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Knowledge: Seasonal, avian and pandemic influenza

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Karen Shaw explains the main differences between seasonal, avian and pandemic influenza viruses and the mode of transmission.

Author Karen Shaw, BHSc, Infection Control Certificate (ICC), MPH, is nurse epidemiologist, the Health Protection Agency, London.
Shaw, K. (2007) Seasonal, avian and pandemic influenza. Nursing Times; 103: 38, 38–40.

Influenza is a respiratory illness caused by infection with an influenza A, B or C virus. It is a cause of significant morbidity and mortality worldwide and outbreaks and epidemics often occur. Immuno-suppressed, young children (<2 years)="" and="" older="" people="" (="">60 years) are most vulnerable. The current outbreaks in humans of highly pathogenic avian influenza (H5N1) have caused concern that another influenza pandemic may be imminent.

Influenza viruses

There are three types of influenza virus: A, B and C. Influenza A is responsible for major outbreaks, epidemics and pandemics. It is the only type found in both humans and animals. Outbreaks may also be caused by type B. Influenza C has not been associated with outbreaks and tends to cause only mild infection (Kitler et al, 2002).

Influenza A viruses have a number of subtypes that are categorised according to their surface antigens (or surface proteins), haemaglutinin (H) and neuraminidase (N). There are 16 H (1–16) and 9 N (1–9) antigens and combinations of these form different influenza A subtypes.
Influenza is made up of a globular particle that is surrounded by a lipid bilayer. This bilayer is studded with the two proteins, H and N, on the surface of the virus. The name of the virus depends on the type of each protein present, for example H1N1 up to H16N9, or combinations of these. This leads to some 144 different subtypes (Department of Health and Human Services, 2007). Of all the subtypes, some infect humans and mammals. Subtypes are, however, commonly species specific.

Antigenic drift and antigenic shift

Influenza A viruses have the ability to undergo changes to the surface antigens or proteins. These can be minor changes that occur all the time or major changes occurring rarely. The minor regular changes are known as ‘antigenic drift’ and the major changes ‘antigenic shift’ (DH, 2005).

Antigenic drift occurs continuously. Small gradual and unpredictable changes, known as mutations, occur in the two genes that contain the genetic material to produce the main surface proteins H and N. Thus, antigenic drift leads to minor changes to the surface proteins. When a person is infected with influenza, the body develops antibodies against that particular strain. As new strains appear in the community as a result of frequent antigenic changes, the antibodies that the body developed previously are no longer able to recognise the new virus and so infection with the new strain may occur (Centers for Disease Control and Prevention, 2006).

Antigenic shift happens very rarely and refers to an unexpected, sudden change to produce a new influenza A virus subtype that has not previously been circulating in the human population. This may result from direct animal-to-human transmission or as a result of human influenza A viruses mixing with animal influenza A viruses, leading to a process of genetic reassortment and, as a result, a new human influenza A subtype. This reassortment may occur in a human host or in an intermediate host, such as a pig. If this occurs and the virus produced has the capacity to cause serious illness in humans and spread easily from human to human in a sustained manner, a global influenza pandemic may occur (DHHS, 2007).

Members of a population would have little or no immunity to this new subtype as they would not have been infected with it previously or vaccinated against it. This lack of immunity allows the virus to spread further than seasonal influenza and lead to a pandemic (DH, 2005). The emergence of a new influenza virus is the first step towards a pandemic.

Human seasonal influenza

In the UK, during a winter where the incidence of flu is low, 3,000–4,000 deaths may be attributed to seasonal influenza. This figure can increase dramatically during an epidemic – in the 1993 epidemic there were approximately 13,000 deaths attributable to seasonal influenza. In the 1989–1990 epidemic this figure was around 29,000 (DH, 2007a).

These epidemics occur because the influenza virus changes constantly through antigenic drift, giving rise to an altered virus strain to which the population is not immune. Each year one or two subtypes of influenza A may be in circulation as well as one type of influenza B (Health Protection Agency, 2005).

Seasonal influenza is generally seen in humans during the winter months. Symptoms can range from mild to quite debilitating, although most people recover well. Vaccines are developed annually based on information provided through laboratory surveillance of circulating influenza viruses in the UK and across the world (DH, 2007b). The surveillance network of the HPA monitors influenza activity in the UK as well as uptake of influenza vaccinations in England (HPA, 2007).

Avian influenza

Avian influenza (or ‘bird flu’) is a contagious viral infection that can affect all species of birds and, less commonly, mammals. The natural reservoir for avian influenza (AI) viruses are wild waterfowl that carry the virus in their intestines (DHHS, 2007).

Generally wild birds may harbour influenza viruses without becoming ill due to natural resistance. However, when introduced to domestic poultry such as turkeys and chickens, the infection can lead to large numbers of poultry becoming ill and dying (CDC, 2006). AI viruses are usually species specific and unable to infect humans but sometimes AI strains cross the species barrier and are able to infect humans directly (Wright and Webster, 2001).

