The flu (or influenza) is an infectious disease highly contagious and frequently caused by three RNA virus of the family Orthomyxoviridae (Myxovirus influenza A, B and C), affecting some birds and mammals including humans.

The transmission of influenza is typically international human respiratory tract, via droplets-rich virus from coughing and sneezing of infected persons. It can also be transmitted through saliva, nasal secretions, feces and blood, either by direct contact or through contaminated surfaces. The contact with infected birds or their droppings is more rarely in question. In humans, its most common symptoms are fever, headache, cough, sore throat, muscle aches, fatigue and loss of appetite, accompanied by a sense of general malaise. These symptoms, elements of the syndrome whose flu is a cause among others, are to refer to the diagnosis by the suddenness of their appearance, their occurrence during a flu epidemic and their disappearance usual after a few days' evolution. In the most serious cases, influenza is complicated by sometimes fatal pneumonia.

Banalisée in the popular mind as synonymous with cold or "cold coup", the flu is a serious disease and other major public health problem on a global scale. Sévissant on a seasonal epidemic, it is responsible in the world of a high morbidity and death of several hundreds of thousands of people every year, mostly young children and elderly people. The cost health and social annual flu and is valued at several billion dollars in the USA, and 460 million euros in France for an epidemic average. Regardless of epidemics, influenza pandemics are likely to occur during the emergence of new viral strains. Since its appearance in the 1990's in Asia, the strain of bird flu virus type A subtype H5N1 raises the risk of a new influenza pandemic, but this virus is not at present transmissible from person to man.

The prevention of influenza is vaccination, proposed in most industrialized countries at risk and administered to poultry breeding. An annual vaccination is necessary because of the antigenic variation of influenza viruses. Some antiviral drugs are available for the treatment and prophylaxis of influenza, including the neuraminidase inhibitors today held a special place.

Comments epidemiological
The symptoms of human influenza were clearly described by Hippocrates there are nearly 2 400 years. Livy described in ancient Rome brutal epidemics that seem in retrospect can be attributed to the flu. Since then, the virus has been responsible for numerous pandemics. Historical data on influenza are difficult to interpret, because the syndrome occurs in other epidemic diseases (diphtheria, bubonic plague, typhoid fever, dengue fever, typhus). The first convincing observation dates back to 1580, with a pandemic, which went to Asia and spread to Europe and Africa. More than eight thousand dead were counted in Rome and several Spanish cities were hit. Pandemics continued on a sporadic basis by the XVIIedécrite Jussieu in 1729 and eighteenth centuries, with a particularly extensive pandemic between 1830 and 1833 (one quarter of those exposed would have been infected). It was not until the years 1850 a systematic description of epidemics was undertaken by the British Theophilus Thompson.

The pandemic's most famous and most deadly known to date is that of "Spanish flu" (influenza virus A, subtype H1N1), which rages between 1918 and 1919. The earliest estimates about forty to fifty million dead while scores deliver the latest figure to one hundred and fifty million deaths worldwide, which would make it one of the most serious health disaster of all Time, like the Black Death of 1347-1350. Another peculiarity of this pandemic that is killing mostly young adults, 99% of deaths have occurred before sixty-five years and more than half between twenty and forty years. This high fatality due to an attack rate very high (nearly 50% of those exposed) and the extreme severity of symptoms, which we suspect it is linked to an excessive immune response ( "storm cytokinique"). The symptoms, unusual for the flu, made the first move for a dengue disease, cholera or typhoid fever. An observer wrote "one of the more striking was bleeding mucous membranes, especially those in the nose, stomach and intestines. The ear bleeding and hemorrhaging occurred pétéchiales also ". The majority of deaths were due to superinfections, including bacterial pneumonia, but the virus also killed directly by causing bleeding and pulmonary oedema mass exceeding the therapeutic possibilities of the time.

