneumococcal antibiotic resistance has been reported worldwide.5,6,7 In 2000, 7% of invasive isolates reported to the PHLS in England and Wales showed full or intermediate resistance to penicillin and 15% were resistant to erythromycin.3
There are two types of pneumococcal vaccine: a 23-valent pneumococcal polysaccharide vaccine (PPV) and a 7-valent pneumococcal conjugate vaccine (PCV).
Many studies of efficacy have found it difficult to reach firm conclusions, but overall efficacy in preventing pneumococcal bacteraemia is probably 50-70%.8,9,10,11 Current evidence suggests that the polysaccharide vaccine is not effective in protecting against nonbacteraemic pneumococcal pneumonia.12 The polysaccharide vaccine is less effective in children under 2 years of age 13 and in those with immunosuppression. In particular, it has been relatively ineffective in patients with multiple myeloma, Hodgkins and non-Hodgkins lymphoma, especially during treatment, and in chronic alcoholism. It does not prevent otitis media or exacerbations of chronic bronchitis, and since so much pneumococcal meningitis is in young children, its scope for preventing this disease is limited. The length of protection is not known and may vary between serotypes. Post-immunisation antibody levels usually begin to wane after about 5 years, but may decline more rapidly in asplenic patients and children with nephrotic syndrome.11
Data on efficacy comes from a large randomised study in the United States in which children were vaccinated at 2, 4 and 6 months of age and were given a 4th dose at 15 months. At the time of the study, the serotypes included in the vaccine accounted for 89% of invasive pneumococcal infections in the US. The serotype specific efficacy was 97% after the fourth dose had been given, and 94% if all cases arising after the first dose were included. The vaccine protected against meningitis, bacteraemia, pneumonia and otitis media.14
Pneumococcal polysaccharide vaccine is supplied in a single dose vial of 0.5ml. It should be stored unopened at +2 C to +8oC and not frozen. The vaccine is used as supplied: no dilution or reconstitution is necessary. It should be inspected before being given to check that it is clear, colourless and without suspended particles.
Pneumococcal conjugate vaccine is supplied in a single dose vial of 0.5ml. It should be stored at +2 to +8 C and not frozen. Upon storage, a white deposit and clear supernatant can be observed. The vaccine should be well shaken to obtain a homogeneous white suspension and be inspected visually for any particulate matter and/or variation of physical aspect prior to administration. Do not use if the content appears otherwise.
The pneumococcal polysaccharide and pneumococcal conjugate vaccines do not contain thiomersal. The pneumococcal polysaccharide vaccine contains phenol, sodium chloride and water for injections. The pneumococcal conjugate vaccine contains sodium chloride and water for injections.
Pneumococcal vaccine is recommended for all those in whom pneumococcal infection is likely to be more common and/or serious, i.e.
The routine vaccine is the 23-valent polysaccharide vaccine. Pneumococcal conjugate vaccine is recommended for children in the high risk groups above, who are less than 2 years of age. All children who have had conjugate vaccine as part of the current policy should also be given the 23-valent polysaccharide vaccine after their second birthday (see schedule below) to cover the wider range of serotypes. It is recommended that GPs actively identify and contact unimmunised asplenic patients to offer them advice and immunisation.
It is also recommended that GPs identify patients on their lists in the other groups for whom vaccine is recommended and that opportunities are taken to immunise them (if not previously immunised):
Pneumococcal polysaccharide vaccine: A single dose of 0.5ml is given subcutaneously or intramuscularly preferably into the deltoid muscle or lateral aspect of the mid-thigh. Intradermal injection may cause a severe local reaction. The vaccine must not be given intravenously.
Pneumococcal polysaccharide vaccine may be given at the same time as influenza vaccine, at a different site, with no reduction in the individual antibody responses, but note that in contrast to influenza vaccine, which must be given annually, for most patients pneumococcal polysaccharide vaccine is given only once (see Re-immunisation, below).
Pneumococcal conjugate vaccine is given by intramuscular injection. The vaccine can be given at the same time as other routinely recommended vaccines, but it should not be mixed with other concurrently administered vaccines: it must be given at a separate site in a separate limb. Infants who are less than 6 months of age should be given three doses of vaccine with an interval of at least 1 month between doses. A fourth dose should be given after the first birthday. Infants aged seven to eleven months should be given two doses of vaccine with an interval of at least 1 month between doses. A third dose should be given after the first birthday, and at least 1 month after the second dose. Children aged 12 to 23 months should have two doses of conjugate vaccine with an interval of at least 2 months between doses. The interval between conjugate vaccine and the 23-valent polysaccharide vaccine should ideally be 2 months.
Pneumococcal conjugate vaccine may be given at the same time as other paediatric vaccines in accordance with the recommended immunisation schedules. Different injectable vaccines should always be given at separate sites.
Where possible, the vaccine should be given, together with advice about the increased risk of pneumococcal infection, 4 to 6 weeks (but at least 2 weeks) before splenectomy and before courses of chemotherapy. If this is not practicable, as in traumatic splenectomy, the vaccine should be given after recovery from the operation. While there is some evidence that functional antibody responses may be better if immunisation is delayed for 14 days after splenectomy,16 immunisation should not be delayed if this is likely to result in failure to vaccinate. If not given before chemotherapy and/or radiotherapy, immunisation should be delayed until at least 3 months after completion of therapy.
Additional measures for asplenic and hyposplenic patients: Haemophilus influenzae b, influenza and meningococcal C conjugate vaccines are additionally recommended and antibiotic prophylaxis (usually phenoxymethyl penicillin) is advisable at least until the age of 16 years. Guidelines have been published17,18 and a patient card and information sheet are available from the Department of Health (details at the end of this chapter).
Re-immunisation is not currently recommended except, every 5 years19, in individuals in whom antibody levels are likely to have declined more rapidly such as those with no spleen, with splenic dysfunction or with nephrotic syndrome20. Testing of antibody levels prior to vaccination is not required. Individuals who have previously received 7 or 14-valent polysaccharide vaccines should still be immunised with 23-valent polysaccharide vaccine to gain protection from the additional serotypes.
Mild soreness and induration at the site of injection lasting 1-3 days and, less commonly, a low grade fever may occur. More severe systemic reactions are infrequent. In general, local and systemic reactions are more common in people with higher concentrations of antibodies to pneumococcal polysaccharides. In HIV-infected patients there may be a transient increased viral load. The clinical significance of this is unknown.
Swelling and redness at the injection site and low grade fever are amongst the most commonly reported adverse reactions ( 10%). No increased local or systemic reactions have been reported with repeated doses throughout the primary series, although a higher rate of transient tenderness has been reported after the 4th dose.
23-valent plain polysaccharide pneumococcal vaccine (Pneumovax® II) is supplied by Aventis Pasteur MSD (Tel: 0800 085 5511 Fax 0800 085 8958).
7-valent conjugate vaccine (Prevenar ™) is supplied by Wyeth Vaccines. Medical Information 01628 415330 (Distribution through Farillon Tel: 01708 330200, Fax 01708 376554)
A patient card and information sheet for asplenic and hyposplenic patients is available from: Department of Health, PO Box 410, Wetherby, LS23 7LL. Tel: 01937 840 250, Fax: 01937 845 381 or in Scotland from: Chris Sinclair, Public Health Division 1, Health Department, Scottish Executive , Room 3ES, St Andrew's House, Regent Road, Edinburgh, EH1 3DG Tel: 0131 244 2241, Fax: 0131 244 2157 (Email: Chris.sinclair@scotland.gsi.gov.uk)