1580 influenza pandemic

The earliest pandemic that can definitely be attributed to flu occurred in 1580. It began in Asia, spread to Africa and then hit Europe. It left entire Spanish cities depopulated and killed 8,000 people in Rome. The outbreaks in Italy led directly to the name of the illness. "Influenza" comes from the Italian phrase Influenza del Freddo, or "influence of the cold". However, the word would not appear in the English language for another 160 years.

1830-1848 influenza pandemic