Influenza: clinical review

The clinical features of influenza, the risk groups for serious illness, plus advice on treatment, prophylaxis and recognising complications.

The symptoms of influenza were clearly described by Hippocrates around 2,400 years ago.1 More recently, the 1918 Spanish flu pandemic was responsible for the death of more than 20m people worldwide, and for 250,000 deaths in the UK.2 

The high mortality of influenza in 1918 was due to two main parameters that are considered important today – firstly, the high infectivity rate (around 50% of people caught the disease when exposed) and a higher than usual mortality rate among those who caught the disease (between 2 and 20%).

Background

Influenza is an acute viral infection of the respiratory tract which is often highly infectious and spreads rapidly in communities. Even people with mild or no symptoms can infect others, which is why it is recommended that health care professionals are immunised to avoid infecting immunocompromised patients.3

There are three types of influenza viruses described. A viruses cause outbreaks most years, and can affect animals and wildfowl, as well as humans. B viruses tend to cause less severe disease and smaller outbreaks, often in children. C viruses cause minor respiratory illness only.

Type A viruses are usually described in terms of surface antigens on the virus - haemagglutinin (H) and neuraminidase (N). There are currently 18 types of H antigen and 11 types of N antigen identified.

The surface antigens (H&N) constantly change by antigenic drift - minor changes occurring from season to season - and antigenic shift, when a new subtype is identified which is a major change, and immunity from previous virus exposure may not protect the individual.

These are monitored by the World Health Organization to help countries to predict the strains of influenza A and B which are most likely to circulate every winter, and hence the vaccine that is produced.

Detailed information on national recommendations on influenza immunisation, and on indications and contraindications of the influenza vaccine, is available and is regularly updated.4

Clinical features

Influenza is easily transmitted by large droplets, small particles, and by hand-to-mouth/eye contamination from infected surfaces or respiratory secretions of an infected person. People with minimal or no symptoms can still infect others.

Usually the incubation period is 1–5 days (the average is 2-3 days), although it can be longer in those who are immunodeficient.

Common symptoms include sudden onset of fever, chills, headache, myalgia, and fatigue. There is often a dry cough, sore throat, and stuffy nose. It is not uncommon for children to have vomiting or diarrhoea.

Risk groups for serious illness

Serious illness is higher in children under 6 months, pregnant women, older people, and those with underlying health conditions such as respiratory disease, cardiac disease, chronic neurological conditions, or immunosuppression.

Influenza during pregnancy may be associated with perinatal mortality, prematurity, smaller neonatal size, and lower birth weight.

Who should be offered immunisation?

The following groups should be offered an influenza vaccine (Adapted from Public Health England flu plan5):

  • People over the age of 65 years
  • People aged between 6 months and 65 years with a serious medical condition, such as:
    • chronic lung disease (such as asthma requiring an inhaled corticosteroid or other treatment, COPD, bronchitis, cystic fibrosis)
    • chronic heart disease (such as heart failure)
    • chronic kidney disease (stage 3, 4, or 5)
    • chronic liver disease
    • chronic neurological disease (for example, Parkinson’s disease, or motor neurone disease)
    • diabetes
    • splenic dysfunction
    • weakened immune system (such as HIV/AIDs or cancer treatments)
    • all pregnant women
    • all those aged 2-4 years, through the GP practice
    • all those in school years 1 and 2, and in primary school, through local systems
    • people living in long-stay residential care homes or long-stay facilities where infection would cause high morbidity/mortality (this does not include prison or university halls of residence)
    • carers who have a carer’s allowance, or who are the main carer for an older or disabled person
    • household contacts of immunocompromised individuals

It should be noted that the influenza immunisation is a mix of three strains of influenza that are predicted to affect the population significantly. The immunisation is changed annually linked to WHO information. Most years this is predictable, although from time to time - with antigenic shift and/or increased availability of world travel - immunisation is less effective, as was the case in 2014-2015.6

Treatment of influenza

People with suspected influenza who are not in at-risk groups should stay at home, rest, drink plenty of fluids, and seek advice from a pharmacist about simple remedies for their symptoms.5 Paracetamol and ibuprofen based remedies can help to lower temperature and relieve symptoms.

Public Health England recommends that people should avoid visiting GP surgeries and hospitals where they may infect other more vulnerable people, and use community pharmacists as a first port of call.

Antiviral medications

Although there has been debate about efficacy of antiviral medicines,7-9 current national advice is that they can prevent the influenza virus from replicating inside the body (see box). They can lessen symptoms by a couple of days and reduce their severity, and help to reduce the likelihood of complications.

Public health departments generally issue guidance when an outbreak locally warrants wider use of antiviral medicines.

When to prescribe antivirals: DH advice and NICE guidance

Antivirals may be prescribed at NHS expense for the prophylaxis and treatment of influenza in accordance with NICE guidance and the Selected List Scheme. Department of Health advice states that GPs should consider prescribing antiviral medicines for patients if they are at risk of severe illness and/or complications from influenza if not treated, whether or not they are in a clinical at-risk group.

NICE guidance recommends oseltamivir and zanamivir to treat people with flu, if all of the following apply:

  • the person is in an at-risk group
  • the person has a flu-like illness and can start treatment within 48 hours (36 hours for zanamivir treatment in children) of the first sign of symptoms
  • the flu virus is known to be going around and it is likely that a flu-like illness has been caused by the flu virus

NICE guidance on prophylaxis is that oseltamivir and zanamivir are recommended if all of the following apply:

  • the amount of flu virus going around is enough that if someone has a flu-like illness it is likely that it has been caused by the flu virus
  • the person is in an at-risk group
  • the person has been in contact with someone with a flu-like illness and can start treatment within 36 hours (for zanamivir) or within 48 hours (for oseltamivir)
  • the person has not been effectively protected by vaccination
  • The NICE guidance does not cover widespread epidemics.

