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The disease

  • Influenza is an acute viral infection of the respiratory tract. There are three types of influenza virus: A, B, and C. Influenza A and influenza B are responsible for most clinical illness. Influenza is highly infectious with a usual incubation period of 1–3 days
  • The disease is characterised by the sudden onset of fever, chills, headache, myalgia, and extreme fatigue. Other common symptoms include a dry cough, sore throat, and stuffy nose
  • For otherwise healthy individuals, influenza is an unpleasant but usually self-limiting disease with recovery usually within 2–7 days. The illness may be complicated by (and may present as) bronchitis, secondary bacterial pneumonia or, in children, otitis media
  • Influenza can be complicated more unusually by meningitis, encephalitis, or meningoencephalitis
  • The risk of serious illness from influenza is higher amongst children under 6 months of age, older people, and those with underlying health conditions such as respiratory or cardiac disease, chronic neurological conditions, or immunosuppression, and pregnant women
  • Influenza during pregnancy may also be associated with perinatal mortality, prematurity, smaller neonatal size, and lower birth weight

The influenza vaccination

  • All but one of the influenza vaccines available in the UK are inactivated and do not contain live viruses. One vaccine (Fluenz Tetra®) contains live viruses that have been attenuated (weakened) and adapted to cold so that they cannot replicate efficiently at body temperature
  • None of the influenza vaccines can therefore cause clinical influenza in those that can be vaccinated, although mild coryzal symptoms can occur with the live vaccine
  • The live vaccine (Fluenz Tetra®) is administered by nasal spray, and the inactivated vaccines are all administered by intramuscular injection with the exception of one preparation (Intanza®) which is administered by the intradermal route. Most of the vaccines are prepared from viruses grown in embryonated hens eggs
  • The live attenuated influenza vaccine (LAIV) is also thought to provide broader protection than inactivated vaccines, and therefore has potential to offer better protection against strains that have undergone antigenic drift compared to the original virus strains in the vaccine
  • After immunisation, protective immune responses may be achieved within 14 days. Although influenza activity is not usually significant in the UK before the middle of November, the influenza season can start early, and therefore the ideal time for immunisation is between September and early November. Protection afforded by the vaccine is thought to last for at least one influenza season. However, as the level of protection provided in subsequent seasons is likely to reduce and there may be changes to the circulating strains from one season to the next, annual revaccination is important
  • A list of the influenza vaccines available in the UK is is published ahead of the influenza season in the annual flu letter for England (available at: www.gov.uk/government/collections/annual-flu-programme )

Storage

  • Vaccines should be stored in the original packaging at +2°C to +8°C and protected from light. All vaccines are sensitive to some extent to heat and cold. Heat speeds up the decline in potency of most vaccines, thus reducing their shelf life. Efficacy, safety, and quality may be adversely affected if vaccines are not stored at the temperatures specified in the license. Freezing may cause increased reactogenicity and loss of potency for some vaccines and can also cause hairline cracks in the container, leading to contamination of the contents
  • Fluenz Tetra® may be left out of the refrigerator for a maximum period of 12 hours at a temperature not above 25°C as indicated in the SPC. If the vaccine has not been used after this 12 hour period, it should be disposed of

Presentation

  • Inactivated influenza vaccines for intramuscular administration are supplied as suspensions in pre-filled syringes. They should be shaken well before they are administered
  • Intanza®, the intradermal vaccine, is supplied in a micro-needle injection system
  • Fluenz Tetra®, the intranasal vaccine, is supplied as a nasal spray suspension in a special applicator

Dosage and schedule

  • The dosages and schedules for influenza vaccines should be given according to the recommendations for use of the vaccines (see later)
  • Some of the summaries of product characteristics (SPCs) for intramuscular inactivated influenza vaccines indicate that young children can be given either a 0.25 ml or a 0.5 ml dose. The Joint Committee on Vaccination and Immunisation (JCVI) has advised that where these alternative doses are indicated in the SPC, the 0.5 ml dose of intramuscular inactivated influenza vaccine should be given to infants aged 6 months or older and young children because there is evidence that this dose is effective in young children
  • Children aged 6 months to under 9 years who are in clinical risk groups and have not received influenza vaccine previously should be offered a second dose of vaccine. JCVI has advised that children aged 2 years to under 9 years of age who are not in a clinical risk group, only require a single dose of LAIV irrespective of whether they have received influenza vaccine previously. This advice differs from that in the SPC for Fluenz Tetra®. Children who have received one or more doses of any influenza vaccine before (including pandemic monovalent influenza A(H1N1)v vaccine) should be considered as previously vaccinated (see later section on children)

