Treatment

In swine

As swine influenza is rarely fatal to pigs, little treatment beyond rest and supportive care is required. Instead veterinary efforts are focused on preventing the spread of the virus throughout the farm, or to other farms. Vaccination and animal management techniques are most important in these efforts. Antibiotics are also used to treat this disease, which although they have no effect against the influenza virus, do help prevent bacterial pneumonia and other secondary infections in influenza-weakened herds.

In humans

If a person becomes sick with swine flu, antiviral drugs can make the illness milder and make the patient feel better faster. They may also prevent serious flu complications. For treatment, antiviral drugs work best if started soon after getting sick (within 2 days of symptoms). Beside antivirals, supportive care at home or in hospital, focuses on controlling fevers, relieving pain and maintaining fluid balance, as well as identifying and treating any secondary infections or other medical problems. The U.S. Centers for Disease Control and Prevention recommends the use of Tamiflu (oseltamivir) or Relenza (zanamivir) for the treatment and/or prevention of infection with swine influenza viruses; however, the majority of people infected with the virus make a full recovery without requiring medical attention or antiviral drugs. The virus isolates in the 2009 outbreak have been found resistant to amantadine and rimantadine.

In the U.S., on April 27, 2009, the FDA issued Emergency Use Authorizations to make available Relenza and Tamiflu antiviral drugs to treat the swine influenza virus in cases for which they are currently unapproved. The agency issued these EUAs to allow treatment of patients younger than the current approval allows and to allow the widespread distribution of the drugs, including by non-licensed volunteers.

Types of Vaccine & Manufacturing Methods

Types of vaccine

Two types of influenza vaccines are available:

• TIV (flu shot (injection) of trivalent (three strains; usually A/H1N1, A/H3N2, and B) inactivated (killed) vaccine) or
• LAIV (nasal spray (mist) of live attenuated influenza vaccine.)

TIV works by putting into the bloodstream those parts of three strains of flu virus that the body uses to create antibodies; while LAIV works by inoculating the body with those same three strains, but in a modified form that cannot cause illness.

LAIV is not recommended for individuals under age 2 or over age 50, but might be comparatively more effective among children over age 2.

Manufacturing methods

For the inactivated vaccines, the virus is grown by injecting it, along with some antibiotics, into fertilized chicken eggs. About one to two eggs are needed to make each dose of vaccine.The virus replicates within the allantois of the embryo, which is the equivalent of the placenta in mammals. The fluid in this structure is removed and the virus purified from this fluid by methods such as filtration or centrifugation. The purified viruses are then inactivated ("killed") with a small amount of a disinfectant. The inactivated virus is treated with detergent to break up the virus particles and the proteins released concentrated by centrifugation. The final preparation is suspended in sterile phosphate buffered saline ready for injection. The final product contains the viral proteins in phosphate buffered saline. It may also contain trace amounts of egg proteins and trace residues of the antibiotics, disinfectant and detergent used in the manufacturing process. In multi-dose versions of the vaccine, the preservative thimerosal is added to prevent growth of bacteria. In some versions of the vaccine used in Europe and Canada, such as Arepanrix and Fluad, an adjuvant is also added, this contains a fish oil called squalene, vitamin E and an emulsifier called polysorbate 80.

For the live vaccine, the virus is first adapted to growth at 25°C and grown at this temperature until it loses the ability to cause illness in humans, which would require the virus to grow at our normal body temperature of 37°C. This process seems to be irreversible, since once the virus has lost virulence (become "attenuated"), it cannot regain the ability to infect people. To make the vaccine, the attenuated virus is grown in chicken eggs as before. The virus-containing fluid is harvested and the virus purified by filtration; this step also removes any contaminating bacteria. The filtered preparation is then diluted into a solution that stabilizes the virus. This solution contains monosodium glutamate, potassium phosphate, gelatin, the antibiotic gentamicin, and sugar.

A new method of producing influenza virus is used to produce the Novartis vaccine Optaflu. In this vaccine the virus is grown in cell culture instead of in eggs. This method is faster than the classic egg-based system and removes the need to use antibiotics and preservatives. There are also no traces of egg proteins in the final product, so the vaccine is safe for people with egg allergies.

Vaccination

Vaccines are available for different kinds of swine flu. The U.S. Food and Drug Administration (FDA) approved the new swine flu vaccine for use in the United States on September 15, 2009. Studies by the National Institutes of Health (NIH), show that a single dose creates enough antibodies to protect against the virus within about 10 days.

Around three billion doses of a vaccine for H1N1/09 (swine flu) will be produced annually, with delivery from November 2009.

Developing, testing, and manufacturing sufficient quantities of a vaccine is a process that takes many months. According to Keiji Fukuda of the World Health Organization (WHO), "There’s much greater vaccine capacity than there was a few years ago, but there is not enough vaccine capacity to instantly make vaccines for the entire world’s population for influenza." Nasal mist version of the vaccine started shipping on October 1, 2009. Health care workers in the U.S. states of Tennessee and Indiana were the first recipients of the H1N1 vaccine, while two-thirds of Americans plan to be vaccinated against the flu.

Prevention

Prevention of swine influenza has three components: prevention in swine, prevention of transmission to humans, and prevention of its spread among humans.
In swine

Methods of preventing the spread of influenza among swine include facility management, herd management, and vaccination (ATCvet code: QI09AA03). Because much of the illness and death associated with swine flu involves secondary infection by other pathogens, control strategies that rely on vaccination may be insufficient.

Control of swine influenza by vaccination has become more difficult in recent decades, as the evolution of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine flu vaccines are effective in controlling the infection when the virus strains match enough to have significant cross-protection, and custom (autogenous) vaccines made from the specific viruses isolated are created and used in the more difficult cases. Present vaccination strategies for SIV control and prevention in swine farms typically include the use of one of several bivalent SIV vaccines commercially available in the United States. Of the 97 recent H3N2 isolates examined, only 41 isolates had strong serologic cross-reactions with antiserum to three commercial SIV vaccines. Since the protective ability of influenza vaccines depends primarily on the closeness of the match between the vaccine virus and the epidemic virus, the presence of nonreactive H3N2 SIV variants suggests that current commercial vaccines might not effectively protect pigs from infection with a majority of H3N2 viruses. The United States Department of Agriculture researchers say that while pig vaccination keeps pigs from getting sick, it does not block infection or shedding of the virus.

Facility management includes using disinfectants and ambient temperature to control virus in the environment. The virus is unlikely to survive outside living cells for more than two weeks, except in cold (but above freezing) conditions, and it is readily inactivated by disinfectants.Herd management includes not adding pigs carrying influenza to herds that have not been exposed to the virus. The virus survives in healthy carrier pigs for up to 3 months and can be recovered from them between outbreaks. Carrier pigs are usually responsible for the introduction of SIV into previously uninfected herds and countries, so new animals should be quarantined. After an outbreak, as immunity in exposed pigs wanes, new outbreaks of the same strain can occur.

In humans

Prevention of pig to human transmission

Swine can be infected by both avian and human influenza strains of influenza, and therefore are hosts where the antigenic shifts can occur that create new influenza strains.

The transmission from swine to human is believed to occur mainly in swine farms where farmers are in close contact with live pigs. Although strains of swine influenza are usually not able to infect humans this may occasionally happen, so farmers and veterinarians are encouraged to use a face mask when dealing with infected animals. The use of vaccines on swine to prevent their infection is a major method of limiting swine to human transmission. Risk factors that may contribute to swine-to-human transmission include smoking and not wearing gloves when working with sick animals.

