Newsletter

January 2006

Volume 1, No 2

Avian Flu: The Virus & Its Spread

Influenza viruses that infect birds are called avian influenza viruses. 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 subtypes that typically infect both people and birds. Within subtypes of avian influenza A viruses there also are different strains.

Avian influenza A H5 and H7 viruses can be distinguished as “low pathogenic” and “high pathogenic” forms on the basis of genetic features of the virus and the severity of the illness they cause in poultry; influenza H9 virus has been identified only in a “low pathogenicity” form. Each of these three avian influenza A viruses (H5, H7, and H9) theoretically can be partnered with any one of nine neuraminidase surface proteins; thus, there are potentially nine different forms of each subtype (e.g., H5N1, H5N2, H5N3, H5N9).

Summary information follows about these three prominent subtypes
of avian influenza A viruses:

Influenza A H5

Potentially nine different subtypes
Can be highly pathogenic or low pathogenic
H5 infections have been documented among humans,
sometimes causing severe illness and death

Influenza A H7

Potentially nine different subtypes
Can be highly pathogenic or low pathogenic
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

Influenza A H9

Potentially nine different subtypes
Documented only in low pathogenic form
At least three H9 infections in humans have been confirmed

Page last modified by CDC on October 14, 2005

Types, Subtypes, and Strains

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. 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.

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. 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.

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

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. 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.

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.

From Center for Disease Control

(Last modified by CDC on November 18, 2005)

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Avian A/Hong Kong/97 (H591)Influenza Virus (Bird Flu)

In the race to develop vaccines against an ever-widening array of infectious diseases, Aviron, a biopharmaceutical research and development company located in Mountain View, California, may be leading by a nose. Working in collaboration with the National Institutes of Health and the Centers for Disease Control and Prevention, Aviron is developing a novel technology in antiviral vaccinations: the cold-adapted live influenza vaccine. A major advantage of the new technology is that the vaccine may be administered through a nasal spray, bypassing the need for injections. Currently, Aviron is using its technology to develop two candidate vaccines against the avian A/Hong Kong/97 (H5N1) influenza virus, more commonly
known as the "bird flu."

The bird flu, which first appeared in humans in May 1997, is the latest in a string of what are known as "Hong Kong flu" epidemics--outbreaks that start in southeast China, where the densely packed population lives cheek to beak with large numbers of chickens, ducks, and other poultry. It is believed that the birds carry various viral strains that are then transmitted somehow--perhaps through pig intermediaries--to humans. Scientists aren't sure why or how the viruses cross over to humans, but the results in the past have been devastating, as evidenced by outbreaks such as one in 1968 that killed thousands worldwide. In December, Hong Kong officials launched what appears to have been a successful strike against the disease by slaughtering over 1 million chickens and other poultry.

Martin Bryant, vice president of research for Aviron, says, "With the elimination of the Hong Kong poultry population, the epidemic was aborted; the virus never got up the steam to pass from one person to another. What happens is that a virus may be modified as it passes from person to person, and that did not occur." Still, says Bryant, although the bird flu didn't spread to epidemic proportions this time, it's not a matter of whether such an epidemic will come, but when--and public health officials should be prepared.

Aviron scientists are using a "reverse genetics," or recombinant, approach to introduce specific protective genes into an attenuated (weakened) master donor virus strain from which all flu vaccines are developed. The vaccine could also be used as a platform to prepare an inactivated version of the vaccine in large quantities.

Aviron's live-virus vaccines are attenuated viruses that are adapted to grow in the relatively cool nasal region as well as in the lungs. The cold-adapted flu virus triggers an immune response at the place of entry of the influenza virus, leaving the vaccine recipient free of flu but armed with immune capabilities to combat future attacks by the virus.

Exposure to the flu is believed to occur largely through inhalation of droplets containing the live virus, and some view the nasal spray as working directly at the site of infection. In a 1997 trial of 1,602 children aged six years and younger, the nasal spray vaccine showed an amazing 93% efficacy rate against culture-confirmed influenza. This efficacy rate may be due to the fact that spraying the vaccine in the nose stimulates the mucosal antibodies found in the nose, throat, and mouth, and circulating antibodies in the bloodstream. These antibodies are an added boost to the cell-mediated immune responses triggered
by the traditional flu shot.

The absence of needles is seen as an advantage in getting the vaccine to people who are afraid of shots, particularly children, who are one of the primary vectors of influenza. Says Bryant, "The first wave of any epidemic in a community usually starts with kids." Plus, because it's a simple nose-spray, the vaccine wouldn't need to be administered by a health-care professional. Eventually, the vaccine may even be available over the counter.

From: The National Institutes of Health
From: http://ehp.niehs.nih.gov/docs/1998/106-7/forum.html#bird

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ANA Hails U.S. House Democrats' Pandemic Influenza Plan

Bill assuages nurses', patients' concerns over vaccine liability, compensation issues.

Silver Spring, MD - The American Nurses Association (ANA) commends members of the U.S. House of Representatives for their unveiling of a comprehensive strategy for combating a possible avian influenza pandemic.

The House bill will take a multi-pronged approach to fighting a potential influenza pandemic
by increasing international surveillance, boosting domestic supplies of vaccines
and anti-viral medications, and allocating more funding to state and
local public health infrastructures.

The bill also addresses key issues surrounding proposed liability protections for manufacturers who develop influenza vaccines and health care workers who administer influenza vaccine, as well as compensation for victims of adverse vaccine reactions.