Administration

  • The inactivated influenza vaccines given by intramuscular injection should be given preferably into the upper arm (or anterolateral thigh in infants). However, individuals with a bleeding disorder should be given vaccine by deep subcutaneous injection to reduce the risk of bleeding
  • The inactivated influenza vaccine administered by the intradermal route (Intanza®) is supplied in a micro-needle injection system that is held at right- angles to the skin. The device allows intradermal vaccination to be performed without the need for additional training
  • The LAIV is administered by the intranasal route (Fluenz Tetra®) and is supplied in an applicator that allows a divided dose to be administered in each nostril (total dose of 0.2 ml, 0.1 ml in each nostril)
  • The device allows intranasal administration to be performed without the need for additional training
  • Administration of either dose does not need to be repeated if the patient sneezes or blows their nose following administration
  • Inactivated influenza vaccines can be given at the same time as other vaccines
  • The LAIV can also be given at the same time as other live or inactivated vaccines. Although it was previously recommended that, where vaccines cannot be administered simultaneously; a 4-week interval should be observed between live viral vaccines, JCVI has advised that no specific intervals need to be observed between the live attenuated intranasal influenza vaccine and other live vaccines
  • Intramuscular and intradermal vaccines should be given at separate sites, preferably in a different limb. If given in the same limb, they should be given at least 2.5cm apart
  • As a wide variety of influenza vaccines are on the UK market each year, it is especially important that the exact brand of vaccine, batch number, and site at which each vaccine is given is accurately recorded in the patient records
  • Where the vaccine is given for occupational reasons, it is recommended that the employer keep a vaccination record
  • It is important that vaccinations given either at a general practice or elsewhere (for example, at community pharmacies, or antenatal clinics) are recorded on appropriate health records for the individual (using the appropriate clinical code) in a timely manner, including the relevant Child Health Information System. If given elsewhere, a record of vaccination should be returned to the patient’s general practice to allow clinical follow up and to avoid duplicate vaccination

Recommendations for the use of the vaccines

  • Patients should be advised that many other organisms cause respiratory infections similar to influenza during the influenza season, for example, the common cold and respiratory syncytial virus. Influenza vaccine will not protect against these diseases
  • Influenza vaccine should be offered, ideally before influenza viruses start to circulate, to:
    • all those aged 65 years or older (for definition please see the annual flu letter for the coming/current season)
    • all those aged 6 months or older in the clinical risk groups shown in Table 1
    • children not in clinical risk groups that are eligible for vaccination as part of the ongoing phased roll out of the extension of the programme to all children aged 2 to less than 17 years old*
Table 1: Clinical risk groups who should receive the influenza immunisation—influenza vaccine should be offered to people in the clinical risk categories set out
Clinical risk categoryExamples (this list is not exhaustive and decisions should be based on clinical judgement)
Chronic respiratory disease

Asthma that requires continuous or repeated use of inhaled or systemic steroids or with previous exacerbations requiring hospital admission

Chronic obstructive pulmonary disease (COPD) including chronic bronchitis and emphysema; bronchiectasis, cystic fibrosis, interstitial lung fibrosis, pneumoconiosis, and bronchopulmonary dysplasia (BPD)

Children who have previously been admitted to hospital for lower respiratory tract disease

see precautions section on live attenuated influenza vaccine

Chronic heart disease Congenital heart disease, hypertension with cardiac complications, chronic heart failure, individuals requiring regular medication and/or follow-up for ischaemic heart disease
Chronic kidney disease Chronic kidney disease at stage 3, 4, or 5, chronic kidney failure, nephrotic syndrome, kidney transplantation
Chronic liver disease Cirrhosis, biliary atresia, chronic hepatitis
Chronic neurological disease (included in the DES directions for Wales) Stroke, transient ischaemic attack (TIA). Conditions in which respiratory function may be compromised due to neurological disease (e.g. polio syndrome sufferers). Clinicians should offer immunisation, based on individual assessment, to clinically vulnerable individuals including those with cerebral palsy, learning disabilities, multiple sclerosis and related or similar conditions; or hereditary and degenerative disease of the nervous system or muscles; or severe neurological disability
Diabetes Type 1 diabetes, type 2 diabetes requiring insulin or oral hypoglycaemic drugs, diet controlled diabetes
Immunosuppression (see contraindications and precautions section on live attenuated influenza vaccine)

Immunosuppression due to disease or treatment, including patients undergoing chemotherapy leading to immunosuppression, bone marrow transplant, HIV infection at all stages, multiple myeloma, or genetic disorders affecting the immune system (e.g. IRAK-4, NEMO, complement disorder)

