Avian

Avian

Avian Influenza Virus Between Animals and Humans (People)

Influenza A viruses have infected many different animals, including ducks, chickens, pigs, whales, horses, and seals. However, certain subtypes of influenza A virus are specific to certain species, except for birds, which are hosts to all known subtypes of influenza A. Subtypes that have caused widespread illness in people either in the past or currently are H3N2, H2N2, H1N1, and H1N2. H1N1 and H3N2 subtypes also have caused outbreaks in pigs, and H7N7 and H3N8 viruses have caused outbreaks in horses.

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Influenza A viruses normally seen in one species sometimes can cross over and cause illness in another species. For example, until 1998, only H1N1 viruses circulated widely in the U.S. pig population. However, in 1998, H3N2 viruses from humans were introduced into the pig population and caused widespread disease among pigs. Most recently, H3N8 viruses from horses have crossed over and caused outbreaks in dogs.

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Avian influenza A viruses may be transmitted from animals to humans in two main ways:
- Directly from birds or from avian virus-contaminated environments to people.
- Through an intermediate host, such as a pig.

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Influenza A viruses have eight separate gene segments. The segmented genome allows influenza A viruses from different species to mix and create a new influenza A virus if viruses from two different species infect the same person or animal. For example, if a pig were infected with a human influenza A virus and an avian influenza A virus at the same time, the new replicating viruses could mix existing genetic information (reassortment) and produce a new virus that had most of the genes from the human virus, but a hemagglutinin and/or neuraminidase from the avian virus. The resulting new virus might then be able to infect humans and spread from person to person, but it would have surface proteins (hemagglutinin and/or neuraminidase) not previously seen in influenza viruses that infect humans.

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This type of major change in the influenza A viruses is known as antigenic shift. Antigenic shift results when a new influenza A subtype to which most people have little or no immune protection infects humans. If this new virus causes illness in people and can be transmitted easily from person to person, an influenza pandemic can occur.

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It is possible that the process of genetic reassortment could occur in a human who is co-infected with avian influenza A virus and a human strain of influenza A virus. The genetic information in these viruses could reassort to create a new virus with a hemagglutinin from the avian virus and other genes from the human virus. Theoretically, influenza A viruses with a hemagglutinin against which humans have little or no immunity that have reassorted with a human influenza virus are more likely to result in sustained human-to-human transmission and pandemic influenza. Therefore, careful evaluation of influenza viruses recovered from humans who are infected with avian influenza is very important to identify reassortment if it occurs.

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Although it is unusual for people to get influenza virus infections directly from animals, sporadic human infections and outbreaks caused by certain avian influenza A viruses and pig influenza viruses have been reported. These sporadic human infections and outbreaks, however, rarely result in sustained transmission among humans.

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Spread Of Avian Influenza Virus

Avian influenza viruses circulate among birds worldwide. Certain birds, particularly water birds, act as hosts for influenza viruses by carrying the virus in their intestines and shedding it. Infected birds shed virus in saliva, nasal secretions, and feces. Susceptible birds can become infected with avian influenza virus when they have contact with contaminated nasal, respiratory, or fecal material from infected birds. Fecal-to-oral transmission is the most common mode of spread between birds.

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Most often, the wild birds that are host to the virus do not get sick, but they can spread influenza to other birds. Infection with certain avian influenza A viruses (for example, some H5 and H7 strains) can cause widespread disease and death among some species of domesticated birds. (For more information, see “Low Pathogenic versus Highly Pathogenic Avian Influenza Viruses.”)

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Avian Influenza Outbreaks in Poultry
Domesticated birds may become infected with avian influenza virus through direct contact with infected waterfowl or other infected poultry, or through contact with surfaces (such as dirt or cages) or materials (such as water or feed) that have been contaminated with virus. People, vehicles, and other inanimate objects such as cages can be vectors for the spread of influenza virus from one farm to another. When this happens, avian influenza outbreaks can occur among poultry.

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Avian influenza outbreaks among poultry occur worldwide from time to time. Since 1997, for example, more than 16 outbreaks of H5 and H7 influenza have occurred among poultry in the United States. The U.S. Department of Agriculture monitors these outbreaks. Low pathogenic forms of avian influenza viruses are responsible for most avian influenza outbreaks in poultry. Such outbreaks usually result in either no illness or mild illness (e.g., chickens producing fewer or no eggs), or low levels of mortality.

