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Influenza
SpecialtyFamily medicine, pulmonology, infectious diseases, emergency medicine Edit this on Wikidata

Influenza, commonly known as the flu, is an infectious disease of birds and mammals caused by an RNA virus of the family Orthomyxoviridae (the influenza viruses). In people, common symptoms of influenza are fever, sore throat, muscle pains, severe headache, coughing, and weakness and fatigue.[1] In more serious cases, influenza causes pneumonia, which can be fatal, particularly in young children and the elderly. Although the common cold is sometimes confused with influenza, the common cold is a much less severe disease and caused by a different virus.[2] Similarly, gastroenteritis is sometimes called "stomach flu" or "24-hour flu", but is unrelated to influenza.

Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes creating aerosols containing the virus, and from infected birds through their droppings. Influenza can also be transmitted by saliva, nasal secretions, feces and blood. Infections either occur through direct contact with these bodily fluids, or by contact with contaminated surfaces. Flu viruses remain infectious for over 30 days at 0°C (32°F) and about one week at human body temperature, although they are rapidly inactivated by disinfectants and detergents.[3]

Flu spreads around the world in seasonal epidemics, killing millions of people in pandemic years and hundreds of thousands in non-pandemic years. Three influenza pandemics occurred in the 20th century—each following a major genetic change in the virus—and killed tens of millions of people. Often, these pandemics result from the spread of a flu virus between animal species. Since it first killed humans in Asia in the 1990s a deadly avian strain of H5N1 has posed the greatest influenza pandemic threat. However, this virus has not yet mutated to spread easily between people.[4]

Vaccinations against influenza are most common in high-risk humans in industrialised countries[5] and farmed poultry.[6] The most common human vaccine is the trivalent flu vaccine that contains purified and inactivated material from three viral strains. Typically this vaccine includes material from two influenza A virus subtypes and one influenza B virus strain.[7] A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes every year and different strains become dominant. Antiviral drugs can be used to treat influenza, with neuraminidase inhibitors being particularly effective.

Influenza (flu)
H1N1 virus
Types
Vaccines
Treatment
Pandemics
Outbreaks
See also

Etymology

The term influenza has its origins in fifteenth-century Italy, where the cause of the disease was ascribed to unfavourable astrological influences. Evolution in medical thought led to its modification to influenza di freddo, meaning "influence of the cold". The word "influenza" was first attested in English in 1743 when it was borrowed during an outbreak of the disease in Europe.[8] Archaic terms for influenza include epidemic catarrh, grippe, (sometimes spelt "grip" or "gripe"), sweating sickness and Spanish fever (particularly for the 1918 pandemic strain).[9]

History

Further information: [[:Influenza pandemic, Spanish flu]]
Negatively stained flu viruses. These were the causative agents of Hong Kong Flu. (Magnified approximately 70,000 times.)

The symptoms of human influenza were clearly described by Hippocrates roughly 2400 years ago.[10][11] Since then, the virus has caused numerous pandemics. Historical data on influenza are difficult to interpret, as the symptoms can be similar to those of other diseases, such as diphtheria, pneumonic plague, typhoid fever, dengue or typhus. The first convincing record of an influenza pandemic was of an outbreak in 1580, which began in Asia and spread to Europe via Africa. In Rome over 8,000 people were killed and several Spanish cities were almost wiped out.[12] Pandemics continued sporadically throughout the 17th and 18th centuries, with the pandemic of 1830-1833 being particularly widespread; it infected approximately a quarter of the people exposed.[12]

