For information on Pandemic Influenza A(H1N1)v 2009 please refer to chapter 23a.
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 an incubation period of one to three 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 in two to seven days. The illness may be complicated by (and may present as) bronchitis, secondary bacterial pneumonia and (in children) otitis media. Severe influenza can be complicated by meningitis, encephalitis or meningoencephalitis. Serious illness and mortality from influenza is highest amongst neonates, older people and those with underlying disease, particularly chronic respiratory and cardiac disease, or who are immunosuppressed. Primary influenzal pneumonia is a rare complication that may occur at any age and carries a high case fatality rate.1 Serological studies in healthcare professionals show that approximately 30 to 50% of influenza infections are asymptomatic.2
Influenza infections are spread by respiratory droplets produced by coughing or sneezing. Spread can also occur through fine aerosols and by hand to mucous membrane contact. Influenza spreads rapidly, especially in closed communities. Most cases in the UK tend to occur during a six to eight-week period during the winter. The timing, extent and severity of this ‘seasonal’ influenza vary. Influenza A viruses cause outbreaks most years and these viruses are the usual cause of epidemics. Large epidemics occur intermittently. Influenza B tends to cause less severe disease and smaller outbreaks, although in children the severity of illness may be similar to that associated with influenza A.
Changes in the principal surface antigens of influenza A - haemagglutinin (H) and neuraminidase (N) - make these viruses antigenically labile. Minor changes (antigenic drift) occur progressively from season to season. Major changes (antigenic shift) occur periodically resulting in the emergence of a new sub-type with a different haemagglutinin protein. A new subtype can cause widespread epidemics or even a pandemic if populations have little or no immunity. Three influenza pandemics occurred in the last century and the conditions continue to exist for the emergence of future strains with pandemic potential. Influenza B viruses are subject to antigenic drift but with less frequent changes.
Influenza activity is monitored in the UK through reports of new consultations for influenza-like illness from sentinel GP practices, combined with virological surveillance. Activity was modest during the four influenza seasons from 2000/01 to 2003/04 compared with 1996/97, 1998/99 and 1999/2000.3 Severe epidemics were recorded in 1975/76 and 1989/90, resulting in an estimated 29,646 and 23,046 deaths respectively in England and Wales.4 Even in winters when the incidence is low, 3000-4000 deaths have been attributed to influenza.5 Figure 1.1 shows the number of GP consultations for influenza-like illness per 100,000 population in England over the last five years.
In this period, the GP consultation rate reached its highest (231 per 100,000 per week) in 1999/00. However, this compares to a peak rate of 583 per 100,000 per week in the epidemic of 1989/90. In Scotland, the same pattern was seen where consultation rates peaked in calender week 1 of 1999/00 at 839 per 100,000 compared to a peak rate of 1184 per 100,000 during 1989/90. Influenza immunisation has been recommended in the UK since the late 1960s with the aim of directly protecting those at a higher risk of serious morbidity and mortality. In 2000, the policy was extended to include all people aged 65 years and over. Uptake of vaccination in those aged 65 years and over in the UK is shown in Table 1.
Because of their changing nature, the World Health Organization (WHO) monitors influenza viruses throughout the world. Each year the WHO makes recommendations about the strains to be included in vaccines for the forthcoming winter.6 (http://www.who.int/csr/disease/influenza/vaccinerecommendations1/en/ (accessed 18 May 2004). To provide continuing protection, annual immunisation is necessary with vaccine against the currently prevalent strains. Influenza vaccines are prepared using virus strains in line with the WHO recommendations. Current vaccines are trivalent, containing two subtypes of influenza A and one type B virus; in recent years these have closely matched viruses circulating subsequently. Should a new influenza A subtype emerge with epidemic or pandemic potential, a monovalent vaccine against that strain would be considered.
The viruses are grown in embryonated hens' eggs, chemically inactivated and then further treated and purified. Three types of influenza vaccine are currently available:
The vaccines are equivalent in efficacy and adverse reactions. As the vaccines are inactivated and do not contain live organisms, they cannot cause the disease against which they protect.
Some influenza vaccines currently contain thiomersal. Other influenza vaccines are thiomersal-free. They have equivalent efficacy and safety. If a thiomersalfree influenza vaccine is not available, then a thiomersal-containing vaccine should be given.
The currently available influenza vaccines give 70-80% protection against infection with influenza virus strains well matched with those in the vaccine.7 Protection lasts for about one year. In the elderly, protection against infection may be less, but immunisation has been shown to reduce the incidence of bronchopneumonia, hospital admissions and mortality.8 After immunisation, antibody levels may take up to 10-14 days to reach protective levels. While influenza activity is not usually significant before the middle of November, the influenza season can start early (as it did in 2003/04), and therefore the ideal time for immunisation is between September and early November.
