Changes

Possibly the first influenza pandemic occurred around 6000 BC in China. The symptoms of human influenza seem to have been clearly described by Hippocrates, roughly 2,400 years ago<ref name="Arti9">2,500-year Evolution of the Term Epidemic, Emerging infectious diseases, 2006, Martin PM, Martin-Granel E, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373038/</ref>[208].

The most infamous and lethal outbreak was the 1918 flu pandemic (Spanish flu) (type A influenza, H1N1 subtype), which lasted into 1920. The number of deaths is unknown, but estimates range from 17 to 100 million people. This pandemic has been described as "the greatest medical holocaust in history" and may have killed as many people as the plague (Black Death). This huge death toll was caused by an extremely high infection rate of up to 50% and the severity of the symptoms, suspected to be caused by cytokine storms in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines.

One of the most recent outbreaks of influenza was the 2009 Swine Flu. Similar to the Spanish Flu, it was also of the subtype H1N1. The death toll of the 2009 pandemic is estimated to be around 150,000 to 575,000.