Individuals treated with or likely to be treated with systemic steroids for more than a month at a dose equivalent to prednisolone at 20 mg or more per day (any age), or for children under 20 kg, a dose of 1 mg or more per kg per day

It is difficult to define at what level of immunosuppression a patient could be considered to be at a greater risk of the serious consequences of influenza and should be offered influenza vaccination. This decision is best made on an individual basis and left to the patient’s clinician

Some immunocompromised patients may have a suboptimal immunological response to the vaccine

Asplenia or dysfunction of the spleen This also includes conditions such as homozygous sickle cell disease and coeliac syndrome that may lead to splenic dysfunction
Pregnant women

Pregnant women at any stage of pregnancy (first, second, or third trimesters)

see precautions section on live attenuated influenza vaccine

Morbid obesity (class III obesity)* Adults with a body mass index ≥40 kg/m²
*Many of this patient group will already be eligible due to complications of obesity that place them in another risk category

Other groups

  • The list in Table 1 is not exhaustive, and the medical practitioner should apply clinical judgment to take into account the risk of influenza exacerbating any underlying disease that a patient may have, as well as the risk of serious illness from influenza itself

Children

  • JCVI has advised, as set out below, the use of different dosage schedules of influenza vaccine for children depending on their age, the clinical indications, the type of vaccine offered, and whether they have received influenza vaccine previously. This advice differs from some of the SPCs

Children aged 2 to less than 17 years old NOT IN clinical risk groups

  • Starting from September 2013, an extension of the programme to all children aged 2 to less than 17 years old is being phased in from the youngest age groups. Please see the respective annual flu letters for England and the Devolved Administrations for the cohorts of children that are eligible for influenza vaccination for the coming/current season
  • A single dose of Fluenz Tetra® should be offered, irrespective of whether influenza vaccine has been received previously

Children aged 6 months to less than 2 years of age IN clinical risk groups

  • These children should be offered inactivated trivalent influenza vaccine. Those who have not received influenza vaccine previously should be offered a second dose of vaccine, at least 4 weeks later. The inactivated influenza vaccines are interchangeable; the second dose, if required, should be given at least 4 weeks after the first dose in accordance with the manufacturer’s SPC for that vaccine

Children aged 2 to less than 18 years of age IN clinical risk groups

  • Children aged 2 years to less than 18 years in clinical risk groups should be offered Fluenz Tetra® unless it is medically contraindicated (see contraindications and precautions sections). Those children who have never received influenza vaccine before and are aged between 2 and less than 9 years should be offered a second dose of Fluenz Tetra® at least 4 weeks later. If Fluenz Tetra is unavailable for this second dose (due to batch expiry) an inactivated influenza vaccine can be given
  • For those children for whom Fluenz Tetra® is medically contraindicated, a suitable inactivated influenza vaccine should be offered. The quadrivalent inactivated influenza vaccine (Fluarix™ Tetra) is authorised for children from the age of 3 years and is preferred because of the additional protection offered. The quadrivalent vaccine has both lineages of influenza B and may therefore provide better protection against the circulating B strain(s) than trivalent inactivated influenza vaccines
  • Otherwise, children aged 2 years should be given an inactivated trivalent vaccine
  • Children aged 2 to less than 9 years old offered inactivated influenza vaccine who have not received influenza vaccine previously should be offered a second dose of the vaccine at least 4 weeks later
  • The inactivated influenza vaccines are interchangeable; the second dose, if required, should be given at least 4 weeks after the first dose in accordance with the manufacturer’s SPC for that vaccine
  • Table 2 summarises the advice on influenza vaccination for children

Preterm infants

  • It is important that preterm infants who have risk factors have their immunisations at the appropriate chronological age. Influenza immunisation should be considered after the child has reached 6 months of age
Eligible cohortVaccine available: children in clinical risk groups*Vaccine available: children not in clinical risk groups
Table 2: Influenza vaccination for children under 18 years old
6 months to less than 2 years old Offer suitable inactivated flu vaccine Not applicable
Children aged 2 years to less than 18 years old Offer live attenuated influenza vaccine (Fluenz Tetra®) (unless medically contraindicated) Offer live attenuated influenza vaccine (Fluenz Tetra®)

* Children in clinical risk groups aged two to less than nine years who have not received flu vaccine before should be offered two doses of Fluenz Tetra® or inactivated vaccine (given at least 4 weeks apart)

Please see the respective annual flu letters for England and the Devolved Administrations for the cohorts of children not in clinical risk groups that are eligible for influenza vaccination for the coming/current season

