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, commonly known as '''flu''', is an
Infectious Disease of
Bird s and
Mammal s caused by an
RNA Virus of the
Family Orthomyxoviridae (the influenza viruses). In humans, common symptoms of influenza infection are
Fever ,
Sore Throat ,
Muscle Pains , severe
Headache ,
Cough ing,
Weakness and
General Discomfort .
1 In more serious cases, influenza
Causes Pneumonia , which can be fatal, particularly in young children and the elderly. Sometimes confused with the
Common Cold , influenza is a much more severe disease and is caused by a different type of virus.
2 Although
Nausea and
Vomiting can be produced, especially in children, these symptoms are more characteristic of the unrelated
Gastroenteritis , which is sometimes called "stomach flu" or "24-hour flu."
Seasonal Flu vs. Stomach Flu by Kristina Duda, R.N.; accessed March 12, 2007 (Website: "About, Inc., A part of The New York Times Company")
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 occur through contact with these bodily fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0
°C (32
°F ), and indefinitely at very low temperatures (such as lakes in northeast
Siberia ). Most influenza strains can be inactivated easily by
Disinfectant s and
Detergent s.
3[http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html Avian Influenza (Bird Flu)]: Implications for Human Disease. Physical characteristics of influenza A viruses. UMN CIDRAP.[http://www.nzherald.co.nz/category/story.cfm?c_id=204&objectid=10413124 Flu viruses 'can live for decades' on ice], NZ Herald, November 30, 2006.
Flu spreads around the world in seasonal
Epidemic s, killing millions of people in
Pandemic years and hundreds of thousands in non-pandemic years. Three influenza pandemics occurred in the 20th century and killed tens of millions of people, with each of these pandemics being caused by the appearance of a new
Strain of the virus in humans. Often, these new strains result from the spread of an existing flu virus to humans from other animal
Species . Since it first killed humans in Asia in the 1990s, a deadly avian strain of
H5N1 has posed the greatest risk for a new
Influenza Pandemic ; however, this virus has not
Mutated to spread easily between people.
4
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.
6 A vaccine formulated for one year may be ineffective in the following year, since the influenza virus changes rapidly over time and different strains become dominant.
Antiviral Drug s can be used to treat influenza, with
Neuraminidase Inhibitor s being particularly effective.
The term influenza has its origins in 15th-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.
7 Archaic terms for influenza include epidemic catarrh, grippe (from the
French grippe, meaning flu; sometimes spelled "grip" or "gripe"), sweating sickness, and Spanish fever (particularly for the
1918 Pandemic strain).
8
. (magnified approximately 70,000 times)]]
The symptoms of human influenza were clearly described by
Hippocrates roughly 2400 years ago.
1011 Since then, the virus has caused numerous pandemics. Historical data on influenza are difficult to interpret, because 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. 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 . This huge death toll was caused by an extremely high infection rate of up to 50% and the extreme severity of the symptoms, suspected to be caused by
Cytokine Storm s. 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." 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 between 2 and 20% of those infected, as opposed to the more usual flu epidemic
Mortality Rate of 0.1%. 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.
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 later pandemics
Antibiotic s were available to control secondary infections and this may have helped reduce mortality compared to the Spanish Flu of 1918.
The
Etiological cause of influenza, the Orthomyxoviridae family of viruses, was first discovered in
Pig s by
Richard Schope in 1931.
18 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.
19 However, it was not until
Wendell Stanley first crystallized
Tobacco Mosaic Virus in 1935 that the
Non-cellular nature of viruses was appreciated.
The first significant step towards preventing influenza was the development in 1944 of a killed-virus vaccine for influenza by to develop the first
Flu Vaccine , with support from the
U.S. Army .
20 The 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.
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.
. 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).]]
(for a
Fujian Flu virus)]]
The influenza virus is an ,
Influenzavirus B , and
Influenzavirus C . Influenza A and C infect multiple species, while influenza B almost exclusively infects humans.
21
The type A viruses are the most virulent human pathogens among the three influenza types and cause the most severe disease. The Influenza A virus can be subdivided into different
Serotype s based on the
Antibody response to these viruses. 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 .
23 This type of influenza mutates at a rate 2–3 times lower than type A
24 and consequently is less genetically diverse, with only one influenza B serotype. As a result of this lack of
Antigen ic 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.
25 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.
26
The influenza C virus infects humans and pigs, and can cause severe illness and local epidemics.
27 However, influenza C is less common than the other types and usually seems to cause mild disease in children.
2829
The following applies for
Influenza A viruses, although other strains are very similar in structure:International Committee on Taxonomy of Viruses descriptions of:
Orthomyxoviridae ,
Influenzavirus B and
Influenzavirus C
The influenza A virus particle or ''virion'' is 80–120
Nm in diameter and usually roughly spherical, although filamentous forms can occur.
