Influenza

Synonym: Flu
Acute respiratory illness due to infection with the influenza virus. There are three serotypes: A, B and C. Influenza A & 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, who 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 produces 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 in:

• December to March in temperate regions of Northern hemisphere
• May to September in Southern hemisphere
• Cases 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 >400/100,000 population/week. This occurred in UK in 1989/90, partial outbreak and Northern European epidemic in 2003.
Rarely, there are pandemics. There have been 3 in the last 100 years. Their effects can be devastating; the 1918 outbreak killed around 21 million worldwide.² That is 6x 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 incubation period of around 2 days 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.²
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% children aged <4 years, and in around 10% 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.

There are many, the most important being listed below:

• Common cold/upper respiratory tract infection caused by multitude of viruses
• 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)

Non-Drug

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 <12 years due to the danger of Reye's syndrome.

Drugs

Three antiviral drugs are licensed for the treatment of influenza:

• Zanamivir³; a neuraminidase inhibitor, licensed for treatment of influenza A & B in patients age >12 years when given within 48 hours of onset of symptoms and influenza is circulating.
• Oseltamivir⁴; also a neuraminidase inhibitor like zanamivir active against all strains of A & B viruses, licensed in patients aged >1 year with same conditions as zanamivir. Also licensed for prophylaxis in patients age >13 years. Cochrane recommends the use of neuraminidase inhibitors is restricted to epidemics and pandemics.⁵
• Amantadine⁶; (and related Rimantadine) thought to work by blocking cellular membrane ion channels, are only active against influenza A viruses. Although licensed for treatment of and prophylaxis against influenza A in patients at risk of complications, it has low rates of effectiveness⁷ and NICE does not recommend it's use.⁸ Should also be started within 48 hours of symptoms.

All three above have been shown to reduce duration of symptoms by approx. 1 day. Their role in reducing the incidence of complications is less clear and heavily dependent on the patient group taking the drug.
NICE recommends the use of zanamivir and oseltamivir for the treatment of at-risk adults who fulfil the above conditions.⁸ At-risk patients include those with:

• Chronic respiratory disease, including asthma
• Chronic heart disease, excluding uncomplicated, controlled hypertension
• Chronic renal disease
• Diabetes mellitus
• Immunosuppression - including asplenia or splenic dysfunction, or have received systemic steroids equivalent to 20mg prednisolone daily for more than 2 weeks.

Oseltamivir is licensed in some countries for use as a prophylactic agent against infection after exposure in non-immunised individuals. NICE recommends oseltamivir for post-exposure prophylaxis in people who are¹¹:

• Aged 13 years and older
• At-risk
• Not effectively protected by vaccination
• In very close contact (i.e. someone who lives in the same house as a person suffering from symptoms of flu-like illness
• Able to begin prophylaxis within 48 hours of exposure

Oseltamivir is therefore available on an NHS prescription for post-exposure prophylaxis under these circumstances, and the prescription must be endorsed 'SLS'. NICE do not recommend use of oseltamivir for seasonal prophylaxis of influenza (prescribing for a period of 6 weeks or so when the virus is circulating in the community).
In the event of a new pandemic strain emerging, new guidance on prophylaxis is expected.

Respiratory complication include:

• Acute bronchitis (about 20% cases with increased risk in the elderly and those with chronic disease)
• Secondary bacterial pneumonia (especially Staph. aureus)
• Primary viral pneumonia
• Exacerbations of asthma and 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 age >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 3-4,000 deaths are attributed to influenza in the UK.
During epidemics, can be much higher, e.g. 30,000 excess deaths in 1989-90 with 89% of these being in people aged over 65 years.¹²

See Influenza Vaccination