If it is true that nothing succeeds like success, then it is equally true that nothing challenges like change. People have historically been creatures of habit and curiosity at the same time, two parts of the human condition that constantly conflict with each other. This has always been true, but at certain moments in history it has been abundantly true, especially during the mid-14th century, when a boon in exploration and travel came up against a fear of the unknown. Together, they both introduced the Black Death to Europe and led to mostly incorrect attempts to explain it.
The Late Middle Ages had seen a rise in Western Europe's population in previous centuries, but these gains were almost entirely erased as the plague spread rapidly across all of Europe from 1346-1353. With a medieval understanding of medicine, diagnosis, and illness, nobody understood what caused Black Death or how to truly treat it. As a result, many religious people assumed it was divine retribution, while superstitious and suspicious citizens saw a nefarious human plot involved and persecuted certain minority groups among them.