Prevention of human to human transmission

Influenza spreads between humans through coughing or sneezing and people touching something with the virus on it and then touching their own nose or mouth.Swine flu cannot be spread by pork products, since the virus is not transmitted through food. The swine flu in humans is most contagious during the first five days of the illness although some people, most commonly children, can remain contagious for up to ten days. Diagnosis can be made by sending a specimen, collected during the first five days for analysis.

Recommendations to prevent spread of the virus among humans include using standard infection control against influenza. This includes frequent washing of hands with soap and water or with alcohol-based hand sanitizers, especially after being out in public.Chance of transmission is also reduced by disinfecting household surfaces, which can be done effectively with a diluted chlorine bleach solution.

Experts agree that hand-washing can help prevent viral infections, including ordinary influenza and the swine flu virus. Also avoiding touching eyes, nose and mouth with hands prevents flu. Influenza can spread in coughs or sneezes, but an increasing body of evidence shows small droplets containing the virus can linger on tabletops, telephones and other surfaces and be transferred via the fingers to the mouth, nose or eyes. Alcohol-based gel or foam hand sanitizers work well to destroy viruses and bacteria. Anyone with flu-like symptoms such as a sudden fever, cough or muscle aches should stay away from work or public transportation and should contact a doctor for advice.

Social distancing is another tactic. It means staying away from other people who might be infected and can include avoiding large gatherings, spreading out a little at work, or perhaps staying home and lying low if an infection is spreading in a community. Public health and other responsible authorities have action plans which may request or require social distancing actions depending on the severity of the outbreak.

Signs-Symptoms & Diagnosis

In swine

In pigs influenza infection produces fever, lethargy, sneezing, coughing, difficulty breathing and decreased appetite. In some cases the infection can cause abortion. Although mortality is usually low (around 1–4%), the virus can produce weight loss and poor growth, causing economic loss to farmers. Infected pigs can lose up to 12 pounds of body weight over a 3 to 4 week period.

In humans

Direct transmission of a swine flu virus from pigs to humans is occasionally possible (called zoonotic swine flu). In all, 50 cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two were known to be previously healthy. Despite these apparently low numbers of infections, the true rate of infection may be higher, since most cases only cause a very mild disease, and will probably never be reported or diagnosed.

According to the Centers for Disease Control and Prevention (CDC), in humans the symptoms of the 2009 "swine flu" H1N1 virus are similar to those of influenza and of influenza-like illness in general. Symptoms include fever, cough, sore throat, body aches, headache, chills and fatigue. The 2009 outbreak has shown an increased percentage of patients reporting diarrhea and vomiting. The 2009 H1N1 virus is not zoonotic swine flu, as it is not transmitted from pigs to humans, but from person to person.

Because these symptoms are not specific to swine flu, a differential diagnosis of probable swine flu requires not only symptoms but also a high likelihood of swine flu due to the person's recent history. For example, during the 2009 swine flu outbreak in the United States, CDC advised physicians to "consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the 7 days preceding their illness onset." A diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple nose and throat swab).

The most common cause of death is respiratory failure. Other causes of death are pneumonia (leading to sepsis), high fever (leading to neurological problems), dehydration (from excessive vomiting and diarrhea) and electrolyte imbalance. Fatalities are more likely in young children and the elderly.

Diagnosis

Thermal scanning of passengers arriving at Singapore Changi airport. The CDC recommends real time RT-PCR as the method of choice for diagnosing H1N1. This method allows a specific diagnosis of novel influenza (H1N1) as opposed to seasonal influenza. Near-patient point of care tests are in development.

Transmission

Transmission between pigs

Influenza is quite common in pigs, with about half of breeding pigs having been exposed to the virus in the US. Antibodies to the virus are also common in pigs in other countries.

The main route of transmission is through direct contact between infected and uninfected animals. These close contacts are particularly common during animal transport. Intensive farming may also increase the risk of transmission, as the pigs are raised in very close proximity to each other. The direct transfer of the virus probably occurs either by pigs touching noses, or through dried mucus. Airborne transmission through the aerosols produced by pigs coughing or sneezing are also an important means of infection. The virus usually spreads quickly through a herd, infecting all the pigs within just a few days. Transmission may also occur through wild animals, such as wild boar, which can spread the disease between farms.

Transmission to humans

People who work with poultry and swine, especially people with intense exposures, are at increased risk of zoonotic infection with influenza virus endemic in these animals, and constitute a population of human hosts in which zoonosis and reassortment can co-occur. Vaccination of these workers against influenza and surveillance for new influenza strains among this population may therefore be an important public health measure.Transmission of influenza from swine to humans who work with swine was documented in a small surveillance study performed in 2004 at the University of Iowa. This study among others forms the basis of a recommendation that people whose jobs involve handling poultry and swine be the focus of increased public health surveillance. Other professions at particular risk of infection are veterinarians and meat processing workers, although the risk of infection for both of these groups is lower than that of farm workers.

Interaction with avian H5N1 in pigs

Pigs are unusual as they can be infected with influenza strains that usually infect three different species: pigs, birds and humans. This makes pigs a host where influenza viruses might exchange genes, producing new and dangerous strains. Avian influenza virus H3N2 is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. H3N2 evolved from H2N2 by antigenic shift. In August 2004, researchers in China found H5N1 in pigs.

These H5N1 infections may be quite common: in a survey of 10 apparently healthy pigs housed near poultry farms in West Java, where avian flu had broken out, five of the pig samples contained the H5N1 virus. The Indonesian government has since found similar results in the same region. Additional tests of 150 pigs outside the area were negative.

2009 Outbreak in Humans

The H1N1 viral strain implicated in the 2009 flu pandemic among humans often is called "swine flu" because initial testing showed many of the genes in the virus were similar to influenza viruses normally occurring in North American swine. Further research has shown that three-quarters or six out of the eight gene segments of the 2009 virus arose from the 1998 North American swine flu strains which emerged from the first-ever reported triple-hybrid virus of 1998.

In late April, Margaret Chan, the World Health Organization's director-general, declared a "public health emergency of international concern" under the rules of the WHO's new International Health Regulations when the first two cases of the H1N1 virus were reported in the United States, followed by hundreds of cases in Mexico. the initial cases in the USA and Mexico, on May 2, 2009, it was reported in pigs at a farm in Alberta, Canada, with a link to the outbreak in Mexico. The pigs are suspected to have caught this new strain of virus from a farm worker who recently returned from Mexico, then showed symptoms of an influenza-like illness. These are probable cases, pending confirmation by laboratory testing.

The new strain was initially described as an apparent reassortment of at least four strains of influenza A virus subtype H1N1, including one strain endemic in humans, one endemic in birds, and two endemic in swine. Subsequent analysis suggested it was a reassortment of just two strains, both found in swine. Although initial reports identified the new strain as swine influenza (i.e., a zoonosis originating in swine), its genetic origin was only later revealed to have been mostly a descendant of the triple-reassortment virus which emerged in factory farms in the United States in 1998. Several countries took precautionary measures to reduce the chances for a global pandemic of the disease. The 2009 swine flu has been compared to other similar types of influenza virus in terms of mortality: "in the US it appears that for every 1000 people who get infected, about 40 people need admission to hospital and about one person dies."There are fears that swine flu will become a major global pandemic at the end of the year (coinciding with the Northern Hemisphere winter months), with many countries planning major vaccination campaigns.

