Influenza is a major cause of morbidity and mortality each year in the UK. Vaccination has been available since the late 1960s. It is offered annually to patients aged 65, and all those aged 6 months and over in clinical risk groups identified by the Department of Health (DH).¹

The World Health Organization (WHO) monitors influenza viruses throughout the world and recommends which strains are to be included in the current year's vaccine.²

The UK uses trivalent vaccines (against two strains of influenza A and one of B), which give about 70-80% protection as long as the virus matches the strains against which the vaccine was prepared. It takes 10-14 days to produce active antibody levels.¹ The influenza A strain of virus (H1N1v) is still expected during 2011/2012 and the WHO has recommended that this strain be included in the trivalent seasonal influenza vaccine.

• Protection may be less in the elderly, but immunisation has been shown to reduce the incidence of bronchopneumonia, mortality and hospital admission.
• In children it has been shown to reduce influenza-associated respiratory illness in the 1- to 15-year age group by up to 90%, and may reduce influenza-associated otitis media by up to 30%.³
• The vaccine needs to be given annually to provide protection from the antigenically changed nature of the prevailing virus. In the event of a major antigenic shift liable to cause an epidemic or pandemic, it is likely that a monovalent vaccine would be prepared.
• Immunisation should be carried out between September and early November. Although most cases occur from mid-November, it is not unknown for the influenza season to start earlier.⁴

Method of administration

• Vaccines are normally given intramuscularly (IM) into the upper arm or anterolateral thigh.
• Intanza® is also available as an intradermal preparation for patients 60 years or older.⁵
• If patients have a bleeding disorder, e.g. haemophilia, deep subcutaneous injection is appropriate.
• Children aged <3 years require a reduced dose of vaccine and all <13 years require a second dose of vaccine 4-6 weeks after the first, if they are receiving the vaccine for the first time, to achieve satisfactory antibody level.
• Influenza vaccine can be given with other vaccines, preferably in different limbs. If both vaccines have to be given in the same limb, the sites should be at least 2.5 cm apart.⁶
• The batch numbers and sites of the vaccines should be recorded in the patient's notes.
• If the vaccine is given for employment purposes, the employer should also keep a record.¹

Uptake

The percentage uptake for patients aged 65 years and over in England in 2010/2011 was 73%. Vaccine uptake in risk groups aged under 65 years was approximately 50% in England.⁷ Uptake has been noted to be low in healthcare workers.^8,9

Storage, presentation and disposal

• Store at 2-8°C and protect from light.
• Discard if frozen.
• Extremes of temperature can reduce potency. Freezing can cause hairline cracks in the container.
• All vaccines are supplied in the inactive form in pre-filled syringes which should be shaken before use.¹ Dispose of the vaccination equipment in a sealable, puncture-proof sharps box (UN approved BN7390).

Types of vaccine

All currently available vaccines are grown in embryonic hens' eggs and then chemically inactivated and purified. There are two types available:¹

1. 'Split virion, inactivated' or 'disrupted virus' vaccines - the whole virus is inactivated by exposing to organic solvents or detergents.
2. 'Surface antigen, inactivated' vaccines - these contain haemagglutinin and neuraminidase antigens prepared from disrupted viruses.

There is no difference between the types of vaccines in efficacy or adverse reactions.¹
Being inactivated, they do not cause the diseases against which they protect. Some vaccines contain the preservative thiomersal and, since rare allergic reactions have been reported, thiomersal-free vaccine should be given if available, especially to children or pregnant women.¹⁰ If a thiomersal-free vaccine is not available, the vaccine should still be given, as the benefits of giving it outweigh the risks.
The trivalent vaccine should be used in most circumstances.

Dosage and schedule¹

Two doses of trivalent seasonal influenza vaccine are required to achieve adequate antibody levels in children under 13 years of age if they have never had the influenza vaccination before (and all immunocompromised children under 13 years of age):

Immunocompetent patients

• Immunocompetent adults, including pregnant women, and children aged 13 years and over should be given a single dose of trivalent vaccine.
• Immunocompetent children aged 6 months to 13 years should be given one dose of trivalent seasonal flu vaccine. They will also need a further dose of trivalent seasonal influenza vaccine four weeks later if they have never had seasonal flu vaccination before.