The most famous and lethal outbreak was the so-called Spanish flu pandemic (type A influenza, H1N1 subtype), which lasted from 1918 to 1919. Older estimates say it killed 40-50 million people[13] while current estimates say 50 million to 100 million people worldwide were killed.[14] This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the black death.[12] This huge death toll was caused by an extremely high infection rate of up to 50%, and the extreme severity of the symptoms.[13] Indeed, symptoms in 1918 were so unusual that initially influenza was misdiagnosed as dengue, cholera, or typhoid. One observer wrote, "One of the most striking of the complications was hemorrhage from mucous membranes, especially from the nose, stomach, and intestine. Bleeding from the ears and petechial hemorrhages in the skin also occurred."[14] The majority of deaths were from bacterial pneumonia, a secondary infection caused by influenza, but the virus also killed people directly, causing massive hemorrhages and edema in the lung.[15]

The Spanish flu pandemic was truly global, spreading even to the Arctic and remote Pacific islands. The unusually severe disease killed 2.5 % of those infected, as opposed to the more usual flu epidemic mortality rate of 0.1 %.[15] Another unusual feature of this pandemic was that it mostly killed young adults, with 99% of pandemic influenza deaths occurring in people under 65 and more than half in young adults 20 to 40 years old.[16] This is unusual since influenza is normally most deadly to the very young (under age 2) and the very old (over age 70). The total mortality of the 1918-1919 pandemic is not known, but it is estimated that 2.5 % to 5 % of the world's population was killed. As many as 25 million may have been killed in the first 25 weeks; in contrast, HIV/AIDS has killed 25 million in its first 25 years.[14]

The different age-distribution of the mortality of the 1918 influenza from normal epidemics. Deaths by age at death, per 100,000 persons in each age group, United States, 1911–1918. Influenza death rates for the interpandemic years 1911–1917 (dashed line) and the pandemic year 1918 (solid line).[17]

Later flu pandemics were not so devastating. They included the 1957 Asian Flu (type A, H2N2 strain) and the 1968 Hong Kong Flu (type A, H3N2 strain), but even these smaller outbreaks killed millions of people. In contrast to 1918 Spanish flu, in later pandemics antibiotics were available to control secondary infections, and this may have helped reduce mortality.[15]

Known flu pandemics [18]
Name of pandemic Date Deaths Subtype involved
Asiatic (Russian) Flu 1889-90 1 million possibly H2N2
Spanish Flu 1918-20 40 million H1N1
Asian Flu 1957-58 1 to 1.5 million H2N2
Hong Kong Flu 1968-69 0.75 to 1 million H3N2

The etiological cause of influenza, the Orthomyxoviridae family of viruses, was first discovered in pigs by Richard Schope in 1931.[19] This discovery was shortly followed by the isolation of the virus from humans by a group headed by Patrick Laidlaw at the Medical Research Council of the United Kingdom in 1933.[20] However, it was not until Wendell Stanley first crystallised tobacco mosaic virus in 1935 that the non-cellular nature of viruses was appreciated.

The first significant step towards preventing influenza was the discovery by Thomas Francis, Jr. in 1944 of a live vaccine for influenza. This built on work by Frank Macfarlane Burnet, who showed that the virus lost virulence when it was cultured in fertilised hen's eggs.[21] Application of this observation by Francis allowed his group of researchers at the University of Michigan to develop the first flu vaccine, with support from the U.S. army.[22] The U.S. army was deeply involved in this research due to its experience of influenza in World War I, when thousands of troops were killed by the virus in a matter of months.[14]

Although there were scares in New Jersey in 1976 (with the Swine Flu), world-wide in 1977 (with the Russian Flu), and in Hong Kong and other Asian countries in 1997 (with H5N1 avian influenza), there have been no major pandemics since the 1968 Hong Kong Flu. Immunity to previous pandemic influenza strains and vaccination may have limited the spread of the virus, and may have helped prevent further pandemics.[18]

Microbiology

Structure of the influenza viron. The hemagglutinin (HA) and neuraminidase (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to Ribonuclear Proteins (RNPs).

Types of influenza virus

The influenza virus is an RNA virus of the family Orthomyxoviridae, which comprises the influenzaviruses, Isavirus and Thogotovirus. There are three types of influenza virus: Influenzavirus A, Influenzavirus B or Influenzavirus C. Influenza A and C infect multiple species, while influenza B almost exclusively infects humans.[23]

Diagram of influenza virus nomenclature.