The 2009 flu pandemic, or swine flu, is a global outbreak of a new strain of influenza A virus subtype H1N1, a type of swine influenza, that was first detected in March and April 2009.The outbreak began in Veracruz, Mexico, with evidence that there had been an ongoing epidemic for months before it was officially recognized as such. The Mexican government closed most of Mexico City's public and private facilities in an attempt to contain the spread of the virus. However the virus continued to spread globally, clinics were overwhelmed by people infected, and the World Health Organization (WHO) and US Centers for Disease Control (CDC) stopped counting all cases and focused on tracking major outbreaks. On June 11, 2009, the WHO declared the outbreak a pandemic. As of November 20, 2009 (2009 -11-20)[update], the swine flu virus activity may have peaked in the U.S. and some European countries, while other countries report sharp increases.

While only mild symptoms are experienced by the majority of people,some have more severe symptoms. Mild symptoms may include include fever, sore throat, cough, headache, muscle or joint pains, and nausea, vomiting, or diarrhea. Those at risk of a more severe infection include: asthmatics, diabetics, those with obesity, heart disease, the immunocompromised, children with neurodevelopmental conditions, and pregnant women.

In addition, even for persons previously very healthy, a small percentage of patients will develop viral pneumonia. This manifests itself as increased breathing difficulty and typically occurs 3 to 6 days after initial onset of flu symptoms.

Similar to other influenza viruses, pandemic H1N1 is typically contracted by person to person transmission through respiratory droplets. Symptoms usually last 4 to 6 days. To avoid spreading the infection, it is recommended that those with symptoms stay home, away from school, work, and crowded places. Those with more severe symptoms or those in an at risk group may benefit from antivirals (oseltamivir or zanamivir). As of November 25, 2009 (2009 -11-25)[update], there are 8,452 confirmed deaths worldwide.

2007 Philippine Outbreak in Swine

On August 20, 2007 Department of Agriculture officers investigated the outbreak (epizootic) of swine flu in Nueva Ecija and Central Luzon, Philippines. The mortality rate is less than 10% for swine flu, unless there are complications like hog cholera. On July 27, 2007, the Philippine National Meat Inspection Service (NMIS) raised a hog cholera "red alert" warning over Metro Manila and 5 regions of Luzon after the disease spread to backyard pig farms in Bulacan and Pampanga, even if these tested negative for the swine flu virus.

1998 US Outbreak in Swine

In 1998, swine flu was found in pigs in four U.S. states. Within a year, it had spread through pig populations across the United States. Scientists found that this virus had originated in pigs as a recombinant form of flu strains from birds and humans. This outbreak confirmed that pigs can serve as a crucible where novel influenza viruses emerge as a result of the reassortment of genes from different strains. Genetic components of these 1998 triple-hybrid stains would later form six out of the eight viral gene segments in the 2009 flu outbreak.

1988 Zoonosis

In September 1988, a swine flu virus killed one woman and infected others. 32-year old Barbara Ann Wieners was eight months pregnant when she and her husband, Ed, became ill after visiting the hog barn at a county fair in Walworth County, Wisconsin. Barbara died eight days later, after developing pneumonia. The only pathogen identified was an H1N1 strain of swine influenza virus. Doctors were able to induce labor and deliver a healthy daughter before she died. Her husband recovered from his symptoms.

Influenza-like illness (ILI) was reportedly widespread among the pigs exhibited at the fair. Of the 25 swine exhibitors aged 9 to 19 at the fair, 19 tested positive for antibodies to SIV, but no serious illnesses were seen. The virus was able to spread between people, since 1-3 health care personnel who had cared for the pregnant woman developed mild influenza-like illnesses, and antibody tests suggested that they had been infected with swine flu. However, there was no community outbreak.

1976 U.S Outbreak

On February 5, 1976, in the United States an army recruit at Fort Dix said he felt tired and weak. He died the next day and four of his fellow soldiers were later hospitalized. Two weeks after his death, health officials announced that the cause of death was a new strain of swine flu. The strain, a variant of H1N1, is known as A/New Jersey/1976 (H1N1). It was detected only from January 19 to February 9 and did not spread beyond Fort Dix.

This new strain appeared to be closely related to the strain involved in the 1918 flu pandemic. Moreover, the ensuing increased surveillance uncovered another strain in circulation in the U.S.: A/Victoria/75 (H3N2) spread simultaneously, also caused illness, and persisted until March.Alarmed public-health officials decided action must be taken to head off another major pandemic, and urged President Gerald Ford that every person in the U.S. be vaccinated for the disease.

The vaccination program was plagued by delays and public relations problems. On October 1, 1976, immunizations began and three senior citizens died soon after receiving their injections. This resulted in a media outcry that linked these deaths to the immunizations, despite the lack of any proof that the vaccine was the cause. According to science writer Patrick Di Justo, however, by the time the truth was known—that the deaths were not proven to be related to the vaccine—it was too late. "The government had long feared mass panic about swine flu—now they feared mass panic about the swine flu vaccinations." This became a strong setback to the program.

There were reports of Guillain-Barré syndrome, a paralyzing neuromuscular disorder, affecting some people who had received swine flu immunizations. Although if a link exists is still not clear, this syndrome may be a rare side-effect of influenza vaccines. As a result, Di Justo writes that "the public refused to trust a government-operated health program that killed old people and crippled young people." In total, 48,161,019 Americans, or just over 22% of the population, had been immunized by the time the National Influenza Immunization Program (NIIP) was effectively halted on December 16, 1976.

Overall, there were 1098 cases of Guillain-Barré Syndrome (GBS) recorded nationwide by CDC surveillance, 532 of which occurred after vaccination and 543 before vaccination. There are about one to two cases of GBS per 100,000 people every year, whether or not people have been vaccinated. The vaccination program seems to have increased this normal risk of developing GBS by about to one extra case per 100,000 vaccinations. The CDC states that most studies on modern influenza vaccines have seen no link with GBS, one review gives an incidence of about one case per million vaccinations

1918 Pandemic in Humans

The 1918 flu pandemic in humans was associated with H1N1 and influenza appearing in pigs;this may reflect a zoonosis either from swine to humans, or from humans to swine. Although it is not certain in which direction the virus was transferred, some evidence suggests that, in this case, pigs caught the disease from humans. For instance, swine influenza was only noted as a new disease of pigs in 1918, after the first large outbreaks of influenza amongst people. Although a recent phylogenetic analysis of more recent strains of influenza in humans, birds, and swine suggests that the 1918 outbreak in humans followed a reassortment event within a mammal,the exact origin of the 1918 strain remains elusive. It is estimated that anywhere from 50 to 100 million people were killed worldwide.

The 1918 flu pandemic (commonly referred to as the Spanish Flu) was an influenza pandemic that spread to nearly every part of the world. It was caused by an unusually virulent and deadly influenza A virus strain of subtype H1N1. Historical and epidemiological data are inadequate to identify the geographic origin of the virus. Most of its victims were healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. The flu pandemic has also been implicated in the sudden outbreak of encephalitis lethargica in the 1920s.

The pandemic lasted from March 1918 to June 1920, spreading even to the Arctic and remote Pacific islands. It is estimated that anywhere from 50 to 100 million people were killed worldwide which is from three to seven times the casualties of the First World War (15 million). An estimated 50 million people, about 3% of the world's population (approximately 1.6 billion at the time), died of the disease. An estimated 500 million, or 1/3 were infected.

