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Scientists identify what may have killed millions in the mysterious epidemic

Ancient DNA and a new technique have been used to determine the probable cause of this mysterious epidemic that contributed to a "catastrophic" population decline.

The genomes of Salmonella, which cause typhoid fever, recovered from the DNA inside the teeth of 10 skeletons buried in a cemetery "cocoliztli" or "pestilencia" in Oaxaca, Mexico. This would be the first known occurrence of salmonella in the Americas, according to a new study published in the journal Nature on Monday. Typhoid fever has been suspected for a long time due to the symptoms recorded, but this is the first identification of bacteria on the site.

Researchers also believe that the arrival of Europeans in what was then known as Mesoamerica caused the devastating epidemic. Europeans were susceptible to enteric fever, also known as typhoid fever, and it is very likely that they were carriers of the disease when they arrived to conquer Mesoamerica.

"The cocoliztli is a mysterious historical epidemic, and over the years many have speculated about its cause," Kirsten Bos said in an email, the study's author and leader of the molecular paleopathology group at the Max Planck Institute for Science of Human History in Germany. "This is the first time that ancient DNA has been successful in identifying a candidate pathogen for it."

The Grand Plaza cemetery in Teposcolula-Yucundaa is the only one that is known to be related to this specific outbreak. The epidemic was so devastating that the city moved to a nearby valley, which allowed the cemetery to remain intact for centuries. This, together with the thick and protective floor of the Great Plaza, created the perfect conditions for testing and research.

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While the diseases causing subsequent epidemics, such as the Smallpox, measles, mumps and influenza, are well documented, previous epidemics in the "New World" are not as good-characterized, creating debate among researchers.

Pathogens of infectious diseases also leave no telltale marks on the skeletons, according to the researchers. This is mainly due to the fact that they are fast acting and charge their price very quickly before the skeleton can be deformed in any way.

So, when researchers look at skeletons like those found in the pestilence cemetery, they have to look for possible causes based on what they know about historical accounts. But the diseases and symptoms can change over the years, or the symptoms can be so broad and similar that they could be one of the many causes.

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But a new detection technique called Metagenome analyzer ( Alignment Tool, or MALT, allowed researchers to search all the bacterial DNA present, instead of testing each specific possibility, which can be tedious and disappointing. the classic "needle in a haystack" scenario.

Other factors may also play a role.When archaeological tissues sit on the ground for centuries, DNA from environmental sources can leak, said Bos.

" One limitation that we and all others face is that we can only look for pathogenic organisms that we already know exist and that have been genetically characterized today, "said Åshild Vågene in a run. or electronic, study author and doctoral student in the archeogenetics department of the Max Planck Institute for Science. f Human history. "If the individuals we studied in Oaxaca, Mexico, were infected by something that does not exist today or that has not yet been characterized, then we would not be able to detect it without the current method"

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MALT revealed Salmonella enterica Paratyphi C, the bacterial cause of enteric / typhoid fever, which has been the suspected cause of the epidemic for years. Identifying the bacterium supports the hypothesis of typhoid fever. Symptoms of typhoid fever include high fever, dehydration of red spots, hemorrhage, vomiting and gastrointestinal problems.

"After identifying DNA traces of Salmonella enterica using our new computational technique, we conducted more experiments and computational analyzes that allowed us to study the complete genomes of Salmonella enterica bacteria identified in the teeth of the people included in our study", said Vågene.

  Åshild J. Vågene directing the laboratory at the Max Planck Institute for the Science of Human History.

But the case can not be closed.

"We can not say that it definitely caused the epidemic," Bos said. "It was the only pathogen that emerged from our extensive analysis, and an enteric fever is consistent with the recorded symptoms of the epidemic, but it may not have been the only disease circulating in the population at this time. We were not detectable by us through the techniques we use. "

The MALT technique is opening new research possibilities to diagnose diseases of the past and solve ancient medical mysteries.

"The screening technique used here will be transformative for future work on the archaeological disease: it is no longer necessary to have a candidate pathogen in mind for molecular detection," said Bos. "The flexibility our approach offers is what is needed to address many issues related to the history and ecology of the disease, where often you do not know what disease you are looking for until you have found it.

" We intend to apply similar techniques to look for diseases in other archaeological samples of different periods of time and locations. This technique opens up so many doors for us to learn about the disease in the past. "

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