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Since we don't know exactly what he died of it is entirely possible that he may have had syphilis, a sexually transmitted disease which Christopher Columbus brought back from America and which thereafter spread like an epidemic across Europe. Shakespeare refers often to syphilis, especially in plays which have a lot to do with prostitution, like Henry IV Part II, Measure for Measure or Pericles. And the theatre district and the red light district were the same place in Shakespeare's London, so he could have caught it if he were in the habit of frequenting brothels.

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Q: Did William Shakespeare die of an STD?
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