The type A viruses are the most virulent human pathogens among the three influenza types and causes the most severe disease. The Influenza A virus can be subdivided into different serotypes based on the antibody response to these viruses.[23] The serotypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:

Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the seal.[25] This type of influenza mutates at a rate 2-3 times lower than type A[26] and consequently is less genetically diverse, with only one influenza B serotype.[23] As a result of this lack of antigenic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible.[27] This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species antigenic shift), ensures that pandemics of influenza B do not occur.[28]

The influenza C virus infects humans and pigs, and can cause severe illness and local epidemics.[29] However, influenza C is less common than the other types and usually seems to cause mild disease in children.[30][31]

Structure and properties

The following applies for Influenza A viruses, although other strains are very similar in structure[32]:

The influenza A virus particle or virion is 80-120 nm in diameter and usually roughly spherical, although filamentous forms can occur.[33] Unusually for a virus, the influenza A genome is not a single piece of nucleic acid; instead, it contains eight pieces of segmented negative-sense RNA (13.5 kilobases total), which encode 11 proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2).[34] The best-characterised of these viral proteins are hemagglutinin and neuraminidase, two large glycoproteins found on the outside of the viral particles. Neuraminidase is an enzyme involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. By contrast, hemagglutinin is a lectin that mediates binding of the virus to target cells and entry of the viral genome into the target cell.[35] The hemagglutinin (HA or H) and neuraminidase (NA or N) proteins are targets for antiviral drugs.[36] These proteins are also recognised by antibodies, i.e. they are antigens.[18] The responses of antibodies to these proteins are used to classify the different serotypes of influenza A viruses, hence the H and N in H5N1.

Infection and replication

Invasion and replication of the influenza virus. The steps in this process are discussed in the text.

Influenza viruses bind through hemagglutinin onto sialic acid sugars on the surfaces of epithelial cells; typically in the nose, throat and lungs of mammals and intestines of birds (Stage 1 in infection figure).[37] The cell imports the virus by endocytosis. In the acidic endosome, part of the haemagglutinin protein fuses the viral envelope with the vacuole's membrane, releasing the viral RNA (vRNA) molecules, accessory proteins and RNA-dependent RNA transcriptase into the cytoplasm (Stage 2).[38] These proteins and vRNA form a complex that is transported into the cell nucleus, where the RNA-dependent RNA transcriptase begins transcribing complementary positive-sense vRNA (Steps 3a and b).[39] The vRNA is either exported into the cytoplasm and translated (step 4), or remains in the nucleus. Newly-synthesised viral proteins are either secreted through the Golgi apparatus onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular mRNA and using the released nucleotides for vRNA synthesis and also inhibiting translation of host-cell mRNAs.[40]

Negative-sense vRNAs that form the genomes of future viruses, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7).[41] As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their neuraminidase has cleaved sialic acid residues from the host cell.[37] After the release of new influenza virus, the host cell dies.

Because of the absence of RNA proofreading enzymes, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly-manufactured influenza virus is a mutant.[42] The separation of the genome into eight separate segments of vRNA allows mixing or reassortment of vRNAs if more than one viral line has infected a single cell. The resulting rapid change in viral genetics produces antigenic shifts and allow the virus to infect new host species and quickly overcome protective immunity.[18] This is important in the emergence of pandemics, as discussed in the Epidemiology section.

