Maybe you've already looked into this, but the history of disease and its effect on humanity, and trying to figure out medical conditions based on historical descriptions, is a vibrant area of research, with a number of books written for a mainstream audience. Something like "Plagues and People" by William H. McNeill, for example. Or "Deadly Companions: How Microbes Shaped Our History" by Dorothy H. Crawford, "Post-Mortem: Solving History's Great Medical Mysteries" by Philip A. Mackowiak, or "The Medical Detectives" by Berton Roueche. On Amazon I searched for "medical history mystery" under Books; the History of Medicine category is also a good one.
Maybe they would give you some ideas about how to devise a fictional cause for a real disease, based on how people have sussed out real causes in the past. Something twisty that uses multiple organisms (bacteria --> fleas --> rats --> people) would particularly pernicious, I think.