H5N1

Influenza A virus subtype H5N1 Genetic structure Infection Human mortality Global spread in 2004 in 2005 in 2006 in 2007 Social impact Pandemic

v t e

Influenza (Flu)
Types
Avian (A/H5N1 subtype) Canine Equine Swine (A/H1N1 subtype)
Vaccines
2009 pandemic (Pandemrix) ACAM-FLU-A Fluzone Influvac Live attenuated (FluMist) Optaflu
Treatment
Amantadine Arbidol Laninamivir Oseltamivir Peramivir Rimantadine Vitamin D Zanamivir
Pandemics
2009 Swine 1968–1969 Hong Kong 1918
Outbreaks
2008 West Bengal 2007 Bernard Matthews H5N1 2007 Australian equine 2006 H5N1 India 1976 swine flu
See also
Flu season Influenza evolution Influenza research Influenza-like illness
v t e

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.^[1] 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.^[2]

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".^[3] On October 10, 2011 the WHO announced a total of 566 confirmed human cases which resulted in the deaths of 332 people since 2003.^[4]

A filtered and purified influenza A vaccine for humans is being developed, and many countries have recommended it be stockpiled so, if an avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu.

A novel, highly contagious strain of H5N1 was created by Ron Fouchier of the Erasmus Medical Centre in Rotterdam, the Netherlands, who first presented his work to the public at an influenza conference in Malta in September 2011.^[5] Five mutations were introduced into the H5N1 genome, and the virus was then bred by passing it from the noses of infected ferrets to the noses of uninfected ones, which was repeated 10 times.^[6] Fouchier described the result as "probably one of the most dangerous viruses you can make".^[7]

Overview[link]

HPAI A(H5N1) is considered an avian disease, although there is some evidence of limited human-to-human transmission of the virus.^[8] A risk factor for contracting the virus is handling of infected poultry, but transmission of the virus from infected birds to humans is inefficient.^[9] 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.^[10] 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.^[11] 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.^[12] At least 12 companies and 17 governments are developing prepandemic 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.^[13]

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.^[14] Influenza pandemics from its genetic offspring may include influenza A virus subtypes other than H5N1.^[15] 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,^[16] 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.^[17]

Signs and symptoms[link]

The different sites of infection (shown in red) of seasonal H1N1 versus avian H5N1 influences their lethality and ability to spread.^[18]

The avian influenza hemagglutinin binds alpha 2-3 sialic acid receptors, while human influenza hemagglutinins bind alpha 2-6 sialic acid receptors.^[19] This means when the H5N1 strain infects humans, it will replicate in the lower respiratory tract, and consequently will cause viral pneumonia.^[20] There is as yet no human form of H5N1, so all humans who have caught it so far have caught avian H5N1. In general, humans who catch a humanized influenza A virus (a human flu virus of type A) usually have symptoms that include fever, cough, sore throat, muscle aches, conjunctivitis, and, in severe cases, breathing problems and pneumonia that may be fatal. The severity of the infection depends in large part on the state of the infected persons' immune systems and whether they had been exposed to the strain before (in which case they would be partially immune). No one knows if these or other symptoms will be the symptoms of a humanized H5N1 flu.

The reported mortality rate of highly pathogenic H5N1 avian influenza in a human is high; WHO data indicate 60% of cases classified as H5N1 resulted in death. However, there is some evidence the actual mortality rate of avian flu could be much lower, as there may be many people with milder symptoms who do not seek treatment and are not counted.^[21][22]

In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms.^[23] There have been studies of the levels of cytokines in humans infected by the H5N1 flu virus. Of particular concern is elevated levels of tumor necrosis factor-alpha, a protein associated with tissue destruction at sites of infection and increased production of other cytokines. Flu virus-induced increases in the level of cytokines is also associated with flu symptoms, including fever, chills, vomiting and headache. Tissue damage associated with pathogenic flu virus infection can ultimately result in death.^[10] The inflammatory cascade triggered by H5N1 has been called a 'cytokine storm' by some, because of what seems to be a positive feedback process of damage to the body resulting from immune system stimulation. H5N1 induces higher levels of cytokines than the more common flu virus types.^[24]

Genetics[link]

The H in H5N1 stands for "hemagglutinin", as depicted in this molecular model

The first known strain of HPAI A(H5N1) (called A/chicken/Scotland/59) killed two flocks of chickens in Scotland in 1959, but that strain was very different from the current highly pathogenic strain of H5N1. The dominant strain of HPAI A(H5N1) in 2004 evolved from 1999 to 2002 creating the Z genotype.^[25] It has also been called "Asian lineage HPAI A(H5N1)".