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When highly pathogenic influenza H5 or H7 viruses cause outbreaks, between 90% and 100% of poultry can die from infection. Animal health officials carefully monitor avian influenza outbreaks in domestic birds for several reasons:

- the potential for low pathogenic H5 and H7 viruses to evolve into highly pathogenic forms
- the potential for rapid spread and significant illness and death among poultry during outbreaks of highly pathogenic avian influenza
- the economic impact and trade restrictions from a highly pathogenic avian influenza outbreak.
- the possibility that avian influenza could be transmitted to humans

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When avian influenza outbreaks occur in poultry, quarantine and depopulation (or culling) and surveillance around affected flocks is the preferred control and eradication option.

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Types Of Avian Influenza Virus

There are three types of influenza viruses: A, B, and C. Only influenza A viruses are further classified by subtype on the basis of the two main surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Influenza A subtypes and B viruses are further classified by strains.

Human Influenza Viruses and Avian Influenza A Viruses
Humans can be infected with influenza types A, B, and C viruses. Subtypes of influenza A that are currently circulating among people worldwide include H1N1, H1N2, and H3N2 viruses.
Wild birds are the natural host for all known subtypes of influenza A viruses. Typically, wild birds do not become sick when they are infected with avian influenza A viruses. However, domestic poultry, such as turkeys and chickens, can become very sick and die from avian influenza, and some avian influenza A viruses also can cause serious disease and death in wild birds.

Low Pathogenic versus Highly Pathogenic Avian Influenza A Viruses
Avian influenza A virus strains are further classified as low pathogenic (LPAI) or highly pathogenic (HPAI) on the basis of specific molecular genetic and pathogenesis criteria that require specific testing. Most avian influenza A viruses are LPAI viruses that are usually associated with mild disease in poultry. In contrast, HPAI viruses can cause severe illness and high mortality in poultry. More recently, some HPAI viruses (e.g., H5N1) have been found to cause no illness in some poultry, such as ducks. LPAI viruses have the potential to evolve into HPAI viruses and this has been documented in some poultry outbreaks.

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Avian influenza A viruses of the subtypes H5 and H7,including H5N1, H7N7, and H7N3 viruses, have been associated with HPAI, and human infection with these viruses have ranged from mild (H7N3, H7N7) to severe and fatal disease (H7N7, H5N1). Human illness due to infection with LPAI viruses has been documented, including very mild symptoms (e.g., conjunctivitis) to influenza-like illness. Examples of LPAI viruses that have infected humans include H7N7, H9N2, and H7N2.In general, direct human infection with avian influenza viruses occurs very infrequently, and has been associated with direct contact (e.g., touching) infected sick or dead infected birds (domestic poultry).

How Influenza Viruses Change: Drift and Shift
Influenza viruses are dynamic and are continuously evolving. Influenza viruses can change in two different ways: antigenic drift and antigenic shift. Influenza viruses are changing by antigenic drift all the time, but antigenic shift happens only occasionally. Influenza type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift.

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Antigenic drift refers to small, gradual changes that occur through point mutations in the two genes that contain the genetic material to produce the main surface proteins, hemagglutinin, and neuraminidase. These point mutations occur unpredictably and result in minor changes to these surface proteins. Antigenic drift produces new virus strains that may not be recognized by antibodies to earlier influenza strains. This process works as follows: a person infected with a particular influenza virus strain develops antibody against that strain. As newer virus strains appear, the antibodies against the older strains might not recognize the "newer" virus, and infection with a new strain can occur.

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This is one of the main reasons why people can become infected with influenza viruses more than one time and why global surveillance is critical in order to monitor the evolution of human influenza virus stains for selection of which strains should be included in the annual production of influenza vaccine. In most years, one or two of the three virus strains in the influenza vaccine are updated to keep up with the changes in the circulating influenza viruses. For this reason, people who want to be immunized against influenza need to be vaccinated every year.

