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On the ruins of an ancient castle. the Venetians erected a strong fortress, the design of which was based on the principles of the “bastioned fortification” system. Construction of it began in 1579 to drawings by the engineer Genese Bressani, and the first building phase lasted until 1586. Repairs and modifications to the fortress were carried out before and during the Cretan war (1645-1669). During the period of Venetian rule on Crete, the fortress was used for military purposes.
At the time of the Cretan war (1645-1669) refugees and rebels (chainides) took refuge in the fortress and used the islet as a base from which to harass the Turks. The islet finally surrendered to the Turks after a siege in 1715. The Venetian garrison departed and the rest of the inhabitants were taken prisoner. After 1715 Spinalonga developed into a purely Ottoman settlement. Benefitting from the security offered by the fortifications, the Turks continued to build on the Venetian foundations.
In the 1903 the Cretan Government established a leper colony on Spinalonga, which remained in operation until 1957. The old buildings of the Turkish settlement and additional buildings erected during the 1930 offered a home to the sick. Furthermore the colony had its own medical director, nursing staff, supervisor, cleaners, financial service, and a priest.