Section 1: Epidemiology and aetiology
Influenza is a viral disease that primarily infects the respiratory system, causing an acute and occasionally severe febrile illness.
Public anxiety about influenza has been increased by government and media attention to the possibility of a pandemic outbreak. However, the disease will most frequently be encountered as seasonal flu.
This article will focus on the management of seasonal, not pandemic, influenza, in which management and priorities may change dramatically.
Influenza is an RNA virus of which there are three types: A, B and C. Influenza virus types A and B are responsible for most clinical disease, with influenza A the most virulent.
Influenza is transmitted via droplets, aerosols or contact with infected respiratory secretions. It occurs mainly in winter, usually starting in November, when one or two dominant strains circulate each year.1
Influenza A is classified according to its surface receptors: haemagglutinin (H) and neuraminidase (N). Mutations in these occur between seasons in a process known as antigenic drift, a genetic process with clinical consequences, as lasting immunity derived from previous infections and vaccination does not occur.1,2
When a virus emerges with completely new receptors, this is termed antigenic shift, and can potentially result in a pandemic due to a complete lack of human immunity.
There have been three main pandemics in the past century. Spanish flu (H1N1) in 1918 killed 40-50m people worldwide, mainly young healthy adults. Asian flu (H2N2) in 1957 spread globally from China within six months, resulting in the deaths of more than 1m people. Hong Kong flu (H3N2) in 1968 killed more than 30,000 people in the UK and 1-3m worldwide.1,3
Swine flu (H1N1) originated in Mexico in March 2009. Disease prevalence peaked in the UK in July and October that year, interrupted by the school holidays. It affected mainly children and young adults, with the elderly presumably having a degree of acquired immunity from a similar strain in the 1950s. Swine flu was less virulent than feared and the pandemic was considered mild. H1N1 continues to circulate annually.1,3
Currently there are concerns over the avian strains H5N1 and H7N9, identified in China in 1997 and 2013, respectively. Transmitted via contact with infected poultry, they can cause severe and fatal disease.
There are rare cases of limited human-to-human transmission for both strains, with viral transmission only to very close contacts. The ability of these viruses to mutate to a strain that can spread easily between humans is a pressing concern, given the current lack of immunity.2
Influenza B mutates more slowly and is almost exclusively a human pathogen; antigenic shift and pandemics are not considered possible.3
Section 2: Making the diagnosis
Influenza should be suspected in patients presenting with a temperature of >38 degsC or a history of fever, plus two or more of the following:
- Cough (usually dry)
- Sore throat
- Limb/joint pain
It should also be suspected in any patient with a severe or life-threatening illness suggestive of an infective process.4
Influenza can be defined as uncomplicated or complicated. Uncomplicated influenza presents with fever, coryzal symptoms, headache, malaise, myalgia, arthralgia and occasionally, GI symptoms.
Complicated cases are broadly those patients with signs of organ system impairment.
Such patients may have symptoms and signs of a lower respiratory tract infection, such as hypoxaemia, dyspnoea, or lung infiltrates, nervous system involvement such as febrile seizures or encephalopathy, and/or a significant exacerbation of an underlying comorbidity. These patients should always be referred to hospital and the receiving team should be alerted to the possibility of influenza infection, so appropriate infection control can be arranged before the patient arrives.
The diagnosis of influenza is generally made on clinical grounds once it is known that flu is circulating in the community; this is announced by Public Health England (PHE) as a result of surveillance.
PCR, the investigation of choice for diagnostics, is used at sentinel sites to monitor incidence. Samples for testing are collected as combined swabs of the nose and throat. They should be stored in viral transport medium and sent to the laboratory.
