The Green Book: Influenza

Overview

This Guidelines summary of the Green Book chapter 19 on flu covers the disease and vaccination. This summary contains information relevant to public health professionals. For further information, refer to the full guideline.

View the Guidelines summary on flu immunisation: Summary of Flu Immunisation Guidance for England 2021–2022.

Reflecting on your Learnings

Reflection is important for continuous learning and development, and a critical part of the revalidation process for UK healthcare professionals. Click here to access the Guidelines Reflection Record.

The Disease

• Flu is an acute viral infection of the respiratory tract. There are three types of flu virus: A, B, and C. Influenza A and B are responsible for most clinical illness. Flu 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, flu 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
• Flu can be complicated more unusually by meningitis, encephalitis, or meningoencephalitis
• The risk of serious illness from flu 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
• Flu during pregnancy may also be associated with perinatal mortality, prematurity, smaller neonatal size, and lower birth weight.

Flu Vaccines

• All but one of the flu vaccines available in the UK are inactivated and cannot cause clinical flu in those that are vaccinated. One vaccine, the live attenuated influenza vaccine (LAIV), 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 (IM) injection. The LAIV is administered by nasal spray
• After immunisation, protective immune responses may be achieved within 14 days. Although flu activity is not usually significant in the UK before the middle of November, the flu 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 flu season. However, as the level of protection provided in subsequent seasons is likely to be low and there may be changes to the circulating strains from one season to the next, annual revaccination is recommended and important
• A list of the flu vaccines available in the UK is published ahead of the flu season in the annual flu programme pages, available at gov.uk/government/collections/annual-flu-programme

Vaccine Storage

For further information on storage, also refer to chapter 3 of the Green Book. 

• Vaccines should be stored in the original packaging at +2–8°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 (see individual product’s summary of product characteristics [SPC]). Freezing may also cause increased reactogenicity and a loss of potency for some vaccines and can also cause hairline cracks in the container, leading to contamination of the contents
• LAIV may be left out of the refrigerator/removed from the cold chain 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.

Vaccine Presentation

• Inactivated flu vaccines for IM administration are supplied as suspensions in prefilled syringes. They should be shaken well before they are administered
• LAIV is supplied as a nasal spray suspension in a special applicator.

Vaccine Dosage and Schedule

• The dosages and schedules for flu vaccines should be given according to the recommendations for use of the vaccine (see section on Recommendations for the use of the vaccines)
• Children aged 6 months to under 9 years who are in clinical risk groups and have not received flu vaccine previously should be offered a second dose of vaccine. Children who have received one or more doses of any flu vaccine before (including pandemic monovalent influenza vaccine) should be considered as previously vaccinated
• The Joint Committee on Vaccination and Immunisation (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 flu vaccine previously. This advice differs from that in the SPC for LAIV
• Healthy children under 9 years whose parents request they receive IIV instead of LAIV should be offered a single dose, even if they have not previously received flu vaccine. The same applies to healthy children who cannot receive LAIV due to contraindications.

Administration

• The inactivated flu vaccines should normally be given into the deltoid muscle in the upper arm (or anterolateral thigh in infants) preferably by IM injection
• There is a lack of evidence that the subcutaneous route of vaccination is any safer than the IM route in people taking anticoagulants. The subcutaneous route can itself be associated with an increase in localised reactions
• 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 IM 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 IM injections can be administered with reasonable safety by this route. If the individual receives medication/treatment to reduce bleeding, for example treatment for haemophilia, IM 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 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 does not need to be repeated if the patient sneezes or blows their nose following administration
• As a wide variety of flu 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. Electronic point-of-care data capture systems may support this.

Recommendations For the Use of the Vaccines

• Patients should be advised that many other organisms cause respiratory infections similar to flu during the flu season, for example, COVID-19 (SARS-CoV-2), common cold viruses, and respiratory syncytial virus. Flu vaccine will not protect against these diseases
• Flu vaccine should be offered, ideally before flu 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.

Note: see the respective annual flu letters for England and the devolved administrations (Scotland, Wales, and Northern Ireland) for specific details on the cohorts of children that are eligible for flu vaccination.

Table 1: Clinical Risk Groups Who Should Receive the Flu Immunisation—Flu Vaccine Should be Offered to People in the Clinical Risk Categories Set Out

Other Risk Groups

• The list in Table 1 is not exhaustive, and the medical practitioner should apply clinical judgement to take into account the risk of flu exacerbating any underlying disease that a patient may have, as well as the risk of serious illness from flu itself. Flu vaccine should be offered in such cases even if the individual is not in the clinical risk groups specified in Table 1
• Vaccination should also be offered to household contacts of immunocompromised individuals, that is, individuals who expect to share living accommodation on most days over the winter and therefore for whom continuing close contact is unavoidable. This may include carers 
• In addition to those listed in Table 1, 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 flu 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. This would include: 
  • health and social care staff directly involved in the care of their patients or clients
  • 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 of an elderly or disabled person whose welfare may be at risk if the carer falls ill. Vaccination should be given on an individual basis at the GP’s discretion in the context of other clinical risk groups in their practice
  • others involved directly in delivering health and social care such that they and vulnerable patients/clients are at increased risk of exposure to flu (further information is provided in guidance from UK health departments).

