Influenza

Synonym: flu

Acute respiratory illness due to infection with the influenza virus.

There are three serotypes - A, B and C. 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 virus into host respiratory cell
• N: neuraminidase - facilitates release of virions from 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.

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 sub-type - 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.

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.¹
It is highly infectious with a ratio of infections:clinical cases of between 3:1 and 9:1.
An epidemic can be declared when GP consultation rate for new cases of influenza or flu-like illness is >400 per100,000 population per week. This occurred in the UK in 1989/90.
Rarely, there are pandemics. There have been 4 in the last 100 years. Swine influenza (H1N1) reached pandemic proportions in June 2009.² The effects can be devastating; the 1918 outbreak killed around 21 million worldwide.³ That is 6 x more casualties than The Great War.

Risk factors

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

Transmission is usually by droplet due to coughing/sneezing; direct nasal or eye contact with hands carrying virus can also produce infection. After an incubation period of around 2 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.³
The symptoms typically last for 3-5 days but cough, tiredness and malaise may last for 1-2 weeks.
Infectivity continues for 5 days from onset, though children can remain infectious for 2 weeks, and the severely immunocompromised can shed virus for weeks.
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.
Fever may not be seen in older patients.
Gastrointestinal symptoms are not usual but may occur in a minority of patients.

The most important are listed below:

• Common cold/upper respiratory tract infection
• Pharyngitis - multiple aetiologies
• Meningitis
• Bacterial or viral pneumonia/lower respiratory tract infection
• Malaria or dengue fever in returning travellers
• Infectious mononucleosis
• Cytomegalovirus
• Acute HIV seroconversion illness

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 (not wholly reliable)

General measures

In otherwise healthy individuals with uncomplicated illness, self-management is recommended including rest, increased fluid intake, analgesics and antipyretics. Aspirin should be avoided in children aged <12 years due to the danger of Reye's syndrome.

Pharmacological

Three antiviral drugs are licensed for the treatment of influenza. These are covered in detail in the separate article Antivirals for Influenza.

This is also covered in detail in the separate article Antivirals for Influenza.

Respiratory complications include:

• Acute bronchitis (about 20% 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 chronic obstructive pulmonary disease (COPD)
• Empyema
• Pulmonary aspergillosis
• Sinusitis

Non-respiratory complications include:

• Febrile convulsions
• Otitis media
• Toxic shock syndrome
• Myositis and myoglobinaemia
• Heart failure
• Myocarditis
• Reye's syndrome
• Guillain-Barré syndrome
• Transverse myelitis
• Encephalitis

Risk 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.

Each year 3,000-4,000 deaths are attributed to influenza in the UK.
During epidemics, this can be much higher, e.g. in excess of 30,000 deaths in 1989-90 with 89% of these being in people aged over 65 years.⁴

See Influenza Vaccination.

1. Influenza, Clinical Knowledge Summaries (August 2009)
2. Swine influenza, Health Protection Agency (April 2009)
3. Derlet R, Lawrence R et al; Influenza.; e-Medicine; December 2009
4. Donaldson GC, Keatinge WR; Excess winter mortality: influenza or cold stress? Observational study. BMJ. 2002 Jan 12;324(7329):89-90.

• Immunizations - seasonal influenza, Clinical Knowledge Summaries (July 2009)
• Pandemic flu: clinical management of patients with an influenza-like illness during an influenza pandemic, British Infection Society et al (2007); (Provisional guidelines from the British Infection Society British Thoracic Society Health Protection Agency in collaboration with the Department of Health)
• Flu key documents; Department of Health; Flu documents and resources for patients and health professionals. Includes frequently asked questions, anti-viral agent information, contingency plans and immunisation publicity campaigns.