30 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
Protein s (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2).
31 The best-characterised of these viral proteins are
Hemagglutinin and
Neuraminidase , two large
Glycoprotein s 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.
32 The hemagglutinin (HA or H) and neuraminidase (NA or N) proteins are targets for
Antiviral Drugs .
33 These proteins are also recognised by
Antibodies , i.e. they are
Antigen s. The responses of antibodies to these proteins are used to classify the different
Serotype s of influenza A viruses, hence the ''H'' and ''N'' in ''H5N1''.
Influenza viruses bind through
Hemagglutinin onto
Sialic Acid sugars on the surfaces of
Epithelial Cells ; typically in the nose, throat and
Lung s of mammals and
Intestine s of birds (Stage 1 in infection figure).
34 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).
35 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).
36 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
Nucleotide s for vRNA synthesis and also inhibiting
Translation of host-cell mRNAs.
37
Negative-sense vRNAs that form the
Genome s 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).
38 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. 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.
39 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 Shift s and allow the virus to infect new host species and quickly overcome protective immunity. This is important in the emergence of pandemics, as discussed in
Epidemiology .
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, however, can be deadly, especially for the weak, old or chronically ill.
Symptoms of influenza can start quite suddenly one to two days after infection. Usually the first symptoms are chills or a chilly sensation but fever is also common early in the infection, with body temperatures as high as 39 °C (approximately 103 °F). Many people are so ill that they are confined to bed for several days, with aches and pains throughout their bodies, which are worst in their backs and legs.
Common symptoms of the flu such as fever, headaches, and fatigue come from the huge amounts of proinflammatory
Cytokine s and
Chemokine s (such as
Interferon or
Tumor Necrosis Factor ) produced from influenza-infected cells.
40 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.
41 Symptoms of influenza may include:
It can be difficult to distinguish between the common cold and influenza in the early stages of these infections, but usually the symptoms of the flu are more severe than their common-cold equivalents. Research on signs and symptoms of influenza found that the best findings for excluding the diagnosis of influenza were:
42
Notes to table:
- See Sensitivity And Specificity for explanation of these terms.
- All three findings, especially fever, were less sensitive in patients over 60 years of age.
Since anti-viral drugs are effective in treating influenza if given early (see treatment section, below), it can be important to identify cases early. Of the symptoms listed above, the combinations of findings below can improve diagnostic accuracy.
43 Unfortunately, even combinations of findings are imperfect. However,
Bayes Theorem can combine pretest probability with clinical findings to adequately diagnose or exclude influenza in some patients. The pretest probability has a strong seasonal variation; the current prevalence of influenza among patients in the United States receiving sentinel testing is available at the
CDC .Centers for Disease Control and Prevention.
Weekly Report: Influenza Summary Update. Accessed January 1, 2007. Using the CDC data, the following table shows how the likelihood of influenza varies with prevalence:
:
Combinations of findings for diagnosing influenza
Combinations of findings |
Sensitivity |
Specificity |
As reported in study.
and projected during local outbreaks
(prevalence= 66%)
|
Projected during influenza season
(prevalence=25%) |
Projected in off-season
(prevalence=2%) |
|---|
PPV |
NPV |
PPV |
NPV |
PPV |
NPV |
|---|
Fever and cough |
64% |
67% |
79% |
49% |
39% |
15% |
4% |
1% |
Fever and cough and sore throat |
56 |
71 |
79 |
45 |
39 |
17 |
4 |
2 |
Fever and cough and nasal congestion |
59 |
74 |
81 |
48 |
43 |
16 |
4 |
1 |
Two
Decision Analysis studies
4445 suggest that ''during local outbreaks'' of influenza, the prevalence will be over 70% and thus patients with any of the above combinations of symptoms may be treated with neuramidase inhibitors without testing. Even in the absence of a local outbreak, treatment may be justified in the elderly during the influenza season as long as the prevalence is over 15%.
Most people who get influenza will recover in one to two weeks, but others will develop life-threatening complications (such as ,
Sinus , and
Ear Infection s.
Key Facts about Influenza (Flu) Vaccine CDC publication. Published October 17, 2006. Accessed 18 Oct 2006.
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 is another
Risk Factor associated with more serious disease and increased mortality from influenza.
46
The available laboratory tests for influenza continue to improve. The
United States Centers For Disease Control And Prevention (CDC) maintains an up-to-date summary of available laboratory tests.Centers for Disease Control and Prevention.
Lab Diagnosis of Influenza. Accessed on January 1, 2007 According to the CDC, rapid diagnostic tests have a sensitivity of 70–75% and specificity of 90–95% when compared with viral culture. These tests may be especially useful during the influenza season (prevalence=25%) but in the absence of a local outbreak, or peri-influenza season (prevalence=10%).
