In 1545, disaster struck Mexico’s Aztec nation when people started coming down with high fevers and headaches, bleeding from the eyes, mouth and nose. Death generally followed in three or four days.

Within five years, as many as 15 million people—an estimated 80 per cent of the population—were wiped out in an epidemic the locals named “cocoliztli”.

The word means “pestilence” in the Aztec Nahuatl language. Its cause, however, has been in question for nearly 500 years.

On Monday, scientists swept aside smallpox, measles, mumps, and influenza as likely suspects, fingering a typhoid-like “enteric fever” for which they found DNA evidence on the teeth of long-dead victims.

“The 1545-50 cocoliztli was one of many epidemics to affect Mexico after the arrival of Europeans, but was specifically the second of three epidemics that were most devastating and led to the largest number of human losses,” said Ashild Vagene of the University of Tuebingen in Germany.

“The cause of this epidemic has been debated for over a century by historians and now we are able to provide direct evidence through the use of ancient DNA to contribute to a longstanding historical question,” she said.

Vagene co-authored a study published in the science journal Nature Ecology & Evolution.

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The 1545 cocoliztli pestilence in what is today Mexico and part of Guatemala came just two decades after a smallpox epidemic killed an estimated 5-8 million people in the immediate wake of the Spanish arrival.

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A second cocoliztli outbreak from 1576 to 1578 killed half the remaining population.

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“We cannot say with certainty that S. enterica was the cause of the cocoliztli epidemic,” said team member Kirsten Bos.

“We do believe that it should be considered a strong candidate.”

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