The following pandemics were less devastating. The "Asian flu" of 1957 (virus type A, H2N2 strain) and "Hong Kong Flu" of 1968 (virus type A, H3N2 strain) were still millions of deaths around the world. The development of antibiotics, allowing the treatment of bacterial superinfections, could have played a significant role in reducing mortality. New threats came the day in New Jersey in 1976 ( "flu swan"), worldwide in 1977 ( "Russian flu") and since 1997 in Hong Kong and other Asian countries with H5N1. However since 1968, acquired immunity against strains of previous pandemics and vaccination have limited the spread of the virus and may have helped prevent the risk of new pandemics.

Discoveries microbiological
The flu has been falsely attributed to a bacterium until the etiological agents of influenza viruses of the family Orthomyxoviridae, are identified in pigs by Richard Shope in 1931. This discovery was soon followed by isolation of the virus in humans by a research group headed by Patrick Laidlaw the Medical Research Counsil (Council of Medical Research) in the United Kingdom in 1933. However it was not until that Wandell Stanley crystallizes the Tobacco Mosaic Virus in 1935 for the non-cellular virus is known.

The first important step towards the prevention of influenza was the development in 1944, a vaccine based flu virus found by Thomas Francis, Jr., with the support of the U.S. Army. This discovery was based on the fundamental work of Frank Macfarlane Burnet, which showed that the virus lost its virulence when it was grown in embryonated hen eggs. The U.S. military, hard hit by influenza during the First World War, s'impliqua actively in this research.

The word "influenza" was first used in England in the eighteenth century when the epidemic of 1743, qualify for the flu. It seems to come from the Italian expression "influenza di freddo (influence of cold). He recalled the seasonal nature of the disease, which suggests the influence of the external environment on humans. The virus is deemed better survive outside the body by dry weather and cold, why seasonal epidemics occur in winter in temperate climates. But pandemics have been active across the globe, and the H5N1 avian virus seems appropriate (variants?) The cold and temperate zones (Siberia), as the hot areas especially since it occurred in South Asia and Indonesia , With some homes in Africa in the tropics.

The word french flu would have a Germanic origin, Grippen meaning "seize suddenly." In other words: it does not catch the flu, it makes us "grasps." The flu was also named folette in 1733.

The influenza virus infects other mammals that Man; land and sea. But in birds it is most common. In animals on the call for a long time "avian influenza", "bird flu" or "bird flu". The change in terminology in animals is due to two reasons. The first, the identification of two groups of causal virus that had been described as plague, where a segmentation of Newcastle disease and influenza, deuxiémement the decision to be concerned, the level of health that influenza viruses highly pathogenic for the species Gallus gallus. At the symposium Beltsville (1981), it was decided to no longer speak of "chicken plague" but "highly pathogenic influenza", although the disease does not depend solely on the virus, but also immunity from the individual infected.

Influenza viruses are RNA viruses. They belong to the family Orthomyxoviridae and gender influenza, of which there are three types A, B and C distinguished by their antigenicity nucleoproteins. Among the type A viruses, which are more frequent and more virulent, there are several subtypes based on their surface antigens, hemagglutinin (H1 to H15) and neuraminidase (N1 to N9). The virus type A and B are responsible for annual influenza epidemics, but only type A viruses are at the origin of influenza pandemics. The virus type C appears to be linked to sporadic cases and most often gives flu expression moderate. The A and C viruses infect several species, while the B virus is almost specific to the human species (not on the meeting except that among seals).

Structure of the viral particle
The viral particle is a lipid envelope fraught with spicules formed by the surface glycoproteins. The virus A and B have two glycoproteins surface, haemagglutinin (H) and neuraminidase (N).

The hemagglutinin, which represents about 40% of glycoproteins surface, is formed by combining two units, HA1 and HA2, connected by a bridge disulfide. The association of three monomers HA form a spicule of the hemagglutinin surface of the viral particle. The hemagglutinin allows the fixing of the virus in the terminal sialic acid cells in the epithelium cilié of the respiratory tree: it is very immunogenic inducing the production of antibodies, some of which may be neutralizing.
The hemagglutinin also promotes the fusion of viral and cell membranes during the phase of penetration of the virus.

