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The Plague is a time period in the Smurf Village that lasted for a few years, from 46 to around 50 years after Empath Smurf was taken to Psychelia in the EMPATH: The Luckiest Smurf story series. It began with the death of Painter, Poet, and Sculptor's father Picasso Smurf and eventually spread to all the adult Smurfs except for Papa Smurf, who along with all the young Smurflings was immune to the mysterious and incurable disease. The last known Smurf to die from the disease was Muscles Smurf, the father of Hefty, Handy, Grouchy, and Sassette, the last of whom had run away from home during that time.

As far as its symptoms, the disease begins with a sudden dizziness and a loss of strength, and then is followed by coughing spells that get worse as the disease progresses. Accelerated aging, pale blue skin, and veins visibly showing are also symptoms of the disease. The longest that a Smurf with the disease can hope to last for is about six to nine months.

Over the course of that period, with fewer adult Smurfs remaining alive to handle important village duties and to take care of the children, Papa Smurf eventually adopted all 98 of the Smurflings and was given authority to be the village leader. The children would spend the next 20 years of their lives getting used to having to run things with Papa Smurf as their sole surviving guardian and instructor.

As Papa Smurf himself would learn years later, he actually wasn't immune to the Plague, but rather was spared its effects until he reached his 600th birthday. However, the care he would receive from his little Smurfs from that time meant that he would live until the age of 712.

The same Plague also affected the parent Smurfs of the Smurfettes on Smurfette Island, with Mother Smurfette being the only survivor among her peers of that generation.

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