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Antigenic shift refers to an abrupt, major change to produce a novel influenza A virus subtype in humans that was not currently circulating among people (see more information below under Influenza Type A and Its Subtypes). Antigenic shift can occur either through direct animal (poultry)-to-human transmission or through mixing of human influenza A and animal influenza A virus genes to create a new human influenza A subtype virus through a process called genetic reassortment. Antigenic shift results in a new human influenza A subtype. A global influenza pandemic (worldwide spread) may occur if three conditions are met:
A new subtype of influenza A virus is introduced into the human population.
The virus causes serious illness in humans.
The virus can spread easily from person to person in a sustained manner.

Types, Subtypes, and Strains

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Influenza Type A and Its Subtypes
Influenza type A viruses can infect people, birds, pigs, horses, and other animals, but wild birds are the natural hosts for these viruses. Influenza type A viruses are divided into subtypes and named on the basis of two proteins on the surface of the virus: hemagglutinin (HA) and neuraminidase (NA). For example, an “H7N2 virus” designates an influenza A subtype that has an HA 7 protein and an NA 2 protein.

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Similarly an “H5N1” virus has an HA 5 protein and an NA 1 protein. There are 16 known HA subtypes and 9 known NA subtypes. Many different combinations of HA and NA proteins are possible. Only some influenza A subtypes (i.e., H1N1, H1N2, and H3N2) are currently in general circulation among people. Other subtypes are found most commonly in other animal species. For example, H7N7 and H3N8 viruses cause illness in horses, and H3N8 also has recently been shown to cause illness in dogs.

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Only influenza A viruses infect birds, and all known subtypes of influenza A viruses can infect birds. However, there are substantial genetic differences between the influenza A subtypes that typically infect birds and those that infect both people and birds. Three prominent subtypes of the avian influenza A viruses that are known to infect both birds and people are:
- Influenza A H5
Nine potential subtypes of H5 are known. H5 infections, such as HPAI H5N1 viruses currently circulating in Asia and Europe, have been documented among humans and sometimes cause severe illness or death.
- Influenza A H7
Nine potential subtypes of H7 are known. H7 infection in humans is rare but can occur among persons who have direct contact with infected birds. Symptoms may include conjunctivitis and/or upper respiratory symptoms. H7 viruses have been associated with both LPAI (e.g., H7N2, H7N7) and HPAI (e.g., H7N3, H7N7), and have caused mild to severe and fatal illness in humans.
- Influenza A H9
Nine potential subtypes of H9 are known; influenza A H9 has rarely been reported to infect humans. However, this subtype has been documented only in a low pathogenic form.

Influenza Type B
Influenza B viruses are usually found only in humans. Unlike influenza A viruses, these viruses are not classified according to subtype. Influenza B viruses can cause morbidity and mortality among humans, but in general are associated with less severe epidemics than influenza A viruses. Although influenza type B viruses can cause human epidemics, they have not caused pandemics.

Influenza Type C
Influenza type C viruses cause mild illness in humans and do not cause epidemics or pandemics. These viruses are not classified according to subtype.

Strains
Influenza B viruses and subtypes of influenza A virus are further characterized into strains. There are many different strains of influenza B viruses and of influenza A subtypes. New strains of influenza viruses appear and replace older strains. This process occurs through antigenic drift. When a new strain of human influenza virus emerges, antibody protection that may have developed after infection or vaccination with an older strain may not provide protection against the new strain. Therefore, the influenza vaccine is updated on a yearly basis to keep up with the changes in influenza viruses.

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Prevention Of Avian Influenza Infection

FDA Approves First U.S. Vaccine for Humans Against the Avian Influenza Virus H5N1
The U.S. Food and Drug Administration (FDA) today announced the first approval in the United States of a vaccine for humans against the H5N1 influenza virus, commonly known as avian or bird flu.The vaccine could be used in the event the current H5N1 avian virus were to develop the capability to efficiently spread from human to human, resulting in the rapid spread of the disease across the globe. Should such an influenza pandemic emerge, the vaccine may provide early limited protection in the months before a vaccine tailored to the pandemic strain of the virus could be developed and produced.

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"The threat of an influenza pandemic is, at present, one of the most significant public health issues our nation and world faces," said Andrew C. von Eschenbach, M.D., Commissioner of Food and Drugs. "The approval of this vaccine is an important step forward in our protection against a pandemic." The H5N1 virus is one version of the influenza A virus commonly found in birds. Unlike seasonal influenza, where infection ranges from mild to serious symptoms in most people, the disease caused by H5N1 is far more severe and happens quickly, with pneumonia and multi-organ failure commonly seen.

