Influenza

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oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

Synonym: flu

Influenza is an acute respiratory illness due to infection with the influenza virus.

Uncomplicated influenza is defined as influenza presenting with fever, coryza, generalised symptoms (headache, malaise, myalgia, arthralgia) and sometimes gastrointestinal symptoms, but without any features of complicated influenza.[1] 

Complicated influenza is defined as influenza requiring hospital admission and/or with symptoms and signs of lower respiratory tract infection (hypoxaemia, dyspnoea, lung infiltrate), central nervous system involvement and/or a significant exacerbation of an underlying medical condition.[1] 

There are three serotypes - A, B and C.[2] Influenza A and B viruses cause most clinical disease:

  • A is the more frequent and the cause of major influenza outbreaks.
  • B tends to circulate with A in yearly outbreaks and causes less severe illness.
  • C tends to cause a mild or asymptomatic illness akin to the common cold.

Influenza A serotypes are further categorised by their surface antigens:

  • H: haemagglutinin - facilitates entry of the virus into the host respiratory cell.
  • N: neuraminidase - facilitates release of virions from the infected host cells.

There are 15 H and 9 N subtypes of the A virus in aquatic birds, which together with pigs (often termed the 'mixing vessel' for scrambling human and avian virus genetic material) are the natural reservoir of the virus. Many of the newer types of influenza are thought to have arisen in China because of the often close co-habitation there of pigs, fowl and humans. Swine flu is an influenza A virus most frequently of subtype H1N1, usually found in pigs but able to be transferred to humans.

The influenza virus undergoes minor mutations to one or both of its surface antigens - antigenic drift. This causes seasonal epidemics where people have only partial immunity from previous infection.

In influenza A alone, major and sudden changes in the H and N antigens produce a new virus subtype - antigenic shift. There is little population immunity to the new form and a major epidemic may ensue.

There is evidence emerging that humans can serve as the 'mixing vessel' for at least some of the 15 avian subtypes circulating in bird populations.

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Incidence

Cases peak:

  • From December to March in temperate regions of the Northern hemisphere.
  • From May to September in the Southern hemisphere.
  • Throughout the year in tropical areas.

Up to 15% of the population can develop influenza in any year. There is a 10-20% seroconversion rate with or without symptoms. In an average year, there are 50-200 GP consultations for influenza or flu-like illnesses per 100,000 population per week.[3] It is highly infectious with a ratio of infections to clinical cases of between 3:1 and 9:1.

An epidemic can be declared when the GP consultation rate for new cases of influenza or flu-like illness is >400 per 100,000 population per week.

The World Health Organization (WHO) has defined the criteria for a pandemic:

  • The disease must be new to the population - or at least a disease that had not surfaced for a long time.
  • This disease must be caused by disease-causing agents that infect humans, causing serious illness.
  • The agents must spread easily and sustainably among humans.

There have been four pandemics in the last 100 years. The effects can be devastating; the 1918 outbreak killed around 21 million worldwide (that is 6 x more casualties than in the First World War):

  • The most recent was swine influenza virus (H1N1v), reaching pandemic proportions in June 2009 in the UK. Swine influenza A virus was quite different to previous viruses. The human community initially had little immunity to it. The young were at most risk and those aged over 60 years at least risk.[4] Epidemics occurred worldwide in 209 countries with considerable morbidity and at least 14,142 deaths.[5]
  • The National Pandemic Flu Service (NPFS) was established in the UK at the height of the pandemic; however, this was disbanded in February 2010 as the number of cases fell.
  • Continuing WHO surveillance reveals that in the winter of 2011-12 the majority of cases in Europe were associated with influenza A (H3N2).[6] However, H1N1 was over-represented in severe cases compared with the other two circulating viruses in France, Ireland, Spain and the UK.

Risk factors

  • Closed environments - eg, residential homes, schools and prisons.
  • Advanced age.
  • Pre-existing cardiac or respiratory illness.

Transmission is either by:

  • Droplet due to coughing/sneezing.
  • Direct nasal or eye contact with hands carrying the virus.

After an incubation period of one to three days the patient commonly presents with rapid onset of:

  • Anorexia.
  • Malaise.
  • Headache (retro-orbital).
  • Fever.
  • Myalgia.
  • Non-productive cough and sore throat.

Nasal discharge/obstruction and sneezing can occur but are not usually prominent features of the illness. Fever may not be seen in older patients. Gastrointestinal symptoms are not usual but may occur in a minority of patients.

