Influenza Vaccination

Influenza is a major cause of morbidity and mortality each year in the UK. Even in mild years 3-4000 deaths occur annually due to influenza, and it is easily passed between individuals in close communities.

Vaccination has been available since late 1960s. It is offered annually to patients aged 65 , and all those aged six months and over in clinical risk groups identified by the Department of Health.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 to 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 Organisation 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.⁴
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 to 30%.^5,6
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 likely 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.⁷

Vaccines are normally given intramuscularly into the upper arm or anterolateral thigh, except if patients have a bleeding disorder (eg haemophilia) when 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 2.5cm 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

The percentage uptake for patients aged 65 and over in 2005-6 was:

• 75.3% in England
• 77.8% in Scotland
• 68% in Wales
• 80.9% in N Ireland¹

• Store at 2 to 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.

For the 2007/8 season the there has been a slight change in emphasis concerning recommendations of use. There is no mention of a shortfall but patients are advised to target certain groups (see Tables1 and 2). The letter from the Department of Health also states:
"GPs should take into account the risk of influenza infection exacerbating any underlying disease that the 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 or
• Hereditary and degenerative diseases of the Central Nervous System"

There are few contraindications. When in doubt, seek the guidance of a local communicable disease consultant, paediatrician or immunisation coordinator.
Vaccine should not be given to:

• 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.

• 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 breastfeeding - 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,¹² paraesthesiae, convulsions¹³ and transient thrombocytopenia¹⁴ have been reported rarely.
• Guillain Barré syndrome occurs rarely (2 in 2.5 million vaccinated people in one post-marketing study.¹⁵ A causal relationship has not been established, and reporting rates have declined over time.¹⁶
• Encephalomyelitis,¹⁷ neuritis (mainly optic¹⁸) and vasculitis with transient renal involvement occur very rarely.¹⁹
• 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.²⁰

• Current production methods are based on culture in chick eggs, a process over 40 years old.
• First introduced in the US in 1944, vaccines have never been available during a pandemic, including the last 2 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. Manufacturers must obtain sufficient supplies of eggs for production, the live viral ingredient must be killed, safety data reviewed, before production.
• The rapid introduction of a swine flu vaccine in 1976 in the US which was associated with Guillain-Barré syndrome, is a salutary lesson. The anticipated pandemic did not occur.
• 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.

• The current H5N1 (strain of bird flu) virus has pandemic potential, at a time when conditions are favourable. Although it is not possible to manufacture a vaccine against the new virus strain before a pandemic starts, the Government have produced a pandemic flu strategy and are working with drug manufacturers to ensure that there is a minimal delay between the first cases being identified and the vaccine being produced. Stockpiling of antivirals is also being organised.²³
• The USA also use a live attenuated influenza vaccine (LAIV) administered by nasal spray. Also grown in eggs, it contains the same 3 annually recommended strains: influenza A (H3N2), A (H1N1), and one influenza B. It is licensed for healthy 5-49 yr olds. Trials suggest it is well-tolerated and effective.²⁴
• Recombinant haemagglutinin (rHA) vaccines are undergoing clinical trials (including one to the pathogenic avian H5 strain). 3 rHA proteins (corresponding to the current WHO selected strains) are produced in serum-free insect cells. Animal trials have been promising.²⁵ One company has produced a commercially-available rHA vaccine which they claim will be effective against avian flu.²⁶
• 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.²⁷