The clap

The clap, otherwise known as gonorrhea is a sexually transmitted disease mentioned several times by Knuckles and Cheeto Man. Several characters are implied or stated to have it, including Amy, Rouge, Candy Kong and Jessie. Due to the actions of Knuckles, he, Cheeto Man, and Spyro are also afflicted by the disease.

Full list of the afflicted, time of infection

Peach (Unknown) Rouge Gotten from Donkey Kong, who got it from Peach Knuckles Got it from Rouge. Amy Got it from Knuckles Jessie: unknown Candy Kong probably got it from Donkey Kong