Cocoliztli comeback would be out of left field and fitting for this timeline.
cocoliztli:
physician who witnessed the outbreak in 1576, symptoms included high fever, severe headache, vertigo, black tongue, dark urine, dysentery, severe abdominal and chest pain, head and neck nodules, neurological disorders, jaundice, and profuse bleeding from the nose, eyes, and mouth. Some also describe spotted skin, gastrointestinal hemorrhaging, leading to bloody diarrhea, and bleeding from the eyes, mouth, and vagina.