Many of Shakespeare's plays make mention of a pox,
which was one of many nasty afflictions plaguing people in 16th-century London. The original publication of Romeo and Juliet
(called the First Quarto) finds fatally wounded Mercutio damning his murderer with, "A pox o' your houses." The line later became, "A plague o' both of your houses."
The pox — or plague — that Shakespeare was threatening in his dialogue was the venereal disease syphilis, a disgusting and deadly ailment that spread rapidly throughout the Elizabethan population.
In those days, the sexually transmitted bacterial disease usually became a full-blown infection, affecting its sufferers with intense fevers (also known as "burnt blood"), oozing skin lesions, agonizing aches and pains, massive organ damage, and ultimately insanity. (Now, there's an ad for abstinence!)