Scientists have used tissue samples from frozen victims to reproduce the virus for study. Given the strain's extreme virulence there has been controversy regarding the wisdom of such research. Among the conclusions of this research is that the virus kills via a cytokine storm (overreaction of the body's immune system) which explains its unusually severe nature and the concentrated age profile of its victims. The strong immune systems of young adults ravaged the body, whereas the weaker immune systems of children and middle-aged adults caused fewer deaths.

Surveillance & History of Swine Flu

Surveillance

Although there is no formal national surveillance system in the United States to determine what viruses are circulating in pigs, there is an informal surveillance network in the United States that is part of a world surveillance network.

Veterinary medical pathologist, Tracey McNamara, set up a national disease surveillance system in zoos because the zoos do active disease surveillance and many of the exotic animals housed there have broad susceptibilities. Many species fall below the radar of any federal agencies (including dogs, cats, pet prairie dogs, zoo animals, and urban wildlife), even though they may be important in the early detection of human disease outbreaks.

History

Swine influenza was first proposed to be a disease related to human influenza during the 1918 flu pandemic, when pigs became sick at the same time as humans.The first identification of an influenza virus as a cause of disease in pigs occurred about ten years later, in 1930. For the following 60 years, swine influenza strains were almost exclusively H1N1. Then, between 1997 and 2002, new strains of three different subtypes and five different genotypes emerged as causes of influenza among pigs in North America. In 1997–1998, H3N2 strains emerged. These strains, which include genes derived by reassortment from human, swine and avian viruses, have become a major cause of swine influenza in North America. Reassortment between H1N1 and H3N2 produced H1N2. In 1999 in Canada, a strain of H4N6 crossed the species barrier from birds to pigs, but was contained on a single farm.

The H1N1 form of swine flu is one of the descendants of the strain that caused the 1918 flu pandemic. As well as persisting in pigs, the descendants of the 1918 virus have also circulated in humans through the 20th century, contributing to the normal seasonal epidemics of influenza. However, direct transmission from pigs to humans is rare, with only 12 cases in the U.S. since 2005. Nevertheless, the retention of influenza strains in pigs after these strains have disappeared from the human population might make pigs a reservoir where influenza viruses could persist, later emerging to reinfect humans once human immunity to these strains has waned.

Swine flu has been reported numerous times as a zoonosis in humans, usually with limited distribution, rarely with a widespread distribution. Outbreaks in swine are common and cause significant economic losses in industry, primarily by causing stunting and extended time to market. For example, this disease costs the British meat industry about £65 million every year.

Flu Seasons

2004–2005 flu season

The 2004–05 trivalent influenza vaccine for the United States contained A/New Caledonia/20/99-like (H1N1), A/Fujian/411/2002-like (H3N2), and B/Shanghai/361/2002-like viruses.

2005–2006 flu season

The vaccines produced for the 2005–2006 season use:

• an A/New Caledonia/20/1999-like(H1N1);
• an A/California/7/2004-like(H3N2) (or the antigenically equivalent strain A/New York/55/2004);
• a B/Jiangsu/10/2003-like viruses.

2006–2007 flu season

The 2006–2007 influenza vaccine composition recommended by the World Health Organization on 15 February 2006 and the U.S. FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) on 17 February 2006 use:

• an A/New Caledonia/20/99 (H1N1)-like virus;
• an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 and A/Hiroshima/52/2005 strains);
• a B/Malaysia/2506/2004-like virus from B/Malaysia/2506/2004 and B/Ohio/1/2005 strains which are of B/Victoria/2/87 lineage.

2007–2008 flu season

The composition of influenza virus vaccines for use in the 2007–2008 Northern Hemisphere influenza season recommended by the World Health Organization on 14 February 2007 was:

• an A/Solomon Islands/3/2006 (H1N1)-like virus;
• an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 (H3N2) and A/Hiroshima/52/2005 were used at the time);
• a B/Malaysia/2506/2004-like virus

"A/H3N2 has become the predominant flu subtype in the United States, and the record over the past 25 years shows that seasons dominated by H3N2 tend to be worse than those dominated by type A/H1N1 or type B." Many H3N2 viruses making people ill in this 2007–2008 flu season differ from the strains in the vaccine and may not be well covered by the vaccine strains. "The CDC has analyzed 250 viruses this season to determine how well they match up with the vaccine, the report says. Of 65 H3N2 isolates, 53 (81%) were characterized as A/Brisbane/10/2007-like, a variant that has evolved [notably] from the H3N2 strain in the vaccine—A/Wisconsin/67/2005."

Fujian Flu(2003-2004)

Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus. These strains are named after Fujian, a coastal province of the People's Republic of China that is across the Taiwan strait from Taiwan.

A/Fujian (H3N2) human flu (from A/Fujian/411/2002(H3N2) -like flu virus strains) caused an unusually severe 2003–2004 flu season. This was due to a reassortment event that caused a minor clade to provide a haemagglutinin gene that later became part of the dominant strain in the 2002–2003 flu season. A/Fujian (H3N2) was made part of the trivalent influenza vaccine for the 2004–2005 flu season and its descendants are still the most common human H3N2 strain.

Hong Kong Flu(1968-1969)

The Hong Kong Flu was a category 2 flu pandemic caused by a strain of H3N2 descended from H2N2 by antigenic shift, in which genes from multiple subtypes reassorted to form a new virus. This pandemic of 1968 and 1969 killed an estimated one million people worldwide. The pandemic infected an estimated 500,000 Hong Kong residents, 15% of the population, with a low death rate. In the United States, approximately 33,800 people died.

Both the H2N2 and H3N2 pandemic flu strains contained genes from avian influenza viruses. The new subtypes arose in pigs coinfected with avian and human viruses and were soon transferred to humans. Swine were considered the original "intermediate host" for influenza, because they supported reassortment of divergent subtypes. However, other hosts appear capable of similar coinfection (e.g., many poultry species), and direct transmission of avian viruses to humans is possible. H1N1 may have been transmitted directly from birds to humans (Belshe 2005).

The Hong Kong flu strain shared internal genes and the neuraminidase with the 1957 Asian Flu (H2N2). Accumulated antibodies to the neuraminidase or internal proteins may have resulted in much fewer casualties than most pandemics. However, cross-immunity within and between subtypes of influenza is poorly understood.

The Hong Kong flu was the first known outbreak of the H3N2 strain, though there is serologic evidence of H3N? infections in the late 19th century. The first record of the outbreak in Hong Kong appeared on 13 July 1968 in an area with a density of about 500 people per acre in an urban setting. The outbreak reached maximum intensity in 2 weeks, lasting 6 weeks in total. The virus was isolated in Queen Mary Hospital. Flu symptoms lasted 4 to 5 days.

By July 1968, extensive outbreaks were reported in Vietnam and Singapore. By September 1968, it reached India, Philippines, northern Australia and Europe. That same month, the virus entered California from returning Vietnam War troops. It would reach Japan, Africa and South America by 1969.

"Three strains of Hong Kong influenza virus isolated from humans were compared with a strain isolated from a calf for their ability to cause disease in calves. One of the human strains. A/Aichi/2/68, was detected for five days in a calf, but all three failed to cause signs of disease. Strain A/cal/Duschanbe/55/71 could be detected for seven days and caused an influenza-like illness in calves."