Asian lineage HPAI A(H5N1) is divided into two antigenic clades. "Clade 1 includes human and bird isolates from Vietnam, Thailand, and Cambodia and bird isolates from Laos and Malaysia. Clade 2 viruses were first identified in bird isolates from China, Indonesia, Japan, and South Korea before spreading westward to the Middle East, Europe, and Africa. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections: Map

• Subclade 1, Indonesia
• Subclade 2, Europe, Middle East, and Africa (called EMA)
• Subclade 3, China"^[14][26][27]

A 2007 study focused on the EMA subclade has shed further light on the EMA mutations. "The 36 new isolates reported here greatly expand the amount of whole-genome sequence data available from recent avian influenza (H5N1) isolates. Before our project, GenBank contained only 5 other complete genomes from Europe for the 2004–2006 period, and it contained no whole genomes from the Middle East or northern Africa. Our analysis showed several new findings. First, all European, Middle Eastern, and African samples fall into a clade that is distinct from other contemporary Asian clades, all of which share common ancestry with the original 1997 Hong Kong strain. Phylogenetic trees built on each of the 8 segments show a consistent picture of 3 lineages, as illustrated by the HA tree shown in Figure 1. Two of the clades contain exclusively Vietnamese isolates; the smaller of these, with 5 isolates, we label V1; the larger clade, with 9 isolates, is V2. The remaining 22 isolates all fall into a third, clearly distinct clade, labeled EMA, which comprises samples from Europe, the Middle East, and Africa. Trees for the other 7 segments display a similar topology, with clades V1, V2, and EMA clearly separated in each case. Analyses of all available complete influenza (H5N1) genomes and of 589 HA sequences placed the EMA clade as distinct from the major clades circulating in People's Republic of China, Indonesia, and Southeast Asia."^[28]

Terminology[link]

H5N1 isolates are identified like this actual HPAI A(H5N1) example, A/chicken/Nakorn-Patom/Thailand/CU-K2/04(H5N1):

• A stands for the species of influenza (A, B or C).
• chicken is the species the isolate was found in
• Nakorn-Patom/Thailand is the place this specific virus was isolated
• CU-K2 identifies it from other influenza viruses isolated at the same place
• 04 represents the year 2004
• H5 stands for the fifth of several known types of the protein hemagglutinin.
• N1 stands for the first of several known types of the protein neuraminidase.

Other examples include: A/duck/Hong Kong/308/78(H5N3), A/avian/NY/01(H5N2), A/chicken/Mexico/31381-3/94(H5N2), and A/shoveler/Egypt/03(H5N2).^[29]

As with other avian flu viruses, H5N1 has strains called "highly pathogenic" (HP) and "low-pathogenic" (LP). Avian influenza viruses that cause HPAI are highly virulent, and mortality rates in infected flocks often approach 100%. LPAI viruses have negligible virulence, but these viruses can serve as progenitors to HPAI viruses. The current strain of H5N1 responsible for the deaths of birds across the world is an HPAI strain; all other current strains of H5N1, including a North American strain that causes no disease at all in any species, are LPAI strains. All HPAI strains identified to date have involved H5 and H7 subtypes. The distinction concerns pathogenicity in poultry, not humans. Normally, a highly pathogenic avian virus is not highly pathogenic to either humans or nonpoultry birds. This current deadly strain of H5N1 is unusual in being deadly to so many species, including some, like domestic cats, never previously susceptible to any influenza virus.^[30]

Genetic structure and related subtypes[link]

The N in H5N1 stands for "Neuraminidase", the protein depicted in this ribbon diagram.

H5N1 is a subtype of the species Influenza A virus of the Influenzavirus A genus of the Orthomyxoviridae family. Like all other influenza A subtypes, the H5N1 subtype is an RNA virus. It has a segmented genome of eight negative sense, single-strands of RNA, abbreviated as PB2, PB1, PA, HA, NP, NA, MP and NS.

HA codes for hemagglutinin, an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. NA codes for neuraminidase, an antigenic glycosylated enzyme found on the surface of the influenza viruses. It facilitates the release of progeny viruses from infected cells.^[31] The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify the structure of proteins that are most medically relevant as targets for antiviral drugs and antibodies. HA and NA are also used as the basis for the naming of the different subtypes of influenza A viruses. This is where the H and N come from in H5N1.

Influenza A viruses are significant for their potential for disease and death in humans and other animals. Influenza A virus subtypes that have been confirmed in humans, in order of the number of known human pandemic deaths that they have caused, include:

• H1N1, which caused the 1918 flu pandemic ("Spanish flu") and currently is causing seasonal human flu and the 2009 flu pandemic ("swine flu")
• H2N2, which caused "Asian flu"
• H3N2, which caused "Hong Kong flu" and currently causes seasonal human flu
• H5N1, ("bird flu"), which is noted for having a strain (Asian-linage HPAI H5N1) that kills over half the humans it infects, infecting and killing species that were never known to suffer from influenza viruses before (e.g. cats), being unable to be stopped by culling all involved poultry - some think due to being endemic in wild birds, and causing billions of dollars to be spent in flu pandemic preparation and preventiveness
• H7N7, which has unusual zoonotic potential and killed one person
• H1N2, which is currently endemic in humans and pigs and causes seasonal human flu
• H9N2, which has infected three people
• H7N2, which has infected two people
• H7N3, which has infected two people
• H10N7, which has infected two people

Low pathogenic H5N1[link]

Low pathogenic avian influenza H5N1 (LPAI H5N1) also called "North American" H5N1 commonly occurs in wild birds. In most cases, it causes minor sickness or no noticeable signs of disease in birds. It is not known to affect humans at all. The only concern about it is that it is possible for it to be transmitted to poultry and in poultry mutate into a highly pathogenic strain.

