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In this summary

 

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, the live attenuated influenza vaccine (LAIV) Fluenz Tetra® contains live viruses that have been attenuated (weakened) and adapted to cold so that they can only replicate at the lower temperatures found in the nasal passage
  • These live viruses cannot replicate efficiently elsewhere in the body but may cause mild coryzal symptoms
  • The inactivated vaccines are all administered by intramuscular injection. The LAIV is administered by nasal spray
  • Most of the vaccines are prepared from viruses grown in embryonated hens eggs although cell based production is likely to become more important in future years
  • The 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 published ahead of the influenza season in the National immunisation programme plan (available at: www.gov.uk/government/collections/annual-flu-programme)

Storage (also refer to Chapter 3)

  • 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
  • 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 should normally be given into the upper arm (or anterolateral thigh in infants) preferably by intramuscular injection. Influenza vaccines licensed for intramuscular or subcutaneous administration may alternatively be administered by the subcutaneous route
  • Individuals on stable anticoagulation therapy, including individuals on warfarin who are up-to-date with their scheduled International Normalised Ratio (INR) testing and whose latest INR was below the upper threshold of their therapeutic range, can receive intramuscular vaccination. A fine needle (23 or 25 gauge) should be used for the vaccination, followed by firm pressure applied to the site (without rubbing) for at least 2 minutes. If in any doubt, consult with the clinician responsible for prescribing or monitoring the individual’s anticoagulant therapy
  • Individuals with bleeding disorders may be vaccinated intramuscularly if, in the opinion of a doctor familiar with the individual’s bleeding risk, vaccines or similar small volume intramuscular injections can be administered with reasonable safety by this route. If the individual receives medication/treatment to reduce bleeding, for example treatment for haemophilia, intramuscular vaccination can be scheduled shortly after such medication/treatment is administered. A fine needle (23 or 25 gauge) should be used for the vaccination, followed by firm pressure applied to the site (without rubbing) for at least 2 minutes. The individual/parent/carer should be informed about the risk of haematoma from the injection
  • 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
  • As heavy nasal congestion might impede delivery of the vaccine to the nasopharyngeal mucosa, deferral of administration until resolution of the nasal congestion should be considered, or if appropriate, an alternative intramuscularly administered influenza vaccine
  • 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 (see Chapter 6)
  • Intramuscular vaccines should be given at separate sites, preferably in a different limb. If given in the same limb, they should be given at least 2.5 cm 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. If given outside of general practice, 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. Influenza vaccine should be offered in such cases even if the individual is not in the clinical risk groups specified above
  • In addition to the above, immunisation should be provided to healthcare and social care workers in direct contact with patients/clients to protect them and to reduce the transmission of influenza within health and social care premises, to contribute to the protection of individuals who may have a suboptimal response to their own immunisations, and to avoid disruption to services that provide their care

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 LAIV should be offered per season, unless contraindicated, 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 quadrivalent influenza vaccine. The quadrivalent inactivated influenza vaccine is preferred because of the additional protection offered. 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 LAIV unless it is medically contraindicated or otherwise unsuitable (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 LAIV at least 4 weeks later. If LAIV is unavailable for this second dose (due to batch expiry) an inactivated influenza vaccine can be given
  • For those children in clinical risk groups for whom LAIV is medically contraindicated, a suitable quadrivalent inactivated influenza vaccine should be 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
  • Children aged 2 to less than 9 years old 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 groupsVaccine 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 quadrivalent 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 the appropriate flu 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.

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
  • 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
  • LAIV 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, inhaled corticosteroids or low-dose systemic corticosteroids, or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency
  • It is contraindicated in children and adolescents receiving salicylate therapy (other than for topical treatment of localised conditions) because of the association of Reye’s syndrome with salicylates and wild-type influenza infection as described in the SPC for Fluenz Tetra®

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

Immunosuppression and HIV infection

  • Individuals who have immunosuppression and HIV infection (regardless of CD4 count) should be given influenza vaccine in accordance with the recommendations and contraindications above. These individuals may not make a full antibody response
  • Consideration should also be given to the influenza vaccination of household contacts of immunocompromised individuals, i.e. individuals who expect to share living accommodation on most days over the winter and therefore for whom continuing close contact is unavoidable
  • There is a theoretical potential for transmission of live attenuated influenza virus in Fluenz Tetra® to immunocompromised contacts for one to two weeks following vaccination
  • Where close contact with very severely immunocompromised patients (e.g. bone marrow transplant patients requiring isolation) is likely or unavoidable (for example, household members), however, appropriate alternative inactivated influenza vaccines should be considered
  • Further guidance is provided by the Royal College of Paediatrics and Child Health, the British HIV Association (BHIVA) guidelines on the use of vaccines in HIV-positive adults and the Children’s HIV Association (CHIVA) immunisation guidelines

Severe asthma or active wheezing

  • JCVI have advised that children with asthma on inhaled corticosteroids may safely be given LAIV, irrespective of the dose prescribed
  • LAIV is not recommended for children and adolescents currently experiencing an acute exacerbation of symptoms including those who have had increased wheezing and/or needed additional bronchodilator treatment in the previous 72 hours. Such children should be offered a suitable inactivated influenza vaccine to avoid a delay in protection
  • Children with significant asthma and aged under 9 years who have not been previously vaccinated against influenza will require a second dose (of either LAIV or inactivated vaccine as appropriate)

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. 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 (see www.gov.uk/government/publications/influenza-vaccine-ovalbumin-content)
  • Egg-allergic adults and children over age nine years with egg allergy can also be given the quadrivalent inactivated egg-free vaccine, Flucelvax® TETRA, which is licensed for use in this age group

Children

  • JCVI has advised that children with an egg allergy—including those with previous anaphylaxis to egg—can be safely vaccinated with LAIV in any setting (including primary care and schools). The only exception is for children who have required admission to intensive care for a previous severe anaphylaxis to egg; such children are best given LAIV in the hospital setting. LAIV remains the preferred vaccine for this group and the intranasal route is less likely to cause systemic reactions
  • Children with egg allergy but who also have another condition which contraindicates LAIV should be offered an inactivated influenza vaccine with a very low ovalbumin content (less than 0.12 mcg/ml)
  • 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

  • Adult patients can be immunised in any setting using an inactivated influenza vaccine with an ovalbumin content less than 0.12 mcg/ml (equivalent to 0.06 micrograms for 0.5 ml dose), excepting those with severe anaphylaxis to egg which has previously required intensive care who should be referred to a specialist for assessment with regard to receiving immunisation in hospital

Use with antiviral agents against influenza

  • There is a potential for influenza antiviral agents to lower the effectiveness of the LAIV. Therefore, influenza antiviral agents and LAIV should not be administered concomitantly. The LAIV 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 LAIV 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 LAIV

  • 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 reactions following administration of LAIV
  • 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 quadrivalent cell cultured inactivated influenza vaccine (QIVc), quadrivalent inactivated influenza vaccine (QIV) and high-dose trivalent inactivated influenza vaccine (TIV-HD) 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

full guideline available from…
www.gov.uk/government/publications/influenza-the-green-book-chapter-19

Public Health England. Influenza: the green book, chapter 19. April 2019.
Contains public sector information licensed under the Open Government Licence v3.0.

First included: March 2017. Updated May 2019.