In addition, the proposed legislation provides for the education and prescreening of health care workers as well as the general public, and it requires the government to develop workplace standards and plans to protect health care workers and other first responders in the event of an influenza pandemic - provisions that are critical to ensuring that first responders get vaccinated and are willing and able to do their jobs.

"We commend the House for introducing this much-needed legislation, which offers built-in protections regarding potential liability and compensation issues that otherwise could adversely affect nurses and their patients," said ANA President Barbara Blakeney, MS, RN.
"While we understand the need to protect vaccine manufacturers, we feel it is just as important to cover the nurses and other health care workers who administer influenza vaccine, as well as the people who actually roll up their sleeves and get inoculated."

In early November, ANA commended President Bush for his leadership in developing a national strategy for pandemic influenza, but the association stopped short of giving the administration approval of key components of the plan because of reservations regarding proposed blanket liability protections for vaccine manufacturers, a conspicuous lack of comprehensive compensation program protections for persons receiving the vaccine, and insufficient workplace protections for nurses who care for influenza patients.

Past experiences with broad-scale vaccination campaigns have demonstrated the need for robust education and prescreening as well as injury compensation. For example, in 2003 the Bush administration called upon 500,000 health care workers to be vaccinated against smallpox despite protests from ANA over an absence of meaningful prescreening or injury compensation provisions. The administration's mass inoculation program ultimately failed when nurses and other health care workers across the country heeded ANA's warnings against participating in the program after two health care workers died from heart complications that developed shortly after the vaccine was administered.

Public health experts also have argued that the administration's influenza pandemic plan puts a huge unfunded financial burden on the states (of $510 million) by requiring states to shoulder the cost of purchasing anti-virals. In addition, the president's plan only provides for $100 million for planning activities.

By contrast, the House Democratic proposal provides $200 million to the states to pay for planning for an influenza pandemic, and $300 million to states and localities to restore funding to the general health preparedness plans, to cover the cost of delivering annual influenza shots and to increase funding for surge capacity and ongoing pandemic
influenza planning activities.

The House Democrats' avian influenza pandemic plan was developed in response to mounting concerns regarding the H5N1 avian influenza virus. While no cases of avian influenza have been detected in the United States, more than 60 people in Asia have died from it, and 200 million birds have been killed to help prevent its spread. Also, although there is no evidence that the current virus is transmitted between humans, the concern is that it could quickly mutate into a fast-spreading global outbreak involving many deaths.

"ANA looks forward to ironing out with Congress and the administration the strongest and best possible national campaign to improve pandemic influenza preparedness and response," said Blakeney. "And certainly, developing new vaccines and other influenza countermeasures is an important component of that effort. But these measures will be much more likely to succeed if the persons who administer and receive them are educated regarding their potential benefits and risks, and if these individuals are compensated in the
event of adverse outcomes."

Article from American Nurses Association Press Release for December 14,2005

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The ANA is the only full-service professional organization representing the nation's 2.7 million registered nurses through its 54 constituent member nurses associations. The ANA advances the nursing profession by fostering high standards of nursing practice, promoting the rights of nurses in the workplace, projecting a positive and realistic view of nursing, and by lobbying the Congress and regulatory agencies on health care issues affecting nurses and the public.

Statement taken from the ANA website, Members Only Section

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UPDATE ON JANUARY 07, 2006

Avian Influenza – Situation In Turkey
Update From The World Health Organization

The Ministry of Health in Turkey has confirmed an additional two cases of human infection with the H5N1 avian influenza virus. Both cases are children, aged five and eight years, and both are hospitalized. This brings the total number of laboratory confirmed cases in Turkey to four. Two of these cases were fatal.

A WHO collaborating laboratory in the United Kingdom has today confirmed detection of the H5N1 virus in samples taken from the two fatal cases.

The Ministry of Health has also announced a third death, presumably caused by the H5N1 virus, in a 12-year-old girl. The girl, who died on 6 January, is a sibling of the two children who died. A fourth child in the family, a six-year-old boy, is also hospitalized. Tests on samples from these patients are ongoing; neither is laboratory confirmed at present.

According to Turkish authorities, some 30 patients are being treated and evaluated for possible H5N1 infection at a hospital in Van Province. Most of the patients are children, and the majority come from the rural district of Dogubayazit.

Plans for a team of international experts to travel today to Van Province have been deferred because of adverse weather conditions. Government officials are assisting the team in finding a rapid mode of transportation to the affected area in the eastern part of the country.

To date, all evidence indicates that patients have acquired their infections following close contact with diseased poultry. Contact between people and poultry has likely increased during the present cold weather, when the custom among many rural households is to bring poultry into their homes. Tests have shown that the virus can survive in bird feces for at least 35 days at low temperatures (4^oC).

Based on experiences during the avian H5N1 outbreaks in Asia, behaviors that carry an especially high risk of infection include the slaughtering, defeathering, butchering, and preparation for consumption of diseased poultry. These behaviors tend to occur most frequently in rural areas where populations traditionally slaughter and consume birds once deaths or signs of illness are seen in poultry flocks.

In recent days, vigilance for outbreaks of the disease in poultry has increased considerably. Outbreaks of highly pathogenic H5N1 avian influenza have now been confirmed in six provinces in the eastern and south-eastern part of the country. Outbreaks at additional sites in the area are under investigation.

Avoidance of high-risk behaviors remains the most important way for local populations to protect themselves from infection.

From World Health Organization: For further updates and all related topics,