Influenza A virus subtype H5N1

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H5N1

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

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 manyspecies, especially over a wide area), killing tens of millions ofbirds and spurring the cullingof hundreds of millions of others to stem its spread. Most referencesto "bird flu" and H5N1 in the popular media refer to this strain.^[2]

According to the FAO Avian Influenza Disease Emergency Situation Update, H5N1 pathogenicityis continuing to gradually rise in wild birds in endemic areas but theavian influenza disease situation in farmed birds is being held incheck by vaccination. Eleven outbreaks of H5N1 were reported worldwidein June 2008 in five countries (China, Egypt, Indonesia, Pakistan andVietnam) compared to 65 outbreaks in June 2006 and 55 in June 2007. The"global HPAI situation can be said to have improved markedly in thefirst half of 2008 [but] cases of HPAI are still underestimated andunderreported in many countries because of limitations in countrydisease surveillance systems".^[3]

[edit] Overview

HPAI A(H5N1) is considered an avian disease, although there is someevidence of limited human-to-human transmission of the virus.^[4]A risk factor for contracting the virus is handling of infectedpoultry, but transmission of the virus from infected birds to humans isinefficient.^[5]Still, around 60% of humans known to have been infected with thecurrent 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 Websterpublished an article titled "The world is teetering on the edge of apandemic 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.^[6] On September 29, 2005, David Nabarro,the newly-appointed Senior United Nations System Coordinator for Avianand Human Influenza, warned the world that an outbreak of avianinfluenza could kill anywhere between 5 million and 150 million people.^[7] Experts have identified key events (creating new clades,infecting new species, spreading to new areas) marking the progressionof an avian flu virus towards becoming pandemic, and many of those keyevents have occurred more rapidly than expected.

Due to the high lethality and virulence of HPAI A(H5N1), its endemic presence, its increasingly large hostreservoir, and its significant ongoing mutations, the H5N1 virus is theworld's largest current pandemic threat and billions of dollars arebeing spent researching H5N1 and preparing for a potential influenza pandemic.^[8] At least 12 companies and 17 governments are developing pre-pandemic influenza vaccinesin 28 different clinical trials that, if successful, could turn adeadly pandemic infection into a nondeadly one. Full-scale productionof a vaccinethat could prevent any illness at all from the strain would require atleast three months after the virus's emergence to begin, but it ishoped that vaccine production could increase until one billion doseswere produced by one year after the initial identification of the virus.^[9]

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.^[10] Influenza pandemics from its genetic offspring may include influenza A virus subtypes other than H5N1.^[11]While genetic analysis of the H5N1 virus shows that influenza pandemicsfrom its genetic offspring can easily be far more lethal than the Spanish Flu pandemic,^[12] 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.^[13]

[edit] Genetics

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

The first known strain of HPAI A(H5N1) (calledA/chicken/Scotland/59) killed two flocks of chickens in Scotland in1959; but that strain was very different from the current highlypathogenic strain of H5N1. The dominant strain of HPAI A(H5N1) in 2004 evolved from 1999 to 2002 creating the Z genotype.^[14] 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 H5N1infections that have occurred during late 2005 and 2006, according toWHO. Genetic analysis has identified six subclades of clade 2, three ofwhich have a distinct geographic distribution and have been implicatedin human infections: Map

• Subclade 1, Indonesia
• Subclade 2, Europe, Middle East, and Africa (called EMA)
• Subclade 3, China"^[10][15][16]

A 2007 study focused on the EMA subclade has shed further light onthe EMA mutations. "The 36 new isolates reported here greatly expandthe amount of whole-genome sequence data available from recent avianinfluenza (H5N1) isolates. Before our project, GenBank contained only 5other complete genomes from Europe for the 2004–2006 period, and itcontained no whole genomes from the Middle East or northern Africa. Ouranalysis showed several new findings. First, all European, MiddleEastern, and African samples fall into a clade that is distinct fromother contemporary Asian clades, all of which share common ancestrywith the original 1997 Hong Kong strain. Phylogenetic trees built oneach of the 8 segments show a consistent picture of 3 lineages, asillustrated by the HA tree shown in Figure 1. Two of the clades containexclusively Vietnamese isolates; the smaller of these, with 5 isolates,we label V1; the larger clade, with 9 isolates, is V2. The remaining 22isolates all fall into a third, clearly distinct clade, labeled EMA,which comprises samples from Europe, the Middle East, and Africa. Treesfor the other 7 segments display a similar topology, with clades V1,V2, and EMA clearly separated in each case. Analyses of all availablecomplete influenza (H5N1) genomes and of 589 HA sequences placed theEMA clade as distinct from the major clades circulating in People'sRepublic of China, Indonesia, and Southeast Asia."^[17]

