You can easily have the PC's never be directly infected, and have the pandemic still ravage the countryside. Even in 3e,
Remove Disease is a pretty rare and exceptional thing, certainly out of the means of 99% of the population (and you know, SOME people survived the Black Plague, so there's that). The party might be functionally immune to the disease, but that doesn't mean that the world is, and as society collapses and wars break out and people go mad and grief strikes the land around them, and their only enemy is not a great fiend or a horrible alien monstrosity, but a simple illness, they will begin to feel like they are in a plague-ravaged campaign setting, even if they never get touched by it.
In that general case, you can even have occasional "super-strains" of the illness that DO threaten the PC's to some degree. Give them Spell Resistence (an idea cribbed from
Nyambe), and/or require multiple castings of the spell to weed out the illness, and change up the effects and the durations. Some might kill you in your sleep if you're not aware, others might take a long time, wearing you down gradually, until you are left a husk. Give PC's with the Heal skill something to do in combating the thing, too (in order to spread out the challenge of the disease to party members who may not have CD). And keep new and interesting forms of contamination in the mix: some strains may only be spread by direct injury (perhaps even only with saliva or fluids or intimate contact), others might be airborne, and given the likely understanding of infectious diseases of a pseudomedieval world, they're all piggybacking on the dirty peasants all over the place.
This is even believable -- our own world has the legacy of
antibiotic resistance as the price we pay for factory farming that has real people who study actual pandemics kind of freaked out.