I would have went with P is for Plague but I've got something else in mind for that letter.
In keeping the material in line with books I'm working on or just finished off, disease plays a minor role in C. J. Sansom's third novel of Shardlake, Sovereign. Several of the characters, while not suffering the direct effects of the Black Plague or other plagues, note that the cities tend to breed the plagues and that they are a periodical problem.
Even in the times we live in now, diseases can run rampant if given the right breeding grounds and opportunity. Various things happen, even when the disease is under control, that the GM should take into account.
1. Quarantine. No one gets in or out until its all said and done.
2. Specialist. The doctors of the olden times with their hook beaked masks filled with various incense and herbs to prevent the spreading of disease have a unique look all their own and this look has been used in various fields ranging from movies to comics.
3. Overkill: One of the reasons families may have been large is that disease could come along and wipe out everyone. In Sovereign, one of the characters notes that his own family has died of the plague but he managed to avoid it. What type of mentality does it set up if every dozen years or so a disease cuts through the locals and its a matter of hit or miss?
4. Magic: Dungeons and Dragons has a huge array of races, magic items, locations, planes, and other bits that can be used to spice up the normal disease. In a recent book I just finished, The Wolf Age, Ambrose suffered from a 'ghosting' disease that worked its way from his hand trembling to going insubstantial and that ghost like effect working its way toward his heart. Diseases don't necessarily all have to be about the standard bile and pus.
5. The gods. This goes both ways. While there are gods that help to cure the diseases, such as Lathandar in the Twilight War series, there are gods whose whole specialty is the spreading of diseases, such as Nurgle, one of the four Ruinous powers behind the Warhammer setting and whose creatures plague the witch hunter in that series.
6. A Weapon: Disease can be used as a weapon. In an old movie I recall, I believe, Flesh and Blood, disease is used in the water as a biological weapon.
When using disease, like many other large scale elements though, the GM has to decide what the role of the disease is. It's it a manufactured disease like the Blue Shadow from the Clone Wars that the players have to actively avoid, or is it a background element that for all intents and purposes, the players have plot immunity from unless they do something really stupid?
Is it something already in play or something that is coming? Is it a plot point that the players can stop, and if so, what happens if they fail to stop it? The Years of Rice and Salt provide one answer, but you'll have to decide if that's the answer you want for your own campaign.
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