Of course, this was far from one-way traffic: North America got off far worse by comparison with regard to the Eurasian diseases which came in their direction after first contact. (I've written about the apocalyptic consequences of this before.) But, separating the conceptual from the awfulness of the actuality for a moment, there is something compelling about the idea of explorers/adventurers being unwittingly exposed to some disease which has potentially history-defining consequences when taken back home.
Disease, though, is not a very interesting or appetising subject for a pen & paper RPG. What if instead we were to think about a metaphysical version of the phenomenon? What is metaphysical syphilis and how is it to be made gameable?
Metaphysical Syphilis: Definition and Examples
syphilis, metaphysical noun a condition of corruption, deterioration or confusion which typically accompanies transition through ontological gateways
A metaphysical syphilis would most commonly arise in the context of adventure. After the PCs have gone from the place of safety (the town, the tavern, the guild, etc.) to the place of danger (the dungeon, the wilderness, the underworld, etc.) there is a risk that they bring back with them an ontological disruptor that causes the place of safety to instead become itself dangerous, different, or discombobulated.
This could be as simple as a literal parasite (as in Alien) or a haunting (a poltergeist or somesuch which follows the PCs back home) that spreads when brought home. But there are other more creative examples in the literature.
One that springs to mind is from the Chronicles of Amber. I only recently re-read the Amber books (about 12 months ago) for literally about the fifth time, but I am now a forgetful old sausage and the exact details have already slipped from my mind - somebody will appear in the comments to tell me I am an IDIOT for getting it wrong - but the main superplot of the first five novels concerns the corruption by blood of the 'pattern' by which Amberites are able to transition between realities. This results in a 'black road' of chaos spreading across all known realities and bringing with it all kinds of ghoulies and ghastlies. This eventually comes to threaten 'home', Amber, itself.
Another more leftfield and perhaps benign version is the Star Trek: The Next Generation episode 'Force of Nature', in which it is revealed that travelling by warp speed at too fast a speed (this was conveniently forgotten about the following week) actually causes reality itself to deteriorate. It is only a short step from there to 'causes reality itself to deteriorate and for demons to come through the gaps' (now that I think of it, this is I suppose the plot of Event Horizon), which would be a nice way to add complications to any campaign involving actual physical travel between two different planes of reality. (For example, each time one passes through a Planescape gate, there is a chance the gate loses coherence and opens a branch in a totally random other plane, creating a three-way juncture.)
Then there's magic. In MERP, it's the case that any use of magic might attract the attention of a 'shadow'. What if the use of magic may cause reality to decay in some way? Or may indeed cause magical entities to appear as byproducts?
And, finally, there is the, if you like, biggest 'meta'-metaphysical syphilis of all, which is the PCs themselves. What are the PCs, in the end, other than syphilitic in the purest sense - travelling from one reality to another and, whichever way they go, bringing violence, magic, disruptions, and so on with them - and thereby subjecting it to fundamental change? How about that, eh?
