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Herpes is an STD that has made two appearances on the series.
Old Frida had the disease in the episode Chickenpox. Stan finds out that chickenpox is actually a form of herpes, and the boys get revenge on their parents for deliberately making them contract the virus.
Kenny had contracted the disease in the episode I Should Have Never Gone Ziplining. Throughout the episode, Cartman made fun of him for having the disease, though Kenny claimed that is was only a cold sore. Kenny later died, but surprisingly, not from his herpes.