Avian Flu

Synonyms: bird influenza, bird flu

Avian flu is an infection caused by avian subtypes of influenza A viruses. Avian flu circulates in wild birds, particularly waterfowl such as ducks and geese, often without ill effects. However, in many other species it may cause disease with a high mortality. Transmission to farm birds, particularly poultry, has caused major outbreaks requiring slaughter of poultry on several occasions around the world in recent years - notably, Pennsylvania in 1982 (H5N2), Mexico in 1993 (H5N2), Hong Kong in 1997 (H5N1) and the Netherlands in 2003 (H7N7).

Avian influenza subtypes are usually discrete from those that cause infection in humans and only infrequently have avian influenza viruses transmitted to humans. In the Hong Kong outbreak of 1997 there were 18 confirmed human cases and 6 deaths. However, since 1997 there have been several documented outbreaks of human illness caused by 'avian' viruses.

Influenza A subtypes are determined by the combination of haemagglutinin (H) and neuraminidase (N) proteins expressed in the viral envelope. The 'human' influenza strains are H1N1, H1N2, and H3N2. However, it is thought that some of the genetic makeup of these strains was derived, at some point in the past, from avian subtypes. The possibility of a human influenza A pandemic, caused by a new recombinant human-avian subtype of influenza A, is arousing much interest in these bird flu outbreaks.

The World Health Organization (WHO) considers the avian influenza A/H5N1 virus "a public health risk with pandemic potential". If the next human influenza pandemic were caused by the avian influenza A/H5N1 virus, the estimated fatalities may be more than a hundred million.¹

There are several subtypes of avian influenza viruses that have caused infection in both birds and humans. Viruses which infect other animals such as pigs have, very occasionally, been transmitted to humans. The current subtype which seems to show the most potential for cross-infectivity between birds and humans is H5N1.
There are other subtypes such as H7N3, H7N2 and H9N2 that have caused human illness, but the size of these outbreaks and the severity of the illness has not been as significant as for H5N1. Recent research has shown that intestinal and respiratory tract cells of chickens have receptors for both human and avian subtypes of influenza A, and that cultured chicken lung cells support the replication of both human and avian influenza A subtypes.² This supports the hypothesis that there is a potential for a new pandemic subtype of influenza A virus formed through genetic recombination in infected human or avian cells.

Outbreaks of pandemic influenza affecting many millions of people with associated high mortality have occurred in 1918 ('Spanish'), 1957 (Asian), 1968 (Hong Kong) and 1977 (Russian). These pandemics were caused by new subtypes of influenza, probably formed by the combination of genes from both avian and human influenza viruses. There is concern that the emergence of new highly pathogenic avian influenza may develop with the potential that this new subtype can cause both serious disease and spread from person to person.

Outbreaks of human illness caused by infection with avian influenza A subtypes are rare, infrequent events. However, the number and seriousness of infections involving H5N1 subtypes appears to be gradually increasing. So far, they have occurred largely in South Asia, but have also affected the USA, the Netherlands and Canada. Isolated cases or sporadic infections have occurred more frequently and are carefully monitored by The WHO's unit for communicable disease surveillance and response. At present, it would appear that most infections are bird-to-human transmission, but human-to-human transmission of virus has been a possibility which could not be ruled out in all outbreaks. Thus far, outbreaks have been of relatively low infectivity, but there is potential for a highly infective and highly virulent subtype developing.
Older people appear to be more immune to the infection, possibly because of the cross protection induced by their previous infections with human influenza A viruses.³

Risk factors

• Close contact between human and domesticated bird populations where there is risk of transmission of wild avian flu subtypes to the bird population.
• Disturbance of normal ecological barriers between human and animal populations, due to development, destruction of animal habitats, etc.

This varies from minor illnesses such as conjunctivitis to cold-like symptoms such as fever, cough, sore throat and myalgia through to pneumonia with acute respiratory distress.

• Gastrointestinal symptoms such as diarrhoea are seen relatively frequently.
• There is usually a history of handling poultry or contact with flocks of sick poultry before becoming ill.
• Time between exposure and onset of illness is around 2-4 days.

