Morbus
The clearest choice is the Morbus Bloodline from the main Vampire: the Requiem book. Morbus vampires are restricted to feeding on inflected blood, they are plague carriers. If we made their condition spreadable via their blood then they become a serious threat not only to the mortal population but vampires as well. Their ghouls and surviving victims might become Typhoid Mary's of the city, causing those vampires that feed on them to become Morbus.Soon those vampires not infected might have to choose between starvation and feeding off diseased mortals, potentially becoming infected with Morbus themselves. Then they would become plague carriers and pariahs. Those fleeing infect cities might have to deal with neighbors unwilling to take chances that new comers are already infected. There is a lot of room for dramatic tension.
For non-vampires, they could see disease slowly overcoming their home. Soon doctors, bus drivers, police, and all the key people who keep a city going begin to call in sick. City infrastructure could begin breaking or shutting down as the people who are supposed to maintain it are waylaid by disease.
The plague could bring greater government scrutiny as CDC teams descend on the area. The veil that keeps supernatural creatures hidden could be broken. The situation could escalate into a race against time to eliminate the source of the plague before everyone is exposed or dies for those with mortal biologies (or mortal allies).
The other supernatural creatures would be vulnerable in their own ways. Mage, without Life magic, are as vulnerable to disease as any mortal. As allies and enemies succumb to disease new problems and opportunities arise. Hunters of course will suffer with the city which gives them a strong motivation to take down these plague carriers. Prometheans might find themselves labeled as such if they stray into an infected region. They most likely won't get sick but that just makes them more of a target.
Werewolves would likely be immune but have their kinfolk to look out for. They would also have to deal with growing horde of disease and potentially death spirits. As body counts rise, Sineaters might have their hands full with ghosts, even as they must survive the plague themselves. Changelings have no special resistance to disease but might benefit from people willing to trade anything for immunity to the disease, something that is possible via a Pledge.
Mechanics
The spread of the disease (both the mundane disease and the supernatural one conferring the Morbus bloodline) occurs through blood contact either by ingestion of infected blood or by being bitten and fed on by an infected vampire or mortal.The exposed party must make an extended Resolve + Stamina roll against the infected party's Blood Potency (for infection from a mortal carrier, treat his or her effective Blood Potency as 2 less than the vampire who infected them). Bonuses against disease apply. Each roll represents a 24-hour period since exposure.
For mortals (or non-vampires), any failure on the roll leaves them infected with a mundane disease and able to infect vampires with Morbus for a number of hours equal to the Blood Potency of the vampire that exposed them.
For vampires, any failure on the roll infects them with Morbus. If the source was an infected mortal, this will last for a number of months equal to the original difficulty. If it was from Vitae (like an infected ghoul), then it is permanent.
Those infected can gain no Vitae from healthy mortals and can learn to use the Discipline Cachexy to find and infect more people.
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