The Plague Inc. meme originates from the popular strategy simulation game developed by Ndemic Creations, where players design a pathogen to wipe out humanity. The most famous iterations involve screenshots of the game's global notification bar or the 'Victory' screen, often used to joke about things spreading rapidly—like a new song, a trend, or even a specific internet community. It gained massive cultural relevance during real-world health events, frequently highlighting the difficulty of infecting isolated regions like Madagascar or Greenland, which became a staple joke within the gaming community for being the final hurdles to global infection.