Swine flu is similar to the usual human seasonal influenza infection, with most cases in adults and children being mild. Clinicians are encouraged to diagnose swine flu based on symptoms if there is a pyrexia (≥38°C), fever or history of fever and flu-like illness (two or more of the following symptoms: cough, sore throat, rhinorrhoea, widespread muscle and joint aches, headache). There may also be any of the following: fatigue, loss of appetite and sometimes diarrhoea, nausea, vomiting, otitis media and (rarely) cerebral irritability ± seizures.[4]

Most symptoms typically last for 3-5 days but cough, tiredness and malaise may last for 1-2 weeks. Infectivity continues for five days from onset, although children can remain infectious for two weeks, and the severely immunocompromised can shed virus for weeks.

Atypical symptoms in children

In H1N1 influenza these include haematemesis, photophobia, chest pain, epistaxis, croup, apnoea, and rigors. Very young children and babies can present with apnoea, reduced tone and poor feeding (without classical influenza features) and may exhibit a sudden severe collapse (apparent life-threatening episode).[4] 

With all influenzas, neonates and infants may present with lethargy, poor feeding, apnoea or fever, pneumonia or otitis media. Drowsiness occurs in 50% of children aged <4 years, and in around 10% of children aged 4-15 years. It is uncommon in adults.

The most important are listed below:

In pregnant women, always consider pulmonary embolus (chest pain, tachypnoea and tachycardia) and pre-eclampsia (epigastric pain, headaches and elevated blood pressure).

The diagnosis is a clinical one so investigations are usually reserved for community surveillance purposes. Available tests include:

  • Direct viral culture of nasopharyngeal swabs/aspirates.
  • Immunofluorescence of nasopharyngeal swabs/aspirates.
  • Acute and convalescent sera, 10-14 days apart.
  • Polymerase chain reaction.
  • Rapid bedside antigen tests. These currently have low positive predictive values.[7]

General measures

In otherwise healthy individuals with uncomplicated illness, self-management is recommended, including resting at home, increased fluid intake, analgesics and antipyretics.

NB: aspirin should be avoided in children aged <16 years, due to the danger of Reye's syndrome.

Pharmacological

Antiviral drugs now form one important part of plans to prevent and contain epidemics of influenza infection. However, it is important to consider that use of antivirals in the management of influenza infection (for individuals and in populations) should be selective and appropriate.[8] 

Do not prescribe antiviral drugs for people with influenza who are otherwise healthy. Reassure the person that the worst symptoms of uncomplicated influenza resolve after about one week, although other symptoms (such as cough, headache, insomnia, weakness, and loss of appetite) may take longer than two weeks to resolve. NB: remember to endorse prescriptions 'selected list scheme' (SLS); otherwise, community pharmacies will not be able to dispense on the NHS.

Oseltamivir and zanamivir reduce replication of influenza A and B viruses by inhibiting viral neuraminidase. They are most effective if started within a few hours of the onset of symptoms. In otherwise healthy individuals they reduce the duration of symptoms by about 1-1.5 days. A Cochrane review found that there is evidence for the use of oseltamivir to alleviate symptoms but the evidence is inconclusive about its effect on complications or transmission.[9] 

There is evidence that some strains of influenza A virus have reduced susceptibility to oseltamivir, but may retain susceptibility to zanamivir. Resistance to oseltamivir may be greater in severely immunocompromised patients.

Oseltamivir may be ineffective in neonates but can be used for treatment or post-exposure prophylaxis of influenza in children under 1 year of age.[10] 

Safety data are limited but either oseltamivir or zanamivir can be used in women who are pregnant or breast-feeding when the potential benefit outweighs the risk such as during a pandemic. Oseltamivir is preferred for women who are breast-feeding.

National Institute for Health and Care Excellence (NICE) guidance for the treatment of influenza:[11] 

  • The guidance does not cover treatment in a pandemic, an impending pandemic or a widespread epidemic of a new strain of influenza to which there is little or no immunity in the community.
  • Amantadine is not recommended for treatment of influenza.
  • When influenza is circulating in the community, either oseltamivir or zanamivir is recommended for the treatment of influenza in at-risk patients who can start treatment within 48 hours (within 36 hours for zanamivir in children) of the onset of symptoms.
  • During local outbreaks of influenza-like illness, when there is a high level of certainty that influenza is present, either oseltamivir or zanamivir may be used for treatment in at-risk patients living in long-term residential or nursing homes.
  • At-risk patients include those aged over 65 years or those who have one or more of the following conditions:
    • Chronic respiratory disease (including asthma and chronic obstructive pulmonary disease COPD).
    • Chronic heart disease.
    • Chronic kidney disease.
    • Chronic liver disease.
    • Chronic neurological disease.
    • Immunosuppression.
    • Diabetes mellitus.
    • A pregnancy.

Follow-up

Consider follow-up (particularly in frail people) after about one week, to confirm symptoms are improving and to exclude the development of secondary complications.

