Look, personally I think the Roman Empire example is a good one from a gameplay perspective. Historically, the depopulation of whole cities-as a result of malarial outbreaks from North Africa-did help to hasten the decline of the Roman Empire. Note though that it HASTENED IT, not caused it. The decline had already set in as a result of the Empire being overstretched, hamstrung by greed and corruption at the highest levels, inability to cope with the new 'religious crisis', external pressure from 'Minor Civs' being pushed to within Romes boundries by Near and Far Eastern Nomadic Tribes-and so on. The Malaria was kind of 'the straw that broke the camels back', and could be well represented in a game like civ. i.e. Bad things happen, but one bad thing should not spell doom for your empire. Multiple bad things, though, could represent overall poor management, which should be paid for with possible failure!
Yours,
Aussie_Lurker.