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During the 17th and 18th centuries, measures were taken by the Venetian administration to combat plague on the Ionian Islands. At that time, although the scientific basis of plague was unknown, the Venetians recognized its infectious nature and successfully decreased its spread by implementing an information network. Additionally, by activating a system of inspection that involved establishing garrisons along the coasts, the Venetians were able to control all local movements in plague-infested areas, which were immediately isolated. In contrast, the neighboring coast of mainland Greece, which was under Ottoman rule, was a plague-endemic area during the same period. We conclude that even in the absence of scientific knowledge, close observation and social and political measures can effectively restrain infectious outbreaks to the point of disappearance.