• 1975 – LPAI H5N1 was detected in a wild mallard duck and a wild blue goose in Wisconsin.
• 1981 and 1985 – LPAI H5N1 was detected in ducks by the University of Minnesota conducting a sampling procedure in which sentinel ducks were monitored in cages placed in the wild for a short period of time.
• 1983 – LPAI H5N1 was detected in ring-billed gulls in Pennsylvania.
• 1986 - LPAI H5N1 was detected in a wild mallard duck in Ohio.
• 2005 - LPAI H5N1 was detected in ducks in Manitoba, Canada.
• 2008 - LPAI H5N1 was detected in ducks in New Zealand.
• 2009 - LPAI H5N1 was detected in commercial poultry in British Columbia.^[32]

"In the past, there was no requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so states and universities tested wild bird samples independently of USDA. Because of this, the above list of previous detections might not be all inclusive of past LPAI H5N1 detections. However, the World Organization for Animal Health (OIE) recently changed its requirement of reporting detections of avian influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be reported to the OIE because of their potential to mutate into highly pathogenic strains. Therefore, USDA now tracks these detections in wild birds, backyard flocks, commercial flocks and live bird markets."^[33]

High mutation rate[link]

Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. The segmentation of its genome facilitates genetic recombination by segment reassortment in hosts infected with two different influenza viruses at the same time.^[34][35] A previously uncontagious strain may then be able to pass between humans, one of several possible paths to a pandemic.

The ability of various influenza strains to show species-selectivity is largely due to variation in the hemagglutinin genes. Genetic mutations in the hemagglutinin gene that cause single amino acid substitutions can significantly alter the ability of viral hemagglutinin proteins to bind to receptors on the surface of host cells. Such mutations in avian H5N1 viruses can change virus strains from being inefficient at infecting human cells to being as efficient in causing human infections as more common human influenza virus types.^[36] This doesn't mean that one amino acid substitution can cause a pandemic, but it does mean that one amino acid substitution can cause an avian flu virus that is not pathogenic in humans to become pathogenic in humans.

Influenza A virus subtype H3N2 is endemic in pigs in China, and has been detected in pigs in Vietnam, increasing fears of the emergence of new variant strains. The dominant strain of annual flu virus in January 2006 was H3N2, which is now resistant to the standard antiviral drugs amantadine and rimantadine. The possibility of H5N1 and H3N2 exchanging genes through reassortment is a major concern. If a reassortment in H5N1 occurs, it might remain an H5N1 subtype, or it could shift subtypes, as H2N2 did when it evolved into the Hong Kong Flu strain of H3N2.

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".^[25]

Prevention[link]

There are several H5N1 vaccines for several of the avian H5N1 varieties, but the continual mutation of H5N1 renders them of limited use to date: while vaccines can sometimes provide cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Dr. Daniel Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine".^[37] However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic.^[38][39][40] Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.

Public health[link]

The examples and perspective in this article may not represent a worldwide view of the subject. Please improve this article and discuss the issue on the talk page. (January 2010)

"The United States is collaborating closely with eight international organizations, including the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), the World Organization for Animal Health (OIE), and 88 foreign governments to address the situation through planning, greater monitoring, and full transparency in reporting and investigating avian influenza occurrences. The United States and these international partners have led global efforts to encourage countries to heighten surveillance for outbreaks in poultry and significant numbers of deaths in migratory birds and to rapidly introduce containment measures. The U.S. Agency for International Development (USAID) and the U.S. Department of State, the U.S. Department of Health and Human Services (HHS), and Agriculture (USDA) are coordinating future international response measures on behalf of the White House with departments and agencies across the federal government".^[41]

Together steps are being taken to "minimize the risk of further spread in animal populations", "reduce the risk of human infections", and "further support pandemic planning and preparedness".^[41]

Ongoing detailed mutually coordinated onsite surveillance and analysis of human and animal H5N1 avian flu outbreaks are being conducted and reported by the USGS National Wildlife Health Center, the Centers for Disease Control and Prevention, the World Health Organization, the European Commission, and others.^[42]

Treatment[link]

There is no highly effective treatment for H5N1 flu, but oseltamivir (commercially marketed by Roche as Tamiflu), can sometimes inhibit the influenza virus from spreading inside the user's body. This drug has become a focus for some governments and organizations trying to prepare for a possible H5N1 pandemic.^[43] On April 20, 2006, Roche AG announced that a stockpile of three million treatment courses of Tamiflu are waiting at the disposal of the World Health Organization to be used in case of a flu pandemic; separately Roche donated two million courses to the WHO for use in developing nations that may be affected by such a pandemic but lack the ability to purchase large quantities of the drug.^[44]

