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EDUCATION AND DEBATE:
Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen
BMJ 1996; 312: 430-434 [Full text]
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[Read Rapid Response] Updated guideline
J M Davies   (2 June 2001)
[Read Rapid Response] Any updated guidance?
Ian Nash   (21 August 2009)

Updated guideline 2 June 2001
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J M Davies,
Consultant Haematologist
Western General Hospital, Edinburgh

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THE PREVENTION AND TREATMENT OF INFECTION IN PATIENTS WITH AN ABSENT OR DYSFUNCTIONAL SPLEEN

British Committee for Standards in Haematology Guideline up-date

Prepared on behalf of the British Committee for Standards in Haematology by a Working Party of the Clinical Haematology Task Force.

WORKING PARTY MEMBERS

Dr J Lawton, Consultant in Immunology, St Mary's Hospital, Praed Street, London, W2 1NY Dr P G Baddeley, Principal in General Practice, Beacon Medical Practice, Stepping Stone Lane, Painswick, Stroud, Gloucestershire, GL6 6RU Dr A H R Finn, Senior Lecturer in Infectious Disease & Immunology, Sheffield Children's Hospital, Western Bank, Sheffield, S10 2TH Dr R Barnes, Consultant Microbiologist, Department of Microbiology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN Professor I M Hann, Consultant in Paediatric Haematology, Department of Haematology, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1 3JH Professor A Burnett, Professor of Haematology, Department of Haematology, University of Wales Collegeof Medicine, Heath Park, Cardiff, CF14 4XN Dr J M Davies, Consultant Haematologist, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU

Address for Correspondence: Dr J M Davies

Consultant Haematologist

Western General Hospital

Crewe Road

EDINBURGH

EH4 2XU

INTRODUCTION

Overwhelming post splenectomy infection remains an area of concern. The previous BCSH guideline on the prevention and treatment of infection in patients with an absent or dysfunctional spleen was published in 1996 and significant changes, particularly in vaccine technology, have prompted a review of the recommendations. A reconvened guideline group chose to focus on areas of actual or potential change in clinical management, rather than re-format the original guideline in its entirely. With this remit the group identified two key areas for consideration, that is immunisation and antibiotic prophylaxis and treatment.

Methods The databases, Medline (1996-2000), BIDS Embase (1996-2000) and the current Cochrane Library CD-ROM, were searched using the original keywords, infection, splenectomy, asplenia and hyposplenism. Relevant identified abstracts were reviewed and cross checked.

Background No major alteration in the patient categories at risk of infection was identified. The effect of age and duration of risk appeared similar to that previously reported, with a broad spectrum of infecting micro- organisms remaining responsible for serious infections. There may be an additional risk to splenectomised individuals, in terms of occupational exposure to certain pathogens.1 This additional risk is at present not quantifiable. However, in the absence of firm data, on which to base recommendations, it would seem reasonable to ask both employer and employees to consider carefully the implications of exposure to potentially infective biological material.

GUIDELINES (Table 1)

Immunisation There is no new evidence to suggest that normal inoculations, including live vaccines, can not be given safely to children or adults with an absent or dysfunctional spleen.

Pneumococcal Immunisation The currently available polyvalent pneumococcal vaccine provides a high degree of immunity in normal subjects. There are well documented failures of protection in hyposplenic individuals, although the mechanism underlying this failure is not entirely clear. Despite appropriate efforts some patients remain unvaccinated, while true vaccine failures may also contribute to pneumococcal infection post splenectomy.2

Education of both staff and patients as to the risks of post splenectomy sepsis should continue and the establishment of "At Risk Registries" may help in this regard. Patients and their relatives should be aware that despite pneumococcal vaccine and prophylactic antibiotics, breakthrough pneumococcal infection may occur.3,4

Children under two years of age have an inherently reduced ability to mount an antibody response to polysaccharide antigens and are, therefore, at particular risk of vaccine failure. Where splenectomy is unavoidable under the age of 2 years then a conjugate vaccine (see below) may provide a more reliable serological response.