The neuraminidase (N-acetyl-neuraminyl-hydrolase), is a sialidase in the form of homotétramères the surface of the viral particle. It would allow the release of virions neoformed in lysant sialic acids on the surface of the cell, which detaches the hemagglutinin and thus the viral particle.

In the case of type C virus, there is only one kind of spicule the surface of the viral particle, which serves both the hemagglutinin and neuraminidase.

In addition to glycoproteins surface, the viral envelope is made up of two other viral proteins: the protein matrix, M1, which underlies all of the viral envelope protein and M2, which plays the role of ion channel for the virus type A. For virus subtype B, a surface protein NB fits into the lipid bilayer and provide functions equivalent to those of the M2 protein of the virus type A. Finally, a protein CM2 would be the counterpart for the virus type C.

Within the viral particle, the viral genome is present in the form of seven or nucleocapsid symmetry eight helical arising each of the association of a molecule RNA and many molecules nucléoprotéine, NP. This protein is part of internal antigen of the virus: it determines the viral type A, B or C. Three polymerases, PA (protein acid), PB1, and PB2 (basic protein 1 and 2, respectively), form the complex réplicase / transcriptase and are associated with nucleocapsid. The genome of the virus A and B consists of eight segments of RNA, while that of HCV that would include September

The flu virus is pathogenic for about a week to body temperature, more than thirty days to zero ° C and almost indefinitely at very low temperatures (for example lakes north-east Siberia). Most strains of influenza virus is easily inactivated by disinfectants and detergents.

Classification and Nomenclature
The classification of influenza viruses applies only type A viruses, some of which are highly pathogenic to humans.

It relies on the antigenic properties of hemagglutinin and neuraminidase: there are 16 subtypes H and 9 N subtypes can give 16X9 possible combinations. In humans found viruses in H1, H2, H3 and N1 or N2 responsible for the annual flu. All subtypes exist in the world with avian viruses with a highly variable pathogenicity for birds. Currently a highly pathogenic H5N1 virus (hemagglutinin with a sub-type H5 and neuraminidase sub-type N1) spreads in the form of a panzootic avian influenza and is transmitted as an extremely rare in humans; on known as avian influenza. Other strains (H5 or H7) are transmitted to humans but can cause the same pathogen. Other strains reach other species of mammals such as horses, pigs, etc.. The nomenclature of influenza viruses is as follows: type / place of isolation of the virus strain and number of ethnic / year of isolation (subtype). For the avian influenza virus, the term "H5N1" is very simplistic. At present, different virus strains circulating pathogens with powers vary: for example, strains A/chicken/Shantou/423/2003 (H5N1) or A / bar-headed goose/Qinghai/5/2005 (H5N1).

Variability of influenza viruses
Influenza viruses mutate and evolve according to two mechanisms: the antigenic shifts (or drift) or breaks antigenic (shift).

The shifts are variations antigenic discrete and continuous that do not alter the overall structure of the virus antigen and thus retain a partial immunity in the short term. These shifts are due to mutations that occur during the synthesis of RNA virus due to the high rate of errors of the viral RNA polymerase. To take account of antigenic shifts, influenza vaccines are prepared each year from the viral strains that have circulated the previous year. In February of each new year, the World Health Organization (WHO) sets the viral strains that make up the influenza vaccine next year, according to data from epidemiological surveillance of influenza virus circulating. In 2005, WHO has called for the replacement of the strain influenza A/Fujian/411/2003 (H3N2) strain A/California/7/2004 (H3N2) for the preparation of vaccines.

The antigenic breaks are radical changes in the structure of hemagglutinin. They arise from genetic réassortiments occurring between virus subtypes different. These lead réassortiments including the replacement of a type of hemagglutinin by another. The antigen nucléoprotéique NP, he was retained, it is always a virus type A. The pre-existing immunity to this change does not affect the new virus so that major pandemics occur as a result of antigenic breaks. At present, experts fear a genetic recombination between a virus of the avian influenza A/H5N1 and a human virus circulating which could give birth to a new highly pathogenic virus to humans.