However, WHO expert Hassan al-Bushra has said:

"Even now, we remain unsure about Tamiflu's real effectiveness. As for a vaccine, work cannot start on it until the emergence of a new virus, and we predict it would take six to nine months to develop it. For the moment, we cannot by any means count on a potential vaccine to prevent the spread of a contagious influenza virus, whose various precedents in the past 90 years have been highly pathogenic".^[45]

Animal and lab studies suggest that Relenza (zanamivir), which is in the same class of drugs as Tamiflu, may also be effective against H5N1. In a study performed on mice in 2000, "zanamivir was shown to be efficacious in treating avian influenza viruses H9N2, H6N1, and H5N1 transmissible to mammals".^[46] In addition, mice studies suggest the combination of zanamivir, celecoxib and mesalazine looks promising producing a 50% survival rate compared to no survival in the placebo arm.^[47] While no one knows if zanamivir will be useful or not on a yet to exist pandemic strain of H5N1, it might be useful to stockpile zanamivir as well as oseltamivir in the event of an H5N1 influenza pandemic. Neither oseltamivir nor zanamivir can currently be manufactured in quantities that would be meaningful once efficient human transmission starts.^[48] In September, 2006, a WHO scientist announced that studies had confirmed cases of H5N1 strains resistant to Tamiflu and Amantadine.^[49] Tamiflu-resistant strains have also appeared in the EU, which remain sensitive to Relenza.^[50][51]

Epidemiology[link]

The earliest infections of humans by H5N1 coincided with an epizootic (an epidemic in nonhumans) of H5N1 influenza in Hong Kong's poultry population. This panzootic (a disease affecting animals of many species, especially over a wide area) outbreak was stopped by the killing of the entire domestic poultry population within the territory. However, the disease has continued to spread. On December 21, 2009 the WHO announced a total of 447 cases which resulted in the deaths of 263.^[4]

Contagiousness[link]

Highly pathogenic H5N1

  Countries with poultry or wild birds killed by H5N1.

  Countries with humans, poultry and wild birds killed by H5N1.

H5N1 is easily transmissible between birds facilitating a potential global spread of H5N1. While H5N1 undergoes mutation and reassortment, creating variations which can infect species not previously known to carry the virus, not all of these variant forms can infect humans. H5N1 as an avian virus preferentially binds to a type of galactose receptors that populate the avian respiratory tract from the nose to the lungs and are virtually absent in humans, occurring only in and around the alveoli, structures deep in the lungs where oxygen is passed to the blood. Therefore, the virus is not easily expelled by coughing and sneezing, the usual route of transmission.^[19][20][52]

H5N1 is mainly spread by domestic poultry, both through the movements of infected birds and poultry products and through the use of infected poultry manure as fertilizer or feed. Humans with H5N1 have typically caught it from chickens, which were in turn infected by other poultry or waterfowl. Migrating waterfowl (wild ducks, geese and swans) carry H5N1, often without becoming sick.^[53][54] Many species of birds and mammals can be infected with HPAI A(H5N1), but the role of animals other than poultry and waterfowl as disease-spreading hosts is unknown.^[55]

According to a report by the World Health Organization, H5N1 may be spread indirectly. The report stated that the virus may sometimes stick to surfaces or get kicked up in fertilizer dust to infect people.^[56]

Virulence[link]

H5N1 has mutated into a variety of strains with differing pathogenic profiles, some pathogenic to one species but not others, some pathogenic to multiple species. Each specific known genetic variation is traceable to a virus isolate of a specific case of infection. Through antigenic drift, H5N1 has mutated into dozens of highly pathogenic varieties divided into genetic clades which are known from specific isolates, but all currently belonging to genotype Z of avian influenza virus H5N1, now the dominant genotype.^[35][34] H5N1 isolates found in Hong Kong in 1997 and 2001 were not consistently transmitted efficiently among birds and did not cause significant disease in these animals. In 2002 new isolates of H5N1 were appearing within the bird population of Hong Kong. These new isolates caused acute disease, including severe neurological dysfunction and death in ducks. This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.^[57] Genotype Z emerged in 2002 through reassortment from earlier highly pathogenic genotypes of H5N1^[2] that first infected birds in China in 1996, and first infected humans in Hong Kong in 1997.^[34][35][58] Genotype Z is endemic in birds in Southeast Asia, has created at least two clades that can infect humans, and is spreading across the globe in bird populations. Mutations are occurring within this genotype that are increasing their pathogenicity.^[59] Birds are also able to shed the virus for longer periods of time before their death, increasing the transmissibility of the virus.

Transmission and host range[link]

Influenza A virus, the virus that causes Avian flu. Transmission electron micrograph of negatively stained virus particles in late passage. (Source: Dr. Erskine Palmer, Centers for Disease Control and Prevention Public Health Image Library)

Infected birds transmit H5N1 through their saliva, nasal secretions, feces and blood. Other animals may become infected with the virus through direct contact with these bodily fluids or through contact with surfaces contaminated with them. H5N1 remains infectious after over 30 days at 0 °C ( 32.0 °F) (over one month at freezing temperature) or 6 days at 37 °C ( 98.6 °F) (one week at human body temperature) at ordinary temperatures it lasts in the environment for weeks. In Arctic temperatures, it doesn't degrade at all.