Symptoms

In humans, influenza's effects are much more severe than those of the common cold, and last longer. Recovery takes about one to two weeks. Influenza can be deadly, especially for the weak, old or chronically ill.[18] According to the on-line version of the Merck Manual of Diagnosis and Therapy:

"Symptoms start 24 to 48 hours after infection and can begin suddenly. Chills or a chilly sensation are often the first indication of influenza. Fever is common during the first few days, and the temperature may rise to 102 to 103 °F (approximately 38 to 39 °C). Many people feel sufficiently ill to remain in bed for days; they have aches and pains throughout the body, most pronounced in the back and legs."[1]

The virus attacks the respiratory tract, is transmitted from person to person by saliva droplets expelled by coughing or sneezing, and can cause the following symptoms:

It can be difficult to distinguish between the common cold and influenza in the early stages of these infections.[2] Since anti-viral drugs are most effective in treating influenza if given early (see treatment section, below), it can be important to identify cases early. Of the symptoms listed above, a combination of cough, fever and nasal congestion is good evidence that the infection is influenza.[43]

Most people who get influenza will recover in one to two weeks, but others will develop life-threatening complications (such as pneumonia). According to the World Health Organization: "Every winter, tens of millions of people get the flu. Most are home, sick and miserable, for about a week. Some—mostly the elderly—die. We know the world-wide death toll exceeds a few hundred thousand people a year, but even in developed countries the numbers are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness."[44] Even healthy people can be affected, and serious problems from influenza can happen at any age. People over 50 years old, very young children and people of any age with chronic medical conditions, are more likely to get complications from influenza: such as pneumonia, bronchitis, sinus, and ear infections.[45]

The flu can worsen chronic health problems. People with emphysema, chronic bronchitis or asthma may experience shortness of breath while they have the flu, and influenza may cause worsening of coronary heart disease or congestive heart failure.[46] Smoking is another risk factor associated with more serious disease and increased mortality from influenza.[47]

Common symptoms of the flu such as fever, headaches, and fatigue, come from the huge amounts of proinflammatory cytokines and chemokines (such as interferon or tumor necrosis factor) produced from influenza-infected cells.[2][48] In contrast to the rhinovirus that causes the common cold, influenza does cause tissue damage, so symptoms are not entirely due to the inflammatory response.[49]

Epidemiology

Confirmed Human Cases of H5N1.[50] The regression curve for deaths is shown extended through the end of November, 2006.

Seasonal variations

Further information: [[:Flu season]]

Influenza reaches peak prevalence in winter, and because the Northern and Southern Hemisphere have winter at different times of the year, there are actually two flu seasons each year. This is why the World Health Organization (assisted by the National Influenza Centers) makes recommendations for two different vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere.[51]

It remains unclear why outbreaks of the flu occur seasonally rather than uniformly throughout the year. One possible explanation is that, because people are indoors more often during the winter, they are in close contact more often, and this promotes transmission from person to person. Another is that cold temperatures lead to drier air, which may dehydrate mucus, preventing the body from effectively expelling virus particles. The virus may also survive longer on exposed surfaces (doorknobs, countertops, etc.) in colder temperatures. Increased travel and visitation due to the Northern Hemisphere winter holiday season may also play a role.[52] However, seasonal changes in infection rates are also seen in tropical regions and these peaks of infection are seen mainly during the rainy season.[53] Seasonal changes in contact rates from school-terms, which are a major factor in other childhood diseases such as measles and pertussis, may also play a role in flu. A combination of these small seasonal effects may be amplified by "dynamical resonance" with the endogenous disease cycles.[54] H5N1 exibits seasonality in both humans and birds.[50]

Epidemic and pandemic spread

File:Antigenic drift vs shift.png
Antigenic drift creates influenza viruses with slightly-modified antigens, while antigenic shift generates viruses with entirely novel antigens.
Further information: [[:Flu pandemic]]

As influenza is caused by a variety of species and strains of viruses, in any given year some strains can die out while others create epidemics while yet another strain can cause a pandemic. Typically, in a year's normal two flu seasons (one per hemisphere) there are between three and five million cases of severe illness and up to 500,000 deaths worldwide, which by some definitions is a yearly influenza epidemic.[55] A recent study by the Centers for Disease Control and Prevention (CDC), an United States government agency concerned with issues of public health, estimated an average of 36,000 deaths each year from influenza-related complications in America.[56] Every ten to twenty years a pandemic occurs, which infects a large proportion of the world's population, and can kill tens of millions of people (see history section).