Influenza reaches peak prevalence in
2006 .
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.
Weather and the Flu Season NPR Day to Day, exhibits seasonality in both humans and birds.
An alternative hypothesis to explain seasonality in influenza infections is an effect of
Vitamin D levels on immunity to the virus.
47 This idea was first proposed by R. Edgar Hope-Simpson in 1965.
48 He proposed that the cause of influenza epidemics during winter may be connected to seasonal fluctuations of vitamin D, which is produced in the skin under the influence of solar (or artificial)
UV Radiation . This could explain why influenza occurs mostly in winter and during the tropical rainy season, when people stay indoors, away from the sun, and their vitamin D levels fall. Furthermore, some studies have suggested that administering
Cod Liver Oil , which contains large amounts of vitamin D, can reduce the incidence of respiratory tract infections.
49
creates influenza viruses with slightly-modified antigens, while
Antigenic Shift generates viruses with entirely novel antigens.]]
As influenza is caused by a variety of species and strains of
2006 Although the incidence of influenza can vary widely between years, approximately 36,000 deaths and more than 200,000 hospitalizations are directly associated with influenza every year in America.
5051 Flu factsheet National Institute of Allergy and Infectious Diseases Accessed 22 Dec 2006 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 . Mutations can cause small changes in the hemagglutinin and neuraminidase
Antigen s 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.
52 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.
53 In contrast to this model of pandemics based on antigenic drift and shift, an alternative approach has been proposed where the periodic pandemics are produced by interactions of a fixed set of viral strains with a human population with a constantly-changing set of immunities to different viral strains.
54
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. 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. 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.
55
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 by the
H3N2 Fujian Flu in the 2003–2004 flu season).
56 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.
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.
Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP) CDC report (MMWR 2006 Jul 28;55(RR10):1–42) accessed 19 Oct 2006. 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.[http://www.cdc.gov/flu/about/qa/flushot.htm Questions & Answers: Flu Shot] CDC publication updated Jul 24, 2006. Accessed 19 Oct 06.
Good Personal Health And Hygiene Habits are reasonably effective in avoiding and minimizing influenza. People who contract influenza are most infective between the second and third days after infection and infectivity lasts for around 10 days.
57 Children are notably more infectious than adults, and shed virus from just before they develop symptoms until 2 weeks after infection.
58
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. Surface sanitizing is recommended in areas where influenza may be present on surfaces.
59 Alcohol is an effective sanitizer against influenza viruses, while
Quaternary Ammonium compounds can be used with alcohol, to increase the duration of the sanitizing action.
60 In hospitals,
Quaternary Ammonium compounds and halogen-releasing agents such as
Sodium Hypochlorite are commonly used to sanitize rooms or equipment that have been occupied by patients with influenza symptoms. During past pandemics, closing schools, churches and theaters slowed the spread of the virus but did not have a large effect on the overall death rate.
6162
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
Paracetamol (acetaminophen) 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's Syndrome , a rare but potentially fatal disease of the
Liver .
63 Since influenza is caused by a virus,
Antibiotic s have no effect on the infection; unless prescribed for
Secondary Infection s such as
Bacterial Pneumonia , they may lead to resistant bacteria. Antiviral medication is sometimes effective, but viruses can develop resistance to the standard antiviral drugs.
The two classes of anti-virals are neuraminidase inhibitors and M2 inhibitors (,
2006 . Retrieved on
2007-01-01
Antiviral drugs such as
Oseltamivir (trade name Tamiflu) and
Zanamivir (trade name Relenza) are
Neuraminidase Inhibitor s that are designed to halt the spread of the virus in the body.
64 These drugs are often effective against both influenza A and B. The
Cochrane Collaboration reviewed these drugs and concluded that they reduce symptoms and complications.
65 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.
66
The
Antiviral Drug s
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.
67 Measured resistance to amantadine and rimantadine in American isolates of
H3N2 has increased to 91% in
2005 .
68
Research on influenza includes studies on
Molecular Virology , how the virus produces disease (
Pathogenesis ), host
Immune Response s,
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.
Influenza A Virus Genome Project at The Institute of Genomic Research. Accessed 19 Oct 06
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.
69 New technologies are also being developed to grow virus in
Cell Culture ; which promises higher yields, less cost, better quality and surge capacity.
70 The U.S. 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.
New York Times article ""Doubt Cast on Stockpile of a Vaccine for Bird Flu"" by Denise Grady. Published: March 30, 2006. Accessed 19 Oct 06
Influenza infects many animal species and transfer of viral strains between species can occur. ,
Human Flu ,
Swine Flu ,
Horse Flu and
Dog Flu . (
Cat Flu generally refers to
Feline Viral Rhinotracheitis or
Feline Calicivirus and not infection from an influenza virus.) In pigs, horses and dogs, influenza symptoms are similar to humans, with cough, fever and loss of appetite. 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.