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While there have been no reported human cases of H5N1 infection in the United States, almost 300 people worldwide have been infected with this virus since 2003 and more than half of them have died. To date, H5N1 influenza has remained primarily an animal disease but should the virus acquire the ability for sustained transmission among humans, people will have little immunity to this virus and the potential for an influenza pandemic would have grave consequences for global public health.

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"The timing and severity of an influenza pandemic is uncertain, but the danger remains very real," said Jesse L. Goodman, M.D., M.P.H., Director of FDA's Center for Biologics Evaluation and Research. "We are working closely with other government agencies, global partners and the vaccine industry to facilitate the development, licensure and availability of needed supplies of safe and effective vaccines to protect against the pandemic threat."

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The vaccine was obtained from a human strain and is intended for immunizing people 18 through 64 years of age who could be at increased risk of exposure to the H5N1 influenza virus contained in the vaccine. H5N1 influenza vaccine immunization consists of two intramuscular injections, given approximately one month apart. The manufacturer, sanofi pasteur Inc., will not sell the vaccine commercially. Instead, the vaccine has been purchased by the federal government for inclusion within the National Stockpile for distribution by public health officials if needed. The vaccine will be manufactured at sanofi pasteur's Swiftwater, Pa., facility.

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A clinical study was conducted to collect safety information and information on recipient's immune responses and to determine the appropriate vaccine dose. A total of 103 healthy adults received a 90 microgram dose of the vaccine by injection followed by another 90 microgram dose 28 days later. In addition, there were approximately 300 healthy adults who received the vaccine at doses lower than 90 micrograms and a total of 48 who received a placebo injection.

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The vaccine was generally well tolerated, with the most common side effects reported as pain at the injection site, headache, general ill feeling and muscle pain. The study showed that 45 percent of individuals who received the 90 microgram, two-dose regimen developed antibodies at a level that is expected to reduce the risk of getting influenza. Although the level of antibodies seen in the remaining individuals did not reach that level, current scientific information on other influenza vaccines suggests that less than optimal antibody levels may still have the potential to help reduce disease severity and influenza-related hospitalizations and deaths. Additional information on this H5N1 influenza vaccine is being collected on safety and effectiveness in other age groups and will be available to FDA in the near future.

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With the support of FDA, the U.S. National Institutes of Health and other government agencies, sanofi pasteur and other manufacturers are working to develop a next generation of influenza vaccines for enhanced immune responses at lower doses, using technologies intended to boost the immune response. Meanwhile, the approval and availability of this vaccine will enhance national readiness and the nation's ability to protect those at increased risk of exposure.

National Institute of Allergy andInfectious Diseases (NIAID) Initiates Trial of Experimental Avian Flu Vaccine
Fast-track recruitment has begun for a trial to investigate the safety of a vaccine against H5N1 avian influenza, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), announced today. Sites in Rochester, NY, Baltimore and Los Angeles will enroll a total of 450 healthy adults. The clinical sites are part of the NIAID-sponsored Vaccine and Treatment Evaluation Units (VTEU).

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“While there have been relatively few cases worldwide of H5N1 avian influenza infection in humans, the public health community is concerned that the virus will develop the capability of efficiently spreading from human to human and thus create a risk for a worldwide pandemic,” says NIAID Director Anthony S. Fauci, M.D. “NIAID has supported research on H5N1, the strain responsible for this deadly form of avian influenza, since 1997 when the first cases in humans were reported. The initiation of this vaccine trial marks a key advance in our efforts to prepare to respond to an avian flu pandemic,” adds Dr. Fauci.

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Sanofi pasteur, Swiftwater, PA, manufactured the trial vaccine, which is an inactivated vaccine made from an H5N1 virus isolated in Southeast Asia in 2004. Sanofi pasteur, formerly Aventis Pasteur, was awarded a contract by NIAID to manufacture the H5N1 vaccine in May 2004. This Phase I trial will test the vaccine’s safety and ability to generate an immune response in 450 healthy adults aged 18 to 64. If the vaccine is shown to be safe in adults, there are plans to test it in other populations, such as the elderly and children.