New influenza viruses are constantly being produced by mutation or by reassortment.[23] Mutations can cause small changes in the hemagglutinin and neuraminidase antigens on the surface of the virus. This is called antigenic drift, which creates an increasing variety of strains over time until one of the variants eventually achieves higher fitness, becomes dominant, and rapidly sweeps through the human population often causing an epidemic.[57] In contrast, when influenza viruses re-assort, they may acquire new antigens - for example by reassortment between avian strains and human strains. This is called antigenic shift. If a human influenza virus is produced with entirely novel antigens, everybody will be susceptible and the novel influenza will spread uncontrollably, causing a pandemic.[58]

Prevention and treatment

Vaccination and hygiene

Further information: [[:Flu vaccine]]
US navy personnel receiving influenza vaccination

Vaccination against influenza with a flu vaccine is strongly recommended for high-risk groups, such as children and the elderly. These vaccines can be produced in several ways; the most common method is to grow the virus in fertilised hen eggs. After purification, the virus is inactivated (for example, by treatment with detergent) to produce an inactivated-virus vaccine. Alternatively, the virus can be grown in eggs until it loses virulence and the avirulent virus given as a live vaccine.[18] The effectiveness of these flu vaccines is variable. Due to the high mutation rate of the virus, a particular flu vaccine usually confers protection for no more than a few years. Every year, the World Health Organization predicts which strains of the virus are most likely to be circulating in the next year, allowing pharmaceutical companies to develop vaccines that will provide the best immunity against these strains.[51] Vaccines have also been developed to protect poultry from avian influenza. These vaccines can be effective against multiple strains and are used either as part of a preventative strategy, or combined with culling in attempts to eradicate outbreaks.[59]

It is possible to get vaccinated and still get influenza. The vaccine is reformulated each season for a few specific flu strains, but cannot possibly include all the strains actively infecting people in the world for that season. It takes about six months for the manufacturers to formulate and produce the millions of doses required to deal with the seasonal epidemics; occasionally, a new or overlooked strain becomes prominent during that time and infects people although they have been vaccinated (as in the 2003-2004 season).[60] It is also possible to get infected just before vaccination and get sick with the very strain that the vaccine is supposed to prevent, as the vaccine takes about two weeks to become effective.[45]

Vaccination is most important in vulnerable populations, such as children or the elderly. The 2006-2007 season is the first in which the CDC has recommended that children younger than 59 months receive the annual flu vaccine.[61] Vaccines can cause the immune system to react as if the body were actually being infected, and general infection symptoms (many cold and flu symptoms are just general infection symptoms) can appear, though these symptoms are usually not as severe or long-lasting as influenza. The most dangerous side-effect is a severe allergic reaction to either the virus material itself, or residues from the hen eggs used to grow the influenza; however, these reactions are extremely rare.[62]

Good personal health and hygiene habits are reasonably effective in avoiding and minimizing influenza. Since influenza spreads through aerosols and contact with contaminated surfaces, it is important to persuade people to cover their mouths while sneezing and to wash their hands regularly.[61]

Treatment

Further information: [[:Flu treatment]]

People with the flu are advised to get plenty of rest, drink a lot of liquids, avoid using alcohol and tobacco and, if necessary, take medications such as acetaminophen (paracetamol) to relieve the fever and muscle aches associated with the flu. Children and teenagers with flu symptoms (particularly fever) should avoid taking aspirin during an influenza infection (especially influenza type B) because doing so can lead to Reye syndrome, a rare but potentially fatal disease of the liver.[63]