The flu is much more common and epidemic in winter, except in the equatorial zone and at some pandemics. This phenomenon is poorly understood. It has seen several explanations;

* Weakening of the immune system by the cold (non hypothesis confirmed in pigs reared in india in a controlled atmosphere; In the laboratory, the cold has not been able to weaken their immunity, which has remained unchanged at 5, 20 and 30 ° C)
* Seasonal decrease of immunity, for example due to a lower intake of vitamins;
* Decrease in the rate of UV in winter, allowing a more sustainable survival of the virus in the environment;
* Synergy with other bacterial infections promoted this season;
* Link with the phenomenon of bird migration (we know that some birds including ducks can be healthy carriers and all birds are potential carriers of influenza, and they can return migration make viruses that have mutated sufficiently months prior to be a source of strain epidemic), but migration is partly earlier that the dates of onset of the flu.
* Viral characteristics; Experiments breeding and transmission of the virus in guinea pigs reared in a controlled environment show that 2 factors seem crucial;
o temperature; cold air (5 ° C) appears to promote viral transmission, which is hampered by 20 ° C and almost zero to 30 ° C. The cold virus could help by making the clearance of the airways more difficult (mucus thicker and more abundant).
o humidity; An air dry (20% to 35% relative humidity) also promotes contagion through the air.

In a dry air and cold, influenza virus would be more stable and sustainable infectious. A temperature over 20 ° C combined with a relative humidity of at least 50% seems to work against the contagion (excluding direct physical contact). However, major infectious outbreaks are found in tropical and equatorial zone, poultry and humans.

Confirming these results, but giving them another explanation, a study by the National Institute of American Health, published in Nature Chemical Biology in early 2008, said that "the flu virus is wrapped with a layer of fat molecules that hardens and protects when temperatures fall. This envelope, made up of cholesterol, substance once the virus has entered the respiratory system of its victim, it may then infect a cell and reproduce. When it's too hot the protective layer can not resist the virus and dies, unless it is inside an organism, which explains its propensity to crack in winter. [...] The result: a temperature of 5 degrees C and a humidity of 20% are perfect so sick hamsters contaminate others. A 30 ° C researchers found no viral transmission."

Epidemiological data general
In France, monitoring of influenza was first made by two networks of doctors Liberals. The network Sentinel of Inserm and the network of GROG (Regional Groups Observation Flu) and a virological surveillance done by two National Reference Centres (Pasteur Institute, Paris to the northern part of France, and CHU Lyon for the southern half). Under the plan pandemic, this network has been gradually completed (2003 to 2007) by:

1. a network to monitor the specific mortality in near real time (via the monitoring of death certificates for about 35% of the metropolitan population, by 22 Ddass)
2. a serious flu monitoring (via a network of 46 emergency services (Network Oscour)
3. an alert epidemics reported by local seniors. (The average time of alert to the INVS rose from 21 to 10 days from 2003 to 2007)

In the French West Indies, monitoring is carried out throughout the year by 39 Liberals sentinel doctors in Guadeloupe and 59 in Martinique. The cell Veille Sanitaire (CVS) of the Department of Health and Social Development (DSDS) and Wax Antilles-Guyana coordinate these two networks.

Diagnostic Clinic
The incubation period is short (1-2 days). The disease begins abruptly with a fever higher than 38.5 ° C with chills, headache, a feeling of general malaise with diffuse pain in particular muscles (myalgia) and joints (arthralgia). At this table added signs of irritation conjunctival-laryngo-tracheal or bronchial (cough). The fever lasts 3 to 5 days, healing is quick but fatigue can persist for several weeks.

Although nausea and vomiting can be encountered with the flu, especially among children, they are more often an expression of viral gastroenteritis which epidemiology is also Winter.

The complicated forms are rare but serious acute lung edema, myocardites, neurological forms. Complications related to a bacterial infection are frequent ear infections, bronchitis, pneumonia.

The severe flu should never be ignored because of the possibility of death: you have to know that influenza is the second leading cause of death by infectious disease in France (2000 to 4000 deaths per year in France), (behind pneumonia Pneumonia). This particular clinical signs associated aspécifiques flu with acute respiratory failure, and failure sometimes multi-visceral. It is always secondary to infection of a subject weakened.