Swine Flu

"In swine, 3 influenza A virus subtypes (H1N1, H3N2, and H1N2) are circulating throughout the world. In the United States, the classic H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. Most H3N2 virus isolates are triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages. Present vaccination strategies for SIV control and prevention in swine farms typically include the use of 1 of several bivalent SIV vaccines commercially available in the United States. Of the 97 recent H3N2 isolates examined, only 41 isolates had strong serologic cross-reactions with antiserum to 3 commercial SIV vaccines. Since the protective ability of influenza vaccines depends primarily on the closeness of the match between the vaccine virus and the epidemic virus, the presence of nonreactive H3N2 SIV variants suggests that current commercial vaccines might not effectively protect pigs from infection with a majority of H3N2 viruses."

Avian influenza virus H3N2 is endemic in pigs in China and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. Health experts say pigs can carry human influenza viruses, which can combine (i.e. exchange homologous genome sub-units by genetic reassortment) with H5N1, passing genes and mutating into a form which can pass easily among humans. H3N2 evolved from H2N2 by antigenic shift and caused the Hong Kong Flu pandemic of 1968 and 1969 that killed up to 750,000 humans. The dominant strain of annual flu in humans in January 2006 is H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 in humans has increased to 91% in 2005. In August 2004, researchers in China found H5N1 in pigs.

Influenza C

Influenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".

Influenza C viruses are known to infect humans and pigs, giving them influenza. Flu due to the type C species is rare compared to types A or B, but can be severe and can cause local epidemics.

Types A and B have 8 RNA segments and encode 11 proteins. Subtype C has 7 RNA segments and encodes 9 proteins.

Enveloped. Usually rounded but can be filamentous. The virions are 80-120 nm in diameter.

GENE EXPRESSION

Viral RNA polymerase (PB1, PB2 and PA) transcribes one mRNA from each genome segment. Transcription is primed by cap cleaved from cellular mRNAS by Cap snatching. mRNA are polyadenylated by the viral polymerase stuttering on a poly U track. NS mRNA can be spliced, giving rise to mRNA coding NEP protein. Polyprotein p42 is cleaved in M1 and CM2 proteins.

REPLICATION

NUCLEUS

Virus attaches to sialic acid receptor though HEF protein and is endocytosed in the host cell.

Endosome acidification induces fusion of virus membrane with the vesicle membrane; encapsidated RNA segments migrate to the nucleus.

Transcription of genomic segments by the viral polymerase produces mRNAs.

Genomic (-)RNA is replicated through antigenomic (+)RNA intermediate.

High level of M1 protein induces genomes segments export from nucleus by NEP protein.

Virus assembly and budding occurs at the plasma membrane.

Influenza B

Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".

Influenza B viruses are only known to infect humans and seals, giving them influenza. This limited host range is apparently responsible for the lack of Influenzavirus B caused influenza pandemics in contrast with those caused by the morphologically similar Influenzavirus A as both mutate by both genetic drift and reassortment.

Further diminishing the impact of this virus "in man, influenza B viruses evolve slower than A viruses and faster than C viruses". Influenzavirus B mutates at a rate 2-3 times lower than type A. However, influenza B mutates enough that lasting immunity is not possible. For example at the U.S.'s Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research's Vaccines and Related Biological Products Advisory Committee's 101st meeting of February 16, 2005, an extensive discussion and vote was held concerning next year's flu vaccine virus selection including which influenza B strain to use in the formulation of the flu vaccine:

"For Influenza B, the question was asked: are there new strains present? And the answer was yes, and in 2004, the majority of the viruses were similar to a strain called B/Shanghai/361/2002, which is from the so-called B/Yamagata/1688 hemagglutinin lineage. That lineage was not the one that was being used in the vaccine that was current last year. In a minority of the strains that were found during the epidemiological studies were similar to the strain that was in the vaccine for last year, which was B/Hong Kong/330/2001, which belongs to the HA lineage that we represent with the strain B/Victoria/287. In answer to the question were these new viruses spreading, the answer, of course, is definitely yes.

The Fujian-like viruses had become widespread around the world and were predominant everywhere, and these B/Shanghai-like strains at the time we were holding this meeting in February were predominant not only in North America and the United States, but also in Asia and Europe."

Morphology

The Influenza B virus capsid is enveloped while its virion consists of an envelope, a matrix protein, a nucleoprotein complex, a nucleocapsid, and a polymerase complex. It is sometimes spherical and sometimes filamentous. Its 500 or so surface projections are made of hemagglutinin and neuraminidase.

Nucleic Acid

The Influenza B virus genome is 14648 nucleotides long and consists of eight segments of linear negative-sense, single-stranded RNA. The multipartite genome is encapsidated, each segment in a separate nucleocapsid, and the nucleocapsids are surrounded by one envelope.

H10N7

H10N7 is a subtype of the species Influenza A virus (sometimes called bird flu virus). In 2004 in Egypt, H10N7 was reported for the first time in humans. It caused illness in two one-year old infants, residents of Ismaillia, Egypt; one child’s father a poultry merchant.

The first reported H10N7 outbreak in the US occurred in Minnesota on two turkey farms in 1979 and on a third in 1980. "The clinical signs ranged from severe, with a mortality rate as high as 31%, to subclinical. Antigenically indistinguishable viruses were isolated from healthy mallards on a pond adjacent to the turkey farms"

H5N2

H5N2 is a subtype of the species Influenzavirus A (avian influenza virus or bird flu virus).

Low pathogenic avian inluenza H5N2 virus in poultry later gained accentuated virulence in the United States and Mexico. A highly pathogenic strain of H5N2 caused flu outbreaks with significant spread to numerous farms, resulting in great economic losses in 1983 in Pennsylvania, USA in chickens and turkeys, in 1994 in Mexico in chickens and a minor outbreak in 1997 in Italy in chickens.

In Korea, ducks have been destroyed at the farm since quarantine officials detected the suspected low pathogenic H5N2 strain of avian influenza on December 1, 2004.

In Japan, H5N2 virus was isolated or an anti-H5 antibody was identified from chickens in 40 chicken farms in Ibaraki Prefecture and in one chicken farm in Saitama Prefecture from June through December 2005. The strain was named as A/ chicken /Ibaraki/1/2005(H5N2).About 5.7 million birds were destroyed in Ibaraki following the H5N2 outbreaks.

It was reported on November 12, 2005 that "One of 2 birds found infected with bird flu in Kuwait has the H5N1 strain of the virus, authorities said. The infected bird was a migrating flamingo found on a Kuwait beach. The other was an imported falcon found to have the milder H5N2 variant."

In China, inactivated H5N2 has been used as a vaccine for H5N1.

In 2006, an H5N2 outbreak on a single farm in South Africa resulted in the destruction of all its sixty ostriches. The strain was similar to the one that caused outbreaks in South Africa 2004/2005.

In 2007, a low-pathogenic strain of H5N2 was found in samples collected from 25,000 turkeys in Pendleton County, West Virginia in a routine testing prior to their slaughter. The birds showed no sign of illness or mortality. Measures were taken to prevent the virus from mutating and spreading.

In late 2007 (December 21), an H5N2 outbreak was found in the Dominican Republic, in a Suburb of Higuey City, on the eastern side of the island. 15 roosters and 2 hens where eliminated even though they had no visible sign of infection.

In May and June 2008, there were three outbreaks of low-pathogenic H5N2 avian flu in birds at three locations in the central, northern, and southern parts of Haiti. "The outbreaks began on May 20 and appeared to be ongoing", as of June 17, 2008.

In Taiwan, outbreaks of H5N2 have been confirmed in December 2008.