Because migratory birds are among the carriers of the highly pathogenic H5N1 virus, it is spreading to all parts of the world. H5N1 is different from all previously known highly pathogenic avian flu viruses in its ability to be spread by animals other than poultry.

In October 2004, researchers discovered that H5N1 is far more dangerous than was previously believed. Waterfowl were revealed to be directly spreading the highly pathogenic strain of H5N1 to chickens, crows, pigeons, and other birds, and the virus was increasing its ability to infect mammals as well. From this point on, avian flu experts increasingly referred to containment as a strategy that can delay, but not ultimately prevent, a future avian flu pandemic.

"Since 1997, studies of influenza A (H5N1) indicate that these viruses continue to evolve, with changes in antigenicity and internal gene constellations; an expanded host range in avian species and the ability to infect felids; enhanced pathogenicity in experimentally infected mice and ferrets, in which they cause systemic infections; and increased environmental stability."^[60]

The New York Times, in an article on transmission of H5N1 through smuggled birds, reports Wade Hagemeijer of Wetlands International stating, "We believe it is spread by both bird migration and trade, but that trade, particularly illegal trade, is more important".^[61]

On September 27, 2007 researchers reported that the H5N1 bird flu virus can also pass through a pregnant woman's placenta to infect the fetus. They also found evidence of what doctors had long suspected—that the virus not only affects the lungs, but also passes throughout the body into the gastrointestinal tract, the brain, liver, and blood cells.^[62]

Confirmed human cases and mortality rate of avian influenza (H5N1)
As of May 29, 2012

Country	2003			2004			2005			2006			2007			2008			2009			2010			2011			2012			Total
	cases	deaths		cases	deaths		cases	deaths		cases	deaths		cases	deaths		cases	deaths		cases	deaths		cases	deaths		cases	deaths		cases	deaths		cases	deaths
Azerbaijan										8	5	63%																			8	5	63%
Bangladesh																1	0	0%							2	0	0%	3	0	0%	6	0	0%
Cambodia							4	4	100%	2	2	100%	1	1	100%	1	0	0%	1	0	0%	1	1	100%	8	8	100%	3	3	100%	21	19	90%
PR China	1	1	100%				8	5	63%	13	8	62%	5	3	60%	4	4	100%	7	4	57%	2	1	50%	1	1	100%	1	1	100%	42	28	67%
Djibouti										1	0	0%																			1	0	0%
Egypt										18	10	56%	25	9	36%	8	4	50%	39	4	10%	29	13	45%	39	15	39%	9	5	56%	167	60	36%
Indonesia							20	13	65%	55	45	82%	42	37	88%	24	20	83%	21	19	90%	9	7	78%	12	10	83%	6	6	100%	189	157	83%
Iraq										3	2	67%																			3	2	67%
Laos													2	2	100%																2	2	100%
Burma													1	0	0%																1	0	0%
Nigeria													1	1	100%																1	1	100%
Pakistan													3	1	33%																3	1	33%
Thailand				17	12	71%	5	2	40%	3	3	100%																			25	17	68%
Turkey										12	4	33%																			12	4	33%
Vietnam	3	3	100%	29	20	69%	61	19	31%				8	5	63%	6	5	83%	5	5	100%	7	2	29%				4	2	50%	123	61	50%
Total	4	4	100%	46	32	70%	98	43	44%	115	79	69%	88	59	67%	44	33	75%	73	32	44%	48	24	50%	62	34	55%	26	17	65%	604	357	59%
edit this table Source: World Health Organization Human Animal Interface)

Society and culture[link]

H5N1 has had a significant effect on human society, especially the financial, political, social, and personal responses to both actual and predicted deaths in birds, humans, and other animals. Billions of U.S. dollars are being raised and spent to research H5N1 and prepare for a potential avian influenza pandemic. Over ten billion dollars have been spent and over two hundred million birds killed to try to contain H5N1.^{[12][63][64][65][66][67][68][69][70]}

People have reacted by buying less chicken causing poultry sales and prices to fall.^[71] Many individuals have stockpiled supplies for a possible flu pandemic. International health officials and other experts have pointed out that many unknown questions still hover around the disease.^[72]

Dr. David Nabarro, Chief Avian Flu Coordinator for the United Nations, and former Chief of Crisis Response for the World Health Organization has described himself as "quite scared" about H5N1's potential impact on humans. Nabarro has been accused of being alarmist before and on his first day in his role for the United Nations he proclaimed the avian flu could kill 150 million people. In an interview with the International Herald Tribune, Nabarro compares avian flu to AIDS in Africa, warning that underestimations led to inappropriate focus for research and intervention.^[73]

See also[link]

• Antigenic shift
• Influenza research
• Fujian flu
• H5N1 clinical trials
• International Conference on Emerging Infectious Diseases
• National Influenza Centers
• Swine influenza
• Zoonosis

References[link]

External links[link]

Wikimedia Commons has media related to: H5N1

Wikinews has related news: Avian Flu

• Influenza Research Database – Database of influenza genomic sequences and related information.

