The 1580 outbreak was the earliest pandemic that can definitely be attributed to the flu. It began in Asia, spread to Africa and then hit Europe. According to a 2001 paper in the Journal of Applied Microbiology, the pandemic left entire Spanish cities devoid of people, and killed 8,000 people in Rome, Italy. In fact, it was flu infections in Italy that lead to the word “influenza”, which comes from the Italian “influenza del freddo”, or “influence of the cold”. “Influenza” would not appear in the English language, however, for another 160 years.