[edit] Terminology

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).^[18]

As with other avian flu viruses, H5N1 has strains called "highlypathogenic" (HP) and "low-pathogenic" (LP). Avian influenza virusesthat cause HPAI are highly virulent,and mortality rates in infected flocks often approach 100%. LPAIviruses have negligible virulence, but these viruses can serve asprogenitors to HPAI viruses. The current strain of H5N1 responsible forthe deaths of birds across the world is an HPAI strain; all othercurrent strains of H5N1, including a North American strain that causesno disease at all in any species, are LPAI strains. All HPAI strainsidentified to date have involved H5 and H7 subtypes. The distinctionconcerns pathogenicity in poultry, not humans. Normally a highlypathogenic avian virus is not highly pathogenic to either humans ornon-poultry birds. This current deadly strain of H5N1 is unusual inbeing deadly to so many species, including some, like domestic cats,never previously susceptible to any influenza virus.

[edit] Genetic structure and related subtypes

The N in H5N1 stands for "Neuraminidase", as 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 glycoproteinfound on the surface of the influenza viruses and is responsible forbinding 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.^[19]The hemagglutinin (HA) and neuraminidase (NA) RNA strands specify thestructure of proteins that are most medically relevant as targets forantiviral 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 diseaseand death in humans and other animals. Influenza A virus subtypes thathave been confirmed in humans, in order of the number of known humanpandemic deaths that they have caused, include:

• H1N1, which caused "Spanish flu" and currently causes seasonal human flu
• H2N2, which caused "Asian flu"
• H3N2, which caused "Hong Kong flu" and currently causes seasonal human flu
• H5N1, "Bird Flu," the world's major current pandemic threat^{[citation needed]}
• 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

[edit] Low pathogenic H5N1

Low pathogenic avian influenza H5N1 (LPAI H5N1) also called "NorthAmerican" H5N1 commonly occurs in wild birds. In most cases, it causesminor sickness or no noticeable signs of disease in birds. It is notknown to affect humans at all. The only concern about it is that it ispossible for it to be transmitted to poultry and in poultry mutate intoa 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 Universityof Minnesota conducting a sampling procedure in which sentinel duckswere 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. ^[20]

"In the past, there was no requirement for reporting or trackingLPAI H5 or H7 detections in wild birds so states and universitiestested wild bird samples independently of USDA. Because of this, theabove list of previous detections might not be all inclusive of pastLPAI H5N1 detections. However, the World Organization for Animal Health(OIE) recently changed its requirement of reporting detections of avianinfluenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypesmust be reported to the OIE because of their potential to mutate intohighly pathogenic strains. Therefore, USDA now tracks these detectionsin wild birds, backyard flocks, commercial flocks and live birdmarkets."^[21]

[edit] Properties of H5N1

[edit] Infectivity

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 variationswhich can infect species not previously known to carry the virus, notall of these variant forms can infect humans. H5N1 as an avian viruspreferentially binds to a type of galactosereceptors that populate the avian respiratory tract from the nose tothe lungs and are virtually absent in humans, occurring only in andaround 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.^[22][23][24]

H5N1 is mainly spread by domestic poultry,both through the movements of infected birds and poultry products andthrough the use of infected poultry manure as fertilizer or feed.Humans with H5N1 have typically caught it from chickens, which were inturn infected by other poultry or waterfowl. Migrating waterfowl (wild ducks, geese and swans) carry H5N1, often without becoming sick.^[25][26]Many species of birds and mammals can be infected with HPAI A(H5N1),but the role of animals other than poultry and waterfowl asdisease-spreading hosts is unknown.^[27]