• WHO World Health Organization
  • WHO's Avian Flu Facts Sheet for 2006
  • Epidemic and Pandemic Alert and Response Guide to WHO's H5N1 pages
  • Avian Influenza Resources (updated) - tracks human cases and deaths
  • National Influenza Pandemic Plans
  • WHO Collaborating Centres and Reference Laboratories Centers, names, locations, and phone numbers
• FAO Avian Influenza portal Information resources, animations, videos, photos
  • FAO Food and Agriculture Organisation - Bi-weekly Avian Influenza Maps - tracks animal cases and deaths
  • FAO Bird Flu disease card
  • FAO Socio-Economic impact of AI Projects, Information resources
• OIE World Organisation for Animal Health - tracks animal cases and deaths
  • Official outbreak reports by country
  • Official outbreak reports by week
  • Chart of outbreaks by country

European Union

• Health-EU Portal EU response to Avian Influenza.
• Avian influenza - Q & A's factsheet from European Centre for Disease Prevention and Control

United Kingdom

• Exotic Animal Disease Generic Contingency Plan — DEFRA generic contingency plan for controlling and eradicating an outbreak of an exotic animal disease. PDF hosted by BBC (a government entity).
• UK Influenza Pandemic Contingency Plan by the National Health Service - a government entity. PDF hosted by BBC
• UK Department of Health

United States

• Center for Infectious Disease Research and Policy Avian Influenza (Bird Flu): Implications for Human Disease - An overview of Avian Influenza
• PandemicFlu.Gov U.S. Government's avian flu information site
• USAID U.S. Agency for International Development - Avian Influenza Response
• CDC, Centers for Disease Control and Prevention - responsible agency for avian influenza in humans in US - Facts About Avian Influenza (Bird Flu) and Avian Influenza A (H5N1) Virus
• USGS - NWHC National Wildlife Health Center - responsible agency for avian influenza in animals in US
• Wildlife Disease Information Node A part of the National Biological Information Infrastructure and partner of the NWHC, this agency collects and distributes news and information about wildlife diseases such as avian influenza and coordinates collaborative information sharing efforts.
• HHS U.S. Department of Health & Human Services's Pandemic Influenza Plan

Coordinates: 22°16′42″N 114°09′32″E / 22.27833°N 114.15889°E / 22.27833; 114.15889

Hong Kong Special Administrative Region of the People's Republic of China[note 1] 中華人民共和國香港特別行政區
Flag Emblem
Anthem: March of the Volunteers 《義勇軍進行曲》
View at night from Victoria Peak
Official language(s)		Chinese, English[note 2]
Spoken languages		Cantonese, English
Writing systems		Traditional Chinese, English alphabet
Demonym		Hong Konger
Government		Special Administrative Region of the People's Republic of China
-	Chief Executive	Donald Tsang
-	Chief Executive-elect	CY Leung
-	Chief Justice	Geoffrey Ma
-	President of the Legislative Council	Jasper Tsang
Legislature		Legislative Council
Establishment
-	Treaty of Nanking	29 August 1842
-	Japanese occupation	25 December 1941 – 15 August 1945
-	Conveyance from British sovereignty to Chinese sovereignty	1 July 1997
Area
-	Total	1,104 km2 (179th) 426 sq mi
-	Water (%)	4.58 (50 km²; 19 mi²)[3]
Population
-	2010 census	7,061,200[4]
-	Density	6,480[5]/km2 (4th) 16,576/sq mi
GDP (PPP)		2011 estimate
-	Total	$351.119 billion[6]
-	Per capita	$49,137[6]
GDP (nominal)		2011 estimate
-	Total	$243.302 billion[6]
-	Per capita	$34,049[6]
Gini (2007)		43.4[7]
HDI (2011)		0.898[8] (very high) (13th)
Currency		Hong Kong dollar (HKD)
Time zone		HKT (UTC+8)
Date formats		yyyy年m月d日 (Chinese) dd-mm-yyyy (English)
Drives on the		left
ISO 3166 code		HK
Internet TLD		.hk and .香港
Calling code		+852

Hong Kong
Chinese	香港
Cantonese Jyutping	Hoeng1gong2
Cantonese Yale	Hēunggóng
Hanyu Pinyin	Xiānggǎng
Literal meaning	Fragrant harbour
Transcriptions Hakka - Romanization Hiông-kóng Mandarin - Hanyu Pinyin Xiānggǎng - Wade–Giles Hsiang1-kang3 - IPA [ɕjáŋkàŋ] Min - Hokkien POJ Hiong-kang Wu - Romanization shian平kaon上 Cantonese (Yue) - Jyutping Hoeng1gong2 - IPA [hœ̂ːŋkɔ̌ːŋ] - Yale Romanization Hēunggóng
Hong Kong Special Administrative Region
Traditional Chinese	香港特別行政區 (or 香港特區)
Simplified Chinese	香港特别行政区 (or 香港特区)
Transcriptions Hakka - Romanization Hiông-kóng Thi̍t-phe̍t Hàng-tsṳn-khî Mandarin - Hanyu Pinyin Xiānggǎng Tèbié Xíngzhèngqū Min - Hokkien POJ Hiong-kang Te̍k-pia̍t Hêng-chèng-khu Wu - Romanization shian平kaon上 deh入bih入 ghan平tsen去chiu平 Cantonese (Yue) - Jyutping Hoeng1gong2 Dak6bit6 Hang4zing3 Keoi1