Immunocompromised patients

Immunocompromised patients (including HIV infection, regardless of CD4 count) should be given influenza vaccine in accordance with the recommendations above. The may not make a full antibody response, so protection may not be as high as for immunocompetent patients. Consideration should also be given to vaccinating household contacts of immunocompromised patients, i.e. those sharing living accommodation on most days over the winter.

Recommendations for use

Target group of at-risk for influenza

The 2011-2012 national policy is that influenza vaccine should be offered to the following groups:^2,11

• All those aged 65 years and over.
• All those aged 6 months or over in a clinical risk group (listed below).

The target groups for a one-off pneumococcal vaccination are very similar (see separate article Pneumococcal Vaccine) so often both are given together in 'flu clinics'.

• Those living in long-stay residential care homes or other long-stay care facilities, where rapid spread is likely to follow introduction of infection and cause high morbidity and mortality (this does not include prisons, young offender institutions, university halls of residence, etc.).
• Those who are in receipt of a carer's allowance, or those who are the main carer for an elderly or disabled person whose welfare may be at risk if the carer falls ill. This should be given on an individual basis, at the GP's discretion, in the context of other clinical risk groups in their practice.

GPs should take into account the risk of influenza infection exacerbating any underlying disease that a patient may have, as well as the risk of serious illness from influenza itself. GPs should consider on an individual basis the clinical needs of their patients, including individuals with:

• Multiple sclerosis and related conditions.
• Hereditary and degenerative diseases of the central nervous system.

• Clinicians, midwives and nurses, paramedics and ambulance drivers.
• Occupational therapists, physiotherapists and radiographers.
• Primary care providers such as GPs, practice nurses and district nurses.
• Staff who look after older people in nursing and care homes.

Contra-indications to all influenza vaccinations

There are few contra-indications.¹ When in doubt, seek the guidance of a local communicable disease consultant, paediatrician or immunisation co-ordinator.
Vaccine should not be given to patients with:

• A confirmed anaphylactic reaction to a previous dose of the vaccine.
• A confirmed anaphylactic reaction to any component of the vaccine.
• A confirmed anaphylactic hypersensitivity to egg products, as the vaccines are prepared in hens' eggs. Egg-free vaccine is available if needed.

A careful history should rule out previous non-life-threatening reactions, e.g. rash, or reactions which were not truly anaphylactic. Seek the advice of a specialist when in doubt.

Precautions¹

• Intercurrent illness - vaccination may be postponed in the event of an acute illness, but minor illness without pyrexia or systemic upset should not be a reason for delay.
• Premature infants - at-risk premature infants should have vaccination at the appropriate chronological age, preferably with thiomersal-free vaccine.
• HIV infection - immunosuppressed patients should be given the vaccine, irrespective of CD4 count. A full antibody response may not be produced.

Side-effects

NB: side-effects may be more pronounced if both seasonal influenza and swine influenza vaccinations are co-administered.

• Angio-oedema, urticaria, bronchospasm and anaphylaxis can occur. This is an immediate reaction, usually due to hypersensitivity to residual egg protein.
• Neuralgia, paraesthesiae, convulsions and transient thrombocytopenia have been reported rarely.¹
• Guillain-Barré syndrome occurs rarely (2 in 2.5 million vaccinated people in one post-marketing study.¹³ A causal relationship has not been established, and reporting rates have declined over time.¹⁴
• Encephalomyelitis,¹⁵ neuritis (mainly optic) and vasculitis with transient renal involvement occur very rarely.¹⁶
• All suspected reactions in children and severe suspected reactions in adults should be reported using the Yellow Card Scheme to the Committee on Safety of Medicines.¹⁷

Current and future developments

• The USA also use a live attenuated influenza vaccine (LAIV) administered by nasal spray. Also grown in eggs, it contains the same three annually recommended strains: influenza A (H3N2), A (H1N1), and one influenza B. It is licensed for healthy 5-49 year-olds. Trials suggest it is well tolerated and effective.^20,21
• Recombinant haemagglutinin (rHA) vaccines are undergoing clinical trials (including one to the pathogenic avian H5 strain). Three rHA proteins (corresponding to the current WHO selected strains) are produced in serum-free insect cells. Animal trials have been promising. One company has produced a commercially-available rHA vaccine which they claim will be effective against avian flu.²²
• Recombinant neuraminidase (rNA) is also under trial as an efficacy-enhancing additive to influenza vaccines and has been used commercially in Mexico and Central American countries to protect birds from avian flu.