According to a report by the World Health Organization,H5N1 may be spread indirectly. The report stated that the virus maysometimes stick to surfaces or get kicked up in fertilizer dust toinfect people.^[28]

[edit] Virulence

H5N1 has mutated into a variety of strainswith differing pathogenic profiles, some pathogenic to one species butnot others, some pathogenic to multiple species. Each specific knowngenetic variation is traceable to a virus isolate of a specific case ofinfection. Through antigenic drift,H5N1 has mutated into dozens of highly pathogenic varieties dividedinto genetic clades which are known from specific isolates, but allcurrently belonging to genotype Z of avian influenza virus H5N1, nowthe dominant genotype.^[29][30] H5N1 isolates found in Hong Kongin 1997 and 2001 were not consistently transmitted efficiently amongbirds and did not cause significant disease in these animals. In 2002new isolates of H5N1 were appearing within the bird population of HongKong. These new isolates caused acute disease, including severeneurological dysfunction and death in ducks. This was the first reported case of lethal influenza virus infection in wild aquatic birds since 1961.^[31] 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.^[30][32][29]Genotype Z is endemic in birds in Southeast Asia, has created at leasttwo clades that can infect humans, and is spreading across the globe inbird populations. Mutations are occurring within this genotype that areincreasing their pathogenicity.^[33]Birds are also able to shed the virus for longer periods of time beforetheir death, increasing the transmissibility of the virus.

[edit] Transmission and host range

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 contactwith these bodily fluids or through contact with surfaces contaminatedwith 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) so at ordinary temperatures itlasts in the environment for weeks. In Arctic temperatures, it doesn'tdegrade at all.

Because migratory birds are among the carriers of the highlypathogenic H5N1 virus, it is spreading to all parts of the world. H5N1is different from all previously known highly pathogenic avian fluviruses 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 infectmammals as well. From this point on, avian flu experts increasinglyreferred to containment as a strategy that can delay, but notultimately prevent, a future avian flu pandemic.

"Since 1997, studies of influenza A (H5N1) indicate that theseviruses continue to evolve, with changes in antigenicity and internalgene constellations; an expanded host range in avian species and theability to infect felids; enhanced pathogenicity in experimentallyinfected mice and ferrets, in which they cause systemic infections; andincreased environmental stability."^[34]

The New York Times, in an article on transmission of H5N1through smuggled birds, reports Wade Hagemeijer of WetlandsInternational stating, "We believe it is spread by both bird migrationand trade, but that trade, particularly illegal trade, is moreimportant".^[35]

On September 27, 2007researchers reported that the H5N1 bird flu virus can also pass througha pregnant woman's placenta to infect the fetus. They also foundevidence of what doctors had long suspected -- that the virus not onlyaffects the lungs, but also passes throughout the body into thegastrointestinal tract, the brain, liver, and blood cells.^[36]

[edit] High mutation rate

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.^[30][29] 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 receptorson the surface of host cells. Such mutations in avian H5N1 viruses canchange virus strains from being inefficient at infecting human cells tobeing as efficient in causing human infections as more common humaninfluenza virus types.^[37]This doesn't mean that one amino acid substitution can cause apandemic, but it does mean that one amino acid substitution can causean avian flu virus that is not pathogenic in humans to becomepathogenic in humans.

H3N2 ("Swine influenza")^{[clarification needed]}is endemic in pigs in China, and has been detected in pigs in Vietnam,increasing fears of the emergence of new variant strains. The dominantstrain 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 reassortmentis a major concern. If a reassortment in H5N1 occurs, it might remainan 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 influenzavirus RNA segments. "While the pandemic human influenza viruses of 1957(H2N2) and 1968 (H3N2) clearly arose through reassortment between humanand avian viruses, the influenza virus causing the 'Spanish flu' in1918 appears to be entirely derived from an avian source".^[14]

[edit] Humans and H5N1

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 widearea) outbreak was stopped by the killing of the entire domesticpoultry population within the territory.