AI viruses are type A influenza viruses and can be further classified as low pathogenic AI (LPAI) or highly pathogenic AI (HPAI) according to their genetic make-up and the severity of illness they cause in poultry (CDC, 2005). Most AI viruses are LPAI and often associated with infection in poultry. HPAI viruses can cause very severe disease characterised by sudden onset of severe illness and rapid death; mortality in poultry can reach 100% (WHO, 2007a; CDC, 2006).

The discovery of swan with AI (H5N1) in Scotland was confirmed in April 2006 and, more recently, a cluster of illness caused by AI (H7N2) was confirmed in a small flock of poultry in Wales. Nine people were tested and four confirmed to be positive for AI (H7N2). Three had direct contact with poultry but the exact route of transmission of the fourth is unknown (HPA, 2007). Human infection with AI virus is, however, very rare and has usually been associated with direct contact with infected sick or dead poultry (WHO, 2007a).

The current outbreak of HPAI A (H5N1) virus in birds and in humans has concerned public health officials worldwide due to the possibility that the virus might eventually become capable of efficient human-to-human transmission, thereby increasing the threat of the next influenza pandemic. The current outbreaks began in Southeast Asia in 2003 and human cases infected with the AI (H5N1) virus continue to be reported. Up to 29 June 2007, globally there were 317 cases of AI (H5N1) in humans with 191 deaths reported from 12 countries (WHO, 2007b). AI is now considered endemic in some parts of Southeast Asia, such as Indonesia, Vietnam, Cambodia, China, Thailand, and possibly other areas (WHO, 2007a).

Where information is available the majority of those infected are known to have been in close contact with dead or live domestic poultry. There is, however, some evidence of limited human-to-human transmission (WHO, 2007a).

Pandemic influenza

Three major influenza A pandemics occurred during the last century. The 1918–1919 (‘Spanish flu’) pandemic was caused by the emergence of a new influenza virus subtype, influenza A (H1N1). This is estimated to have resulted in more than 40–50 million deaths worldwide (WHO, 2007c). Two subsequent pandemics occurred in 1957 (‘Asian flu’ – H2N2) and in 1968 (‘Hong Kong flu’ – H3N2), which resulted in an estimated 1–4 million deaths each (Lazzari and Stohr, 2004).

There is increasing concern that the spread of the current strain of HPAI A (H5N1) may lead to the next influenza pandemic, although how severe it will be cannot be determined with any certainty. Some have estimated that a future pandemic could result in anywhere between 2 million and 50 million deaths globally, and the UK pandemic plans assume that about a quarter of the population could be potentially affected, with 50,000 deaths (DH, 2005).

Conclusion

With the information available, public health experts throughout the world are preparing for the next pandemic. It is important that healthcare workers understand and remain up to date with current knowledge and prevention strategies.

References

Centers for Disease Control and Prevention (2006) Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices; 55 (RR10): 1–42 www.cdc.gov/mmwr/preview/mmwrhtml/rr5510a1.htm

Centers for Disease Control and Prevention (2005) Influenza Viruses. www.cdc.gov/flu/avian/gen-info/flu-viruses.htm

Department of Health (2007a) Bird Flu and Pandemic Influenza: What are the Risks? London: DH.
Department of Health (2007b) Summary of Flu Immunisation Policy. www.dh.gov.uk/en/Policyandguidance/Healthandsocialcaretopics/Flu/Flugeneralinformation/DH_4001688
Department of Health (2005) Explaining Pandemic Flu. A Guide From the Chief Medical Officer. London: DH.
Department of Health and Human Services (2007) An Early Detection System for Highly Pathogenic H5N1 Avian Influenza in Wild Migratory Birds. www.pandemicflu.gov/issues/screening.html
Health Protection Agency (2007) Avian Influenza H7N2 Questions & Answers. www.hpa.org.uk/infections/topics_az/influenza/avian/avianfluH7N2_QA
Health Protection Agency (2005) Seasonal Influenza: Frequently Asked Questions. www.hpa.org.uk/infections/topics_az/influenza/seasonal/flufaq.htm#vacc
Kitler, M.E. et al (2002) Influenza and the work of the World Health Organization. Vaccine; 20: S5–S14.
Lazzari, S., Stohr, K. (2004) Avian influenza and pandemics. Bulletin of the World Health Organization; 82: 4.
World Health Organization (2007a) Avian influenza, including Influenza A (H5N1) in Humans: WHO Interim Infection Control Guideline for Healthcare Facilities. http://www.who.int/csr/disease/avian_influenza/guidelines/infectioncontrol1/en/index.html
World Health Organization (2007b) Cumulative Number of Confirmed Human Cases of Avian influenza A (H5N1). Geneva: WHO. World Health Organization
(2007c) Pandemic Preparedness. Geneva: WHO.
Wright, P.F., Webster, R.G. (2001) Orthomyxoviruses. In: Knipe, D.M. et al (eds). Fields Virology (4th ed). Philadelphia, PA: Lippincott Williams & Wilkins.

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