Avian influenza is an infectious disease of birds caused by type A strains of the influenza virus. The disease, which was first identified in Italy more than 100 years ago, occurs worldwide.

All birds are thought to be susceptible to infection with avian influenza, though some species are more resistant to infection than others. Infection causes a wide spectrum of symptoms in birds, ranging from mild illness to a highly contagious and rapidly fatal disease resulting in severe epidemics. The latter is known as “highly pathogenic avian influenza”. This form is characterized by sudden onset, severe illness, and rapid death, with a mortality that can approach 100%.

Fifteen subtypes of influenza virus are known to infect birds, thus providing an extensive reservoir of influenza viruses potentially circulating in bird population. To date, all outbreaks of the highly pathogenic form have been caused by influenza A viruses of subtypes H5 and H7.

Migratory waterfowl – most notably wild ducks – are the natural reservoir of avian influenza viruses, and these birds are also the most resistant to infection. Domestic poultry, including chickens and turkeys, are particularly susceptible to epidemics of rapidly fatal influenza.

Direct or indirect contact of domestic flocks with wild migratory waterfowl has been implicated as a frequent cause of epidemics. Live bird markets have also played an important role in the spread of epidemics.

Recent research has shown that viruses of low pathogenicity can, after circulation for some short periods in a poultry population, mutate into highly pathogenic viruses.

During a 1983–1984 epidemic in the United States of America, the H5N2 virus initially caused low mortality, but within six months became highly pathogenic, with a mortality approaching 90%. Control of the outbreak required destruction of more than 17 million birds at a cost of nearly US$ 65 million. During a 1999–2001 epidemic in Italy, the H7N1 virus, initially of low pathogenicity, mutated within 9 months to a highly pathogenic form. More than 13 million birds died or were destroyed.

The quarantining of infected farms and destruction of infected or potentially exposed flocks are standard control measures aimed at preventing spread to other farms and eventual establishment of the virus in a country’s poultry population. Apart from being highly contagious, avian influenza viruses are readily transmitted from farm to farm by mechanical means, such as by contaminated equipment, vehicles, feed, cages, or clothing. Highly pathogenic viruses can survive for long periods in the environment, especially when temperatures are low. Stringent sanitary measures on farms can, however, confer some degree of protection.

In the absence of prompt control measures backed by good surveillance, epidemics can last for years. For example, an epidemic of H5N2 avian influenza, which began in Mexico in 1992, started with low pathogenicity, evolved to the highly fatal form, and was not controlled until 1995.

A constantly mutating virus: two consequences

All type A influenza viruses, including those that regularly cause seasonal epidemics of influenza in humans, are genetically labile and well adapted to elude host defences.

Influenza viruses lack mechanisms for the “proofreading” and repair of errors that occur during replication. As a result of these uncorrected errors, the genetic composition of the viruses changes as they replicate in humans and animals, and the existing strain is replaced with a new antigenic variant. These constant, permanent and usually small changes in the antigenic composition of influenza A viruses are known as antigenic “drift”.

The tendency of influenza viruses to undergo frequent and permanent antigenic changes necessitates constant monitoring of the global influenza situation and annual adjustments in the composition of influenza vaccines. Both activities have been a cornerstone of the WHO Global Influenza Programme since its inception in 1947.

Influenza viruses have a second characteristic of great public health concern: influenza A viruses, including subtypes from different species, can swap or “reassort” genetic materials and merge. This reassortment process, known as antigenic “shift”, results in a novel subtype different from both parent viruses.

As population will have no immunity to the new subtype, and as no existing vaccines can confer protection, antigenic shift has historically resulted in highly lethal pandemics. For this to happen, the novel subtype needs to have genes from human influenza viruses that make it readily transmissible from person to person for a sustainable period.

Conditions favourable for the emergence of antigenic shift have long been thought to involve humans living in close proximity to domestic poultry and pigs. Because pigs are susceptible to infection with both avian and mammalian viruses, including human strains, they can serve as a “mixing vessel” for the scrambling of genetic material from human and avian viruses, resulting in the emergence of a novel subtype.

Recent events, however, have identified a second possible mechanism. Evidence is mounting that, for at least some of the 15 avian influenza virus subtypes circulating in bird population, humans themselves can serve as the “mixing vessel”.

Human infection with avian influenza viruses: a timeline

Avian influenza viruses do not normally infect species other than birds and pigs. The first documented infection of humans with an avian influenza virus occurred in Hong Kong in 1997, when the H5N1 strain caused severe respiratory disease in 18 humans, of whom 6 died.

The infection of humans coincided with an epidemic of highly pathogenic avian influenza, caused by the same strain, in Hong Kong’s poultry population. Extensive investigation of that outbreak determined that close contact with live infected poultry was the source of human infection. Studies at the genetic level further determined that the virus had jumped directly from birds to humans. Limited transmission to health care workers occurred, but did not cause severe disease.

Rapid destruction – within three days – of Hong Kong’s entire poultry population, estimated at around 1.5 million birds, reduced opportunities for further direct transmission to humans, and may have averted a pandemic.

That event alarmed public health authorities, as it marked the first time that an avian influenza virus was transmitted directly to humans and caused severe illness with high mortality.

Alarm mounted again in February 2003, when an outbreak of H5N1 avian influenza in Hong Kong caused 2 cases and 1 death in members of a family who had recently travelled to southern China. Another child in the family died during that visit, but the cause of death is not known.

Two other avian influenza viruses have recently caused illness in humans. An outbreak of highly pathogenic H7N7 avian influenza, which began in the Netherlands in February 2003, caused the death of one veterinarian two months later, and mild illness in 83 other humans.

Mild cases of avian influenza H9N2 in children occurred in Hong Kong in 1999 (two cases) and in mid-December 2003 (one case). H9N2 is not highly pathogenic in birds.