This article contains Chinese text. Without proper rendering support, you may see question marks, boxes, or other symbols instead of Chinese characters.

Full view of Kowloon and Hong Kong. The old Kai Tak Airport can be seen on the left.

The Lei Cheng Uk Han Tomb Museum located in northwest Kowloon was built in 1969 after the tomb's discovery in 1955.

Hong Kong^{[note 3]} (Chinese: 香港) is one of two special administrative regions (SARs) of the People's Republic of China (PRC), the other being Macau. A city-state^[9] situated on China's south coast and enclosed by the Pearl River Delta and South China Sea,^[10] it is known for its expansive skyline and deep natural harbour. With a land mass of 1,104 km² (426 sq mi) and a population of seven million people, Hong Kong is one of the most densely populated areas in the world.^[11] Hong Kong's population is 95 percent ethnic Chinese and 5 percent from other groups.^[12] Hong Kong's Han Chinese majority originate mainly from the cities of Guangzhou and Taishan in the neighbouring Guangdong province.^[13]

Hong Kong became a colony of the British Empire after the First Opium War (1839–42). Originally confined to Hong Kong Island, the colony's boundaries were extended in stages to the Kowloon Peninsula in 1860 and then the New Territories in 1898. It was occupied by Japan during the Pacific War, after which the British resumed control until 1997, when China resumed sovereignty.^[14][15] The region espoused minimum government intervention under the ethos of positive non-interventionism during the colonial era.^[16] The time period greatly influenced the current culture of Hong Kong, often described as "East meets West",^[17] and the educational system, which used to loosely follow the system in England^[18] until reforms implemented in 2009.^[19]

Under the principle of "one country, two systems", Hong Kong has a different political system from mainland China.^[20] Hong Kong's independent judiciary functions under the common law framework.^[21][22] Hong Kong Basic Law, its constitutional document, stipulates that Hong Kong shall have a "high degree of autonomy" in all matters except foreign relations and military defence, governs its political system.^[23][24] Although it has a burgeoning multi-party system, a small-circle electorate^{[clarification needed]} controls half of its legislature. The Chief Executive of Hong Kong, the head of government, is selected by a Selection Committee / Election Committee with 400 to 1200 members, during the first 20 years.^{[25] [26][27] [28]}

As one of the world's leading international financial centres, Hong Kong has a major capitalist service economy characterised by low taxation and free trade, and the currency, Hong Kong dollar, is the eighth most traded currency in the world.^[29] The lack of space caused demand for denser constructions, which developed the city to a centre for modern architecture and the world's most vertical city.^[30][31] Hong Kong has one of the highest per capita income in the world.^[6] The dense space also led to a highly developed transportation network with public transport travelling rate exceeding 90 percent,^[32] the highest in the world.^[33] Hong Kong has numerous high international rankings in various aspects. For instance, its economic freedom, financial and economic competitiveness, quality of life, corruption perception, Human Development Index, etc., are all ranked highly.^{[34][35][36][37][38][39][40]} According to both UN and WHO estimates, Hong Kong has the second longest life expectancy of any country in the world. ^[41][42]

Etymology[link]

The name "Hong Kong" is an approximate phonetic rendering of the pronunciation of the spoken Cantonese or Hakka name "香港", meaning "fragrant harbour".^[43] Before 1842, the name referred to a small inlet – now Aberdeen Harbour or 香港仔 hoeng¹ gong² zai² "Little Hong Kong" – between the Aberdeen Island and the south side of Hong Kong Island, which was one of the first points of contact between British sailors and local fishermen.^[44]

The reference to fragrance may refer to the harbour waters sweetened by the fresh water estuarine influx of the Pearl River, or to the incense from factories lining the coast to the north of Kowloon, which was stored around Aberdeen Harbour for export before the development of Victoria Harbour.^[43] In 1842, the Treaty of Nanking was signed, and the name Hong Kong was first recorded on official documents to encompass the entirety of the island.^[45]

History[link]

Pre-colonial[link]

Archaeological studies support a human presence in the Chek Lap Kok area from 35,000 to 39,000 years ago, and in Sai Kung Peninsula from 6,000 years ago.^[46][47][48] Wong Tei Tung and Three Fathoms Cove are the two earliest sites of human habitation in the Paleolithic period. It is believed the Three Fathom Cove was a river valley settlement and Wong Tei Tung was a lithic manufacturing site. Excavated Neolithic artefacts suggest cultural differences from the Longshan culture in northern China and settlement by the Che people prior to the migration of the Baiyue.^[49][50] Eight petroglyphs were discovered on surrounding islands, which dated to the Shang Dynasty in China.^[51]