Usually under the direction of experts in infectious disease and communicable disease surveillance.

• The viruses are usually typed by direct culture or by performing reverse-transcriptase polymerase chain reaction analysis.
• Serum antibody analysis is used to confirm exposure to infection amongst suspected cases.
• Lymphopenia, raised aminotransferases and creatinine have been observed in some sufferers of the highly pathogenic cases.
• Severe cases nearly always show widespread CXR abnormalities.

In one outbreak, 8 out of 10 patients died, and had marked abnormalities on chest radiography.⁴
Lymphopenia is often a feature of severe, highly pathogenic cases. H5N1 is the subtype most usually associated with highly pathogenic features.
There is evidence to suggest that the high fatality of this infection may not purely be a result of a cytokine storm triggered by the pulmonary disease.⁵

Current guidance should be followed.⁶ Local advice from local health protection units should be sought if guidance is not helpful or cases are atypical. Detailed and timely advice is given in the event of such outbreaks but some general points can be made:

• When treating affected individuals, management is as for standard 'human' influenza A with anti-viral agents such as amantadine, rimantadine, oseltamavir and zanamivir. Their efficacy against new subtypes is uncertain. It appears that there is some evidence of resistance to amantadine and rimantadine amongst H5N1 subtypes.⁷
• Supportive therapy with oxygen, artificial ventilation and ventilatory support, IV fluids, antibiotics for secondary infection, etc. is as for any other case of influenza.

Apart from being highly contagious among poultry, avian influenza viruses are readily transmitted from farm to farm by the movement of live birds, people (especially when shoes and other clothing are contaminated), and contaminated vehicles, equipment, feed, and cages. Highly pathogenic viruses can survive for long periods in the environment, especially when temperatures are low. For example, the highly pathogenic H5N1 virus can survive in bird faeces for at least 35 days at low temperature (4°C). At a much higher temperature (37°C), H5N1 viruses have been shown to survive, in faecal samples, for six days.⁸

• Culling of any affected or exposed poultry; also proper disposal of carcasses and quarantining and rigorous disinfection of farms. It may be necessary to implement strict sanitary, or biosecurity measures.
• Restrictions on the movement of live poultry, both within and between countries, are another important control measure. This is most straightforward when applied to large commercial farms, where birds are housed indoors, usually under strictly controlled sanitary conditions, in large numbers. Control is far more difficult under poultry production systems in which most birds are raised in small backyard flocks scattered throughout rural or peri-urban areas.
• Outbreaks in backyard flocks are associated with a heightened risk of human exposure and infection. These situations create many opportunities for human exposure to the virus, especially when birds enter households or are brought into households during adverse weather, or when they share areas where children play or sleep. Poverty exacerbates the problem: in situations where a prime source of food and income cannot be wasted, households frequently consume poultry when deaths or signs of illness appear in flocks. This practice carries a high risk of exposure to the virus during slaughtering, defeathering, butchering, and preparation of poultry meat for cooking, but has proved difficult to change. Moreover, as deaths of birds in backyard flocks are common, especially under adverse weather conditions, owners may not interpret deaths or signs of illness in a flock as a signal of avian influenza and a reason to alert the authorities. This tendency may help explain why outbreaks in some rural areas have smouldered undetected for months. The frequent absence of compensation to farmers for destroyed birds further works against the spontaneous reporting of outbreaks and may encourage owners to hide their birds during culling operations.
• When culling fails or proves impractical, vaccination of poultry in a high-risk area can be used as a supplementary emergency measure, provided quality-assured vaccines are used. The use of poor-quality vaccines, or vaccines that poorly match the circulating virus strain, may accelerate mutation of the virus. Poor-quality animal vaccines may also pose a risk for human health, as they may allow infected birds to shed virus while still appearing to be disease-free.
• Administering appropriate prophylactic anti-viral agents (preferably based on sensitivity testing results) to exposed individuals.
• Nursing of affected individuals in an infection-control environment with negative-pressure isolation and trained staff.
• Vigilance and adequate health provision for exposed poultry workers during suspected outbreaks.

