In real life, a disease that springs out of nowhere and lays waste large portions of the population is either a mutation of a less dangerous bug or a leap from another species -- that animal husbandry is big there -- but in fantasy a more magical source is feasible.
Even diabolical, though I think that won't work in this world. And having them be whipped up by wizards has other plot disadvantages. A site of natural if ugly magic -- or the product of a magical disaster -- could also work.
The thing is, it has to be localized so someone can seal off a region from it. Now, they know quite a bit about that time, even though it was centuries (millennia?) ago -- in fact, more than of more recent times. So I need to know whether it was the knowledge that those other regions had gone for that disgusting habit of associating with beasts, or whether they were preserving themselves from those accursed regions touched with disease spots.