The Joker Infection was a unique condition created by the Joker's mutated blood that slowly turned those infected into direct copies of him.
Before Arkham City
Prior to the events of Batman: Arkham City, the chances for a cure to the Titan Disease were looking slim. Joker had the doctors Hugo Strange sent him drain his infected blood and transfuse healthy blood to extend his life while also having Strange send him Mr. Freeze's wife Nora Fries as leverage to get Freeze to develop a cure.
Not wanting to go out by himself, Joker blackmailed Strange into sending his blood to hospitals all over Gotham City and throughout the state by reminding him about his experiments with the Arkham Lunatics, Mad Hatter and Quincy Sharp. Joker even managed to poison Batman with his blood forcing the Dark Knight into helping him get the cure for the disease. Unfortunately for Joker, when Batman gained the cure and took his share the Clown Prince of Crime caused him to drop the vial which made the spilled cure lose its potency and fail to heal Joker.
Before Arkham Knight
Although Batman managed to replicate and distribute the cure, also rounding up most of Joker's blood samples with the help of James 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 infection leading to their discovery and incarceration by Batman.
Batman linked the infection to Creutzfeldt-Jakob disease (CJD) but it was mutated beyond anything on all medical records. Like CJD, the infection attacked the brain and damaged the tissue affecting the victim's mood and behavior. However, this unique infection was not fatal and instead slowly made the host inherit the personality, traits and behavior of the Joker until they would likely become a literal copy of the Clown Prince of Crime, although the disease could not change their body structure and/or gender.
After repeated nightmares and attempts to understand them Batman feared the infection would take him over as he still had the mad clown's blood in him as well, keeping a fifth quarantine cell ready at Panessa Studios.
To his horror, he found Scarecrow's new strain of Fear Toxin could exaggerate the infection to the point of causing hallucinations. In Batman's case a vivid hallucination of Joker appeared that represented the embodiment of his worst fears and darkest desires along with Scarecrow Nightmares and flashbacks to Joker's past crimes.
So far the only known way to cure oneself is to fight the infection from within their mind. The infection took the form of Joker, who Batman was finally able to genuinely scare and lock away in a dark corner of his mind represented by Arkham Asylum's Extreme Isolation, purging himself of Joker's insanity for good. In that case it is heavily implied that Batman exploited the use of Scarecrow's toxin to ensure he could take on the infection. Other than that a quick death would be needed.
Aside from the obvious adoption of Joker-like traits and to a certain extent hallucinating Joker, the disease also results in the infected having intrusive flashbacks to heinous actions Joker had caused in the past, regardless of whether the infected ever witnessed such actions. In Batman's case it was the crippling of Barbara Gordon and the end of her career as Batgirl as well as bits and pieces of Joker's torture of Jason Todd.
- It was speculated that the very first time Batman showed symptoms of the Joker Infection was right after defeating Mr. Freeze in Arkham City as he hallucinated Joker's face in place of Freeze's while subduing him. This was actually confirmed by Sefton Hill in a Reddit AMA.
- The first time Batman became truly aware of his infection was in Batman: Arkham VR since it turned out all the events that took place were part of a nightmare in which he was unknowingly responsible for the deaths of Nightwing and Robin along with blowing up the Iceberg Lounge while imitating Joker.
- 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 was a famous singer; the infection boosted his egomania.
- Albert King was a professional boxer; he became more violent.
- Henry Adams was a biology teacher; he came to believe in survival of the fittest.
- Bruce Wayne as Batman was more ruthless but refrained from killing, although he implied [see below] that his restraints would disappear if infected long enough. Batman also understood Joker better than anyone resulting in a near-perfect copy. However, the Joker he hallucinated was too consistent and driven, constantly striving to eliminate Batman.
- Most of the infected resembled alternate versions of the Joker from the comic books.
- Christina Bell is visually modelled after Earth-37 Bianca Steeplechase from Thrillkiller.
- Johnny Charisma appears to be modelled after the Joker of Earth-31 (Batman: The Dark Knight Returns). He dresses in a white suit like Joker from this story and is a singer which could be an allusion to Earth-31 Joker.
- Henry Adams looks like an elderly Joker which could be an allusion to Earth-22 Joker from Kingdom Come.
- It was never fully revealed what the exact cause for the creation of the 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 infection.
- Aside from the two names stated above, Joker referred to the illness as Joker-itis and Mad Clown Disease (a parody of hepatitis and Mad Cow Disease).
- It was shown that despite having cured himself in Arkham City, Batman was still infected by the events of Arkham Knight — considering that Batman only took half the cure and intended to give Joker the other half it could be assumed that 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. The hallucination of Joker revealed he had pumped four pints of his blood into Batman which could explain why the cure was ineffective.
- It is unclear whether or not Joker knew the long-term effects of his blood. While the hallucinated Joker is aware of the effects and implies he knew it all along, it doesn't confirm that the real Joker knew. In addition, Harley shows no signs of the blood's effects thus meaning Joker either didn't know of the disease or didn't trust her sanity enough to infect her.
- Similarly, it was also not made clear whether the various hallucinations of the Joker were hallucinations or his ghost, although some of the scenes (most notably flashing back to Jason Todd's torture as well as Barbara Gordon's crippling, despite him not being directly present to witness these events) imply that those infected, or at the very least Batman managed to at least gain Joker's memories.
- It is possible that this disease helped inspire an alternate version of Batman known as The Batman Who Laughs who killed Joker and was subsequently infected by a toxin from within Joker's body, failing to resist and becoming a Jokerized version of himself who went on to jokerize and slaughter countless people including his family and allies.
- There is one notable difference as the Joker infection appears to largely suppress the victim's original identity and effectively turn them into Joker copies while The Batman Who Laughs inherited many of Joker's traits but never actually considers himself to be Joker.
- This disease was possibly inspired by Batman Beyond: Return of the Joker in which DCAU Joker took over Tim Drake's body using Project Cadmus technology to copy his mind and implant it within Tim following torture sessions that turned him into a surrogate son named Joker Jr.
- The Joker Infection as well as gradually stripping Batman of his restraints was given an indirect allusion in the ending of the Gunrunner Most Wanted mission where Batman, after he subtly threatened to kill Penguin by having him choose between the GCPD or local morgue after the latter referenced his capture of Nightwing admitted when Penguin reminded him of his rule against killing that the Caped Crusader wasn't feeling himself that night, implying that if the infection lasted long enough it would ultimately force Batman to break his one rule. It should be noted that this exchange only happens if the player hasn't surrendered to Scarecrow yet.