Running a Steampunk campaign with some friends. The idea is that a massive a destructive plague wiped out the population of an island that was really technologically advanced. The plague needs to somehow still be around, as explorers and such have not successfully returned from the isle. The implication is that the plague was caused by the people on the island reached too far into the realm of science and technology with devastating consequences. What could have caused the plague? How could you combat it? What is the most interesting side-effect you could imagine for a plague?
We already have diseases that can infect humans but contain environmental components that remain present in their absence.
Malaria is the big one: It's very lethal to humans, but not to the mosquito carriers. This is one is getting very scary, as malaria is quickly becoming resistant to literally everything we can throw at it. But being a "3rd world disease," it isn't profitable enough for drug companies to focus significant resources on total eradication (though the Bill and Melinda Gates foundation is trying.) Preventative measures are the cheapest method to directly lower the infection rate, but they don't entirely "cure" malaria (but I have heard tell about some really cool tech to help on that front). That said, I don't know whether malaria will remain for long in the environment without humans around to complete it's development cycle.
Toxoplasma gondii, also known as 'toxo,' is probably your best bet here. It's a protozoan that can infect virtually all warm blooded mammals (unlike malaria). Generally, it's benign overall (though there is some speculation on it's ability to alter human behavior via chemical imbalance) but can be dangerous in immunocompromised individuals (like babies, people with HIV, or chemo patients). It can be spread by contact with saliva and feces, most commonly from cats.
Plausible scenario: Either 'toxo' seemed a good fit for genetic engineering to handle a more dangerous threat, or it evolved to be expressed in the sweat glands or something similar that humans possess in abundance but not cats or most mammals. Animal trials (for the genetic engineering) wouldn't pick up this significant change in behavior, which would cause rapid spreading among human populations but keep it comparatively low in native animals. At this point, it just needs a long enough incubation period for the majority of the population to get infected before it's lethal effects start to show.