If Fluenz Tetra® is medically contraindicated or otherwise unsuitable, then offer suitable inactivated flu vaccine. If quadrivalent inactivated vaccine available, consider for children age 3 years and older only. Children aged 2 to less than 9 years who have not received flu vaccine before require two does of inactivated vaccine (given at least 4 weeks apart)

Pregnancy

  • Pregnant women should be offered inactivated influenza vaccine as the risk of serious illness from influenza is higher in pregnant women. In addition, a number of studies show that influenza vaccination during pregnancy provides passive immunity against influenza to infants in the first few months of life following birth
  • A review of studies on the safety of influenza vaccine in pregnancy concluded that inactivated influenza vaccine can be safely and effectively administered during any trimester of pregnancy and that no study to date has demonstrated an increased risk of either maternal complications or adverse foetal outcomes associated with inactivated influenza vaccine
  • Whilst there is no evidence of risk with LAIV, inactivated influenza vaccines are preferred for those who are pregnant. There is no need, however, to specifically test eligible girls for pregnancy or to advise avoidance of pregnancy in those who have been recently vaccinated

Contraindications

  • The SPCs for individual products should always be referred to when deciding which vaccine to give. There are very few individuals who cannot receive any influenza vaccine. When there is doubt, appropriate advice should be sought promptly from the screening and immunisation team in the NHS England area team, a consultant in communicable disease control, or a consultant paediatrician, so that the period the individual is left unvaccinated is minimised
  • None of the influenza vaccines should be given to those who have had:
    • a confirmed anaphylactic reaction to a previous dose of the vaccine, or
    • a confirmed anaphylactic reaction to any component of the vaccine (other than ovalbumin—see precautions)
  • Confirmed anaphylaxis is rare (see Chapter 8 for further information). Other allergic conditions such as rashes may occur more commonly and are not contraindications to further immunisation. A careful history of the event will often distinguish between true anaphylaxis and other events that are either not due to the vaccine or are not life threatening. In the latter circumstance, it may be possible to continue the immunisation course. Specialist advice must be sought on the vaccines and the circumstances in which they could be given (see Chapter 6 for further information). The risk to the individual of not being immunised must be taken into account
  • The LAIV (Fluenz Tetra®) should not be given to children or adolescents who are clinically severely immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; HIV infection not on highly active antiretroviral therapy (HAART); cellular immune deficiencies; and high dose corticosteroids
  • It is not contraindicated for use in children or adolescents with stable HIV infection receiving antiretroviral therapy; or who are receiving topical corticosteroids, standard dose inhaled corticosteroids or low-dose systemic corticosteroids, or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency

Precautions

  • Minor illnesses without fever or systemic upset are not valid reasons to postpone immunisation. If an individual is acutely unwell, immunisation may be postponed until they have fully recovered. This is to avoid confusing the differential diagnosis of any acute illness by wrongly attributing any signs or symptoms to the adverse effects of the vaccine

Severe asthma or active wheezing

  • The LAIV (Fluenz Tetra®) is not recommended for children and adolescents with severe asthma or active wheezing, for example, those who are currently taking oral steroids or who have been prescribed oral steroids in the last 14 days for respiratory disease
  • Vaccination with Fluenz Tetra® should be deferred in children with a history of active wheezing in the past 72 hours or those who have increased their use of bronchodilators in the previous 72 hours. If their condition has not improved after a further 72 hours then, to avoid delaying protection in this high risk group, these children should be offered an inactivated influenza vaccine
  • Children in this clinical risk group and aged under 9 years who have not been previously vaccinated against influenza will require a second dose whether given LAIV or inactivated vaccine

Egg allergy

  • In all settings providing vaccination, facilities should be available and staff trained to recognise and treat anaphylaxis (see Chapter 8)
  • Inactivated influenza vaccines that are egg-free or have a very low ovalbumin content are available (see below) and studies show they may be used safely in individuals with egg allergy. LAIV Fluenz Tetra®, which has an upper ovalbumin limit of 1.2 mcg/ml, has also been recently shown to be safe for use in most egg allergic children (see below). The ovalbumin content of influenza vaccines will be published prior to the influenza season in May of each year in a special edition of vaccine update (www.gov.uk/government/collections/vaccine-update )