Migratory birds

Scientists have recently been considering that at least some migratory waterfowl are now carrying the H5N1 virus in its highly pathogenic form, sometimes over long distances. They may introduce the virus to poultry flocks in areas that lie along their migratory routes. This has yet to be scientifically confirmed.
More than 6,000 migratory birds, infected with the highly pathogenic H5N1 virus died at the Qinghai Lake nature reserve in central China in late April 2005. Before this, wild bird deaths from highly pathogenic avian influenza viruses were rare. Scientific studies comparing viruses from different outbreaks in birds have found that viruses from the most recently affected countries, all of which lie along migratory routes, are almost identical to viruses recovered from dead migratory birds at Qinghai Lake. Viruses from Turkey's first two human cases were also (virtually) identical to viruses from Qinghai Lake.

• Good veterinary and animal-husbandry practice is mandatory.
• Import/export of bird species should be controlled to prevent worldwide spread of new viruses.
• On April 17 2007, the USA's Food and Drug Administration (FDA) approved the first vaccine to prevent human infection with one strain of the avian influenza (bird flu) H5N1 virus.⁹
• Healthcare systems worldwide need to be vigilant when dealing with illness in persons in contact with poultry/poultry workers.
• Anti-viral agents (particularly neuraminidase inhibitors) should be used as treatment/prophylaxis, as directed by developing clinical evidence, during outbreaks.

There is theoretical evidence that these measures could be used to bring a potential pandemic under control and prevent worldwide spread.^10,11

1. Thomas JK, Noppenberger J; Avian influenza: a review. Am J Health Syst Pharm. 2007 Jan 15;64(2):149-65. [abstract]
2. Kim JA, Ryu SY, Seo SH; Cells in the respiratory and intestinal tracts of chickens have different proportions of both human and avian influenza virus receptors. J Microbiol. 2005 Aug;43(4):366-9. [abstract]
3. Chen JM, Chen JW, Dai JJ, et al; A survey of human cases of H5N1 avian influenza reported by the WHO before June 2006 for infection control. Am J Infect Control. 2007 Jun;35(5):351-3. [abstract]
4. Tran Tinh Hien et al., Avian Influenza A (H5N1) in 10 Patients in Vietnam.;NEJM; March 18th 2004
5. Wong SS, Yuen KY; Avian influenza virus infections in humans. Chest. 2006 Jan;129(1):156-68. [abstract]
6. Avian Influenza Guidance and Algorithms, Health Protection Agency (Revised 2009); Guidance on management of suspected or confirmed avian influenza in humans
7. Centers for Disease Control and Prevention (CDC) US Government agency, Avian Influenza Resources page
8. Avian Flu Factsheet, World Health Organization
9. Centers for Disease Control and Prevention (CDC) US Government agency, Interim Guidance for Protection of Persons Involved in U.S. Avian Influenza Outbreak Disease Control and Eradication Activities February 17, 2004
10. Parry J News: Avian flu pandemic could be brought under control in three weeks.;BMJ; 13th August 2005
11. Oxford J, Lambkin-Williams R, Mann A; The threat of avian influenza H5N1: 'do we have the tools for the job'? Antivir Chem Chemother. 2007;18(2):71-4. [abstract]

• Pandemic influenza - guidance for primary care trusts and primary care professionals on the provision of healthcare in a community setting in England, Department of Health (December 2008)
• Pandemic flu: a national framework for responding to an influenza pandemic, Department of Health (November 2007)
• Department of Health; Pandemic Flu Emergency Plan (2005)
• 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)
• Centers for Disease Control and Prevention (CDC) US Government agency, Avian Influenza Resources page
• Avian Influenza Guidance and Algorithms, Health Protection Agency (Revised 2009); Guidance on management of suspected or confirmed avian influenza in humans
• Avian Influenza - World Health Organization, Information Page
• Working with highly pathogenic avian influenza virus, Health and Safety Executive (updated 15/12/09)