Manufacture of influenza vaccines is complex and conducted to a tight schedule, constrained by the length of time available between the WHO recommendations and the opportunity to vaccinate before the influenza season. Manufacturers may not be able to respond to unexpected demands for vaccine at short notice. Other influenza vaccines are being developed such as an intranasal vaccine and an attenuated live vaccine but these are not currently available in the UK.
The vaccines should be stored in a refrigerator at +2 to +8oC and protected from light. They must not be frozen. They should be shaken well before they are given. Vaccines should be disposed of by incineration at a suitably authorised facility.
Vaccines are routinely given intramuscularly into the upper arm or anterolateral thigh. Intradermal injection may cause a severe local reaction and should be avoided. Vaccines should be given by deep subcutaneous injection to individuals with a bleeding disorder. Vaccines must not be given intravenously. Influenza vaccine can be given at the same time as other vaccines such as pneumococcal vaccine and routine childhood vaccines. The influenza vaccine should not be mixed with other concurrently administered vaccines and should be given at a separate site, preferably in a different limb. If given in the same limb, they should be at least 2.5cm apart.8 The site at which each vaccine was given must be noted in the individual's records.
| Age | Dose |
| Children aged 6-35 months | 0.25 ml or 0.5 ml (depending on manufacturers SPC) repeated 4-6 weeks later if receiving influenza for the first time |
| Children aged 3 - 12 years | 0.5 ml, repeated after 4-6 weeks if receiving influenza for the first time |
| Adults and children over 13 years | A single injection of 0.5 ml |
Children and pregnant women should preferably receive a thiomersal-free influenza vaccine. If a thiomersal-free vaccine is not available then a thiomersal containing vaccine should be given. The benefits of vaccination outweigh the risks, if any, of exposure to thiomersal-containing vaccines.
The aim of the influenza immunisation programme is to protect those who are most at risk of serious illness or death should they develop influenza. To facilitate this, general practitioners are required to compile a register of those patients for whom influenza is recommended. Sufficient vaccine can then be ordered in advance and patients invited to planned immunisation sessions or appointments.
Patients should be advised that many other organisms cause respiratory infections similar to influenza during the influenza season, e.g. the common cold and RSV. Influenza vaccine will not protect against these diseases.
Influenza vaccine is offered annually between September and early November to:
| Clinical risk category | Examples (decision based on clinical judgement) |
| Chronic respiratory disease, including asthma | This includes chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema, bronchiectasis, cystic fibrosis, interstitial lung fibrosis, pneumoconiosis, asthma requiring continuous or repeated use of inhaled or systemic steroids or with previous exacerbations requiring hospital admission, children who have previously been admitted to hospital for lower respiratory tract disease. |
| Chronic heart disease | This includes those requiring regular medication and/or follow-up for ischaemic heart disease, congenital heart disease, hypertensive heart disease (excluding uncomplicated controlled hypertension) and chronic heart failure. |
| Chronic renal disease | Including nephrotic syndrome, chronic renal failure, renal transplantation. |
| Diabetes | Diabetes mellitus requiring insulin or oral hypoglycaemic drugs. |
| Immunosuppression | Immunosuppression due to disease or treatment, including asplenia or splenic dysfunction, and also including those on or likely to be on 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 1mg or more per kg per day. HIV infection at all stages. However, some immunocompromised patients may have a suboptimal immunological response to the vaccine. |
* The medical practitioner 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.
In addition to the above, immunisation is provided 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, or to avoid disruption to services that provide their care. Annual immunisation is recommended for:
Children who have medical conditions that increase their risk of complications from influenza should be vaccinated before the influenza season.
Studies have shown that two doses of inactivated vaccine are required to achieve adequate antibody levels in children under 13 years of age as they may have not previously been exposed to influenza or been vaccinated (Wright et al., 1977) The vaccines are interchangeable; the second dose should be given 4-6 weeks after the first dose in accordance with the manufacturer’s SPC for that vaccine.
There are very few individuals who cannot receive influenza vaccine. Where there is doubt, appropriate advice should be sought from an immunisation coordinator, consultant in communicable disease control or consultant paediatrician so that the period the individual is left unvaccinated is minimised.
The vaccines should not be given to those who have had:
Confirmed anaphylaxis is rare. 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. The risk to the individual of not being immunised must be taken into account.
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 wrongly attributing any new symptom or the progression of symptoms to the vaccine.
