The Flue

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 are fever, sore throat, muscle pains, severe headache, coughing, and weakness and fatigue. 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 caused by a different type of virus. Similarly, the unrelated gastroenteritis is sometimes called "stomach flu" or "24-hour flu".

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 over 30 days at 0°C (32°F), about one week at human body temperature, and indefinitely at very cold temperatures (such as lakes in northeast Siberia). They can be inactivated easily by disinfectants and detergents.

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.

Vaccinations against influenza are most common in high-risk humans in industrialised countries and farmed poultry. 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. 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.

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.[10] Archaic terms for influenza include epidemic catarrh, grippe, (sometimes spelt "grip" or "gripe"), sweating sickness and Spanish fever (particularly for the 1918 pandemic strain.

Seasonal variation
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.

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. However, seasonal changes in infection rates are also seen in tropical regions and these peaks of infection are seen mainly during the rainy season. 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. H5N1 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. This idea was first proposed by R. Edgar Hope-Simpson in 1965. 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.

Vaccination and hygiene
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.

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). 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.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.

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.

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. Since influenza is caused by a virus, antibiotics have no effect on the infection; unless prescribed for secondary infections 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 (adamantanes). Neuraminidase inhibitors are currently prefered for flu virus infections. The CDC Health Alert recommended against using M2 inhibitors during the 2005–06 influenza season.

Neuraminidase inhibitors
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.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. Resistance has not yet been a problem with neuraminidase inhibitors. Resistant viruses have been identified but, unlike the situation with amantadine, in which the resistant viruses are fully virulent and able to transmit, that does not appear to be the case with neuraminidase. 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.

M2 inhibitors (adamantanes)
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. Measured resistance to amantadine and rimantadine in American isolates of H3N2 has increased to 91% in 2005.