New Pneumococcal Vaccines A seven valent conjugate vaccine has recently completed clinical studies and should be available for use in late 2000. Early data suggests that the new conjugate vaccine is more immunogenic but has a more limited repertoire, in terms of sero-types.5 The seven valent vaccine may have a future role in primary immunisation of hypo or asplenic patients in tandem with the currently available vaccine, however, no data specifically related to asplenic or hyposplenic patients is currently available to support this approach.

Timing of Vaccination The current pneumococcal vaccine should be given at least two weeks before splenectomy. Following splenectomy post vaccination immunoglobulin G, serum antibody concentrations to pneumococcal antigens do not differ significantly from normal control subjects, whether vaccination is undertaken immediately or at 14 days post splenectomy. Functional antibody responses are, however, better with delayed (14 day) vaccination. 6

All other non-immunised patients at risk should be immunised at the first opportunity. In general immunisation should be delayed at least six months after immunosuppressive chemotherapy or radiotherapy.

Re-immunisation of asplenic patients is currently recommended every 5 years. 7 However, it is known that antibody levels may decline more rapidly, particularly in patients with Sickle cell anaemia and lymphoproliferative disorders. Decisions on re-immunisation in these particular circumstances may be made on the basis of antibody levels.

Haemophilus Influenza Type B Immunisation There is no new data to support an alteration in the recommendations given in the original guideline. Patients not previously immunised should, therefore, receive Haemophilus Influenza Type B vaccine. There is no data to support routine re-immunisation at the present time.

Meningococcal Immunisation Background In the United Kingdom there has been a shift in the strains responsible for Meningococcal infection. Group A strains remain rare and account for less the 2% of clinical infections. However, Group A strains are epidemic in other areas of the world. Group B strains now account for 60% of all isolates, while there has been an increase in Group C strains, which now contribute 40% of the total. Overall mortality from Meningococcal infection remains significant, at around 10%.

Meningococcal C Conjugate Vaccine Immunisations with Meningococcal C conjugate vaccine is now part of the routine childhood immunisation programme in the UK. The conjugate vaccine is immunogenic, even in children under two years of age and is likely to provide long term immunological memory. There is no data specific to hyposplenic individuals. However, the administration of three doses to infants and two doses to previously non-immunised children between four months and twelve months of age would seem appropriate.

In previously non-immunised older children and adults a single dose of conjugate vaccine is recommended in normal individuals and by extra- polation should afford protection in hyposplenic or asplenic patients.

The conjugate vaccine is likely to support long standing protection against Group C Meningococcal disease, in a similar way to the conjugate Haemophilus Influenza B vaccine. It is, therefore, recommended that routine Meningococcal immunisation be given pre-splenectomy and for hyposplenic previously non-immunised individuals. Travellers abroad should, in addition, receive a Meningococcal vaccine which protects against Group A infections. There appears to be no contra-indication to the administration of Meningococcal plain polysaccharide A and C vaccine to subjects who have previously received Meningococcal C conjugate vaccine.

Conversely, protection afforded by plain polysaccharide A and C vaccine is short lived. The immunisation of hyposplenic individuals who have previously received the plain polysaccharide A and C vaccine with Meningococcal C conjugate vaccine is, therefore, recommended. Highly satisfactory serological responses are demonstrable if six months is allowed between administration of the plain polysaccharide A and C vaccine and subsequent re-immunisation with Meningococcal C conjugate vaccine.8

Influenza Vaccination Influenza vaccine continues to be recommended yearly for hypo or asplenic patients.7

Antibiotic Prophylaxis and Treatment There are no data to support or refute the previously published recommendations, as regards antibiotic prophylaxis and treatment of infection in asplenic individuals. It is accepted, however, that compliance may be a problem with life long oral antibiotic prophylaxis.8 Overall pneumococcal resistance to penicillins remains low in the United Kingdom. However, knowledge of local resistant patterns may be used to guide the choice of chemoprophylactic agents.

RESEARCH AND AUDIT There is an unmet need for a prospective assessment of serological response to vaccination in hyposplenic or asplenic patients, particularly those immunised with the more recently available vaccines. Such information, if available, would be invaluable in guiding future vaccination strategies.

