Influenza Vaccination

Influenza is a major cause of morbidity and mortality each year in the UK. Even in mild years, 3,000-4,000 deaths occur annually due to influenza, and it is easily passed between individuals in close communities.

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

Influenza virus strains change over time as indicated by minor changes (antigenic shift) or major changes (antigenic drift) in the haemagglutinins (H) and neuraminidases (N) on the surface of the viruses. Antigenic drift sometimes leads to the production of a new haemagglutinin. This occurs more commonly in A than B strains, and can result in a pandemic. Three such pandemics have occurred in the last century.¹ Antigenic drift sometimes occurs in animal species. Avian flu is caused by a type of A strain called A(H5N1).²

The activity of the influenza virus was modest in the five seasons between 2000-2005 compared with the period between 1996-1999. GP consultations during 2000-2005 reached their highest level in England in 2000-2001 (70/100,000).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.³ The UK uses trivalent vaccines (against two strains of influenza A and one of B), which give about 70-80% protection, provided the virus matches the strains against which the vaccine was prepared, and take 10-14 days to produce active antibody levels.¹

• 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 1-15 year age group by up to 90%, and may reduce influenza-associated otitis media by up to 30%.^4,5
• 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.⁶

• Vaccines are normally given intramuscularly into the upper arm or anterolateral thigh.
• If patients have a bleeding disorder, e.g. haemophilia, deep subcutaneous injection is appropriate.
• Children aged <3 require 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.⁵
• 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

The percentage uptake for patients aged 65 and over in England in 2007/8 was 74%. Vaccine uptake in risk groups aged under 65 years increased to 45% in England.

• 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).

All currently available vaccines are grown in embryonic hens' eggs and then chemically inactivated and purified. There are three 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.
3. 'Surface antigen, inactivated virosome' vaccines - these contain haemagglutinin and neuraminidase antigens reconstituted into virosomes with phospholipids.

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.^7,8 If a thiomersal-free vaccine is not available, the vaccine should still be given, as the benefits of giving it outweigh the risks.

Target group of at-risk for influenza

The 2009/10 national policy is that influenza vaccine should be offered to the following groups⁹ (unchanged from 2008/9):¹⁰

• All those aged 65 years and over
• All those aged 6 months or over in a clinical risk group:

The target groups for a one-off pneumococcal vaccination are very similar (see pneumococcal vaccination article) 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.⁹ 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

Employers, e.g. Healthcare Trusts, should offer influenza vaccination to staff directly involved in patient care as as an adjunct to good infection control procedures:⁹

• 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

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.

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.

• 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.
• Pregnancy and breast-feeding - women in an at-risk category (see table above) should be vaccinated before the flu season, regardless of the stage of pregnancy. There is no evidence of risk from vaccinating pregnant or breast-feeding women.¹¹ Thiomersal-free vaccine should be used if available.
• 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.

• Angioedema, urticaria, bronchospasm and anaphylaxis can occur. This is an immediate reaction, usually due to hypersensitivity to residual egg protein.
• Neuralgia, paraesthesiae, convulsions¹² and transient thrombocytopenia¹³ have been reported rarely.
• Guillain Barré syndrome occurs rarely (2 in 2.5 million vaccinated people in one post-marketing study.¹⁴ A causal relationship has not been established, and reporting rates have declined over time.¹⁵
• Encephalomyelitis,¹⁶ neuritis (mainly optic) and vasculitis with transient renal involvement occur very rarely.¹⁷
• 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.¹⁸

• 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.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.²² One company has produced a commercially-available rHA vaccine which they claim will be effective against avian flu.²³
• 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.²⁴

• Current production methods are based on culture in chick eggs, a process over 40 years old.
• First introduced in the USA in 1944, vaccines have never been available during a pandemic, including the last two in 1957 and 1968.
• To date, pandemic viruses have been discovered after international spread has begun and, since this is complete in 6-8 months, there has been insufficient time for identification, development, manufacturing, distribution, and administration.
• Annually, WHO completes its review and makes recommendations for the Northern Hemisphere vaccine by mid-February, completing a similar process for the Southern Hemisphere in September. Before production, manufacturers must obtain sufficient supplies of eggs for production, the live viral ingredient must be killed, and safety data reviewed.
• Influenza vaccination has been recommended since the late 1960s with the objective of protecting those at high risk of mortality and morbidity. In 2000 the policy was extended to include all people aged 65 and over, and the 'at-risk' category has been refined year on year to be as evidence-based and comprehensive as possible.

1. Immunisation Against Infections Disease Chapter 20 Influenza HMSO 2006
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22. 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]
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24. Eurekalert; New influenza vaccine takes weeks to mass produce

• Bridges C., Harper S, Fukuda K et al; Prevention and Control of Influenza CDC 2003;52(RR08):1-36
• Immunizations - seasonal influenza, Clinical Knowledge Summaries (July 2009)
• Swine Flu Clinical Package, Department of Health (July 2009)