Children

  • JCVI has advised that, except for those with severe anaphylaxis to egg which has previously required intensive care, children with an egg allergy can be safely vaccinated with Fluenz Tetra® in any setting (including primary care and schools); those with clinical risk factors that contraindicate Fluenz Tetra®  should be offered an inactivated influenza vaccine with a very low ovalbumin content (less than 0.12 mcg/ml)
  • Children with a history of severe anaphylaxis to egg which has previously required intensive care, should be referred to specialists for immunisation in hospital. LAIV is not otherwise contraindicated in children with egg allergy. Egg-allergic children with asthma can receive LAIV if their asthma is well-controlled (see the above section on severe asthma)
  • Children in a clinical risk group and aged under 9 years who have not been previously vaccinated against influenza will require a second dose whether given LAIV or inactivated vaccine

Adults

  • The ovalbumin-free influenza vaccine Optaflu®, if available, can be used in any setting on patients from the age of 18 years, regardless of the severity of the egg allergy
  • Adult patients can also be immunised in any setting using an inactivated influenza vaccine with an ovalbumin content less than 0.12 mcg/ml (equivalent to 0.06 mcg for 0.5 ml dose), excepting those with severe anaphylaxis to egg which has previously required intensive care who should be referred to specialists for immunisation in hospital

Use with antiviral agents against influenza

  • There is a potential for influenza antiviral agents to lower the effectiveness of the LAIV (Fluenz Tetra®). Therefore, influenza antiviral agents and Fluenz Tetra® should not be administered concomitantly. Fluenz Tetra® should be delayed until 48 hours following the cessation of treatment with influenza antiviral agents. Administration of influenza antiviral agents within 2 weeks of administration of Fluenz Tetra® may adversely affect the effectiveness of the vaccine

Exposure of healthcare professionals to live attenuated influenza vaccine viruses

  • As a precaution, very severely immunosuppressed individuals should not administer LAIV. Other healthcare workers who have less severe immunosuppression or are pregnant, should follow normal clinical practice to avoid inhaling the vaccine and ensure that they themselves are appropriately vaccinated

Inadvertent administration of Fluenz Tetra®

  • If an immunocompromised individual receives LAIV then the degree of immunosuppression should be assessed. If the patient is severely immunocompromised, antiviral prophylaxis should be considered, otherwise they should be advised to seek medical advice if they develop flu-like symptoms in the 4 days (the usual incubation period) following administration of the vaccine. If antivirals are used for prophylaxis or treatment, then in order to maximise their protection in the forthcoming flu season, the patient should also be offered inactivated influenza vaccine. This can be given straight away

Adverse reactions

  • Pain, swelling or redness at the injection site, low grade fever, malaise, shivering, fatigue, headache, myalgia, and arthralgia are among the commonly reported symptoms after intramuscular or intradermal vaccination. A small painless nodule (induration) may also form at the injection site. These symptoms usually disappear within 1–2 days without treatment
  • Nasal congestion/ rhinorrhoea, reduced appetite, weakness, and headache are common adverse reaction following administration of the live attenuated intranasal vaccine (Fluenz Tetra®)
  • Immediate reactions such as urticaria, angio-oedema, bronchospasm, and anaphylaxis can occur
  • All serious suspected reactions following influenza vaccines should be reported to the Medicines and Healthcare products Regulatory Agency using the Yellow Card scheme at yellowcard.mhra.gov.uk/
  • The live attenuated influenza vaccine Fluenz Tetra® and the inactivated quadrivalent vaccines Fluarix™ Tetra and quadrivalent influenza vaccine (split virion inactivated) carry a black triangle symbol (▼). This is a standard symbol added to the product information of a vaccine during the earlier stages of its introduction, to encourage reporting of all suspected adverse reactions

Management of suspected cases, contacts, and outbreaks

  • There are antiviral drugs available that can be used under certain circumstances to either prevent or treat influenza. NICE has issued guidance on the use of antiviral drugs for the prevention and treatment of influenza at:
  • It is always important to encourage and maintain good hand and respiratory hygiene which can help to reduce the spread of influenza.

Supplies

  • Demand for influenza vaccine sometimes increases unpredictably in response to speculation about influenza illness in the community. Therefore, it is recommended that practices order sufficient vaccine for their needs, based on their ‘at risk’ registers, well in advance of the immunisation season
  • A list of the influenza vaccines available in the UK is is published ahead of the influenza season in the annual flu letter for England (available at: www.gov.uk/government/collections/annual-flu-programme)

*Note: please see the respective annual flu letters for England and the Devolved Administrations for specific details on the cohorts of children that are eligible for influenza vaccination

References

full guideline available from…

www.gov.uk/government/uploads/system/uploads/attachment_data/file/456568/2904394_Green_Book_Chapter_19_v10_0.pdf

Public Health England. Influenza: the green book, chapter 19. (updated August 2015).

First included: March 2017.