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There are 4 clues with the answer 'GREATPLAGUE'
# CLUE
1.
Major epidemic from 1665 to 1666 (5,6)
2.
Big place with fever, it was a major epidemic (5,6)
3.
Affliction that killed an estimated quarter of Europe's population in the 14th century: 2 wds.
4.
Big place to have fever, it was a major epidemic (5,6)