The Atlantis Plague begins only days after The Atlantis Gene leaves off, with Dr. Kate Warner trying to cure a disease ravaging the world with her work on the genes of autistic children. A new, incredibly deadly strain of the Atlantis Plague has begun to wreak havoc on the world, leaving billions dead. Some people, however, survive this plague, and there are two types of survivors: people who have lost most of their brain function, and people who seem to have evolved beyond what they had originally been. The disease seems to have come from some kind of alien spacecraft, but most of the world irrationally blames Kate, so she must go on the run while trying to find a cure for this disease.
The Immari organization is still around, and they're more powerful than ever. Martin, Kate's adopted father and the secret leader of the experiment trials, tells Kate that the Immari have essentially taken over the Southern Hemisphere, building regimes that celebrate the "survival of the fittest," organized around those who have withstood the plague to become something stronger.
The plot grows even stranger from there. David and Dorian, who have died killing each at the end of the last novel, are resurrected in some sort of tube by at Atlantean, and as soon as they revive, they continue fighting; Dorian kills David, and the Atlantean, named Ares, begins to explain his mission to Dorian, revealing that he actually is Dorian, and Dorian hosts some residual elements from his personality from previous lives. In that sense, Dorian is an Atlantean, and he was present when the Atlantis gene was given to humans, although it was his partner who actually did it.
His partner, as it turns out, is/was/will be Kate Warner, whose ancestry and Atlantis gene have made her the current host for the other Atlantean, Janus. She begins to have dreams of past events where she was present, and she gradually discovers that she is the Atlantean who delivered the Atlantis gene to the humans. She and Dorian subsequently become the main characters in conflict: Dorian wants to continue using the gene to further evolve humanity and kill off those who can't evolve, while Kate wants to save humanity because she believes that saving human life is more worthwhile than evolving beyond it. Janus also resurrects David for a second time, bringing him and Kate together to continue their mission on the run.
Through the course of their adventure, they learn that the hub of the Atlantis Plague is an ark located in the mountains of Malta. This ark has sent the signals that triggered the plague by trying to activate the Atlantis gene, and it also provides a safety radius from the disease: Malta is a safe zone, free from infection. Kate and David travel to Malta to continue their research and try to stop the plague before it succeeds in wiping out humanity as we know it.