Advise the person that they should seek urgent medical attention if they develop shortness of breath or pleuritic chest pain, or if they start to cough up blood.

Arrange a follow-up appointment if there is no improvement after one week (that is, they are still significantly ill), or if they are deteriorating.

Have a lower threshold for seeking help if they are caring for a young child or baby with influenza, as children cannot accurately communicate their symptoms.

Respiratory complications include:

  • Acute bronchitis (about 20% of cases, with increased risk in the elderly and those with chronic disease).
  • Secondary bacterial pneumonia (especially Staphylococcus aureus).
  • Primary viral pneumonia.
  • Exacerbations of asthma and COPD.
  • Empyema.
  • Pulmonary aspergillosis.
  • Sinusitis.

Non-respiratory complications include:

Risks of complications with hospitalisation and death are higher among:

  • Those aged >65 years.
  • Very young children.
  • Those with at-risk factors shown above.

Residents of nursing homes are particularly at risk of serious complications because of their age, high rate of chronic disease and living in a closed community. In pregnant women there is a slight increase in perinatal mortality rate as well as early and late fetal deaths.

Estimates of excess winter deaths potentially attributable to influenza since 2004 in England and Wales range from not determined (in 2005-6 and 2006-7) to 10,351 (in 2008-9). The highest estimate since the mid-1990s was 21,497 for the 1999-2000 influenza season.

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.

Typically, seasonal influenza (H3N2) has a greater effect on mortality rates in the elderly, but H1N1 tends to affect children and young adults.[12]

See also the separate article on Influenza Vaccination.

Post-exposure prophylaxis[10] 

Oseltamivir and zanamivir are licensed for post-exposure prophylaxis of influenza when influenza is circulating in the community.

Oseltamivir should be given within 48 hours of exposure to influenza. Zanamivir should be given within 36 hours of exposure. For patients with severe influenza or those who are immunocompromised, antivirals may still be effective after this time if viral shedding continues.

Oseltamivir and zanamivir may be used in exceptional circumstances (eg, when vaccination does not cover the infecting strain) to prevent influenza in an epidemic.

NICE guidance for prophylaxis of influenza:[13] 

  • The guidance does not cover treatment in a pandemic, an impending pandemic or a widespread epidemic of a new strain of influenza to which there is little or no immunity in the community.
  • Amantadine is not recommended for prophylaxis of influenza.
  • Oseltamivir or zanamivir are not recommended for seasonal prophylaxis against influenza.
  • When influenza is circulating in the community, either oseltamivir or zanamivir is recommended for post-exposure prophylaxis in at-risk patients who are not effectively protected by influenza vaccine, and who have been in close contact with someone suffering from influenza-like illness in the same household or residential setting.
  • Oseltamivir should be given within 48 hours of exposure to influenza while zanamivir should be given within 36 hours of exposure to influenza.
  • During local outbreaks of influenza-like illness, when there is a high level of certainty that influenza is present, either oseltamivir or zanamivir may be used for post-exposure prophylaxis in at-risk patients who are living in long-term residential or nursing homes, regardless of influenza vaccination status.

Further reading & references

  1. HPA guidance on use of antiviral agents for the treatment and prophylaxis of influenza 2011-12; Health Protection Agency (December 2011 - Reviewed October 2012)
  2. Influenza: the Green Book, Chapter 19; Public Health Englan, 2014
  3. Influenza - seasonal; NICE CKS, October 2013 (UK access only)
  4. Pandemic H1N1 2009 influenza: clinical management guidelines for adults and children; Dept of Health
  5. Swine Influenza; World Health Organization
  6. Weekly epidemiological record. Review of the 2011–2012 winter influenza season; World Health Organization, June 2012
  7. Mahony AA, Cheng AC, Olsen KL, et al; Diagnosing swine flu: the inaccuracy of case definitions during the 2009 Influenza Other Respi Viruses. 2012 Jun 19.
  8. Seasonal influenza - Guidance and Information for health professionals; Public Health England
  9. Jones JT et al; Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children (Review), The Cochrane Collaboration, 2013
  10. British National Formulary
  11. Amantadine, oseltamivir and zanamivir for the treatment of influenza; NICE Technology Appraisals, February 2009
  12. Scalera NM, Mossad SB; The first pandemic of the 21st century: a review of the 2009 pandemic variant Postgrad Med. 2009 Sep;121(5):43-7.
  13. Oseltamivir, amantadine (review) and zanamivir for the prophylaxis of influenza; NICE Technology Appraisals, September 2008

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Hayley Willacy
Current Version:
Peer Reviewer:
Prof Cathy Jackson
Document ID:
2323 (v28)
Last Checked:
29/08/2014
Next Review:
28/08/2019