Who to admit with influenza?

Most people with influenza will not need admission – however high-risk people and those who are significantly unwell should be strongly considered for admission. A variety of tools have been described to assess severity, although none have overwhelming support.

It is sensible to consider admission for those with acute confusion, or those with reduced consciousness level, those with raised or significantly raised pulse rate or lowered blood pressure, and especially if there is an increased respiratory rate or low oxygen saturation in patients for whom respiratory problems are considered more significant.

Hospital admission is sometimes required, and supportive therapy along with management of complications is appropriate. For example, if the infection is thought to have a secondary bacterial infection, intravenous antibiotics will be used in addition to antiviral drugs.

A few critically ill patients require extra-corporeal membrane oxygenation (ECMO). This involves removing blood and adding oxygen to it, then pumping it back into the body while allowing time for the lungs to heal. This is complex and high risk, and used in specialist centres.

Complications and prognosis

Most of the complications seen in people with influenza are respiratory in nature and include:10

  • acute bronchitis, which accounts for around 20% of episodes
  • pneumonia – this can be caused by a secondary bacterial infection, especially Staph aureus, although it is primarily viral
  • exacerbations of asthma or chronic obstructive pulmonary disease
  • otitis media, especially in children
  • sinusitis

Non-respiratory complications, which are rarer, include:

  • febrile convulsions
  • myositis and myoglobinaemia (especially in children)
  • toxic shock syndrome
  • heart failure/myocarditis
  • Reye’s syndrome
  • Guillan-Barre Syndrome
  • Encephalitis

Prognosis and follow-up

It has been estimated that around 10% of people with hospital acquired influenza are likely to die.3 However, most people recover completely in 1-2 weeks. Some can develop life-threatening complications, such as pneumonia.

Influenza has a much higher mortality rate in the weak, young, old, and the chronically ill. Pregnant women and young children appear particularly at risk of complications.

Conclusion

We understand far more about influenza now than we have done in the past. It is still challenging to predict and respond to, as the circulating influenza virus that we are faced with is continually adapting. In general, the UK has a good vaccination programme and a healthy population – however influenza can still be fatal to many in the high-risk groups, and we should not drop our guard.

Case study

Catherine is 22 years old and is now 16 weeks pregnant. She has had routine care for her pregnancy, although she had declined, despite advice, the influenza immunisation that was offered.

She has a 24-hour history of fever, chills, headache, myalgia, and fatigue, with a dry cough and sore throat. She asks initially what she can take safely during her pregnancy.

The nurse practitioner triaging suggests that Catherine stay at home, take more rest, drink plenty of fluids, and use paracetamol to help bring down her temperature and relieve symptoms. Catherine is recommended to seek further advice if her condition deteriorates or she has concerns about her health.

Two days later Catherine contacts the practice again and indicates that she is feeling no better, and indeed is a good deal worse. She is feverish and now more breathless too.

Catherine is asked to come to the practice and is seen by the GP. Careful examination indicates that Catherine has a temperature of 38.5oC, her respiratory rate is 26/minute and pulse 124/m regular. Blood pressure is 90/52 and oxygen saturation is 89% on air. Catherine has coarse creps evident, and reduced air entry in the region of the right lower lobe.

Her GP arranges for urgent hospital assessment/admission having given a dose of 500 mg of clarithromycin for a suspected community-acquired pneumonia. The GP has recognised that there is an increasing frequency of influenza in the area and is thinking about a potential Staph aureus infection, which is why he did not commence the usual amoxicillin.

In hospital Catherine’s X-ray confirms the clinical suspicion and Catherine is given oxygen to maintain her levels between 94 and 98%, along with intravenous antibiotics.

Three days later Catherine feels considerably better. She is apyrexial, her oxygen levels have improved on air, and her pulse reduced to 88/minute. Her medications are changed back to oral and Catherine is allowed home.

Over the next 7-10 days she feels steadily better and is feeling back to normal over the next month. Catherine reflects that if she has a further pregnancy she would be certain to have an influenza immunisation.

  • Dr Steve Holmes is a GP partner in Shepton Mallet, Somerset and education lead with The Primary Care Respiratory Society UK
  • Jane Scullion is a nurse consultant in Leicester,

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References:

  1. Martin PM, Martin-Granel E. 2,500-year evolution of the term epidemic. Emerging infectious diseases (2006); 12(6): 976-80.
  2. Patterson KD, Pyle GF. The geography and mortality of the 1918 influenza pandemic. Bull Hist Med (1991); 65(1): 4-21.
  3. Behrman A, Offley W. Should influenza vaccination be mandatory for healthcare workers? BMJ (2013); 347: f6705.
  4. Public Health England. Influenza: the green book, chapter 19. In Immunisation against infectious disease. London: Department of Health, 2015.
  5. Public Health England. Flu plan: winter 2015/16. London: Department of Health and NHS England, 2015.
  6. Shrikrishna D, Williams S, Restrick L, Hopkinson NS. Influenza vaccination for NHS staff: attitudes and uptake.BMJ Open Resp Res (2015); 2(1): e000079.
  7. Jefferson T, Jones MA, Doshi P et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev (2014); 4: CD008965. DOI: 10.1002/14651858.CD008965.pub4.
  8. Jefferson T, Jones M, Doshi P et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ (2014); 348: g2545.
  9. Heneghan CJ, Onakpoya I, Thompson M et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ (2014); 348: g2547.
  10. National Institute for Health and Clinical Excellence. Clinical knowledge summary - influenza 2016 [17th March 2016].

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