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.Capua I, Mutinelli F. "Low pathogenicity (LPAI) and highly pathogenic (HPAI) avian influenza in turkeys and chicken." In: Capua I, Mutinelli F. (eds.), A Colour Atlas and Text on Avian Influenza, Papi Editore, Bologna, 2001, pp. 13–20 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.
74 In its most highly pathogenic form, influenza in
Chicken s and
Turkeys produces a sudden appearance of severe symptoms and almost 100% mortality within two days.
75 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.
76Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, Rahardjo AP, Puthavathana P, Buranathai C, Nguyen TD, Estoepangestie AT, Chaisingh A, Auewarakul P, Long HT, Hanh NT, Webby RJ, Poon LL, Chen H, Shortridge KF, Yuen KY, Webster RG, Peiris JS.
"The Threat of Pandemic Influenza: Are We Ready?" Workshop Summary The National Academies Press (2005) "Today's Pandemic Threat: Genesis of a Highly Pathogenic and Potentially Pandemic H5N1 Influenza Virus in Eastern Asia", pages 116–130
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.
77 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, and 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 . Rosenthal, E. and Bradsher, K.
Is Business Ready for a Flu Pandemic? The New York Times 16-03-2006 Accessed 17-04-2006
Influenza produces 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.Brainerd, E. and M. Siegler (2003), “The Economic Effects of the 1918 Influenza Epidemic”, ''CEPR Discussion Paper'', no. 3791. 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% of all workers became ill, and 2.5% were killed. A 30% sickness rate and a three-week length of illness would decrease
Gross Domestic Product by 5%. Additional costs would come from medical treatment of 18 million to 45 million people, and total economic costs would be approximately $700 billion.
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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
2006 donor nations pledged US$2 billion to combat bird flu at the two-day International Pledging Conference on Avian and Human Influenza held in China.
Donor Nations Pledge $1.85 Billion to Combat Bird Flu Newswire Accessed 26 Oct 2006.
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.
Avian Influenza and its Global Implications US AID. Accessed 26 Oct 2006. However, as these efforts have been largely ineffective at controlling the spread of the virus, other approaches are being tried: for example, the 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.
Nine poultry farmers commit suicide in flu-hit India Reuters. Published on April 12, 2006. Accessed 26 Oct 2006.
In the Nile Delta, Bird Flu Preys on Ignorance and Poverty The New York Times. Published on April 13, 2006. Accessed 26 Oct 2006.
;Information concerning flu research can be found at:
- NEJM's Avian Influenza
- Bernd Sebastian Kamps, Christian Hoffmann and Wolfgang Preiser (Eds.) Influenza Report 2006 Flying publisher 2006.
- Arnold J. Levine 'Viruses' Scientific American Library, WH Freeman, 1992 ISBN 0-7167-5031-7
- Samuel Baron ''et al.'' '[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed Medical Microbiology]' Fourth Edition, The University of Texas Medical Branch at Galveston 1996 ISBN 0-9631172-1-1.
- Cox NJ, Subbarao K. 'Influenza.' ''Lancet.'' 1999 Oct 9;354(9186):1277–82. PMID 10520648
- Edwin D. Kilbourne Influenza Pandemics of the 20th Century ''Emerging Infectious Diseases'' Special Issue: Influenza Vol. 12, No. 1 January 2006
- Richard Collier 'The Plague of the Spanish Lady' Macmillan publishers (London) 1974 ISBN 0-7490-0246-8
- John M. Barry 'The Great Influenza: the Epic Story of the Deadliest Plague in History' Penguin 2004 ISBN 0-670-89473-7
- Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. "Evolution and ecology of influenza A viruses." ''Microbiol Rev.'' 1992 Mar;56(1):152–79. PMID 1579108
- Scholtissek C. 'Molecular epidemiology of influenza.' Arch Virol Suppl. 1997;13:99–103. PMID 9413530
- Adolfo García-Sastre Antiviral Response in Pandemic Influenza Viruses 'Emerging Infectious Diseases'' Special Issue: Influenza Vol. 12, No. 1 January 2006
- Zambon MC. 'The pathogenesis of influenza in humans.' Rev Med Virol. 2001 Jul–Aug;11(4):227–41. PMID 11479929
- CDC 2005. Centers for Disease Control. [http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5408a1.htm Prevention and Control of Influenza Recommendations] of the Advisory Committee on Immunization Practices (ACIP). MMWR 2005; 54 (RR08): 1–40.
- Arnold S. Monto Vaccines and Antiviral Drugs in Pandemic Preparedness ''Emerging Infectious Diseases'' Special Issue: Influenza Vol. 12, No. 1 January 2006
