So researchers advanced a hypothesis: Cocoliztli was some kind of animal-spread hantavirus or arenavirus normally contained in Mexico’s highlands. When a brief wet period allowed the population of rodents (or otherwise) to boom, cocoliztli was able to take hold. The disease may still lurk in the highlands, waiting for an opportunity to arise.

That, at least, is the hypothesis. Researchers are hampered in part because the 16th century is the last time that the deserts of southern North America experienced a mega-drought. Alas, they may get another opportunity soon.

A new study, published last week in Science Advances, says that climate change will make a similar mega-drought far more likely in the American Southwest. In fact, this kind of phenomenon could become a near certainty: If carbon emissions continue unabated, the risk of a mega-drought could exceed 99 percent.

“This will be worse than anything seen during the last 2,000 years and would pose unprecedented challenges to water resources in the region,” says Toby Ault, a professor of earth science at Cornell University and one of the authors of the study, in a statement. “As we add greenhouse gases into the atmosphere—and we haven’t put the brakes on stopping this—we are weighting the dice for mega-drought conditions.”

Here’s what “weighting the dice” looks like from a scientific perspective: The study found that if carbon emissions continued on their current trajectory, and if global warming did not create a generally rainier climate in the American West, then the chance of a mega-drought would exceed 90 percent. But if climate change decreases precipitation—which is what most models predict—then the rate would sit at 99 percent, making mega-drought a virtual certainty.

Somewhat counterintuitively, even if climate change makes the West rainier, a mega-drought is still more likely than it would be otherwise. A warmer world will put more demand on trees and other plants, requiring them to pull more water out of the ground; water will also evaporate faster from reservoirs and the soil. So even if global warming increases the amount of rain, then the chance of a mega-drought would still exceed 70 percent.

Jonathan Overpeck, a professor at the University of Arizona, invented the word mega-drought in the 1990s with his colleague Connie Woodhouse. He was not involved with this paper. He told me that this new paper actually researches an especially intense form of the phenomenon, only examining a mega-drought that would spell infernal heat and terrific dryness for at least 35 years.

“This isn’t like the drought of our grandfathers,” he says. “It’s a drought that everyone would agree would be devastating as all heck.”

Overpeck said that the paper laid out two scenarios for the American Southwest. In the first, the world continues to pump carbon dioxide into the atmosphere, and a post-2050 “searing mega-drought” becomes a near certainty. In the second, carbon emissions soon begin to decrease, and the region sees about a 66 percent chance of a “warm mega-drought” in the second half of this century.