Japan's Health Ministry said Jan, 2006 that poultry farm workers in Ibaraki prefecture may have been exposed to H5N2 (which was not previously known to infect humans) in 2005.Data were collected from 257 workers at 35 chicken farms by Ibaraki prefectural government. Using a Wilcoxon signed-rank test, it was determined that the H5N2 antibody titers of the second samples of paired sera were significantly higher than those of the first samples (p<0.001). The H5N2 antibody titers of paired sera of 13 subjects increased fourfold or more. The results suggest that this may have been the first avian influenza H5N2 infection from poultry to affect humans.

H7N3

H7N3 is a subtype of the species Influenza A virus (sometimes called bird flu virus).

In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been confirmed in that region. Symptoms included conjunctivitis and mild influenza-like illness. Both fully recovered.

"The H7N3 strain was first detected in turkeys in Britain in 1963 and made one of its last known appearances in poultry in Canada in April and May 2004, according to the WHO and World Organisation for Animal Health. An outbreak of the less virulent H5N2 strain of bird flu in Taiwan in 2004 led to the culling of hundreds of thousands of fowl."

"Taiwan found a highly pathogenic strain of avian flu, H7N3, in droppings left by a migratory bird and is carrying out tests to see whether the virus has spread to nearby poultry farms, the agriculture department said 14 November 2005."

For the first time since 1979, H7N3 was found in the UK in April 2006. It infected birds and one poultry worker (whose only symptom was conjunctivitis) in a Norfolk, England Witford Lodge Farm. "Antiviral Tamiflu was administered to poultry workers on the farm as a precautionary measure. 35,000 chickens will be culled in the infected farm and a 1 kilometre exclusion zone has been placed."

In September 27, 2007 another outbreak of H7N3 was detected in a poultry operation in Saskatchewan, Canada. The Canadian Food Inspection Agency has requested the euthanization of the flock, and the disinfection of all building, materials and equipment in contact with the birds or their droppings.

H7N2

H7N2 is a subtype of the species Influenza A virus (sometimes called bird flu virus).

One person in Virginia, US in 2002 and one person in New York, US, in 2003 were found to have serologic evidence of infection from H7N2; both fully recovered.

In February 2004, an outbreak of low pathogenic avian influenza (LPAI) A (H7N2) was reported on 2 chicken farms in Delaware and in four live bird markets in New Jersey supplied by the same farms. In March 2004, surveillance samples from a flock of chickens in Maryland tested positive for LPAI H7N2. It is likely that this was the same strain.

A CDC study following the 2002 outbreaks of H7N2 in commercial poultry farms in western Virginia concluded:

An important factor contributing to rapid early spread of AI virus infection among commercial poultry farms during this outbreak was disposal of dead birds via rendering off-farm. Because of the highly infectious nature of AI virus and the devastating economic impact of outbreaks, poultry farmers should consider carcass disposal techniques that do not require off-farm movement, such as burial, composting, or incineration.

On 24 May 2007, an outbreak of H7N2 was confirmed at a poultry farm near Corwen, in Wales from tests on chickens that died from H7N2. The owners of the Conwy farm bought 15 Rhode Island Red chickens two weeks prior but all died from H7N2. The 32 other poultry at the site were slaughtered. A one kilometer exclusion zone was put in force around the property in which birds and bird products cannot be moved and bird gathering can only take place under licence. Nine people who were associated with the infected or dead poultry and reported flu-like symptoms were tested. Four tested positive for evidence of infection from H7N2 and were successfully treated for mild flu. In early June it was discovered that the virus had spread to a poultry farm 70 miles (113 km) away near St. Helens in north-west England. All the poultry at the farm were slaughtered and a 1 km exclusion zone imposed.

A 2008 analysis of the New York 2003 case concluded that the H7N2 virus responsible could be evolving toward the same strong sugar-binding properties of the three worldwide viral pandemics in 1918, 1957 and 1968. (Human flus and bird flus differ in the molecules they are good at binding with because mammals and birds differ in the molecules on the cell surface to be bound with. Humans have very few cells with the bird sugar on its cell surface.) A study with ferrets showed that this H7N2 strain could be passed from mammal to mammal.

H9N2

H9N2 is a subtype of the species Influenza A virus (sometimes called bird flu virus). In 1999 and 2003, an H9N2 influenza strain caused illness in three people, aged one, four and five years old, in Hong Kong. All three patients recovered. In 2007 an H9N2 influenza strain caused illness in a 9-month old baby in Hong Kong.

"H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages. Among the chicken H9N2 viruses, six of the gene segments were apparently derived from an earlier chicken H9N2 virus isolated in China, whereas the PB1 and PB2 genes are closely related to those of the H5N1 viruses and a quail H9N2 virus A/quail/Hong Kong/G1/97 (Qa/HK/G1/97) suggesting that many of the 1997 chicken H9 isolates in the markets were reassortants."

"The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), has issued a task order under an existing contract to Chiron Corporation of Emeryville, CA, for the production of an investigational vaccine based on an H9N2 strain of avian influenza virus that has infected humans and has the potential to trigger a modern-day pandemic."

H1N2

H1N2 is a subtype of the species Influenza A virus (sometimes called bird flu virus). It is currently pandemic in both human and pig populations.

H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans.

The new A(H1N2) strain appears to have resulted from the reassortment of the genes of the currently circulating influenza A(H1N1) and A(H3N2) subtypes. The hemagglutinin protein of the A(H1N2) virus is similar to that of the currently circulating A(H1N1) viruses and the neuraminidase protein is similar to that of the current A(H3N2) viruses.

It is unknown where the A(H1N2) virus originated, but on February 6, 2002, the World Health Organization (WHO) in Geneva and the Public Health Laboratory Service (PHLS) in the United Kingdom reported the identification influenza A(H1N2) virus from humans in the UK, Israel, and Egypt. In addition to the virus isolates reported by WHO and PHLS, the Centers for Disease Control and Prevention has identified influenza A(H1N2) virus from patient specimens collected during the 2001-2002 and 2002-2003 seasons.* Influenza A(H1N2) viruses have circulated transiently in the past. Between December 1988 and March 1989, 19 influenza A(H1N2) virus isolates were identified in 6 cities in China, but the virus did not spread further.

A(H1N2) was also identified during the 2001-2002 flu season (northern hemisphere) in Canada, the U.S.A., Ireland, Latvia, France, Romania, Oman, India, Malaysia, and Singapore.

The H1N2 virus is not very different from the currently circulating influenza viruses. The H1 protein of the H1N2 virus is like the H1 protein of the currently circulating H1N1 viruses and the N2 protein is similar to the N2 protein in the currently circulating H3N2 viruses. The difference is that we don't commonly see the H1 and N2 proteins on the same virus.

The A(H1N2) virus is not causing a more severe illness than other influenza viruses, and no unusual increases in influenza activity have been associated with the A(H1N2) virus. Because both the hemagglutinin and neuraminidase protein on the A(H1N2) virus closely matches the hemagglutinin and neuraminidase proteins of viruses included in the current influenza vaccine, the vaccine should provide good protection against influenza A(H1N2) virus as well as protection against the currently circulating A(H1N1), A(H3N2), and B viruses.

H7N7

H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains (HPAI) and low pathogenic strains (LPAI) exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies. This unusual zoonotic potential represents a pandemic threat.

