Influenza

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Template:Flu Influenza, commonly known as the flu or the grippe, is a contagious disease of the upper airways and the lungs, caused by an RNA virus of the orthomyxoviridae family. It rapidly spreads around the world in seasonal epidemics, killing millions of people in pandemic years and hundreds of thousands in nonpandemic years. It creates health care costs and lost productivity. Three influenza pandemics in the 20th century, each following a major genetic change in the virus, killed millions of people all over the world.

It is not connected to gastroenteritis, which is commonly known as "stomach flu" or the "24 hour flu".

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", which by the 18th century became the prevalent terminology in the English-speaking world as well.

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History

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Image:Influenza virus.png

"Influenza was first described by Hippocrates as early as 412 b.c., and the tiny virus has spent the succeeding centuries shifting, drifting and wreaking havoc. Humanity has been seeking ways to eliminate the threat since the first pandemic was recorded in 1580."<ref>[1] In 2003 world renowned virologist Robert Webster published The world is teetering on the edge of a pandemic that could kill a large fraction of the human population in American Scientist.</ref> "The fact that flu is caused by a virus was a British discovery, made in 1933 by scientists of the Medical Research Council (MRC)." <ref>Times on-line Battle of time, luck and science - published April 09, 2006</ref>

The most known outbreaks are caused by antigenic shift, when two strains of influenza recombine forming a lethal new strain. The most famous outbreak (and the most lethal) was the so-called Spanish Flu pandemic (type A influenza, H1N1 strain), which lasted from 1918 to 1919, and is believed to have killed more people in total than World War I. While the war casualties accumulated over several years, the pandemic took most of its toll over a period of weeks. Lesser flu epidemics included the 1957 Asian Flu (type A, H2N2 strain) and the 1968 Hong Kong Flu (type A, H3N2 strain).

Known flu pandemics <ref>Influenza PDF</ref>

Although there were scares in New Jersey in 1976 (the Swine Flu), worldwide in 1977 (the Russian Flu), and in Hong Kong (as well as in other Asian countries, namely continental China, as became known later) in 1997 (Avian influenza), there have been no major pandemics subsequent to the 1968 infection. Increased immunity from antibodies, and the development of flu vaccines have limited the spread of the virus, and so far prevented any further pandemics.

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Symptoms

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

Influenza's effects are much more severe than those of the "cold", and last longer. Recovery takes about one to two weeks. Influenza can be deadly, especially for the weak, old or chronically ill. Some flu pandemics have killed millions of people.

Most people who get influenza will recover in one to two weeks, but others will develop life-threatening complications (such as pneumonia). Millions of people in the United States (about 10% to 20% of U.S. residents) are infected with influenza each year. An average of about 36,000 people per year in the United States die from influenza, and 114,000 per year are admitted to a hospital as a result of influenza. According to estimates by the World Health Organization, between 250,000 and 500,000 die from influenza infection each year worldwide. Even healthy people can be affected, and serious problems from influenza can happen at any age. People age 65 years and older, people of any age with chronic medical conditions, and very young children are more likely to get complications from influenza. Pneumonia, bronchitis, sinus, and ear infections are four examples of such complications.

The flu can make chronic health problems worse. For example, people with asthma may experience asthma attacks while they have the flu, and people with chronic congestive heart failure may have a worsening of this condition, that is triggered by the flu.

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Flu season

Template:Main 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. Therefore, the World Health Organization (assisted by the National Influenza Centers) makes two vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere.

While most influenza outbreaks in the Northern Hemisphere tend to peak in January or February, not all do. For example, the influenza pandemic of 1918 and 1919 reached peak virulence during late spring and summer worldwide, and not until October in the US. 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 linger longer on exposed surfaces (doorknobs, countertops, etc.) in colder temperatures. Increased travel and visitation due to the holiday season may also play a role. <ref>NPR</ref>

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Prevention

It is possible and in many cases recommended to get vaccinated against influenza with a flu vaccine. Its effectiveness varies with many criteria.

Due to the high mutability of the virus, a particular flu vaccine formulation usually only works for about a year. The World Health Organization co-ordinates the contents of the vaccine each year to contain the most likely strains of the virus that probably will attack the next year.

