Any student of the history of the Americas knows that indigenous populations in the New World were decimated — sometimes intentionally! — by diseases from Europe. While we have stories of smallpox and similar diseases being used as an effective biological weapon against these people, there are some pandemics that don’t have a clear culprit. During the 16th century, Mexico’s Aztec nation was inundated by some kind of illness the locals called the “cocoliztli,” whose symptoms included terrible fevers and bleeding from the eyes, mouth, and nose. Most didn’t survive past day four. The “cocoliztli” killed as many as 17 million people — 80 percent of the Aztec population.

What exactly was this mysterious disease? On Monday, scientists finally figured it out. It wasn’t smallpox, nor measles, nor influenza, nor anything similar. In findings reported in Nature Ecology and Evolution, a team of researchers report that this typhoid-like “enteric fever” was basically caused by a form of salmonella.

Trying to determine what pathogen of old caused a region-wide epidemic is not easy. Microbial DNA doesn’t exactly stay fresh over hundreds of years. In order to figure out what caused the 1545 and 1976 “cocoliztli” events, the researchers had to collect and analyze samples from 29 unearthed skeletons belonging to victims who succumbed to “cocoliztli.” Some of that DNA was collected from just extremely small traces left within old tooth enamel. New genomics tools have augmented this type of once-fraught work and allowed the team to match fragments of the old salmonella bacterium DNA to the rest of the species.

The pathogen that caused “cocoliztli”, Salmonella enterica, of the Paratyphi C variety, was just one of many that devastated the indigenous Mexicans, but it was perhaps the most detrimental to the civilization’s populace and stability. It spread through water and food contaminated by infected fecal matter. Records actually indicate that European settlers in Mexico were falling victim to “cocoliztli” at the same time as the Aztecs. The bacteria was probably brought over to Mexico via Spanish livestock and other domesticated animals.

It’s also possible S. enterica worked in tangent with other pathogens to created a horrendous cocktail of an epidemic that accounted for “cocoliztli”. “We cannot say with certainty that S. enterica was the cause of the cocoliztli epidemic,” Kirsten Bos, a molecular paleopathologist at the Max Planck Institute in Germany and co-author of the new study, told The Guardian. “We do believe that it should be considered a strong candidate.”

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