The first European syphilis epidemic emerged in 1495, following the Italian Wars, resulting in tens of thousands of deaths and igniting fierce debates about the disease's origins and moral implications. This outbreak marked a significant moment in medical history, as it prompted increased attention to public health and the social stigma associated with venereal diseases. The epidemic influenced cultural perceptions of sexuality and health in Renaissance Europe.

Syphilis generated an enormous body of early modern verse and prose; poets from Fracastoro to Ronsard used the disease to explore sexuality, shame, divine punishment, and the vulnerability of the body. This exploration laid the groundwork for later discussions of morality and human experience in literature.