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H5N1 avian influenza leads to severe disease in both birds and humans. Between January 2004 and March 11, 2005, there were 69 confirmed cases of and 46 deaths from H5N1 infection in humans reported to the World Health Organization. To date, there has been a small number of cases where human-to-human transmission of the virus may have occurred. However, public health experts fear that the virus may evolve into one that is more easily transmitted between people. If this were to happen, a worldwide pandemic could follow.

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Influenza pandemics are global outbreaks that emerge infrequently and unpredictably and involve strains of virus to which humans have little or no immunity. H5N1 is one such flu virus strain. The last influenza pandemic swept the globe in 1968; many public health officials believe the world is overdue for another one.

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Avian Influenza Infection In Human

Although avian influenza A viruses usually do not infect humans, rare cases of human infection with avian influenza viruses have been reported since 1997. More recently, more than 200 confirmed cases of human infection with avian influenza A (H5N1) viruses have been reported since 2004. The World Health Organization (WHO) maintains situation updates and cumulative reports of human cases of avian influenza A (H5N1). Most cases of avian influenza infection in humans are thought to have resulted from direct contact with infected poultry or contaminated surfaces. However, there is still a lot to learn about how different subtypes and strains of avian influenza virus might affect humans. For example, it is not known how the distinction between low pathogenic and highly pathogenic strains might impact the health risk to humans.

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Because of concerns about the potential for more widespread infection in the human population, public health authorities closely monitor outbreaks of human illness associated with avian influenza. To date, human infections with avian influenza A viruses detected since 1997 have not resulted in sustained human-to-human transmission. However, because influenza A viruses have the potential to change and gain the ability to spread easily between people, monitoring for human infection and person-to-person transmission is important.

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Instances of Avian Influenza Infections in Humans
Confirmed instances of avian influenza viruses infecting humans since 1997 include:

- H5N1, Hong Kong, Special Administrative Region, 1997: Highly pathogenic avian influenza A (H5N1) infections occurred in both poultry and humans. This was the first time an avian influenza A virus transmission directly from birds to humans had been found. During this outbreak, 18 people were hospitalized and six of them died. To control the outbreak, authorities killed about 1.5 million chickens to remove the source of the virus. Scientists determined that the virus spread primarily from birds to humans, though rare person-to-person infection was noted.

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- H9N2, China and Hong Kong, Special Administrative Region, 1999: Low pathogenic avian influenza A (H9N2) virus infection was confirmed in two children and resulted in uncomplicated influenza-like illness. Both patients recovered, and no additional cases were confirmed. The source is unknown, but the evidence suggested that poultry was the source of infection and the main mode of transmission was from bird to human. However, the possibility of person-to-person transmission could not be ruled out. Several additional human H9N2 infections were reported from China in 1998-99.

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- H7N2, Virginia, 2002: Following an outbreak of H7N2 among poultry in the Shenandoah Valley poultry production area, one person was found to have serologic evidence of infection with H7N2.

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- H5N1, China and Hong Kong, Special Administrative Region, 2003: Two cases of highly pathogenic avian influenza A (H5N1) infection occurred among members of a Hong Kong family that had traveled to China. One person recovered, the other died. How or where these two family members were infected was not determined. Another family member died of a respiratory illness in China, but no testing was done.

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- H7N7, Netherlands, 2003: The Netherlands reported outbreaks of influenza A (H7N7) in poultry on several farms. Later, infections were reported among pigs and humans. In total, 89 people were confirmed to have H7N7 influenza virus infection associated with this poultry outbreak. These cases occurred mostly among poultry workers. H7N7-associated illness included 78 cases of conjunctivitis (eye infections) only; 5 cases of conjunctivitis and influenza-like illnesses with cough, fever, and muscle aches; 2 cases of influenza-like illness only; and 4 cases that were classified as “other.” There was one death among the 89 total cases. It occurred in a veterinarian who visited one of the affected farms and developed acute respiratory distress syndrome and complications related to H7N7 infection. The majority of these cases occurred as a result of direct contact with infected poultry; however, Dutch authorities reported three possible instances of transmission from poultry workers to family members. Since then, no other instances of H7N7 infection among humans have been reported.

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- H9N2, Hong Kong, Special Administrative Region, 2003: Low pathogenic avian influenza A (H9N2) infection was confirmed in a child in Hong Kong. The child was hospitalized and recovered.

