section_path: History
section_name: History
paragraph_text: History
  
  The first influenza epidemic may have occurred around 6,000 BC in China, and possible descriptions of influenza exist in Greek writings from the 5th century BC. In both 1173–1174 AD and 1387 AD, epidemics occurred across Europe that were named "influenza". Whether these epidemics or others were caused by influenza is unclear since there was then no consistent naming pattern for epidemic respiratory diseases, and "influenza" did not become clearly associated with respiratory disease until centuries later. Influenza may have been brought to the Americas as early as 1493, when an epidemic disease resembling influenza killed most of the population of the Antilles.
  
  The first convincing record of an influenza pandemic was in 1510. It began in East Asia before spreading to North Africa and then Europe. Following the pandemic, seasonal influenza occurred, with subsequent pandemics in 1557 and 1580. The flu pandemic in 1557 was potentially the first time influenza was connected to miscarriage and death of pregnant women. The 1580 influenza pandemic originated in Asia during summer, spread to Africa, then Europe, and finally America. By the end of the 16th century, influenza was beginning to become understood as a specific, recognizable disease with epidemic and endemic forms. In 1648, it was discovered that horses also experience influenza.
  
  Influenza data after 1700 is more accurate, so it is easier to identify flu pandemics after this point. The first flu pandemic of the 18th century started in 1729 in Russia in spring, spreading worldwide over the course of three years with distinct waves, the later ones being more lethal. Another flu pandemic occurred in 1781–1782, starting in China in autumn. From this pandemic, influenza became associated with sudden outbreaks of febrile illness. The next flu pandemic was from 1830 to 1833, beginning in China in winter. This pandemic had a high attack rate, but the mortality rate was low.
  
  A minor influenza pandemic occurred from 1847 to 1851 at the same time as the third cholera pandemic and was the first flu pandemic to occur with vital statistics being recorded, so influenza mortality was clearly recorded for the first time. Fowl plague (now recognised as highly pathogenic avian influenza) was recognized in 1878 and was soon linked to transmission to humans. By the time of the 1889 pandemic, which may have been caused by an H2N2 strain, the flu had become an easily recognizable disease.
  
  The microbial agent responsible for influenza was incorrectly identified in 1892 by R. F. J. Pfeiffer as the bacteria species Haemophilus influenzae, which retains "influenza" in its name. From 1901 to 1903, Italian and Austrian researchers were able to show that avian influenza, then called "fowl plague", was caused by a microscopic agent smaller than bacteria by using filters with pores too small for bacteria to pass through. The fundamental differences between viruses and bacteria, however, were not yet fully understood.
  
  From 1918 to 1920, the Spanish flu pandemic became the most devastating influenza pandemic and one of the deadliest pandemics in history. The pandemic, caused by an H1N1 strain of influenza A, likely began in the United States before spreading worldwide via soldiers during and after the First World War. The initial wave in the first half of 1918 was relatively minor and resembled past flu pandemics, but the second wave later that year had a much higher mortality rate. A third wave with lower mortality occurred in many places a few months after the second. By the end of 1920, it is estimated that about a third to half of all people in the world had been infected, with tens of millions of deaths, disproportionately young adults. During the 1918 pandemic, the respiratory route of transmission was clearly identified and influenza was shown to be caused by a "filter passer", not a bacterium, but there remained a lack of agreement about influenza's cause for another decade and research on influenza declined. After the pandemic, H1N1 circulated in humans in seasonal form until the next pandemic.
  
  In 1931, Richard Shope published three papers identifying a virus as the cause of swine influenza, a then newly recognized disease among pigs that was characterized during the second wave of the 1918 pandemic. Shope's research reinvigorated research on human influenza, and many advances in virology, serology, immunology, experimental animal models, vaccinology, and immunotherapy have since arisen from influenza research. Just two years after influenza viruses were discovered, in 1933, influenza A virus was identified as the agent responsible for human influenza. Subtypes of influenza A virus were discovered throughout the 1930s, and influenza B virus was discovered in 1940.
  
  During the Second World War, the US government worked on developing inactivated vaccines for influenza, resulting in the first influenza vaccine being licensed in 1945 in the United States. Influenza C virus was discovered two years later in 1947. In 1955, avian influenza was confirmed to be caused by influenza A virus. Four influenza pandemics have occurred since WWII. The first of these was the Asian flu from 1957 to 1958, caused by an H2N2 strain and beginning in China's Yunnan province. The number of deaths probably exceeded one million, mostly among the very young and very old. This was the first flu pandemic to occur in the presence of a global surveillance system and laboratories able to study the novel influenza virus. After the pandemic, H2N2 was the influenza A virus subtype responsible for seasonal influenza. The first antiviral drug against influenza, amantadine, was approved in 1966, with additional antiviral drugs being used since the 1990s.
  
  In 1968, H3N2 was introduced into humans through a rearrangement between an avian H3N2 strain and an H2N2 strain that was circulating in humans. The novel H3N2 strain emerged in Hong Kong and spread worldwide, causing the Hong Kong flu pandemic, which resulted in 500,000–2,000,000 deaths. This was the first pandemic to spread significantly by air travel. H2N2 and H3N2 co-circulated after the pandemic until 1971 when H2N2 waned in prevalence and was completely replaced by H3N2. In 1977, H1N1 reemerged in humans, possibly after it was released from a freezer in a laboratory accident, and caused a pseudo-pandemic. This H1N1 strain was antigenically similar to the H1N1 strains that circulated prior to 1957. Since 1977, both H1N1 and H3N2 have circulated in humans as part of seasonal influenza. In 1980, the classification system used to subtype influenza viruses was introduced.
  
  At some point, influenza B virus diverged into two strains, named the B/Victoria-like and B/Yamagata-like lineages, both of which have been circulating in humans since 1983.
  
  In 1996, a highly pathogenic H5N1 subtype of influenza A was detected in geese in Guangdong, China and a year later emerged in poultry in Hong Kong, gradually spreading worldwide from there. A small H5N1 outbreak in humans in Hong Kong occurred then, and sporadic human cases have occurred since 1997, carrying a high case fatality rate.
  
  The most recent flu pandemic was the 2009 swine flu pandemic, which originated in Mexico and resulted in hundreds of thousands of deaths. It was caused by a novel H1N1 strain that was a reassortment of human, swine, and avian influenza viruses. The 2009 pandemic had the effect of replacing prior H1N1 strains in circulation with the novel strain but not any other influenza viruses. Consequently, H1N1, H3N2, and both influenza B virus lineages have been in circulation in seasonal form since the 2009 pandemic.
  
  In 2011, influenza D virus was discovered in pigs in Oklahoma, USA, and cattle were later identified as the primary reservoir of influenza D virus.
  
  In the same year, avian H7N9 was detected in China and began to cause human infections in 2013, starting in Shanghai and Anhui and remaining mostly in China. Highly pathogenic H7N9 emerged sometime in 2016 and has occasionally infected humans incidentally. Other avian influenza viruses have less commonly infected humans since the 1990s, including H5N1, H5N5, H5N6, H5N8, H6N1, H7N2, H7N7, and H10N7, and have begun to spread throughout much of the world since the 2010s. Future flu pandemics, which may be caused by an influenza virus of avian origin, are viewed as almost inevitable, and increased globalization has made it easier for a pandemic virus to spread, so there are continual efforts to prepare for future pandemics and improve the prevention and treatment of influenza.