Routine respiratory viruses screened for can vary between regions, so may need to be confirmed with the local laboratory. If patients have a recent relevant travel history, this should be detailed on the form, so additional viruses can be tested for as appropriate.1
If Middle East respiratory syndrome coronavirus is suspected in a patient returning from Saudi Arabia, or avian flu (H5N1/H7N9) in patients returning from China, these cases should be discussed urgently with the local microbiologist and advice sought from PHE.5
Other investigations include serological testing for anti-influenza antibodies, which although still used for surveillance, is no longer used routinely for clinical diagnosis, and the culture of influenza virus for vaccination production.
Such investigations are usually unnecessary in uncomplicated flu.4 Patients with complicated disease should be referred for investigation and management. If secondary bacterial infection is suspected, a sputum sample should be sent for microscopy, culture and sensitivities.
Section 3: Managing the condition
In most cases, flu is self-limiting and requires only symptom management. Otherwise healthy patients with influenza should be advised to stay off work or school (about one week is sufficient), drink plenty of fluids and take paracetamol or ibuprofen for symptomatic relief.4
The use of antivirals is focused on patients likely to develop complications, who are considered high risk.
Once flu is known to be circulating in the community, the DH will notify GPs. At this point, the NHS will fund the supply of antivirals to patients 'at clinical risk' and on the following list:
- Patients over 65 years of age.
- Patients with chronic respiratory disease.
- Patients with asthma requiring continuous or repeated use of inhaled or systemic steroids or with previous exacerbations requiring hospital admission.
- Patients with chronic heart disease, chronic renal failure, or chronic liver disease.
- Patients with chronic neurological disease.
- Patients with diabetes.
- Immunosuppressed patients (including post-splenectomy).
- Pregnant women and those less than two weeks postpartum.6
Two classes of antiviral are available for influenza - neuraminidase inhibitors, such as oseltamivir and zanamivir, and the M2 receptor blockers amantadine and rimantadine.
This latter class has been rendered ineffective by resistance, which is also increasingly prevalent for oseltamivir.7,8
Neuraminidase inhibitors work by binding to the neuraminidase receptor and preventing the virus from escaping its host cell.
Oseltamivir is a prodrug; after administration, it is hydrolysed in the liver to its active metabolite.7
It is thought to reduce the time to resolution of flu symptoms and to decrease the incidence of complications.8
The dose of oseltamivir is weight dependent; the normal adult dose is 75mg every 12 hours for five days.9
Side-effects include nausea and vomiting, and abdominal pain.9
Zanamivir decreases the time to resolution of symptoms compared with placebo.8 It is delivered by dry powder inhalation. The normal adult dose is 10mg twice daily for five days, although this can be extended if oseltamivir resistance is suspected (unlicensed).9
Its use is cautioned against in patients with respiratory disease, owing to the risk of bronchospasm.
Current guidance is that patients taking oseltamivir and zanamivir should be observed for behavioural changes, owing to reports of neuropsychiatric side-effects.10
Post-exposure prophylaxis with oseltamivir or zanamivir can be offered to patients at clinical risk (see above) who have had close contact with someone with flu, and if flu is known to be circulating in the community and they have not been immunised in the current season.6 They must be able to take the prophylactic therapy within 48 hours of contact.
Patients should be advised that the drugs may not be effective in preventing symptoms, and the same advice given to these patients regarding follow-up and symptoms of complicated influenza.
Arrangements should be made for patients to receive the current season's immunisation. The oseltamivir dose for prophylaxis is 75mg once daily for 10 days; the dose of zanamivir should be 10mg once daily for 10 days for prophylaxis.9
Vaccines are developed each year against the strains predicted to be prevalent in the forthcoming season. Vaccination is recommended for all patients over the age of 65, children aged between two and three years, pregnant women and those considered at high risk of complications.
Vaccination reduces the incidence of clinical influenza by 59% in adults and reduces the rate of complications in those who develop symptoms.
Immune protection usually develops within 14 days and lasts for at least 12 months. More detailed information is available in the Green Book.1
Section 4: Prognosis
Patients should be advised that although the most debilitating symptoms will resolve within seven days, residual symptoms, such as cough, weakness and lethargy, may persist for up to two weeks.
