This site is intended for health professionals only

The flu: current treatments and future strategies

Daphne Miller
RGN BSc RCN NPDip PgCUT
Nurse Practitioner
Belfast
Lecturer in Nursing
University of Ulster
Jordanstown

Influenza was first described by Hippocrates in 412 BC and is one of the oldest and most common diseases known to us.(1) It remains an important cause of morbidity and mortality. In the UK, 3,000-4,000 deaths are attributed to influenza, the "flu", each year, and this figure increases tenfold during epidemics.(2)
Influenza viruses that affect humans are divided into two types, A and B, plus subtypes of A. Influenza A usually causes more severe illness than influenza B, and can result in pneumonia, hospitalisation or death, the elderly and chronically ill being particularly susceptible.
The viruses are antigenically unstable and mutate constantly. Each year one or two subtypes of influenza A may be in circulation and one type of influenza B.(3) Hence vaccines are determined yearly, prominent strains are detected and this information is used to predict future strains for inclusion into future vaccines.
Epidemics in the UK do not occur on a cyclical basis and therefore are largely unpredictable. The level of infection within a population depends on how much the virus mutates in a given year and the consequent levels of immunity within the population. The bigger the change, the greater the likelihood of a larger outbreak.(3)
The UK is one of the few countries in the world to have a pandemic plan with which to react should a pandemic occur in any given year.

The disease
Influenza is a highly contagious, acute viral infection that affects the nose, throat and lungs. It cannot be distinguished from other acute respiratory illnesses on clinical grounds alone; laboratory tests are necessary.(3) Studies aimed at attempting to improve the predictive value of symptomatology have served only to raise the diagnostic success rate to one in three.(4)

Symptoms
Influenza has a sudden onset, with symptoms including headache, chills and cough, usually followed by fever, appetite loss, muscle ache and tiredness.(5) Alternatively, cold symptoms are confined to the upper respiratory tract and associated with runny nose, sneezing, throat irritation and watery eyes. Gastrointestinal symptoms such as nausea, vomiting or diarrhoea can sometimes accompany influenza, particularly in children; however, the term "stomach flu" often incorrectly describes gastrointestinal illness due to other causes. The period of infectiousness from the onset of symptoms is usually 3-5 days in adults and up to seven days in young children.

Management
Management of influenza is based largely on relief of symptoms (Tables 1 and 2).

[[NIP02_table1_87]]

[[NIP02_table2_88]]

Vaccine recommendations
Much of the illness and death caused by influenza can be prevented by annual influenza vaccination.(6)
In the UK, advice on who should be offered the vaccine is given each year by the Chief Medical Officer (CMO), who is advised by an expert statutory group, the Joint Committee on Vaccination and Immunisation.(3) In preparation for the winter months, patients should be encouraged to have the vaccination administered between September and November, and should not wait until a flu epidemic occurs.(3,7) The CMO advises flu vaccination for those listed in Table 3.

[[NIP02_table3_88]]

The vaccine
The vaccine normally contains three different flu viruses. The Public Health Laboratory Service (PHLS) Respiratory Virus Laboratory analyses the antigenic and genetic properties of viruses from throughout the UK. The World Health Organization (WHO) monitors the worldwide influenza situation and, based on information from the PHLS and other countries, advises on the components of the vaccination, depending on the strains expected to develop in the coming season. The viruses are cultured in eggs, then killed and purified before being manufactured into the vaccine.(3)

Administration route
Intramuscular injection is recommended. Adults and older children should be vaccinated in the deltoid muscle: a needle length of 1 inch or longer can be considered for this group. Infants and young children should be vaccinated in the anterolateral aspect of the thigh.

Contraindications
As vaccines are cultured in eggs, it follows that individuals who have a serious allergy to hens' eggs should not be vaccinated. There is no evidence to suggest that the flu vaccine damages the fetus; however, it should be avoided in pregnancy unless specifically indicated.

Side-effects
Flu vaccines may cause some local discomfort to the vaccination site and, more rarely, a slight temperature and muscle ache for a few days. Side-effects such as Guillain-Barré syndrome (GBS), a severe paralytic illness, and life-threatening allergic reactions are extremely rare.(6) The flu vaccine cannot cause the flu because it does not contain live viruses.
 
Vaccine efficacy
Research has shown that the flu vaccine is most beneficial for those "at-risk" individuals, particularly those with existing chronic conditions. Antibodies are produced about 7-10 days postvaccination, which helps protect against any similar virus infection.
According to the PHLS, flu vaccinations are 70-80% effective in years where there is a good match between vaccine and viral strains circulating, and prediction of strains in the UK is becoming increasingly more accurate.(3) The good news is that vaccinated persons do not get the strains of flu from which the vaccine was made, and if you do catch flu it is likely to be milder than if no vaccination had occurred.