In 2003 in the Netherlands 89 people were confirmed to have the H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded.Antibodies were found in over half of 500 people tested according to the final official report by the Dutch government:

As at least 50% of the people exposed to infected poultry had H7 antibodies detectable with the modified assay, it was estimated that avian influenza A/H7N7 virus infection occurred in at least 1000, and perhaps as many as 2000 people. The seroprevalence of H7 antibodies in people without contact with infected poultry, but with close household contact to an infected poultry worker, was 59%. This suggests that the population at risk for avian influenza was not limited to those with direct contact to infected poultry, and that person to person transmission may have occurred on a large scale. Final analysis of Dutch avian influenza outbreaks reveals much higher levels of transmission to humans than previously thought .

In August 2006, low pathogenic (LP) H7N7 was found during routine testing at a poultry farm in Voorthuizen in the central Netherlands. As a precautionary measure, 25,000 chickens were culled from Voorthuizen and surrounding farms.

In June 2008, high pathogenic (HP) H7N7 was confirmed on a 25,000-bird laying unit at Shenington, England; probably derived from a pre-existing low pathogenic variety. "Increased mortality (2.5 per cent in one shed) and a drop in egg production had been recorded two weeks before birds started dying in large numbers on June 2, leading to the diagnosis of HP H7N7 on June 4."

In October 2009, high pathogenic (HP) H7N7 was confirmed on a farm in Almoguera, Guadalajara, Spain. Hong Kong announced that it would suspend the import of poultry from Spain.

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A(H5N1) or simply H5N1, is a subtype of the Influenza A virus which can cause illness in humans and many other animal species. A bird-adapted strain of H5N1, called HPAI A(H5N1) for "highly pathogenic avian influenza virus of type A of subtype H5N1", is the causative agent of H5N1 flu, commonly known as "avian influenza" or "bird flu". It is enzootic in many bird populations, especially in Southeast Asia. One strain of HPAI A(H5N1) is spreading globally after first appearing in Asia. It is epizootic (an epidemic in nonhumans) and panzootic (affecting animals of many species, especially over a wide area), killing tens of millions of birds and spurring the culling of hundreds of millions of others to stem its spread. Most references to "bird flu" and H5N1 in the popular media refer to this strain. According to the FAO Avian Influenza Disease Emergency Situation Update, H5N1 pathogenicity is continuing to gradually rise in endemic areas but the avian influenza disease situation in farmed birds is being held in check by vaccination. Eleven outbreaks of H5N1 were reported worldwide in June 2008 in five countries (China, Egypt, Indonesia, Pakistan and Vietnam) compared to 65 outbreaks in June 2006 and 55 in June 2007. The "global HPAI situation can be said to have improved markedly in the first half of 2008 [but] cases of HPAI are still underestimated and underreported in many countries because of limitations in country disease surveillance systems".

HPAI A(H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus.A risk factor for contracting the virus is handling of infected poultry, but transmission of the virus from infected birds to humans is inefficient.Still, around 60% of humans known to have been infected with the current Asian strain of HPAI A(H5N1) have died from it, and H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. In 2003, world-renowned virologist Robert G. Webster published an article titled "The world is teetering on the edge of a pandemic that could kill a large fraction of the human population" in American Scientist. He called for adequate resources to fight what he sees as a major world threat to possibly billions of lives.On September 29, 2005, David Nabarro, the newly-appointed Senior United Nations System Coordinator for Avian and Human Influenza, warned the world that an outbreak of avian influenza could kill anywhere between 5 million and 150 million people.Experts have identified key events (creating new clades, infecting new species, spreading to new areas) marking the progression of an avian flu virus towards becoming pandemic, and many of those key events have occurred more rapidly than expected.

Due to the high lethality and virulence of HPAI A(H5N1), its endemic presence, its increasingly large host reservoir, and its significant ongoing mutations, the H5N1 virus is the world's largest current pandemic threat and billions of dollars are being spent researching H5N1 and preparing for a potential influenza pandemic. At least 12 companies and 17 governments are developing pre-pandemic influenza vaccines in 28 different clinical trials that, if successful, could turn a deadly pandemic infection into a nondeadly one. Full-scale production of a vaccine that could prevent any illness at all from the strain would require at least three months after the virus's emergence to begin, but it is hoped that vaccine production could increase until one billion doses were produced by one year after the initial identification of the virus.

H5N1 may cause more than one influenza pandemic as it is expected to continue mutating in birds regardless of whether humans develop herd immunity to a future pandemic strain.Influenza pandemics from its genetic offspring may include influenza A virus subtypes other than H5N1. While genetic analysis of the H5N1 virus shows that influenza pandemics from its genetic offspring can easily be far more lethal than the Spanish Flu pandemic, planning for a future influenza pandemic is based on what can be done and there is no higher Pandemic Severity Index level than a Category 5 pandemic which, roughly speaking, is any pandemic as bad as the Spanish flu or worse; and for which all intervention measures are to be used.

H3N2

Influenza A virus subtype H3N2 (also H3N2) is a subtype of viruses that cause influenza (flu). H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains. H3N2 is increasingly abundant in seasonal influenza, which kills an estimated 36,000 people in the United States each year.

H3N2 is a subtype of the viral genus Influenzavirus A, which is an important cause of human influenza. Its name derives from the forms of the two kinds of proteins on the surface of its coat, hemagglutinin (H) and neuraminidase (N). By reassortment, H3N2 exchanges genes for internal proteins with other influenza subtypes.

Seasonal influenza kills an estimated 36,000 people in the United States each year. Flu vaccines are based on predicting which mutants of H1N1, H3N2, H1N2, and influenza B will proliferate in the next season. Separate vaccines are developed for the northern and southern hemispheres in preparation for their annual epidemics. In the tropics, influenza shows no clear seasonality. In the past ten years, H3N2 has tended to dominate in prevalence over H1N1, H1N2, and influenza B. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005.

Seasonal H3N2 flu is a human flu from H3N2 that is slightly different from one of last year's flu season H3N2 variants. Seasonal influenza viruses flow out of overlapping epidemics in East and Southeast Asia, then trickle around the globe before dying off. Identifying the source of the viruses allows global health officials to better predict which viruses are most likely to cause the most disease over the next year. An analysis of 13,000 samples of influenza A/H3N2 virus that were collected across six continents from 2002 to 2007 by the WHO's Global Influenza Surveillance Network showed that newly emerging strains of H3N2 appeared in East and Southeast Asian countries about 6 to 9 months earlier than anywhere else. The strains generally reached Australia and New Zealand next, followed by North America and Europe. The new variants typically reached South America after an additional 6 to 9 months, the group reported.

H2N2

H2N2 is a subtype of the species influenzavirus A (sometimes called bird flu virus). H2N2 has mutated into various strains including the Asian Flu strain (now extinct in the wild), H3N2, and various strains found in birds. It is also suspected of causing a human pandemic in 1889.

Some believe that the 1889 - 1890 Russian flu was caused by the influenzavirus A virus subtype H2N2, but the evidence is not conclusive. It is the earliest flu pandemic for which detailed records are available. "The 1889 pandemic, known as the Russian Flu, began in Russia and spread rapidly throughout Europe. It reached North America in December 1889 and spread to Latin America and Asia in February 1890. About 1 million people died in this pandemic."

The "Asian Flu" was a category 2 flu pandemic outbreak of avian influenza that originated in China in early 1956 lasting until 1958. It originated from mutation in wild ducks combining with a pre-existing human strain. The virus was first identified in Guizhou. It spread to Singapore in February 1957, reached Hong Kong by April, and US by June. Death toll in the US was approximately 69,800. Estimates of worldwide deaths caused by this pandemic varies widely depending on source; ranging from 1 million to 4 million, with WHO settling on "about 2 million".

