Plague is a feature added in Rhye's and Fall of Civilization. It adds 7 Unhealthiness in affected cities. Cities with plague lose 1 population point per turn and can spread it to other cities. Plague reduces the health of and kills units within the cultural borders of these cities.
Plague disappears after a couple of turns. The exact number is determined by city health, environment, and city size. Higher health and a better environment (see below) will shorten the duration of a plague outbreak; higher population will extend the duration of a plague outbreak. Plague won't spawn in or spread to the territory of civs with the tech Medicine.
Some Plague is preset in the mod and usually forms in 400 AD, 1400 AD, 1650 AD, and 1800 AD, symbolizing historic plagues. If the Maya, Aztecs, and/or Incans contact European civilizations, they will get the plague.
Other, non-preset plagues are possible. Cities with higher population and poor health are more likely to get the plague. Jungles and flood plains further increase the risk of plague, whereas forests and coasts decrease the risk.
When a city gets the plague, a church bell rings and groaning noises are heard, yellow text in the event log reads "Plague has spread to <name of city> <AI Civilization>," and a large, misty skull looms over the city.
In the Civilopedia, Plague is described as "one of the most controversial additions" to Rhye's and Fall of Civilization and is found in section "Rhye's and Fall of Civilization Concepts." Bizarrely, if a player enters world builder, plague is shown as a building.