Check this game out that I just happened upon called Pandemic II.
Basically you creat your own disease and try and destroy the world. As your disease involves it can cause different symptoms, pick up different immunities, and develop different mediums of transmission. The game depends on a lot of chance as well, just like in real life. If there are 20 infected people in a country, what are the chances that one of them are gonna get on a plane and go to another country. A lot less than if there are 30 million people infected. Also the governments start to close borders, shut down airports, and close sea ports as the disesase becomes a more visible and serious problem. The world will try and engineer a vaccine that may work and put a halt to the spread of your disease, may fail and they may have to try again, or it may cause a mutation in your disease that will make it so that there can never be another vaccine made to stop your disease. I'm not sure how realistic the last possibility is, but you can always knock out the world's major hospitals and then they can't try and make a vaccine anyway.
Perfect example of what most people picture the apocalyptic disease that is going to destroy the world.
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