Document references

1. Immunisation Against Infectious Disease, The Green Book, Dept of Health, 2006
2. Key vaccine information: Seasonal flu, Dept of Health, January 2011
3. Heikkinen T, Ruuskanen O, Waris M, et al; Influenza vaccination in the prevention of acute otitis media in children. Am J Dis Child. 1991 Apr;145(4):445-8. [abstract]
4. Fleming DM, Watson JM, Nicholas S, et al; Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989-90 using a general practice database. Epidemiol Infect. 1995 Dec;115(3):581-9. [abstract]
5. Summary of Product Characteristics (SPC) - Intanza® 15 microgram/strain suspension for injection, Sanofi Pasteur MSD Limited. Updated August 2011
6. Principi N, Esposito S; Paediatric Influenza Prevention and Control, Emerging Infections Diseases, Centers for Disease Control & Prevention (2004)
7. Seasonal Influenza Vaccine Uptake amongst GP Patient Groups in England 2010/11, Dept of Health, September 2011
8. Chor JS, Pada SK, Stephenson I, et al; Seasonal influenza vaccination predicts pandemic H1N1 vaccination uptake among Vaccine. 2011 Oct 6;29(43):7364-9. Epub 2011 Jul 30. [abstract]
9. Daugherty EL, Speck KA, Rand CS, et al; Perceptions and influence of a hospital influenza vaccination policy. Infect Control Hosp Epidemiol. 2011 May;32(5):449-55. [abstract]
10. Lee-Wong M, Resnick D, Chong K; A generalized reaction to thimerosal from an influenza vaccine. Ann Allergy Asthma Immunol. 2005 Jan;94(1):90-4. [abstract]
11. Immunizations - seasonal influenza, Prodigy (September 2011)
12. The influenza immunisation programme 2010/11, Chief Medical Officer, Dept of Health, June 2010
13. Izurieta HS, Haber P, Wise RP, et al; Adverse events reported following live, cold-adapted, intranasal influenza vaccine. JAMA. 2005 Dec 7;294(21):2720-5. [abstract]
14. Haber P, DeStefano F, Angulo FJ, et al; Guillain-Barre syndrome following influenza vaccination. JAMA. 2004 Nov 24;292(20):2478-81. [abstract]
15. Nakamura N, Nokura K, Zettsu T, et al; Neurologic complications associated with influenza vaccination: two adult cases. Intern Med. 2003 Feb;42(2):191-4. [abstract]
16. Tavadia S, Drummond A, Evans CD, et al; Leucocytoclastic vasculitis and influenza vaccination. Clin Exp Dermatol. 2003 Mar;28(2):154-6. [abstract]
17. Reporting Adverse Drug Reactions; Yellow Card Scheme - Medicines and Healthcare products Regulatory Agency (MHRA)
18. Influenza - zanamivir, amantadine and oseltamivir (review), NICE Technology Appraisal (February 2009); Amantadine, oseltamivir and zanamivir for the treatment of influenza (review of existing guidance No. 58)
19. Flu key documents, Dept of Health; Flu documents and resources for patients and health professionals. Includes frequently asked questions, antiviral agent information, contingency plans and immunisation publicity campaigns
20. Treanor J, Nolan C, O'Brien D, et al; Intranasal administration of a proteosome-influenza vaccine is well-tolerated and induces serum and nasal secretion influenza antibodies in healthy human subjects. Vaccine. 2006 Jan 16;24(3):254-62. Epub 2005 Aug 15. [abstract]
21. Burt D, Mallett C, Plante M, et al; Proteosome-adjuvanted intranasal influenza vaccines: advantages, progress and Expert Rev Vaccines. 2011 Mar;10(3):365-75. [abstract]
22. Brett IC, Johansson BE; Immunization against influenza A virus: comparison of conventional inactivated, live-attenuated and recombinant baculovirus produced purified hemagglutinin and neuraminidase vaccines in a murine model system. Virology. 2005 Sep 1;339(2):273-80. [abstract]

Internet and further reading

• Influenza - seasonal, Prodigy (August 2009)
• Jamieson DJ, Honein MA, Rasmussen SA, et al; H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet. 2009 Aug 8;374(9688):451-8. Epub 2009 Jul 28. [abstract]