Those who are clear of infection are ordered by martial law to reside within a Quarantine Zone. They believe they can create a vaccine through study of the fungus and its hosts, one of the last organizations to do so. The Fireflies – a militia group formed in response to military oppression – have conducted a mostly futile war against the barely-functional government. As the vicious fungus has taken hold of the majority of the population, the worldwide pandemic causes the total breakdown and destruction of society through widespread violence the failure of martial law to contain the outbreak, the military's increasingly violent efforts to censor information, and the near-extinction of humankind. Public reaction to the Infected has been catastrophic. Eventually the fungus kills its host, and will then grow out of the host's body to spread spores. This erases their memories and drives them insane, modifying their instincts to seek no goal other than spreading the spores to others.
The fungus infects the human brain, growing mycelium inside the brain tissue and killing the brain's cells. The fungus reportedly originated in South American crops various newspapers in Austin in 2013 support this claim. The Infected are the result of a sudden outbreak of a mutant Cordyceps fungus that now affects human beings as opposed to insects.