It is possible to get vaccinated for the season and still catch the flu. The vaccine is reformulated each season for a few specific flu strains, but cannot possibly include all the different strains actively infecting people in the world for that season. This means that you could catch a virus not covered by the vaccine. Also, it takes about six months for the manufacturers to formulate and make the millions of doses required to deal with the seasonal epidemics; occasionally a new or overlooked strain becomes prominent during that six months and infects people even though they've been vaccinated (as in the 2003-2004 season). The vaccine may have partial coverage for these unexpected strains. It is also possible to get infected and then get vaccinated the next day, before flu symptoms appear, and still get sick with the very strain that the vaccine is supposed to prevent. The vaccine can take a few days to become effective.

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 as long lasting as the flu.

"The viruses in the flu shot are killed (inactivated), so you cannot get the flu from a flu shot. The risk of a flu shot causing serious harm, or death, is extremely small. However, a vaccine, like any medicine, may rarely cause serious problems, such as severe allergic reactions. Almost all people who get influenza vaccine have no serious problems from it." <ref>CDC</ref>

Personal health and hygiene are important in avoiding and minimizing influenza.

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Treatment

See main article:Flu treatment

If you get the flu, get plenty of rest, drink a lot of liquids, and avoid using alcohol and tobacco. You can take medications such as acetaminophen to relieve the fever and muscle aches associated with the flu. Children and teenagers with flu symptoms (particularly fever) should avoid taking aspirin as taking aspirin in the presence of influenza infection (especially influenza type B) can lead to Reye syndrome, a rare but potentially fatal disease of the liver. <ref>CDC</ref>

During the 2005-2006 flu season in the United States, CDC encourages the use of oseltamivir for flu prevention and the use of oseltamivir or zanamivir for flu treatment. <ref>CDC</ref>

The CDC says:

Three antiviral drugs (amantadine, rimantadine, and oseltamivir) are approved for use in preventing the flu. These are prescription medications, and a doctor should be consulted before they are used. During the 2005-2006 influenza season, CDC recommends against the use of amantadine or rimantadine for the treatment or prophylaxis of influenza in the United States. <ref>CDC</ref>

The annual flu (also called "seasonal flu" or "human flu") kills an estimated 36,000 people in the United States each year. The annually updated trivalent flu vaccine consists of hemagglutinin (HA) surface glycoprotein components from influenza H3N2, H1N1, and B influenza viruses. <ref>CDC</ref> The dominant strain in January 2006 is H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005. <ref>Reason New York Times</ref>

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Variability

Template:H5N1 Influenza is an extremely variable disease and is also found in pigs (swine flu), birds (bird flu), and other animals. In areas where there are high concentrations of humans, pigs and birds in close proximity, such as parts of Asia, simultaneous infections across species enable genetic material to be exchanged between the various strains of flu. It is believed that sooner or later, a recombination may occur to produce a strain as lethal as the 1918 virus. In late 1997, a new strain of avian influenza (also known as bird flu) called H5N1 infected 18 people in Hong Kong, of whom 6 died.

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Avian influenza

Template:Main Genetic reassortment ("mixing") of a human flu virus with the current H5N1 avian influenza has been identified as the most likely source of the next pandemic.

The natural host for influenza virus is aquatic birds. Pandemic influenza often occurs when an avian-adapted virus infects a porcine host, which can be infected by human and avian varieties of influenza A virus. The virus may then recombine within the pig, to form a genetically new virus which is able to infect humans and be transmitted from person to person.

The current avian flu threat is due to the H5N1 virus. It is thought likely that the virus will eventually become adapted and able to spread from person to person. If this happens, a pandemic may be unavoidable, since there will be very little immunity to this genetically new virus, and international travel coupled with densely populated cities will spread the virus rapidly.

Currently, governments are stockpiling anti-viral drugs such as oseltamivir, which can reduce the effects of the virus. It is difficult to design a vaccine for the virus until it has changed into a human adapted form, but if a pandemic does occur a vaccine will be required urgently.

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How H5N1 kills

H5N1 is a virus. It has eight RNA molecules in each virion. The exact molecular makeup of hundreds of genotypes (variants) of both H5N1 and other avian flu viruses are known. The NS RNA molecule codes for two proteins called NS1 and NEP.

The NS1 protein of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia is currently believed to be responsible for an enhanced proinflammatory cytokine response. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, researchers were able to abrogate the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus.

