Prior to the events of Batman: Arkham City, the changes for a cure to the Titan Disease were looking slim. Not wanting to go out alone, the Joker had the doctors Strange sent him drain and store his infected blood, while transfusing healthy blood to extend his life. Joker managed to blackmail Strange into sending his blood to hospitals all over Gotham City, by reminding him that he knew about his illegal experiments with Lunatics, the Mad Hatter and Quincy Sharp. Joker even managed to poison Batman with his blood, forcing the Dark Knight into helping him get a cure for the disease. Unfortunately for the Joker, when Batman had gained the cure and took his share, the Clown Prince of Crime caused him to drop the vial of cure; accepting his death, the Joker died with a smile on his face.
Although Batman managed to find and distribute a cure to the infected and rounded up most of Joker's blood samples with the help of Commissioner Gordon, four people were given blood transfusions with blood samples they missed due to hospital errors. It was sometime afterwards, that those individuals began showing signs of the Joker Infection, leading to their discovery and incarceration by Batman.Batman linked the infection to Creutzfeldt-Jakob disease (or CJD) but it was mutated beyond anything on medical record. Like CJD, the Joker Infection attacked the brain and damaged the brain tissue, affecting the victim's mood and behavior. Unlike CJD however, this unique infection was not fatal, and instead it slowly made the host inherit the personality, traits and behavior of the Joker until they likely would eventually become a literal copy of the Clown Prince of Crime. (Although the disease could not change their body structure or gender.)Batman feared that the infection would take him (as he had the mad clown's blood in him as well), keeping a quarantine cell ready. To his own horror, he found Scarecrow's new strain of toxin could exaggerate the Joker Infection's symptoms and its effects to the point of causing hallucinations. In Batman's case, a vivid hallucination of the Joker appeared that represented the embodiment of his worst fears.
So far, the only known way to cure one's self of the disease is to fight the infection within one's mind. The infection took the form of the Joker, who Batman was finally able to scare and lock away in a dark corner of his mind, purging himself of the Joker's insanity for good. Other than that, a merciful death would be needed.
- Christina Bell (Killed by Henry Adams.)
- Johnny Charisma (Killed by Henry Adams.)
- Albert King (Killed by Henry Adams.)
- Henry Adams (Suppressed most (if not all) of the effects to fool Batman before being revealed, committed suicide.)
- Batman (Used sheer iron will and possibly Fear Toxin to combat the infection and finally remove Joker from his thoughts and lock him away forever, preventing himself from becoming the Joker.)
- It was speculated that the very first time that Batman showed symptoms of the Joker Infection was right after he defeated Mr. Freeze in Arkham City, as he hallucinated the Joker's face in place of Freeze's while subduing him. This was actually later confirmed by Sefton Hill in a "Ask me anything" event in reddit.
- Ironically, the infection enhanced a quality the victim already had.
- Christina Bell: suffered a miscarriage, thus losing a baby; she became fixated on Batman
- Johnny Charisma: a famous singer; the infection boosted his egomania
- Albert King: boxer; he became more violent
- Henry Adams: biology teacher; he believed in "survival of the fittest"
- Batman: More ruthless, but refrained from killing.
- It was never fully revealed what the exact cause for the creation of the Joker Infection was other than it originating from Joker's mutated blood. However, it was probable that the chemicals that caused the Titan Disease (and maybe chemicals already in the clown's blood) caused Joker's blood to mutate, creating the Joker Infection.
- Aside from the two names stated above, Joker referred the illness as Joker-itis and Mad Clown Disease (a parody on Mad Cow Disease).
- It's shown that, despite having cured himself in Arkham City, Batman was still infected with Joker's blood by the events of Arkham Knight — considering that Batman only took half a dose of the cure, and intended to give Joker the other half, it could be assumed it was not enough to completely cure him in the long run and was only intended to save him and Joker from immediate death to allow curing later. It's also possible that the particular sample of Joker's blood that was injected into Batman couldn't be cured along with the Titan Disease because the Joker Infection was a result of a mutation and was not really a poison like the Titan Disease.
- It's not clear whether or not Joker knew of the effects of his blood. While the hallucinated Joker is aware of the effects and implies that he knew it all along, it doesn't confirm that the real Joker knew of them. In addition, Harley shows no signs of the blood's effects, thus meaning that Joker either didn't know of the disease or didn't trust her sanity enough to infect her with his blood.