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- H7N2, New York, 2003: In November 2003, a patient with serious underlying medical conditions was admitted to a hospital in New York with respiratory symptoms. One of the initial laboratory tests identified an influenza A virus that was thought to be H1N1. The patient recovered and went home after a few weeks. Subsequent confirmatory tests conducted in March 2004 showed that the patient had been infected with avian influenza A (H7N2) virus.

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- H7N3, Canada, 2004: In February 2004, human infections of highly pathogenic avian influenza A (H7N3) among poultry workers were associated with an H7N3 outbreak among poultry. The H7N3-associated, mild illnesses consisted of eye infections.

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- H5N1, Thailand and Vietnam, 2004: In late 2003, outbreaks of highly pathogenic influenza A (H5N1) in poultry in Asia were first reported by the World Health Organization. Human infections with H5N1 were reported beginning in 2004, mostly resulting from contact with infected poultry. However, in Thailand one instance of probable human-to-human spread is thought to have occurred.

- H5N1, Cambodia, China, Indonesia, Thailand and Vietnam, 2005: Human infections with H5N1 occurred in association with the ongoing H5N1 epizootic in the region. At least two persons in Vietnam were thought to have been infected through consumption of uncooked duck blood.

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- H5N1, Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Thailand, Turkey, 2006: Human infections with H5N1 occurred in association with the ongoing and expanding epizootic. While most of these cases occurred as a result of contact with infected poultry, in Azerbaijan , the most plausible cause of exposure to H5N1 in several instances of human infection is thought to be contact with infected dead wild birds (swans).

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Symptoms of Avian Influenza in Humans
The reported symptoms of avian influenza in humans have ranged from typical influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to eye infections (conjunctivitis), pneumonia, acute respiratory distress, viral pneumonia, and other severe and life-threatening complications.

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Antiviral Agents for Influenza
Four different influenza antiviral drugs (amantadine, rimantadine, oseltamivir, and zanamivir) are approved by the U.S. Food and Drug Administration (FDA) for the treatment and prevention of influenza. All four have activity against influenza A viruses. However, sometimes influenza strains can become resistant to these drugs, and therefore the drugs may not always be effective. For example, analyses of some of the 2004 H5N1 viruses isolated from poultry and humans in Asia have shown that the viruses are resistant to two of the medications (amantadine and rimantadine). Also, please note the January 14, 2006 CDC Health Alert Notice (HAN), in which CDC recommends that neither amantadine nor rimantadine be used for the treatment or prevention (prophylaxis) of influenza A in the United States for the remainder of the 2005-06 influenza season. Monitoring of avian influenza A viruses for resistance to influenza antiviral medications is ongoing.

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Avian Influenza Virus in Birds

Avian influenza is an infection caused by avian (bird) influenza (flu) viruses. These influenza viruses occur naturally among birds. Wild birds worldwide carry the viruses in their intestines, but usually do not get sick from them. However, avian influenza is very contagious among birds and can make some domesticated birds, including chickens, ducks, and turkeys, very sick and kill them.

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Infected birds shed influenza virus in their saliva, nasal secretions, and feces. Susceptible birds become infected when they have contact with contaminated secretions or excretions or with surfaces that are contaminated with secretions or excretions from infected birds. Domesticated birds may become infected with avian influenza virus through direct contact with infected waterfowl or other infected poultry, or through contact with surfaces (such as dirt or cages) or materials (such as water or feed) that have been contaminated with the virus.

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Infection with avian influenza viruses in domestic poultry causes two main forms of disease that are distinguished by low and high extremes of virulence. The “low pathogenic” form may go undetected and usually causes only mild symptoms (such as ruffled feathers and a drop in egg production). However, the highly pathogenic form spreads more rapidly through flocks of poultry. This form may cause disease that affects multiple internal organs and has a mortality rate that can reach 90-100% often within 48 hours.

Human infection with avian influenza viruses
There are many different subtypes of type A influenza viruses. These subtypes differ because of changes in certain proteins on the surface of the influenza A virus (hemagglutinin [HA] and neuraminidase [NA] proteins). There are 16 known HA subtypes and 9 known NA subtypes of influenza A viruses. Many different combinations of HA and NA proteins are possible. Each combination represents a different subtype. All known subtypes of influenza A viruses can be found in birds.

