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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<ref name="Arti10">Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic, American journal of epidemiology, 2018, Spreeuwenberg P, Kroneman M, Paget J, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314216/</ref>. This pandemic has been described as "the greatest medical holocaust in history"<ref name="Arti11">Reviewing the History of Pandemic Influenza: Understanding Patterns of Emergence and Transmission
, Pathogens, 2016, Saunders-Hastings PR, Krewski D, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198166/</ref> 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<ref name="Arti12">2009 H1N1 Pandemic (H1N1pdm09 virus), centers for disease control and prevention, 2010, https://www.cdc.gov/flu/pandemic-resources/2009-h1n1-pandemic.html</ref>.
==Structure of the influenza virus==