Asian Flu was of the H2N2 subtype (a notation that refers to the configuration of the hemagglutinin and neuraminidase proteins in the virus) of type A influenza, and an influenza vaccine was developed in 1957 to contain its outbreak.The Asian Flu strain later evolved via antigenic shift into H3N2 which caused a milder pandemic from 1968 to 1969.

Both the H2N2 and H3N2 pandemic strains contained avian influenza virus RNA segments. "While the pandemic human influenza viruses of 1957 (H2N2) and 1968 (H3N2) clearly arose through reassortment between human and avian viruses, the influenza virus causing the 'Spanish flu' in 1918 appears to be entirely derived from an avian source (Belshe 2005)."

H1N1

H1N1Influenza A (H1N1) virus is a subtype of influenza A virus and the most common cause of influenza (flu) in humans. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent all human flu infections in 2004-2005. Other strains of H1N1 are endemic in pigs (swine influenza) and in birds (avian influenza).

In June 2009, World Health Organization declared that flu due to a new strain of swine-origin H1N1 was responsible for the 2009 flu pandemic. This strain is often called swine flu by the public media.

In 1976, a novel swine influenza A (H1N1) caused severe respiratory illness in 13 soldiers with 1 death at Fort Dix, New Jersey. The virus was detected only from January 19 to February 9 and did not spread beyond Fort Dix.

The 1977–1978 Russian flu epidemic was caused by strain Influenza A/USSR/90/77 (H1N1). It infected mostly children and young adults under 23 because a similar strain was prevalent in 1947–57, causing most adults to have substantial immunity. The virus was included in the 1978–1979 influenza vaccine.

Influenza A

Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Influenzavirus A includes only one species: Influenza A virus which causes influenza in birds and some mammals. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates of influenza A virus cause severe disease both in domestic poultry and, rarely, in humans. Occasionally viruses are transmitted from wild aquatic birds to domestic poultry and this may cause an outbreak or give rise to human influenza pandemics.

Influenza A viruses are negative sense, single-stranded, segmented RNA viruses. There are several subtypes, labeled according to an H number (for the type of hemagglutinin) and an N number (for the type of neuraminidase). There are 16 different H antigens (H1 to H16) and nine different N antigens (N1 to N9). The newest H type (H16) was isolated from black-headed gulls caught in Sweden and the Netherlands in 1999 and reported in the literature in 2005.

Each virus subtype has mutated into a variety of strains with differing pathogenic profiles; some pathogenic to one species but not others, some pathogenic to multiple species.

Variants

Variants are identified and named according to the isolate that they are like and thus are presumed to share lineage (example Fujian flu virus like); according to their typical host (example Human flu virus); according to their subtype (example H3N2); and according to their deadliness (example LP, Low Pathogenic). So a flu from a virus similar to the isolate A/Fujian/411/2002(H3N2) is called Fujian flu, human flu, and H3N2 flu.

Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. The main variants named using this convention are:

Bird flu
Human flu
Swine flu
Horse flu
Dog flu
Cat flu

Variants have also sometimes been named according to their deadliness in poultry, especially chickens:

• Low Pathogenic Avian Influenza (LPAI)
• Highly Pathogenic Avian Influenza (HPAI), also called: deadly flu or death flu

Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong Flu.

Subtypes

H1N1
H1N1 is currently pandemic in both human and pig populations. A variant of H1N1 was responsible for the Spanish flu pandemic that killed some 50 million to 100 million people worldwide over about a year in 1918 and 1919. Another variant was named a pandemic threat in the 2009 swine flu outbreak. Controversy arose in October, 2005, after the H1N1 genome was published in the journal, Science, because of fears that this information could be used for bioterrorism. "When he compared the 1918 virus with today's human flu viruses, Dr. Taubenberger noticed that it had alterations in just 25 to 30 of the virus's 4,400 amino acids. Those few changes turned a bird virus into a killer that could spread from person to person."

H2N2
The Asian Flu was a pandemic outbreak of H2N2 avian influenza that originated in China in 1957, spread worldwide that same year during which a influenza vaccine was developed, lasted until 1958 and caused between one and four million deaths. H3N2

H3N2
H3N2 is currently endemic in both human and pig populations. It evolved from H2N2 by antigenic shift and caused the Hong Kong Flu pandemic of 1968 and 1969 that killed up to 750,000. "An early-onset, severe form of influenza A H3N2 made headlines when it claimed the lives of several children in the United States in late 2003."The dominant strain of annual flu in January 2006 is H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005. "[C]ontemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host."

H5N1
H5N1 is the world's major influenza pandemic threat.

H7N7
H7N7 has unusual zoonotic potential. In 2003 in Netherlands 89 people were confirmed to have H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded.

H1N2
H1N2 is currently endemic in both human and pig populations. The new H1N2 strain appears to have resulted from the reassortment of the genes of the currently circulating influenza H1N1 and H3N2 subtypes. The hemagglutinin protein of the H1N2 virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase protein is similar to that of the current H3N2 viruses.

H9N2
Low pathogenic avian influenza A (H9N2) infection was confirmed in 1999, in China and Hong Kong in two children, and in 2003 in Hong Kong in one child. All three fully recovered.

H7N2 One person in New York in 2003 and one person in Virginia in 2002 were found to have serologic evidence of infection with H7N2. Both fully recovered.

H7N3 In North America, the presence of avian influenza strain H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans with avian influenza have been confirmed in that region. "Symptoms included conjunctivitis and mild influenza-like illness." Both fully recovered.

H5N2
Japan's Health Ministry said Jan, 2006 that poultry farm workers in Ibaraki prefecture may have been exposed to H5N2 in 2005. The H5N2 antibody titers of paired sera of 13 subjects increased fourfold or more.

H10N7
In 2004 in Egypt H10N7 was reported for the first time in humans. It caused illness in two infants in Egypt. One child’s father is a poultry merchant.

Classification of Swine Flu

Of the three genera of influenza viruses that cause human flu, two also cause influenza in pigs, with influenza A being common in pigs and influenza C being rare. Influenza B has not been reported in pigs. Within influenza A and influenza C, the strains found in pigs and humans are largely distinct, although because of reassortment there have been transfers of genes among strains crossing swine, avian, and human species boundaries.

Influenza A

Swine influenza is known to be caused by influenza A subtypes H1N1, H1N2, H2N3, H3N1, and H3N2. In pigs, three influenza A virus subtypes (H1N1, H1N2, and H3N2) are the most common strains worldwide. In the United States, the H1N1 subtype was exclusively prevalent among swine populations before 1998; however, since late August 1998, H3N2 subtypes have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants, containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) lineages.

Influenza B

Influenza B viruses are only known to infect humans and seals, giving them influenza. This limited host range is apparently responsible for the lack of Influenzavirus B caused influenza pandemics in contrast with those caused by the morphologically similar Influenzavirus A as both mutate by both genetic drift and reassortment.

Influenza C

Influenza C viruses infect both humans and pigs, but do not infect birds. Transmission between pigs and humans have occurred in the past. For example, influenza C caused small outbreaks of a mild form of influenza amongst children in Japan and California. Because of its limited host range and the lack of genetic diversity in influenza C, this form of influenza does not cause pandemics in humans