Those infected are contagious as symptoms last.

Diagnostic virological
The clinical picture of the syndrome can be caused by other virus (paramyxovirus, adenovirus that produce syndromes febrile painful). The diagnosis of certainty is essential to date the beginning of an epidemic.

The diagnosis is done by analysing samples respiratory: nasal swabs, naso-pharyngeal aspiration. In case of pneumonia, especially in adults, a washing liquid bronchoalvéolaire can be taken.

Early detection of the virus via an immunological (indirect immunofluorescence) is the most used, because producing a result in 3 to 4 hours for a low cost, to meet the requirements of sensitivity and specificity of virology laboratories.

Increasingly laboratories also use molecular biology techniques: extraction of viral RNA from the levy, then RT-PCR endpoint or quantitative RT-PCR. These techniques allow a diagnosis fast enough (less than 2 hours for extraction followed by quantitative RT-PCR) and reliable, which also has the advantage of allowing a first typing. The RT-PCR can then be supplemented by a viral genome sequencing, with a view primarily epidemiological. For instance, this is what is done in the National Reference Center for influenza in France.

The isolation of the virus in cell culture (cells of kidneys dog, MDCK) is exceptionally necessary. It is useful for monitoring epidemiological annual influenza. In the absence of cytopathic effect of the virus, culture must be supplemented by a reaction Haemagglutination (HA), hemagglutination inhibition (IHA) or immunofluorescence (IF).

Outlook: In September 2007, a team announced have a handheld scanner capable of detecting (bullet) H5N1 in a sample of mucus or stool (human or avian), in less than 30 mn. According to the team, it is "sensitive 440% faster and 2,000 to 5,000% cheaper" than the best existing tests, and could be adapted to SARS, HIV, AIDS, hepatitis B. Commercial production is still not done, and WHO seems to remain cautious pending more information.

Prevention and treatment
In addition to hygiene, immunization in countries where it is accessible seems to be the best parade, with rates of protection by vaccines at around 60% (up to 90% for seasonal influenza). It significantly reduces the number of hospitalization and mortality. The quarantine is an effective way, but difficult to implement.

In some countries (France, Belgium) subjects at risk; more than 65 years, chronic respiratory failure, heart attacks or kidney, and so on. are entitled to a free vaccination. It is recommended for health professionals and people working in positions "socially" exposed (teachers, hotel, transport share ...)

The most common vaccine is a suspension of inactivated viral particles and purified which offers protection against three virus strains. Most often it contains particles of two subtypes of influenza A virus and a subtype of influenza B virus.

There are antiviral drugs:

* Amantadine and rimantadine, which have an efficiency of about 80% if administered as a preventive measure;
* Oseltamivir and zanamivir are neuraminidase inhibitors. These treatments, taken early, can reduce a little the importance of symptoms and duration of the disease. But they are expensive, are not reimbursed by social security in France, Belgium and Switzerland must be taken within 48 hours after the onset of symptoms.

The doctors quickly found that epidemics occurred almost all of November to April in the northern hemisphere and April to October in the southern hemisphere, what was initially explained by the conjunction of planets. Some had indeed noted coincidences they tried troubling between the dates of the beginning of the epidemic and certain astronomical events (sunspots, streams of protons, position of Venus, etc.). Long before the invention of science fiction, we had imagined microbes from the sky or space (Venus). Then it was the influence of weather changes and cold, which was considered the trigger.

New questions arise, for example about the impact the virus from ultraviolet radiation (mutagenic?), Radioactivity (mutagenic factor?), Biocides, disinfectants, genetic impoverishment of populations of birds or other carriers, the possible impact of other pollutants mutagenic or weakened immunity, or even nosocomiaux aspects related to vaccines, hospitalizations, hygiene in schools or retirement homes, etc.. These questions remain open while the ecology of the virus is not yet understood, especially for the AI virus H5N1 that HP is developing since 1996 and which since 2003 has the characteristics of a virus that could - if mutait to become most contagious - to cause a pandemic.

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