In 214 BC, Qin Shi Huang, the first emperor of China, conquered the Baiyue tribes in Jiaozhi (modern Liangguang region) and incorporated the territory into imperial China for the first time. Modern Hong Kong is located in Nanhai commandery (modern Nanhai District) and near the ancient capital city Pun Yue.^[52][53][54] The area was consolidated under the kingdom of Nanyue, founded by general Zhao Tuo in 204 BC after the Qin Dynasty collapsed.^[55] When the kingdom was conquered by Emperor Wu of Han in 111 BC, the land was assigned to the Jiaozhi commandery under the Han Dynasty. Archaeological evidence indicates the population increased and early salt production flourished in this time period. Lei Cheng Uk Han Tomb in the Kowloon Peninsula is believed to have been built during the Han Dynasty.^[56]

During the Tang Dynasty period, the Guangdong region flourished as a regional trading center. In 736, Emperor Xuanzong of Tang established a military town in Tuen Mun to defend the coastal area in the region.^[57] The first village school, Li Ying College, was established around 1075 in the New Territories under the Northern Song Dynasty.^[58] During the Mongol invasion in 1276, the Southern Song Dynasty court moved to Fujian, then to Lantau Island and later to Sung Wong Toi (modern Kowloon City), but the child Emperor Bing of Song committed suicide by drowning with his officials after being defeated in the Battle of Yamen. Hau Wong, an official of the emperor is still worshipped in Hong Kong today.^[59]

The earliest recorded European visitor was Jorge Álvares, a Portuguese explorer who arrived in 1513.^[60][61] After establishing settlements in the region, Portuguese merchants began trading in southern China. At the same time, they invaded and built up military fortifications in Tuen Mun. Military clashes between China and Portugal led to the expulsion of the Portuguese. In the mid-16th century, the Haijin order banned maritime activities and prevented contact with foreigners; it also restricted local sea activity.^[59] In 1661–69, the territory was affected by the Great Clearance ordered by Kangxi Emperor, which required the evacuation of the coastal areas of Guangdong. It is recorded that about 16,000 persons from Xin'an County were driven inland, and 1,648 of those who left are said to have returned when the evacuation was rescinded in 1669.^[62] What is now the territory of Hong Kong became largely wasteland during the ban.^[63] In 1685, Kangxi became the first emperor to open limited trading with foreigners, which started with the Canton territory. He also imposed strict terms for trades such as requiring foreign traders to live in restricted areas, staying only for the trading seasons, banning firearms, and trading with silver only.^[64] The East India Company made the first sea venture to China in 1699, and the region's trade with British merchants developed rapidly soon after. In 1711, the company established its first trading post in Canton. By 1773, the British reached a landmark 1,000 chests of opium in Canton with China consuming 2,000 chests annually by 1799.^[64]

British colonial era[link]

• 

  Flag of the British colony of Hong Kong(used in between 1870-1876)

• 

  Flag of the British colony of Hong Kong(used in between 1876-1910)

• 

  Flag of the British colony of Hong Kong(used in between 1910-1959)

• 

  Flag of the British colony of Hong Kong (Unofficial Red ensign for Hong Kong used in between 1959 to prior the Handover of Hong Kong to the PRC in 1997)

General Post Office in Central,City of Victoria, 1911

The Queen's Pier in front of City Hall in Edinburgh Place.

Victoria City in the 1890s.

View of Hong Kong Island from Kowloon (published 1843)

In 1839, the refusal by Qing Dynasty authorities to import opium resulted in the First Opium War between China and Britain. Hong Kong Island was occupied by British forces on 20 January 1841 and was initially ceded under the Convention of Chuenpee as part of a ceasefire agreement between Captain Charles Elliot and Governor Qishan, but the agreement was never ratified due to a dispute between high ranking officials in both governments.^[65] It was not until 29 August 1842 that the island was formally ceded in perpetuity to the United Kingdom under the Treaty of Nanking. The British established a crown colony with the founding of Victoria City the following year.^[66]

Under British rule, the population of Hong Kong island had increased from 7,450 Chinese residents, mostly fishermen, in 1841 to over 115,000 Chinese and 8,754 Europeans in Hong Kong (including Kowloon) in 1870.^[67]

In 1860, after China's defeat in the Second Opium War, the Kowloon Peninsula and Stonecutter's Island were ceded in perpetuity to Britain under the Convention of Peking.

In 1894, the deadly Third Pandemic of bubonic plague spread from China to Hong Kong, causing 50,000–100,000 deaths.^[68]

In 1898, under the terms of the Convention for the Extension of Hong Kong Territory, Britain obtained a 99-year lease of Lantau Island and the adjacent northern lands, which became known as the New Territories.^[69] Hong Kong's territory has remained unchanged to the present.^[70][71]