These patients require no follow-up, but should be advised to seek advice if they develop symptoms suggestive of complicated influenza, such as shortness of breath, haemoptysis or chest pain.
Patients experiencing symptoms for more than two weeks should be advised to seek a further appointment. Those seeking information and advice can be directed to online sources (see Section 6).
Section 5: Case study
Sarah is a 36-year-old nursery nurse and mother of two children. She describes a cough, headache and sore throat, and says she has been feeling 'terrible' for the past 48 hours.
She knows that many of her colleagues have had flu and one has been given tablets to take.
On examination, she has a temperature of 38.2 degsC, a pulse rate of 105bpm and BP of 106/68mmHg. Her oxygen saturations are 97% breathing room air, with a respiratory rate of 22 breaths per minute.
Auscultation of her chest is normal, but she looks unwell.
She wants to know whether she can have antivirals. The GP considers that although she is very likely to have influenza, she has no major risk factors and is unlikely to develop complications.
It is more than 48 hours since the onset of her symptoms, so antivirals are unlikely to have any effect.
She is advised to stay off work and rest, and told to look out for any further worrying symptoms and to make another appointment if she does not feel better in the next week.
Five days later, she sees the duty GP. She complains of not being able to take a deep breath because of pain in the right side of her chest. She has a cough productive of yellow sputum, but no blood. Her temperature is again >38 degsC, her pulse is 110bpm and her BP is 110/56mmHg. Her pulse oximetry reading is 96%.
Examination of her chest reveals crepitations in the lower zone of her right hemithorax.
The duty doctor suspects that she now has influenza complicated by a secondary pneumonia and starts her on oral antibiotics.
At a booked appointment a week later, she states she is feeling much better, although she is not sleeping well, mainly because of her cough.
Section 6: Evidence base
Both sites offer information for patients on self-treatment and the use of antivirals for influenza.
- NICE. Influenza -seasonal.
Professional resources are also available from Patient.co.uk and NICE, where a clinical knowledge summary is available with a full evaluation of the clinical evidence and economic evaluation.
An algorithm to guide the selection of antivirals is contained in the Health Protection Agency (HPA) guidance.11
The HPA's Green Book provides full details on vaccination of patients against influenza.1
- Full guidance on prescribing rules is available from the DH and the NHS Drug Tariff at www.nhsbsa.nhs.uk/924.aspx
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- Contributed by Dr Christopher Bassford, consultant in respiratory and intensive care medicine, and Dr Dawn Matthews, specialist trainee in microbiology, University Hospital Coventry
1. Immunisation against infectious disease: the green book. Public Health England, 2013. www.gov.uk
2. Labella AM, Merel SE. Influenza. Med Clin N Amer 2013; 97(4): 621-45. Epub 2013/07/03.
3. Pandemic Influenza. Public Health England, 2013. www.hpa.org.uk
4. Clinical Knowledge Summary: Seasonal Influenza. London, NICE, 2013. http://cks.nice.org.uk/influenza-seasonal
5. Public Health England, 2013.
6. NHS Business Services Authority. NHS Drug Tariff 2013. www.nhsbsa.nhs.uk/924.aspx
7. CRD/CHE Technology Assessment Group, University of York. Antiviral drugs
for the treatment of influenza: a systematic review and economic evaluation. London, NICE, 2008.
8. Hsu J, Santesso N, Mustafa R et al. Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies. Ann Intern Med 2012; 156(7): 512-24.
9. BMJ Publishing Group, RCPCH Publications, Royal Pharmaceutical Society of Great Britain. British National Formulary 2013. www.bnf.org/bnf/index.htm
10. MIMS. October 2013.
11. Health Protection Agency. Guidance on use of antiviral agents for the treatment and prophylaxis of influenza. Version 3. London, Health Protection Agency, 2012.