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Avian influenza and the significance of its transmission to humans--information from WHO.

The Disease in Birds: Impact and Control Measures

Avian influenza is caused by Type A strains of the influenza virus. First identified in Italy more than 100 years ago, the disease occurs worldwide. All birds are thought to be susceptible, although some species are more resistant to infection than others. Infection causes a wide spectrum of symptoms, ranging from mild illness to a highly contagious, rapidly fatal disease resulting in severe epidemics. The latter is known as "highly pathogenic avian influenza."

Fifteen subtypes of influenza virus are known to infect birds, thus providing an extensive reservoir of influenza viruses. 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. 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 epidemics.

Recent research has shown that viruses of low pathogenicity can, after circulating in a poultry population for sometimes short periods, mutate into highly pathogenic viruses. During a 1983-1984 epidemic in the United States, the H5N2 virus initially caused low mortality, but within six months became highly pathogenic, with mortality approaching 90 percent. Control of the outbreak required destruction of more than 17 million birds at a cost of nearly $65 million.

In the absence of prompt control measures backed by good surveillance, epidemics can last for years. An epidemic of H5N2 avian influenza that 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: Drift and Shift

All Influenza A viruses, including those that cause seasonal epidemics of influenza in humans, are genetically labile and well adapted to elude host defenses. Influenza viruses lack mechanisms for the "proofreading" and repair of errors that occur during replication. As a result, 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 World Health Organization (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 populations have no immunity to the new subtype, and as no existing vaccines can confer protection, antigenic shift has historically resulted in highly lethal pandemics.

Conditions favorable 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.

Recent events have identified a second possible mechanism. Evidence is mounting that, for at least some of the 15 avian influenza virus subtypes circulating in bird populations, 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, six of whom 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.

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.

Alarm mounted again in February 2003, when an outbreak of H5N1 avian influenza in Hong Kong caused two cases and one death in members of a family who had recently traveled to southern China.

The most recent cause for alarm occurred in January 2004, when laboratory tests confirmed the presence of H5N1 avian influenza virus in human cases of severe respiratory disease in the northern part of Vietnam.

Why H5N1 Is of Particular Concern

H5N1 mutates rapidly and has a documented propensity to acquire genes from viruses infecting other animal species. Its ability to cause severe disease in humans has now been documented on two occasions. Also, birds that survive infection excrete the virus for at least 10 days, orally and in feces, thus facilitating further spread at live-poultry markets and by migration.

The epidemic of highly pathogenic avian influenza caused by H5N1, which began in mid-December 2003 in the Republic of Korea and is now occurring in other Asian countries, is therefore of particular public health concern. The spread of infection in birds increases the opportunities for direct infection of humans. If more humans become infected over time, the likelihood also increases that humans could serve as the "mixing vessel" for the emergence of a novel subtype with sufficient human genes to be easily transmitted from person to person. Such an event would mark the start of an influenza pandemic.

Clinical Course and Treatment of Human Cases of H5N1 Avian Influenza in Humans

In the 1997 Hong Kong outbreak, patients developed symptoms of fever, sore throat, cough, and, in several of the fatal cases, severe respiratory distress secondary to viral pneumonia.

Tests for diagnosing all influenza strains of animals and humans are rapid and reliable. Rapid bedside tests for the diagnosis of human influenza are also available, but do not have the precision of the more extensive laboratory testing that is currently needed to fully understand the most recent cases and determine whether human infection is spreading, either directly from birds or from person to person.

Antiviral drugs, some of which can be used for both treatment and prevention, are effective against Influenza A strains in otherwise healthy adults and children, but have some limitations. Some of these drugs are also expensive, and supplies are limited.

Experience in the production of influenza vaccines is also considerable, particularly because vaccine composition changes each year to match the antigenic drift in circulating virus. At least four months would be needed, however, to produce significant quantities of a new vaccine capable of conferring protection against a new virus subtype.

Influenza Pandemics: Can They Be Averted?

Based on historical patterns, influenza pandemics can be expected to occur, on average, three to four times each century. The occurrence of pandemics is, however, unpredictable. In the 20th century, the great pandemic of 1918-1919, which caused an estimated 40 to 50 million deaths worldwide, was followed by pandemics in 1957-1958 and 1968-1969. Experts agree that another influenza pandemic is inevitable and possibly imminent.

Several measures can help minimize the global public health risks that could arise from large outbreaks of highly pathogenic H5N1 avian influenza in birds. An immediate priority is to halt further spread of epidemics in poultry populations. Vaccination of people at high risk of exposure to infected poultry, using existing vaccines effective against currently circulating human influenza strains, can reduce the likelihood of co-infection of humans with avian and influenza strains, and thus reduce the risk that genes will be exchanged. Workers involved in the culling of poultry flocks must be protected against infection by proper clothing and equipment. These workers should also receive antiviral drugs as a prophylactic measure.

When cases of avian influenza in humans occur, information on the extent of influenza infection in animals as well as humans and on circulating influenza viruses is urgently needed. Thorough investigation of each case is essential. While WHO and the members of its global influenza network, together with other international agencies, can assist with many of these activities, the successful containment of public health risks also depends on the epidemiological and laboratory capacity of affected countries and the adequacy of surveillance systems in place.

For more information on avian influenza, visit WHO's Web site at
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Title Annotation:Technical Briefs
Publication:Journal of Environmental Health
Date:Oct 1, 2005
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