Simultaneous administration of other vaccines
Target groups for influenza and pneumococcal vaccination overlap considerably. These can be administered concurrently at different sites without increasing side- effects. Remember, the influenza vaccine is administered annually whereas the pneumococcal vaccination lasts for ten years.
Children at high risk for influenza-related complications may receive the influenza vaccination at the same time as other routine vaccinations.(6)
 
Antiviral agents

Zanamivir
Zanamivir is a neuraminidase inhibitor that attacks the flu virus and prevents it spreading within the body, and is effective for both influenza viruses A and B.
The National Institute for Clinical Excellence (NICE) recommended in 2000 that the antiflu drug zanamivir be made available to selected groups of patients with influenza.(3) These groups comprise those at high risk of developing more serious complications from influenza infection, including the elderly or those with underlying conditions such as asthma or heart disease.
It is recommended for those in these risk groups who present within 36 hours of the onset of symptoms and can start treatment within 48 hours of the onset of symptoms.(3)
To ensure appropriate use of zanamivir, NICE has recommended that it should be made available only when the influenza virus is circulating. There is also evidence to suggest that zanamivir is effective in prevention of influenza; however, it cannot as yet be prescribed for prophylaxis.

Amantadine
Amantadine is an older antiviral drug that works by impairing the function of the ion channel protein M2. Since M2 protein is found only in influenza A, it is ineffective against influenza B.(8) Research has shown amantadine to be as effective as zanamivir in the treatment and prevention of influenza A.(9,10) Amantadine is more cost-effective than zanamivir but is only licensed in the UK for prophylaxis in an outbreak. It is recommended for unimmunised patients in the high-risk groups and for those for whom vaccination is contraindicated.(11)

Neuraminidase inhibitors
Information from analysis of the structure and chemical composition of the catalytic site of neuraminidase has led to the development of new inhibitors such as zanamivir and oseltamivir. Further analysis of the neuraminidase molecule should give rise to additional compounds active against influenza viruses.

Influenza - the future
 
Surveillance
Enhanced surveillance of influenza is taking place across the UK. A selection of GPs throughout the four countries take nasal and throat swabs from 4-5 patients presenting with clinical influenza per week. This involves linked laboratory and community data gathered weekly. The aim is to gather information on:

  • Epidemiology.
  • Viruses.
  • The age and sex distribution of patients presenting with flu-like illness.

Diagnosis
Clinical studies are underway to assess tests for influenza. Improved diagnostic tests would also be useful in surveillance of circulating strains of influenza.

Pandemic influenza
Greater communication and coordination between the WHO and national centres has afforded an increase in the response rate to any emerging pandemic.

[[NIP02_pp_90]]

References

  1. WHO. World Health Organisation Factsheet. Geneva: WHO; 1999. (www.who.int/inf-fs/en/fact.html)
  2. Gupta A. Influenza: Improving uptake of vaccination in older people. Geriatr Med 1999;September:11-13.
  3. PHLS. Public Health Laboratory Service; 2001. (www.phls.co.uk/facst/influenza/flu.html)
  4. Govaert TM, Dinant GJ, Aretz K, et al. The predictive value of influenza symptomatology in elderly people. Fam Pract 1998;15(1):16-22.
  5. Population and Public Health Branch. Canada: PPHB; 2000. (www.hc-sc.gc.ca/hpb/lcdc/publicat/info.html)
  6. Centers for Disease Control and Prevention. CDC; 2001. (www.cdc.gov/ncidod/diseases/flu/fluvac.html)
  7. Health! Canada. Does the flu shot work? Canada: 2000. (www.hc-sc.gc.ca/english/magazine/2000-11/flu.html)
  8. Mooney J. A role for amantadine in the treatment and prevention of influenza. SCIEH Wkly Rep 2001;35(1):2-4.
  9. Oxford J. New strategies for the therapy of influenza A with amantadine: a review of the antiviral, past, present and future. Obtained from Alliance Pharmaceuticals, licensed to manufacture and distribute Lysovir (amantadine) in the UK. October 1999.
  10. Nicholson KG. Use of antivirals in influenza in the elderly: prophylaxis and therapy. Gerontology 1995;48:280-9.
  11. British Medical Association. British national formulary. London: British Medical Association; 2000.

Resources
Public Health Laboratory Service (PHLS)
England
W:www.phls.co.uk.html

Wales W:www.phls.wales.nhs.uk.html
World Health Organization Influenza Programme
W:www.who.int/inffs/en.html

National Foundation for Infectious Diseases
W:www.nfid.org/inflfacts.html

Influenza Protocol
W:www.shef.ac.uk/uni/projects/wrp/fluprot.html