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Wikipedia's list of epidemics shows that epidemics have plagued us for almost as long as recorded history. Some great works of literature describe events caused or triggered by an epidemic, for example:

  • in the play Oedipus Rex, the plague is ravaging Thebes,
  • in Giovanni Boccaccio's Decameron, a number of young people flee to the countryside while the plague rages in Florence and tell each other stories to while away the time,
  • Daniel Defoe's novel A Journal of the Plague Year (1722) is based on the bubonic plague that struck London in 1665-1666,
  • Jean Giono's novel Le Hussard sur le toit / The Horseman on the Roof (1951) describes events set during a cholera epidemic, and
  • perhaps most famously, Albert Camus' novel La Peste / The Plague (1947) describes the effects of the plague in the French Algerian city of Oran.

The oldest novel in the above list is Daniel Defoe's A Journal of the Plague Year (1722), since The Decameron is not a novel but a collection of short stories tied together by a frame story. However, what was the oldest European novel that was set during an epidemic? Note that it is not sufficient that a novel merely mentions the epidemic; the epidemic needs to determine the main character's action for at least 50% of the story. It does not matter whether the epidemic is to be taken literally (see Boccaccio and Defoe) or whether it symbolizes something else (Giono).

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