Pregnant women in the risk groups above should be vaccinated before the influenza season, regardless of the stage of pregnancy. A study of over 2000 pregnant women who received influenza vaccine demonstrated no associated adverse fetal effects (Heinonen et al., 1973). There is no evidence of risk from vaccinating pregnant women or those who are breast-feeding with inactivated viral or bacterial vaccines or toxoids (Plotkin and Orenstein, 2004). Where possible pregnant women should receive a thiomersal-free influenza vaccine. If a thiomersal-free influenza vaccine is unavailable then a thiomersal-containing vaccine should be given. The benefits of vaccination outweigh the risks, if any, of exposure to thiomersal-containing vaccines.
It is important that premature infants who have risk factors have their immunisations at the appropriate chronological age. Immunisation should be considered after the child has reached six months of age. Where possible, infants should receive a thiomersal-free influenza vaccine. If a thiomersal-free influenza vaccine is unavailable then a thiomersalcontaining vaccine should be given. The benefits of vaccination outweigh the risks, if any, of exposure to thiomersal-containing vaccines.
Individuals with immunosuppression and HIV infection (regardless of CD4 count) should be given influenza vaccine in accordance with the recommendations above. These individuals may not make a full antibody response.
Pain, swelling or redness at the injection site, low grade fever, malaise, shivering, fatigue, headache, myalgia and arthralgia are among the commonly reported symptoms. A small painless nodule (induration) may also form at the injection site. These reactions usually disappear within one to two days without treatment. Immediate reactions such as urticaria, angio-oedema, bronchospasm and anaphylaxis, can occur, most likely due to hypersensitivity to residual egg protein. Neuralgia, paraesthesiae, convulsions, and transient thrombocytopenia have been reported rarely. Guillain-Barré syndrome has been reported very rarely after immunisation with influenza vaccine (one case per million people vaccinated in one US study (Lasky et al., 1998). Although a causal relationship has not been established. Vasculitis with transient renal involvement and neurological disorders such as encephalomyelitis and neuritis occur very rarely.
All suspected reactions in children and severe suspected reactions in adults should be reported to the Committee on Safety of Medicines using the Yellow Card scheme.
There are antiviral drugs available, which can be used under certain circumstances to either prevent influenza or to treat it. Guidance on the treatment and prevention of influenza with antiviral drugs applicable in England, Wales and Northern Ireland was issued by the National Institute for Clinical Excellence (NICE) in February 2003 and September 2003 respectively (http://www.nice.org.uk). These drugs are not a substitute for influenza immunisation.
Similar treatment guidance endorsing the recommendations of NICE was issued by Quality Improvement Scotland (QIS) in February 2003. (http://www.nhshealthquality.org/nhsqis/qis_Publications3.jsp?pContentID=10 96&p_applic=CCC&p_service=Content.show&).
This guidance applies when influenza A or B is known to be circulating in the community. The Department of Health posts this information on its website and this should be checked regularly during the influenza 'season'. (http://www.dh.gov.uk/PolicyAndGuidance/HealthAndSocialCareTopics/Flu/Fl uGeneralInformation/fs/en).
Antiviral drugs can be used for either prevention or treatment of influenza. Oseltamivir and amantadine are licensed for prevention of influenza. Zanamivir, oseltamivir and amantadine are licensed for the treatment of influenza. Zanamivir and oseltamivir are neuraminidase inhibitors, active against influenza A and B; amantadine is an M2 inhibitor, active against influenza A only. Zanamivir is taken using a special inhaler (Diskhaler®) and is licensed for individuals aged 12 years and over; oseltamivir is taken orally and is licensed for individuals aged one year and over; amantadine is taken orally and licensed for individuals aged ten years and over.
When influenza A or B virus is circulating in the community as defined on the Department of Health website, oseltamivir should be prescribed for the prevention of influenza in those who fulfil the following criteria:
Oseltamivir should not be used for the prevention of influenza in otherwise healthy people under 65 years of age, even if they have been in contact with people with influenza-like symptoms. Oseltamivir is not recommended for the prevention of influenza in at-risk children under 13 years of age. NICE does not recommend amantadine for the prevention of seasonal influenza.
Therapy should begin within 48 hours of exposure. A daily dose of oseltamivir 75mg should be given for at least seven days and can be given for up to six weeks during a community outbreak.
Oseltamivir should not be used in children less than 13 years of age.
There are no adequate data for the use of oseltamivir in pregnant or breastfeeding women. Oseltamivir should not be used during pregnancy or in breastfeeding women unless the potential benefit to the mother overrides the potential risk for the fetus or infant. The dose of oseltamivir should be reduced for people with moderate to severe renal impairment.
Nausea, vomiting, diarrhoea, abdominal pains and headache have been reported.
Zanamivir and oseltamivir are recommended for the treatment of influenza in at-risk children or adults who present with influenza-like illness and who can start treatment within 48 hours of the onset of symptoms. NICE does not recommend amantadine for the treatment of influenza.
