Alternative Titles: flu, grippe

Influenza, also called flu or grippe, an acute viral infection of the upper or lower respiratory tract that is marked by fever, chills, and a generalized feeling of weakness and pain in the muscles, together with varying degrees of soreness in the head and abdomen.

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Classification of influenza viruses

Influenza is caused by any of several closely related viruses in the family Orthomyxoviridae (a group of RNA viruses). Influenza viruses are categorized as types A, B, C, and D. These major types generally produce similar symptoms but are completely unrelated antigenically, so that infection with one type confers no immunity against the others. The A viruses cause the great influenza epidemics, and the B viruses cause smaller localized outbreaks. The C viruses cause only mild respiratory illness in humans. Influenza D viruses are not known to infect humans and have been observed only in pigs and cattle.

Influenza A viruses are classified into subtypes, and both influenza B and subtypes of influenza A are further divided into strains. Subtypes of influenza A are differentiated mainly on the basis of two surface antigens (foreign proteins)—hemagglutinin (H) and neuraminidase (N). Examples of influenza A subtypes include H1N1, H5N1, and H3N2. Influenza B viruses are subdivided into two major lineages, B/Yamagata and B/Victoria. Strains of influenza B and strains of influenza A subtypes are further distinguished by variations in genetic sequence.

Evolution and virulence of influenza viruses

Between worldwide outbreaks, known as pandemics, influenza viruses undergo constant, rapid evolution (a process called antigenic drift), which is driven by mutations in the genes encoding antigen proteins. Periodically, the viruses undergo major evolutionary change by acquiring a new genome segment from another influenza virus (antigenic shift), effectively becoming a new subtype. Viral evolution is facilitated by animals such as pigs and birds, which serve as reservoirs of influenza viruses. When a pig is simultaneously infected with different influenza A viruses, such as human, swine, and avian strains, genetic reassortment can occur. This process gives rise to new strains of influenza A.

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Newly emerged influenza viruses tend to be initially highly infectious and virulent in humans because they possess novel antigens to which the human body has no prepared immune defense (i.e., existing antibodies). Once a significant proportion of a population develops immunity through the production of antibodies capable of neutralizing the new virus, the infectiousness and virulence of the virus decreases. Although outbreaks of influenza viruses are generally most fatal to young children and the elderly, the fatality rate in people between ages 20 and 40 is sometimes unexpectedly high, even though the patients receive treatment. This phenomenon is believed to be due to hyper-reaction of the immune system to new strains of influenza virus. Such reaction results from the overproduction of inflammatory substances called cytokines. The release of excessive amounts of these molecules causes severe inflammation, particularly in the epithelial cells of the lungs. Individuals whose immune systems are not fully developed (such as infants) or are weakened (such as the elderly) cannot generate such a lethal immune response.

Pandemics and epidemics

Influenza pandemics are estimated to occur on average once every 50 years. Epidemics happen much more frequently, and seasonal influenza appears annually in most parts of the world, sometimes in epidemic proportions. Influenza type A virus is the most frequent cause of seasonal influenza. When an influenza A virus undergoes an antigenic shift, a pandemic affecting most of the world can occur within a matter of months. The influenza pandemic of 1918–19, the most destructive influenza outbreak in history and one of the most severe disease pandemics ever encountered, was caused by a subtype of influenza A known as H1N1. During this pandemic an estimated 25 million persons throughout the world died of the so-called Spanish flu, which was first widely reported in Spain but originated in the U.S. state of Kansas.

Subsequent pandemics of influenza have been less severe. For example, influenza A subtype H2N2, or 1957 flu pandemic, apparently began in East Asia early in 1957, and by midyear it had circled the globe. The outbreak lasted on a pandemic level until about the middle of 1958 and caused an estimated one million to two million deaths worldwide. After 10 years of evolution that produced annual epidemics, the 1957 flu disappeared in 1968, only to be replaced by a new influenza A subtype, H3N2. This virus is still in circulation. The flu outbreak of 1968 was the third influenza pandemic of the 20th century and resulted in an estimated one million to four million deaths.

In 1997 a type of avian influenza, or bird flu, virus broke out among domesticated poultry in Hong Kong and then infected a small number of people, killing some of them. This same virus, H5N1, reappeared among chicken flocks in Southeast Asia during the winter of 2003–04, again infecting some people fatally, and it has reappeared periodically since, primarily in wild birds, domestic poultry, and humans. Several other subtypes of bird flu viruses are known, including H7N2, H7N3, and H9N2. Though these subtypes rarely cause infection in humans, they are recognized as having epidemic and pandemic potential.

An outbreak of a previously unknown strain of H1N1 occurred in 2009. Originally called swine flu because the virus was suspected to have been transmitted to humans from pigs, the illness first broke out in Mexico and then spread to the United States. The H1N1 virus that caused the outbreak was discovered to possess genetic material from human, avian, and two different swine influenza viruses. The 2009 H1N1 outbreak was not nearly as deadly as the pandemic of 1918–19. However, the virus was highly contagious and spread rapidly. The pandemic potential of the new H1N1 virus was made clear to the international community by the World Health Organization (WHO), which declared a level 5 pandemic alert on April 29, 2009. This prompted the rapid implementation of mitigation procedures, including the distribution of drugs to treatment facilities, in countries worldwide. Despite these measures, the virus continued to spread globally. On June 11, 2009, following an increase in cases in Chile, Australia, and the United Kingdom, WHO raised the H1N1 alert level from 5 to 6, meaning that the outbreak was officially declared a pandemic. By mid-January 2010 the outbreak had affected people in more than 209 countries worldwide. It was the first influenza pandemic of the 21st century. In the United States the high levels of flu-like illness observed during the 2009 H1N1 pandemic were not observed again until 2018.

Research has indicated that each of the four historic influenza pandemics was preceded by a La Niña event—a change in global weather conditions associated with cool sea surface temperatures in the Pacific Ocean—which, some scientists speculate, may have altered the migratory patterns of birds, possibly increasing their interactions with domestic animals and enabling genetic reassortment and the rise of new pandemic strains of influenza viruses.

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