It was a plague of many names. The Spanish called it "pujamiento de sangre" or abundant bleeding. The Mexicans described it as "huey cocoliztli" or the great pestilence as seen in the massive death toll it brought to Mexico's native population.

The cause of this colonial-era plague that nearly wiped the Mexican population had remained unknown since the 16th century. Through time, many have speculated on the cause of this mysterious disease and recently, a study led by an international team of researchers has shed more light on one of the most devastating plagues in history.

Researchers from the Max Planck Institute for the Science of Human History, Harvard University, and the Mexican National Institute of Anthropology and History used a new data processing program in DNA research to pinpoint the probable cause of the ancient plague.

They have positively identified Salmonella enterica Paratyphi C as the culprit behind the epidemic that had killed 80 percent of Mexico's population.

Plagues have spread in the past centuries and indigenous populations of the Americas suffered high mortality rates from infectious diseases introduced by Europeans. However, the biological causes of these diseases were difficult to determine based only on symptoms described in historical documentation.

Groundbreaking Methods in DNA Research

The unexpected unearthing of an epidemic cemetery located in Teposcolula-Yucundaa in Oaxaca, Mexico, proved the extent of the disease. The cemetery where mass burials of plague victims were held was the perfect testing site used by the researchers in looking for direct evidence that could unravel the mystery of the "bleeding disease."

In their analysis of the ancient DNA extracted from 29 skeletons excavated from the ancient cemetery, the scientists used a new computational program to screen and characterize all bacterial DNA in the samples.

Through a new DNA enrichment method called metagenomics or the use of metagenomic analysis tool that was specifically designed for the Mexican plague study, the scientists found traces of Salmonella enterica in the teeth DNA of ten of the samples examined, a direct evidence of the pathogen in the skeletons.

The scientists used the MALT algorithm to align and sequence human and microbial DNA present in the samples and match it to a database of known microbial genomes. Salmonella enterica genomes appeared several times.

"This is the first time that ancient DNA has been successful in identifying a candidate pathogen for it," says Kirsten Bos, study author and anthropologist at the Max Planck Institute for the Science of Human History in Germany.

Bos and her team found the Salmonella traces in the teeth of the skeletons. Pathogens remain in the teeth for centuries, making them an excellent source of DNA.

Salmonella As The Culprit

Before the study, the likely cause of the epidemic was suggested as other biological causes such as hemorrhagic fever, measles, small pox, or typhus.  In the end, it was indeed salmonella as proved in the direct evidence.

Salmonella enterica, described as a pathogen that causes enteric fever or typhoid fever, was found in the skeletons of plague victims who died between1545 to 1550 in the "cocoliztli" or Aztec epidemic that spread in Mexico, Guatemala and Peru. The disease caused its victims to bleed from their faces.

Enteric fever, known today as typhoid or paratyphoid fever, spreads through contamination of food and water with the feces of an infected person. Typhoid causes high fever, dehydration, and gastrointestinal complications.

The full study has been published in the journal Nature.

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