Elephants crossing the seas!
It is not an infectious disease, but it is a plague upon the world.
For it spawns villains. And not your garden variety villains, but epic villains, master villains of the most dangerous kind Evil Geniuses.
Pnathic sorcery has existed for ages, crudely used by magi who no idea the true forces they were fumbling with.
An article concerning the nature and role of druids in an RPG enviroment.
Plagues and other great diseases are important parts of history and some settings. They defy man and may even defy God in their swift and terrible punishment upon the body of society.
Mining in a certain area turns all exposed skin (maybe just parts that are actively disturbing the chemicals that cause the reaction) of the those doing the mining to a dark blue color. Will wear off taking as many years/days spent in the mine. ... meeting a party of blue-skinned humans armed with pick-axes etc. Strange disease? Demon offspring? Curse? If they meet only one ex-worker, they will very carefully listen to any stories he says, no matter if drunken or insane, or just makes up to get a beer.