Since influenza is caused by a virus, antibiotics have no effect on the infection, but may be prescribed if the influenza causes secondary infections such as bacterial pneumonia. Antiviral medication is sometimes effective, but viruses can develop resistance to the standard antiviral drugs. The antiviral drugs amantadine and rimantadine are designed to block a viral ion channel and prevent the virus from infecting cells. These drugs are sometimes effective against influenza A if given early in the infection, but are always ineffective against influenza B.[64] Measured resistance to amantadine and rimantadine in American isolates of H3N2 has increased to 91% in 2005.[65] Antiviral drugs such as oseltamivir (trade name Tamiflu) and zanamivir (trade name Relenza) are neuraminidase inhibitors that are designed to halt the spread of the virus in the body.[66] These drugs are often effective against both influenza A and B.[64] Different strains of influenza virus have differing degrees of resistance against these antivirals and it is impossible to predict what degree of resistance a future pandemic strain might have.

Research

CDC scientist working on influenza under high bio-safety conditions.
Further information: [[:Flu research]]

Research on influenza includes studies on molecular virology, how the virus produces disease (pathogenesis), host immune responses, viral genomics, and how the virus spreads (epidemiology). These studies help in developing influenza countermeasures; for example, a better understanding of the body's immune response aids in vaccine development, and a detailed picture of how influenza invades cells aids in the development of antiviral drugs. One important basic research program is the Influenza Genome Sequencing Project, which is creating a library of influenza sequences; this library should help to clarify which factors make one strain more lethal than another, which genes most affect immunogenicity, and how the virus evolves over time.[67]

Research into new vaccines is particularly important: as current vaccines are slow and expensive to produce and must be reformulated every year. The sequencing of the influenza genome and recombinant DNA technology may accelerate the generation of new vaccine strains by allowing scientists to substitute new antigens into a previously-developed vaccine strain.[68] New technologies are also being developed to grow virus in cell culture; which promises higher yields, less cost, better quality and surge capacity.[69] The US government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be used in case of an influenza pandemic of H5N1 avian influenza and is conducting clinical trials with these vaccines.[70]

Infection in other animals

H5N1
Further information: [[:Influenzavirus A, H5N1 and Transmission and infection of H5N1]]

Influenza infects many animal species and transfer of viral strains between species can occur. Birds are thought to be the main animal reservoirs of influenza viruses.[71] Sixteen forms of hemagglutinin and 9 forms of neuraminidase have been identified. All known subtypes (HxNy) are found in birds but many subtypes are endemic in humans, dogs, horses, and pigs; populations of camels, ferrets, cats, seals, mink, and whales also show evidence of prior infection or exposure to influenza.[27] Variants of flu virus are sometimes named according to the species the strain is endemic in or adapted to. The main variants named using this convention are: Bird flu, Human Flu, Swine Flu, Horse Flu and Dog Flu. In pigs, horses and dogs influenza symptoms are similar to humans, with cough, fever and loss of appetite.[27] The frequency of animal diseases are not as well-studied as human infection, but an outbreak of influenza in harbour seals caused approximately 500 seal deaths off the New England coast in 1979-1980.[72] On the other hand, outbreaks in pigs are common and do not cause severe mortality.[27]

Flu symptoms in birds are variable and can be unspecific.[73] The symptoms following infection with low-pathogenicity avian influenza may be as mild as ruffled feathers, a small reduction in egg production or weight loss combined with minor respiratory disease.[74] Since these mild symptoms can make diagnosis in the field difficult, tracking the spread of avian influenza requires laboratory testing of samples from infected birds. Some strains such as Asian H9N2 are highly virulent to poultry, and may cause more extreme symptoms and significant mortality.[75] In its most highly pathogenic form, influenza in chickens and turkeys produces a sudden appearance of severe symptoms and almost 100 % mortality within two days.[76] As the virus spreads rapidly in the crowded conditions seen in the intensive farming of chickens and turkeys, these outbreaks can cause large economic losses to poultry farmers.