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Usually, “avian influenza virus” refers to influenza A viruses found chiefly in birds, but infections with these viruses can occur in humans. The risk from avian influenza is generally low to most people, because the viruses do not usually infect humans. However, confirmed cases of human infection from several subtypes of avian influenza infection have been reported since 1997. Most cases of avian influenza infection in humans have resulted from contact with infected poultry (e.g., domesticated chicken, ducks, and turkeys) or surfaces contaminated with secretion/excretions from infected birds. The spread of avian influenza viruses from one ill person to another has been reported very rarely, and has been limited, inefficient and unsustained.

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“Human influenza virus” usually refers to those subtypes that spread widely among humans. There are only three known A subtypes of influenza viruses (H1N1, H1N2, and H3N2) currently circulating among humans. It is likely that some genetic parts of current human influenza A viruses came from birds originally. Influenza A viruses are constantly changing, and they might adapt over time to infect and spread among humans.

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During an outbreak of avian influenza among poultry, there is a possible risk to people who have contact with infected birds or surfaces that have been contaminated with secretions or excretions from infected birds.

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Symptoms of avian influenza in humans have ranged from typical human influenza-like symptoms (e.g., fever, cough, sore throat, and muscle aches) to eye infections, pneumonia, severe respiratory diseases (such as acute respiratory distress), and other severe and life-threatening complications. The symptoms of avian influenza may depend on which virus caused the infection.Studies done in laboratories suggest that some of the prescription medicines approved in the United States for human influenza viruses should work in treating avian influenza infection in humans. However, influenza viruses can become resistant to these drugs, so these medications may not always work. Additional studies are needed to demonstrate the effectiveness of these medicines.

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Avian Influenza A (H5N1)
Influenza A (H5N1) virus – also called “H5N1 virus” – is an influenza A virus subtype that occurs mainly in birds, is highly contagious among birds, and can be deadly to them. H5N1 virus does not usually infect people, but infections with these viruses have occurred in humans. Most of these cases have resulted from people having direct or close contact with H5N1-infected poultry or H5N1-contaminated surfaces.

Human health risks during the H5N1 outbreak
Of the few avian influenza viruses that have crossed the species barrier to infect humans, H5N1 has caused the largest number of detected cases of severe disease and death in humans. However, it is possible that those cases in the most severely ill people are more likely to be diagnosed and reported, while milder cases go unreported. For the most current information about avian influenza and cumulative case numbers, see the World Health Organization (WHO) avian influenza website.

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Of the human cases associated with the ongoing H5N1 outbreaks in poultry and wild birds in Asia and parts of Europe, the Near East and Africa, more than half of those people reported infected with the virus have died. Most cases have occurred in previously healthy children and young adults and have resulted from direct or close contact with H5N1-infected poultry or H5N1-contaminated surfaces. In general, H5N1 remains a very rare disease in people. The H5N1 virus does not infect humans easily, and if a person is infected, it is very difficult for the virus to spread to another person.

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While there has been some human-to-human spread of H5N1, it has been limited, inefficient and unsustained. For example, in 2004 in Thailand, probable human-to-human spread in a family resulting from prolonged and very close contact between an ill child and her mother was reported. Most recently, in June 2006, WHO reported evidence of human-to-human spread in Indonesia. In this situation, 8 people in one family were infected. The first family member is thought to have become ill through contact with infected poultry. This person then infected six family members. One of those six people (a child) then infected another family member (his father). No further spread outside of the exposed family was documented or suspected.

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Nonetheless, because all influenza viruses have the ability to change, scientists are concerned that H5N1 virus one day could be able to infect humans and spread easily from one person to another. Because these viruses do not commonly infect humans, there is little or no immune protection against them in the human population. If H5N1 virus were to gain the capacity to spread easily from person to person, an influenza pandemic (worldwide outbreak of disease) could begin.

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No one can predict when a pandemic might occur. However, experts from around the world are watching the H5N1 situation in Asia and Europe very closely and are preparing for the possibility that the virus may begin to spread more easily and widely from person to person.

Treatment and vaccination for H5N1 virus in humans
The H5N1 virus that has caused human illness and death in Asia is resistant to amantadine and rimantadine, two antiviral medications commonly used for influenza. Two other antiviral medications, oseltamavir and zanamavir, would probably work to treat influenza caused by H5N1 virus, but additional studies still need to be done to demonstrate their effectiveness.

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