In short, this one amino acid difference in the NS1 protein produced by the NS RNA molecule of the H5N1 virus is believed to be largely responsible for an increased pathogenicity (on top of the already increased pathogenicity of its hemagglutinin type which allows it to grow in organs other than lungs) that can manifest itself by causing a cytokine storm in a patient's body, often causing pneumonia and death.<ref>[2] In 2003 world nenowned virologist Robert Webster published The world is teetering on the edge of a pandemic that could kill a large fraction of the human population in American Scientist.</ref>

Other important mechanisms also exist "in the acquisition of virulence in avian influenza viruses". <ref>CDC</ref>

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Research

Template:Main Influenza research includes molecular virology, pathogenesis, host immune responses, and epidemiology. These help in developing influenza countermeasures such as vaccines, therapies and diagnostic tools.

Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response.

The Influenza Genome Sequencing Project is creating a library of influenza sequences that will help us understand what makes one strain more lethal than another, what genetic determinants most affect immunogenicity, and how the virus evolves over time.

Solutions to limitations in current vaccine methods are being researched. The US government has purchased from Sanofi Pasteur and Chiron Corporation several million doses of vaccine meant to be use in case of an influenza pandemic from H5N1 and is conducting clinical trials on them. <ref> New York Times article ""Doubt Cast on Stockpile of a Vaccine for Bird Flu""</ref> ABC News reported on April 1, 2006 that "Beginning in late 1997, the human trials have tested 30 different vaccines, all pegged to the H5N1 virus." <ref>[3]</ref>

A technique called reverse genetics allows scientists to manipulate the genomes of influenza viruses and to transfer genes between viral strains. The technique allows the rapid generation of seed viruses for vaccine candidates that exactly match the anticipated epidemic strain. By removing or modifying certain virulence genes, reverse genetics also can be used to convert highly pathogenic influenza viruses into vaccine candidates that are safer for vaccine manufacturers to handle.

Another technique is use of cell cultures to grow vaccine strains; such as genetically engineering baculovirus to express a gene that encodes an influenza coat protein such as hemagglutinin or neuraminidase. "A recent NIAID-supported Phase II clinical trial of a vaccine produced by Protein Sciences Corporation using this strategy showed that it is well tolerated and immunogenic; the company is conducting further clinical evaluation of this product. Other new pathways for producing influenza vaccines include DNA-based approaches and the development of broadly protective vaccines based on influenza virus proteins that are shared by multiple strains." <ref name="NIH response">The NIH Biomedical Research Response to Influenza</ref>

"To address the H9N2 threat, NIAID contracted with Chiron Corporation to produce investigational batches of an inactivated vaccine, which will be evaluated clinically by NIAID early next year. For H5N1, Sanofi Pasteur--a division of Sanofi-Aventis--and Chiron are both producing investigational lots of inactivated H5N1 vaccine preparations; additionally, DHHS has contracted with Sanofi-Aventis to produce up to 2 million doses to be stockpiled for emergency use, if needed, to vaccinate health workers, researchers, and, if indicated, the public in affected areas. Development and evaluation of a combination antiviral regimen against these potential pandemic influenza strains are also now under way." <ref name="NIH response"/>

AVI Bio Pharma Inc. has evidence of inhibition of multiple subtypes of influenza A virus in cell culture with Morpholino oligomers from the results of their labs and four independent research laboratories. "The key finding here is that our NEUGENE(R) therapeutics continue to show efficacy against all strains of influenza A, including H5N1." <ref> AVI BioPharma Reports Successful Inhibition of Multiple Subtypes of Influenza A Using NEUGENE Antisense Therapeutic</ref>

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Sources

<references/>

  • WHO 2005. The Writing Committee of the World Health Organization (WHO). Avian influenza A (H5N1) infection in humans. N Engl J Med 2005; 353: 1374-85. – Full text.
  • CDC 2005. Centers for Disease Control. Prevention and Control of Influenza Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2005; 54 (RR08): 1-40. - Full text.
  • Moscona A. Neuraminidase inhibitors for influenza. N Engl J Med 2005; 353: 1363-73. – Full text.
  • Osterholm MT. Preparing for the next pandemic. N Engl J Med 2005; 352: 1839-42. - Full text.
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Further reading

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