Confirmed human cases and mortality rate of avian influenza (H5N1)
As of May 6, 2009

Country	2003			2004			2005			2006			2007			2008			2009			Total
	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%				1	0	0%
Cambodia							4	4	100%	2	2	100%	1	1	100%	1	0	0%				8	7	87%
PR China	1	1	100%				8	5	63%	13	8	62%	5	3	60%	4	4	100%	7	4	57%	38	25	66%
Djibouti										1	0	0%										1	0	0%
Egypt										18	10	56%	25	9	36%	8	4	50%	17	0	0%	68	23	34%
Indonesia							20	13	65%	55	45	82%	42	37	88%	24	20	83%				141	115	82%
Iraq										3	2	67%										3	2	67%
Laos													2	2	100%							2	2	100%
Myanmar													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%	4	4	100%	111	56	50%
Total	4	4	100%	46	32	70%	98	43	44%	115	79	69%	88	59	67%	44	33	75%	28	8	29%	423	258	61%
edit this table Source: World Health Organization Communicable Disease Surveillance & Response (CSR)

[edit] Symptoms in humans

The avian influenza hemagglutinin binds alpha 2-3 sialic acid receptors while human influenza hemagglutinins bind alpha 2-6 sialic acid receptors.^[38]This means that when the H5N1 strain infects humans it will replicatein the lower respiratory tract, and consequently will cause viral pneumonia.^[39] There is as yet no human form of H5N1, so all humans who have caught it so far have caught avian H5N1.

The different sites of infection (shown in red) of seasonal H1N1 versus avian H5N1. This influences their lethality and ability to spread.^[40]

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 to a large part on the state of the infected person's immune systemand whether the victim has been exposed to the strain before (in whichcase they would be partially immune). No one knows if these or othersymptoms will be the symptoms of a humanized H5N1 flu.

The reported mortality rate of highly pathogenic H5N1 avian influenza in a human is high; WHOdata indicates that 60% of cases classified as H5N1 resulted in death.However, there is some evidence that the actual mortality rate of avianflu could be much lower, as there may be many people with mildersymptoms who do not seek treatment and are not counted.^[41][42]

In one case, a boy with H5N1 experienced diarrhea followed rapidly by a coma without developing respiratory or flu-like symptoms.^[43] 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 that is associated with tissue destruction at sites ofinfection and increased production of other cytokines. Fluvirus-induced increases in the level of cytokines is also associatedwith flu symptoms including fever, chills, vomiting and headache.Tissue damage associated with pathogenic flu virus infection canultimately result in death.^[6] 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.^[44]

[edit] Treatment and prevention for humans

Influenza

Influenza Virus Avian influenza Swine influenza Flu season Research Vaccine Treatment H5N1 strain H1N1 strain Pandemic

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 theuser's body. This drug has become a focus for some governments andorganizations trying to prepare for a possible H5N1 pandemic.^[45] 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.^[46]

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 wepredict 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 thespread of a contagious influenza virus, whose various precedents in thepast 90 years have been highly pathogenic".^[47]

There are several H5N1 vaccinesfor several of the avian H5N1 varieties, but the continual mutation ofH5N1 renders them of limited use to date: while vaccines can sometimesprovide cross-protection against related flu strains, the bestprotection would be from a vaccine specifically produced for any futurepandemic flu virus strain. Dr. Daniel Lucey, co-director of theBiohazardous 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".^[48]However, "pre-pandemic vaccines" have been created; are being refinedand tested; and do have some promise both in furthering research andpreparedness for the next pandemic.^[49][50][51]Vaccine manufacturing companies are being encouraged to increasecapacity so that if a pandemic vaccine is needed, facilities will beavailable for rapid production of large amounts of a vaccine specificto a new pandemic strain.

