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The year 1510 marked the first recognition of pandemic influenza, which arrived in Sicily and Italy along trade routes from Africa and spread throughout many Mediterranean countries. In 1557, a new epidemic swept over Europe. The Sicilian physician Giovan Filippo Ingrassia, some years before he was appointed Protomedicus for the Kingdom of Sicily, when the severe epidemic of influenza afflicted the Island was asked to give advice to the Senate. He vigorously pursued a new approach to pandemic to afford emergency. Sicilian Government had not to seek from physicians notions about therapies; instead, it had to provide any possible support for the community. G. F. Ingrassia provided the Senate with technical advice on both aspects, cure and prevention, stating that, first of all, it was essential to know the nature and the causes of the epidemic. On September 18th, 1558, he held a public lecture, dealing first with the history of epidemics in Sicily, introducing the doctrine of seminaria principia, learned from Hyeronimus Fracastoro in Padua, which was to be further developed in his treatise on plague, and, finally, concerning remedies he would have applied during the pestilence, which introduced an innovative position regards epidemiology and public medicine: territorial control was the response to the chaos of epidemics.