Interestingly enough, only a few minutes later, I followed a link to a justification of rabies as the source of werewolf myths. Normal guy gets bitten by a strange-acting wolf, then starts lashing out in a bestial rage. But, hey, I'm already thinking about making vampirism a disease, they shouldn't both be diseases. That just looks cheesy.
This starts percolating, and I go see Zombieland this weekend. (Ed. note: This pretty well dates the original post.) Zombies as a disease. Sure, been done to death. But something upstairs clicks, and the mind gnomes present their collage.
What if vampirism, lycanthropy, and zombies are actually all the same disease? Well, three strains. It would be a sort of weaponized rabies, combined with a bacterial agent known to activate certain parts of the human brain that produce psionic effects. It becomes the ultimate biological weapon. Drop it in the urban center of your enemy, and watch them destroy themselves. Just make sure to inoculate your own population before it spreads too far.
The simplest (and most virulent) strain causes you to lose your mind, become horrifically violent, and eat people. (We shall call them ghouls rather than zombies, as it is technically more accurate.) You also totally ignore pain and fear, making you seem indestructible. In a peculiar twist, the disease, in perhaps the only attempt to preserve its host, makes the smell of other infected hosts unappetizing, so ghouls don't try to eat each other.
Another strain, or perhaps just a different reaction to the primary strain, leaves the infected with some intelligence. However, the victim is still overcome with homicidal tendencies. The victim is also activated as a psion, with a number of physical abilities. These typically involve exceptional senses, super strength and speed, and natural weapons. In short, the infected gains the ability to grow in size, transform their body into a bestial form marked by teeth and claws, and easily out-perform most humans in hand-to-hand combat. While actual photographic evidence indicates that the shape is not truly a man-wolf hybrid, many witnesses report it as such (enough to make the old legends stick).
Vampires retain even more of their intelligence, and gain much greater advantages from their psionic abilities. While much more subtle in their use of teeth and claws, the comparisons to lycanthropes are easily drawn. In addition, they gain a number of mental abilities, including the ability to dominate weak minds. Do not be fooled by their urbane appearance and fine manners, however. These are still bloodthirsty, cannibalistic serial killers. They want to eat the world, not rule or bargain with it.
Sufficiently Advanced To Be Indistinguishable
All three varieties are vulnerable to bright lights, to varying degrees. This means that they tend to operate mostly at night, and stick to the shadows where possible. It does not mean that the sun causes them to spontaneously combust. They can also be driven away by particular smells (including garlic and wolfsbane), and generally avoid crossing large bodies of water (rabies is also called hydrophobia, after all).
All three also have amazingly rapid rates of healing, and the ability to function without impairment from injuries. Among vampires, this regeneration also seems to radically slow the effects of natural aging, making them seem immortal.
Destroying the disease is not simple. The viral element makes it exceptionally resistant to common anti-bacterial agents. However, the natural anti-bacterial properties of silver are actually more effective than normal. Inserting silver into an open wound retards the regenerative effects (most commonly accomplished by simply plating the weapon itself with silver). Injecting an infected person with silver nitrate will destroy the disease, killing the patient in the process. Magical healing has a chance of walking the extremely narrow line of removing the disease and returning the patient to normal, but also has a chance of not working at all.
As a note, disease does not actually respond to acts of faith. Vampires, werewolves, and ghouls are not repelled by crosses, can freely enter holy ground, and can be bound by the words of a priest only to the same degree as any mortal.