Amantadine, oseltamivir and zanamivir for the treatment of influenza

Influenza is an acute infection of the respiratory tract caused by the influenza A and B viruses. The symptoms of influenza include fever, cough, sore throat, myalgia and headache. These symptoms are not specific to influenza, and can be caused by other viruses (such as respiratory syncytial virus) which can present as an 'influenza-like illness'. Diagnosis of influenza can only be confirmed by laboratory testing, although the probability that an influenza-like illness is caused by influenza is higher if influenza is known to be circulating and if a person has a high fever. The symptoms of influenza-like illness can be different in infants and children and may include fatigue, irritability, diarrhoea and vomiting. Influenza infection is usually self-limiting and lasts for 3 to 4 days, with some symptoms persisting for 1 to 2 weeks. The severity of the illness can vary from asymptomatic infection to life-threatening complications. The most common complications are secondary bacterial infections such as otitis media, pneumonia and bronchitis. In the UK, the average number of deaths attributed directly to influenza is approximately 600 in non-epidemic years and between 12,000 and 13,800 deaths in epidemic years.

Influenza occurs in a seasonal pattern with epidemics in the winter months, typically between December and March. The illness is highly contagious and is spread from person to person by droplets of respiratory secretions produced by sneezing and coughing. Influenza activity is monitored through surveillance schemes, which record the number of new GP consultations for influenza-like illness per week per 100,000 population. In 1997, normal seasonal activity in England was defined as 30 to 200 consultations, with greater than 200 defined as an epidemic. In Wales, the corresponding figures are 25 to 100, and greater than 400. In addition, there are virological monitoring schemes based on the isolation of the virus from clinical specimens. 'Normal seasonal activity', as measured by these surveillance schemes, corresponds to the term 'circulating' in NICE's technology appraisal guidance on flu treatment – zanamivir, amantadine and oseltamivir. Accurate monitoring of influenza activity requires analysis of clinical, virological and epidemiological information.

The management of influenza is supportive and consists of relieving symptoms while awaiting recovery. Complications require specific management, and antibiotics are used for secondary bacterial infections. Vaccination has been established as the first-line intervention to prevent influenza and its complications. In the UK, the Department of Health currently recommends that people who are at risk of influenza infection or complications are vaccinated at the beginning of each winter. These include people with chronic respiratory, heart, renal, liver or neurological disease, people with diabetes, people who are immunosuppressed, people aged 65 and older, people who work or live in residential care facilities, carers of 'at-risk' people, healthcare and other essential workers and poultry workers.

Antiviral drugs are also used for the prevention of influenza. They may be given to people who have been in contact with a person with influenza-like illness (post-exposure prophylaxis) and may be given in the absence of known contact when it is known that influenza is circulating in the community (seasonal prophylaxis). When antiviral drugs are given for seasonal prophylaxis, they are used for longer periods to cover the duration of the influenza season. Seasonal prophylaxis may be considered in exceptional situations such as an antigenic mismatch between circulating strains of the influenza virus and that used for vaccination, which would mean that 'at-risk' people are not effectively protected by vaccination. Prophylaxis may also be used to control outbreaks of influenza within a residential community. NICE's technology appraisal guidance on the use of antiviral drugs for the prophylaxis of influenza recommends oseltamivir and zanamivir for post-exposure prophylaxis only.