Regular audit, quite properly, continues to be undertaken in this area10. Readily auditable areas include vaccination rates, adherence to antibiotic prophylaxis and the current outcome of severe infection in asplenic or hyposplenic patients.

CONCLUSION Infection in patients with an absent or dysfunctional spleen remains largely preventable. Preventative strategies continue to be based on education of staff and patients, appropriate immunisation schedules and chemoprophylaxis.

REFERENCES

1. Francois B., Gissat V., Moy MC., Vignon P. Recurrent septic shock due to Streptococcus suis. Journal of Clinical Microbiology 1998; 2395.

2. Waghorn DJ., Mayon-Wight RT. A study of 42 episodes of overwhelming post splenectomy infection is current guidance in asplenic individuals being followed. Journal of Infection 1997; 35: 285-294.

3. Shetty N., Aurora P., Ridgway GL. A failure of anti-pneumococcal vaccine and prophylactic penicillin in the splenectomised patient. Journal of Infection 1998; 37: 87-88.

4. Klinge J, Hammersen G., Scharf J., Liufficken R., Reinert RR. Overwhelming post splenectomy infection in vaccine type streptococcus pneumonie in a 12 year old girl, despite vaccination and antibiotic prophylaxis. Journal of Infection 1997; 25: 368-371.

5. Chan CY., Molrine DC., George S., Tarbell NJ., Mauch P., Diller L., Shamberger RC., Phillips NR., Goorin A., Ambrosino DM. Pneumococcal conjugate vaccine primes for antibody responses to polysaccharide pneumococcal vaccine after treatment for Hodgkin's disease. Journal of Infection Disease 1996; 173: 256-258.

6. Shatz DV., Schinskey MF., Pais LB., Romero-Steiner S., Kirton OC., Carlone GM. Immune responses of splenectomized trauma patients to the 23- valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after splenectomy The Journal of Trauma, Injury, Infection and Critical Care 1998; 44: 760-765.

7. Department of Health. Immunisation against infectious disease. HMSO, London 1992.

8. Department of Health. Immunisation against infectious disease. HMSO, London 1999.

9. Cummins D., Heuschkel R., Davies SC. Penicillin prophylaxis in children with Sickle cell disease in Brent. British Medical Journal 1991; 302: 989-990.

10. Pickering J., Campbell H. An audit of the vaccination and antibiotic prophylaxis practices amongst patients splenectomised in Lothian. Health Bulletin 2000; 59: 390-395.

KEY GUIDELINES

1. All splenectomised patients and those with functional hyposplenism should receive pneumococcal immunisation and patients not previously immunised should receive Haemophilus Influenza Type B vaccine (B,C). Patients not previously immunised should receive Meningococcal Group C conjugate vaccine (C). Influenza immunisation should be given (C). Life long prophylactic antibiotics are still recommended (oral Phenoxymethylpenicillin or alternative) (B,C).

2. Patients developing infection, despite measures, must be given systemic antibiotics and admitted urgently to hospital (B,C).

3. Patients should be given written information and carry a card to alert health professionals to the risk of overwhelming infection. Patients may wish to invest in an alert bracelet or pendant (C).

4. Patients should be educated as to the potential risks of overseas travel, particularly with regards malaria and unusual infections, for example resulting from animal bites (B,C).

5. Patient records should be clearly labelled to indicate the underlying risk of infection. Vaccination and re-vaccination status should be clearly and adequately documented (C).

GRADES OF RECOMMENDATIONS

a) Requires at least one randomised controlled trial, as part of the body of literature of overall good quality and consistency addressing the specific recommendations.

b) Requires the availability of well conducted clinical studies, but no randomised clinical trials on topic of recommendation.

c) Requires evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities. Indicates an absence of a directly applicable clinical studies of good quality.

These grades of recommendations have now been widely adopted, but originate from the US Agency for Health Care Policy and Research.

Any updated guidance? 21 August 2009
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Ian Nash,
PCT pharmacist
Devon PCT, Exeter, Devon

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Re: Any updated guidance?

I am writing a PGD on Pneumococcal Vaccine, quoting the article from 2001. Has any further guidance been published since?

thanks

Ian Nash

Competing interests: None declared