The original plans for the Fort are attributed to Louis d'Augbigne Tigné, and are said to have been modified by his friend and colleague Charles François de Mondion, who is buried in a crypt beneath Fort Manoel.
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In 1643 Jean Paul Lascaris, Grandmaster of the Knights of Malta, constructed a quarantine hospital (lazzaretto) on the island, in an attempt to control the periodic influx of plague and cholera on board visiting ships.
Within the harbour and reached by a small bridge from Gzira, Manoel Island houses a yacht yard and the 18th century Fort Manoel.
In 1970 the club moved from Hay Wharf, Floriana, to Fort Manoel, Manoel Island.
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It stands on Manoel Island in Marsamxett Harbour to the north west of Valletta and commands the entrance to Marsamxett Harbour and the anchorage of Sliema Creek.