Treatment should start within 48 hours of the onset of symptoms. Oseltamivir is licensed for the treatment of children over one year of age. The dosage depends on body weight.
| Body weight | Dosage |
| 15kg or under | 30mg every 12 hours; |
| 16-23kg | 45mg every 12 hours; |
| 24-40kg | 60mg every 12 hours; |
| over 40kg | 75mg every 12 hours. |
Zanamivir is not used in this age group.
Treatment should start within 48 hours of the onset of symptoms. For zanamivir, the dose is 10mg, by inhalation, twice a day for five days. For oseltamivir, the dose is 75mg every 12 hours for five days.
Oseltamivir is contraindicated in children under one year; zanamivir should not be used in children less than 13 years of age. Zanamivir is not recommended in women who are breast-feeding.
Zanamivir should be used with caution in individuals with asthma or chronic pulmonary disease because of the risk of bronchospasm. It should not be used during pregnancy unless the potential benefit to the mother overrides the potential risk for the fetus. There are no adequate data for the use of oseltamivir in pregnant or breastfeeding women. It should not be used during pregnancy or in breast-feeding women unless the potential benefit to the mother overrides the potential risk for the fetus or infant. The dose of oseltamivir should be reduced for people with moderate to severe renal impairment.
Nausea, vomiting, diarrhoea, abdominal pains and headache have been reported.
Headache, gastro-intestinal disturbances have been reported rarely.
Demand for influenza vaccine sometimes increases unpredictably in response to speculation about influenza illness in the community. It is, therefore, recommended that practices order sufficient vaccine for their needs, based on their ‘At risk’ registers, well in advance of the immunisation season. Information on current vaccines is given in the latest CMO letter from the Departments of Health. At the time of publication, vaccines are available as follows:
Manufacturer Name of product Vaccine type Contact details Inactivated influenza vaccine Split virion Inactivated influenza vaccine for paediatric use Split virion Sanofi Pasteur MSD Inflexal V Surface antigen 0800 085 5511 Enzira* Split virion Chiron Vaccines Generic brand* Split virion 08457 451 500 GlaxoSmithKline Fluarix* Split virus 0808 100 9997 MASTA MASTAFLU Surface antigen 0113 238 7500 Influvac Surface antigen, inactivated, sub unit 0800 358 7468 Solvay Healthcare Invivac Surface antigen, inactivated, virosome Wyeth Vaccines Begrivac Split virion 01628 685 437 * Contains thiomersal. The Committee on Safety of Medicines (CSM)’s statement on the safety of vaccines containing thiomersal can be found on the following site: http://medicines.mhra.gov.uk/ourwork/monitorsafequalmed/safetymessages/thiomersalstatem ent%5F210203.pdf
Oseltamivir is supplied by Roche, Tel: 0800 731 5711 Zanamivir is supplied by GlaxoSmithkline, Tel: 0808 100 9997
American Academy of Pediatrics (2003) Active immunisation. In Pickering LK (ed) Red Book: 2003 Report of the Committee on Infectious Diseases. Twentysixth edition. Elk Grove Village, IL: American Academy of Pediatrics, p.33. Barker WH and Mullooly JP (1982) Pneumonia and influenza deaths during epidemics Arch Int Med 142:85-9. Fleming DM et al. (1995) Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989/90 using a general practice database. Epidemiol and Infection 115:581-9. Goddard NL et al. (2003) Appropriateness of thresholds currently used to describe influenza activity in England. CDPH 6:238-45. Heinonen OP et al. (1973). Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy. Int J Epidemiol 2:229-35. Lasky T, Terracciano GJ, Magder L et al. (1998). The Guillain-Barre syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med 339:1797-1802. Nicholson KG (1996) Impact of influenza and respiratory syncytial virus on mortality in England and Wales from January 1975 to December 1990. Epidemiol Infect 116:51-63. Plotkin SA and Orenstein WA ( Eds) (2004). Vaccines (Fourth edition). Philadelphia: WB Saunders Company, chapter 8. Watson JM, Goddard N, Joseph C and Zambon MC (2001) Influenza: the impact of the 1999/2000 epidemic on morbidity and mortality in the UK. In: Osterhaus ADME, (ed.) Options for the Control of Influenza. Elsevier, pp.21-3. 21 Wilde JA et al. (1999) Effectiveness of influenza vaccine in health care professionals: a randomised trial. JAMA 281:908-13. Wright PF, Thompson J, Vaughn WK et al. (1977) Trials of influenza A/New Jersey/76 virus vaccine in normal children: an overview of age-related antigenicity and reactogenicity. J Infect Dis 136 (suppl):S731-S741.