Children

• The JCVI has advised the use of different dosage schedules of flu vaccine for children depending on their age, the clinical indications, the type of vaccine offered, and whether they have received flu vaccine previously. This advice differs from some of the SPCs
• LAIV and the inactivated influenza vaccines are interchangeable; a 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 17 Years Old NOT in Clinical Risk Groups

• Eligibility for vaccination may differ across the UK countries. Please see the respective annual flu letters for England and the devolved administrations for the cohorts of children that are eligible for flu vaccination for the coming/current season
• A single dose of LAIV should be offered per season, unless contraindicated, irrespective of whether flu vaccine has been received previously.

Children Aged 6 Months to Less Than 18 Years of Age Who Are Household Contacts of Immunocompromised Individuals

• Children who are household contacts of immunocompromised individuals should be vaccinated in accordance with the advice on children in clinical risk groups. Inactivated vaccine may need to be given instead of LAIV. 

Children Aged 6 Months to Less Than 2 Years of Age IN Clinical Risk Groups

• These children should be offered the recommended inactivated quadrivalent flu vaccine. Those who have not received flu vaccine previously should be offered a second dose of vaccine, at least 4 weeks later. The inactivated flu 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
• LAIV is not licensed or recommended for children under 2 years of age. QIVc is not licensed for use under 2 years of age. For egg-allergic children under 2 years it is advised that QIVc is offered off-label
• It is important that preterm infants who have risk factors have their immunisations at the appropriate chronological age. Flu immunisation should be considered after the child has reached 6 months of age.

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 flu 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 flu vaccine can be given
• For those children in clinical risk groups for whom LAIV is medically contraindicated, a suitable quadrivalent inactivated flu vaccine should be offered
• Children aged 2 to less than 9 years old who have not received flu vaccine previously should be offered a second dose of the vaccine at least 4 weeks later
• Table 2 summarises the advice on flu vaccination for children.

Table 2: Flu Vaccination for Children Under 18 Years Old

Additional groups eligible for flu immunisation during the COVID-19 pandemic

• The flu programme for 2021–2022 included the offer of vaccination to 50–64 year olds, expansion of the childhood programme further into secondary schools (years 7–11), and increasing uptake as much as possible for those groups routinely offered vaccination including health and social care workers
• In December 2021, the JCVI advised that there remained uncertainty around 2022–2023 influenza activity, and endorsed the previous JCVI recommendation of prioritising secondary school expansion and its pandemic-time advice that vaccination of all 50–64-year-olds would be acceptable if funding was available. 

For recommendations on co-administration of flu and other vaccines, refer to the full guideline.

Pregnancy

• Pregnant women should be offered inactivated flu vaccine as the risk of serious illness from flu is higher in pregnant women. In addition, a number of studies show that flu vaccination during pregnancy provides passive immunity against flu to infants in the first few months of life following birth
• A review of studies on the safety of flu vaccine in pregnancy concluded that inactivated flu vaccine can be safely and effectively administered during any trimester of pregnancy
• Whilst there is no evidence of risk with LAIV, inactivated flu 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 flu vaccine. When there is doubt, appropriate advice should be sought promptly from the local NHS England screening and immunisation team, a consultant in communicable disease control/health protection, or a specialist consultant, so that the period the individual is left unvaccinated is minimised
• None of the flu 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 of the Green Book 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 of the Green Book 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; cellular immune deficiencies; HIV infection not suppressed by antiretroviral therapy; and high-dose corticosteroids
• It is not contraindicated for use in children or adolescents living with HIV who are receiving antiretroviral therapy and attaining viral suppression; or those who are receiving topical corticosteroids, inhaled corticosteroids or low-dose systemic corticosteroids, or those receiving corticosteroids as replacement therapy, for example, 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 flu infection as described in the SPC for LAIV.

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.

For recommendations on pregnancy, immunosuppression and people living with HIV, severe asthma or active wheezing, egg allergy, and use with antiviral agents against flu, refer to the full guideline.

Exposure of Healthcare Professionals to LAIV 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 flu 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 IM 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 in adults and all suspected reactions in children following flu vaccines should be reported to the Medicines and Healthcare products Regulatory Agency using the Yellow Card scheme at mhra.gov.uk/yellowcard. Regardless of age, all suspected reactions should also be reported for black triangle products.

For information on febrile convulsions and fever, refer to the full guideline.

Management of Suspected Cases, Contacts, and Outbreaks

• There are antiviral drugs available that can be used under certain circumstances to either prevent or treat flu. NICE has issued guidance on the use of antiviral drugs for the prevention and treatment of flu:
  • oseltamivir, amantadine (review), and zanamivir for the prophylaxis of flu
    nice.org.uk/ta158
  • amantadine, oseltamivir, and zanamivir for the treatment of flu
    nice.org.uk/ta168
• It is always important to encourage and maintain good hand and respiratory hygiene, which can help to reduce the spread of flu.