An avian-adapted, highly pathogenic strain of H5N1 (called HPAI A(H5N1), for "highly pathogenic avian influenza virus of type A of subtype H5N1") causes H5N1 flu, commonly known as "avian influenza" or simply "bird flu", and is endemic in many bird populations, especially in Southeast Asia. This Asian lineage strain of HPAI A(H5N1) is spreading globally. It is epizootic (an epidemic in non-humans) and panzootic (a disease 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 other birds in an attempt to control its spread. Most references in the media to "bird flu" and most references to H5N1 are about this specific strain.[77][78]

At present, HPAI A(H5N1) is an avian disease and there is no evidence suggesting efficient human-to-human transmission of HPAI A(H5N1). In almost all cases, those infected have had extensive physical contact with infected birds.[79] In the future, H5N1 may mutate or reassort into a strain capable of efficient human-to-human transmission. Due to its high lethality and virulence, its endemic presence, its large and increasing biological host reservoir, the H5N1 virus is the world's pandemic threat in the 2006-7 flu season, and billions of dollars are being raised and spent researching H5N1 and preparing for a potential influenza pandemic.[80]

Economic impact

Further information: [[:Social impact of H5N1]]

Influenza produces direct costs due to lost productivity and associated medical treatment, as well as indirect costs of preventative measures. In the United States influenza is responsible for a total cost of over $10 billion per year, while it has been estimated that a future pandemic could cause hundreds of billions of dollars in direct and indirect costs.[81] However, the economic impact of past pandemics have not been intensively studied and some authors have suggested that the Spanish influenza actually had a positive long-term effect on per-capita income growth, despite a large reduction in the working population and severe short-term depressive effects.[82] Other studies have attempted to predict the costs of a pandemic as serious as the 1918 Spanish flu on the U.S. economy, where 30 percent of all workers became ill, and 2.5 percent were killed. A 30 percent sickness rate and a three-week length of illness would decrease gross domestic product by 5 percent. Additional costs would come from medical treatment of 18 million to 45 million people, and total economic costs would be approximately $700 billion.[83]

Preventative costs are also high. Governments worldwide have spent billions of U.S. dollars preparing and planning for a potential H5N1 avian influenza pandemic: with costs associated with purchasing drugs and vaccines as well as developing disaster drills and strategies for improved border controls.[80] On November 1 2005 President George Bush unveiled the National Strategy To Safeguard Against The Danger of Pandemic Influenza[84] backed by a request to Congress for 7.1 billion U.S. dollars to begin implementing the plan.[85] Internationally, on January 18 2006 donor nations pledged two billion U.S. dollars to combat bird flu at the two day International Pledging Conference on Avian and Human Influenza held in China.[86]

Up to 2006, over ten billion dollars have been spent and over two hundred million birds have been killed to try to contain H5N1 avian influenza.[87] However, as these efforts have been largely ineffective at controlling the spread of the virus, other approaches are being tried: for example, the Vietnamese government in 2005 adopted a combination of mass poultry vaccination, disinfecting, culling, information campaigns and bans on live poultry in cities.[88] As a result of such measures, the cost of poultry farming has increased, while the cost to consumers has gone down due to demand for poultry falling below supply. This has resulted in devastating losses for many farmers. Poor poultry farmers can not afford mandated measures keeping their bird livestock from contact with wild birds (and other measures) thus risking losing their livelihood altogether. Multinational poultry farming is increasingly becoming unprofitable as H5N1 avian influenza becomes endemic in wild birds worldwide.[89] Financial ruin for poor poultry farmers, that can be as severe as threatening starvation, has caused some to commit suicide and many others to stop cooperating with efforts to deal with this virus; further increasing the human toll, the spread of the disease and the chances of a pandemic mutation.[90][91]

See also

Information concerning flu research can be found at

References and notes

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Further reading

External links

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source: https://en.wikipedia.org/w/index.php?title=Influenza&oldid=85261136

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