Mad Zombie Disease is the name given to the contagion responsible for the Zombies.
The virus is an evolved strain of Mad Cow Disease. At some point in 2009 (in the Zombieland universe), Mad Cow evolved into Mad Human (presumably meaning that it could now infect humans as well but was otherwise no different from the effects it had on cattle), which itself evolved into a more dangerous strain that turned infected humans into violent cannibals. Columbus states "It's a fast-acting virus that left you with a swollen brain, a raging fever. It made you hateful, violent, and gave you a really, really bad case of the munchies." The outbreak started with people consuming food made from infected cattle. The first person to be infected took a bite out of a burger. Zombieland: Double Tap shows in a post-credit scene that other people were originally infected by eating contaminated food as well.
The virus acts very fast, transforming the infected within a few minutes, leaving little time for a show of symptoms. However, a consistent sign that a person is about to transform is vomiting yellow bile. A person may also show signs of sickness. The last sign before a person transforms is that their skin will change color.
Aside from eating the meat of infected cattle, a person can also be infected by being bitten by another infected person. The virus may also be capable of spreading through transmission of bodily fluids such as through sexual intercourse or by being scratched by a zombie, though this is not confirmed.
The virus has a 100% infection rate, as any human infected will become a zombie. Furthermore, the potency of the virus is proven by the fact that, even after 10 years, no vaccine or antidote had been created.