Animal and lab studies suggest that Relenza (zanamivir),which is in the same class of drugs as Tamiflu, may also be effectiveagainst H5N1. In a study performed on mice in 2000, "zanamivir wasshown to be efficacious in treating avian influenza viruses H9N2, H6N1,and H5N1 transmissible to mammals".^[52]While no one knows if zanamivir will be useful or not on a yet to existpandemic strain of H5N1, it might be useful to stockpile zanamivir aswell as oseltamivir in the event of an H5N1 influenza pandemic. Neitheroseltamivir nor zanamivir can currently be manufactured in quantitiesthat would be meaningful once efficient human transmission starts.^[53]

In September, 2006, a WHO scientist announced that studies hadconfirmed cases of H5N1 strains resistant to Tamiflu and Amantadine.^[54] Tamiflu-resistant strains have also appeared in the EU, which remain sensitive to Relenza.^[55][56]

[edit] Preparations for pandemic

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

Cumulative Human Cases of and Deaths from H5N1
As of April 11, 2007

Notes:

• Source WHO Confirmed Human Cases of H5N1
• "[T]he incidence of human cases peaked, in each of the threeyears in which cases have occurred, during the period roughlycorresponding to winter and spring in the northern hemisphere. If thispattern continues, an upsurge in cases could be anticipated starting inlate 2006 or early 2007." Avian influenza – epidemiology of human H5N1 cases reported to WHO
• The regression curve for deaths is y = a + e^k x, and is shown extended through the end of April, 2007.

"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 throughplanning, greater monitoring, and full transparency in reporting andinvestigating avian influenza occurrences. The United States and theseinternational partners have led global efforts to encourage countriesto heighten surveillance for outbreaks in poultry and significantnumbers of deaths in migratory birds and to rapidly introducecontainment 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 onbehalf of the White House with departments and agencies across thefederal government".^[57]

Together steps are being taken to "minimize the risk of furtherspread in animal populations", "reduce the risk of human infections",and "further support pandemic planning and preparedness".^[57]

Ongoing detailed mutually coordinated onsite surveillance andanalysis of human and animal H5N1 avian flu outbreaks are beingconducted 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.^[58]

[edit] Effect on human society

H5N1 has had a huge 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.^{[59][60][61][62][63][64][65][66]}

People have reacted by buying less chicken causing poultry sales and prices to fall.^[67] Many individuals have stockpiled supplies for a possible flu pandemic. One of the best known experts on H5N1, Dr. Robert Webster,told ABC News he had a three month supply of food and water in hishouse as he prepared for what he considered a reasonably likelyoccurrence of a major pandemic.

International health officials and other experts have pointed out that many unknown questions still hover around the disease^[68]

Dr. David Nabarro,Chief Avian Flu Coordinator for the United Nations, and former Chief ofCrisis Response for the World Health Organization has described himselfas "quite scared" about H5N1's potential impact on humans. Nabarro hasbeen accused of being alarmist before and on his first day in his rolefor the United Nations he proclaimed the avian flu could kill 150million 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.^[69]

[edit] See also

Wikimedia Commons has media related to: H5N1

Wikinews has related news: Avian Flu

• Antigenic shift
• Influenza research
• Fujian flu
• Global spread of H5N1
• H5N1 clinical trials
• ICEID
• National Influenza Centers
• Reporting disease cases
• Zoonosis

[edit] Sources and notes

[edit] External links

This article may require cleanup to meet Wikipedia's quality standards. Please improve this article if you can. (October 2007)

Official - international

• UN United Nations
  • WHO World Health Organization
    • The United Nation's World Health Organization'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

Official - United States

• PandemicFlu.Gov U.S. Government's avian flu information site
• USAID U.S. Agency for International Development - Avian Influenza Response
• CDCCenters for Disease Control - responsible agency for avian influenza inhumans in US - Facts About Avian Influenza (Bird Flu) and AvianInfluenza A (H5N1) Virus
• USGS - NWHC National Wildlife Health Center - responsible agency for avian influenza in animals in US
• Wildlife Disease Information NodeA part of the National Biological Information Infrastructure andpartner of the NWHC, this agency collects and distributes news andinformation about wildlife diseases such as avian influenza andcoordinates collaborative information sharing efforts.
• HHS U.S. Department of Health & Human Services - Pandemic Influenza Plan

Official - European Union

• Avian influenza - Q & A's factsheet from European Centre for Disease Prevention and Control, agency of European Union

Official - 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 — NHS (a government entity). Contingency planning for an influenza pandemic. PDF hosted by BBC
• Government[1]

Technical

External links dealing with technical aspects can be found here.

News and General information

External links dealing with news and general information can be found here.

Databases

• BioHealthBase Bioinformatics Resource Center Database of influenza genomic sequences and related information.