Plague is commonly associated with rats, overcrowded medieval cities and the devastating epidemics that swept across Europe during and after the Middle Ages.

However, a new study published in the journal Nature shows that the disease was already lethal 5,500 years ago, when it killed people living in small, mobile hunter-gatherer communities — long before the rise of agriculture and cities created the conditions typically associated with large-scale plague epidemics.

An international team of researchers analysed ancient DNA from human remains discovered at four hunter-gatherer cemeteries in the Lake Baikal region of eastern Siberia. Using advanced DNA sequencing techniques, the researchers reconstructed ancient bacterial genomes preserved in teeth, revealing previously unknown early strains of Yersinia pestis, the bacterium that causes plague.

“Based on the plague DNA, the genetic relationships between the victims, the archaeological analysis and the radiocarbon dating, we’ve built a really clear, complete picture of what happened during these outbreaks,” said Dr Ruairidh Macleod, who conducted the research at the universities of Cambridge and Oxford and is the first author of the study.

The study combines genetic, archaeological and radiocarbon evidence to reconstruct how the outbreaks unfolded within prehistoric hunter-gatherer communities.

“Whether the earliest forms of plague were mild or virulent has been a matter of debate, but our findings demonstrate that these ancient strains were already highly lethal,” said Professor Eske Willerslev of the University of Cambridge’s Department of Genetics and the University of Copenhagen, who led the research.

In total, Yersinia pestis DNA was detected in 40 per cent of the individuals studied — 18 out of 46. This is higher than the detection rate reported from some medieval plague pits.

A more lethal disease than previously thought

Previous studies have shown that early strains of Yersinia pestis lacked some of the genetic traits that later enabled bubonic plague to spread efficiently through fleas and rodent hosts. This led many researchers to believe that the earliest forms of plague were unlikely to have caused major outbreaks.

The new study challenges that assumption.

The mortality profiles at the two largest cemeteries showed an exceptionally high number of children and young teenagers among the dead — a pattern that had puzzled archaeologists studying the graves for decades.

“The unusually high number of children and the short time-span was a real puzzle that we’ve been trying to solve since the 1990s. Finding out that plague was the cause is extraordinary, but it makes so much sense,” said archaeologist Andrzej Weber of the University of Alberta and principal investigator of the Baikal Archaeology Project.

Radiocarbon dating showed that many of the burials occurred within a very short period. In several cases, siblings or parents and children appear to have died and been buried together.

Did extreme immune responses contribute to the deaths?

The ancient plague strains also carried a unique superantigen — a toxin-producing genetic factor that has not been identified in historic plague strains. Superantigens can trigger extreme immune responses and are associated with severe inflammatory complications, potentially increasing the severity of an infection.

“This finding changes our understanding of the earliest plague outbreaks: even before the bacterium evolved efficient flea-borne transmission, these ancient strains appear to have carried a potent combination of virulence factors that could make infection highly lethal,” said senior author Martin Sikora, associate professor at the University of Copenhagen.

Taken together, the findings suggest that some of the earliest known plague outbreaks may already have been as deadly as later historical forms of the disease, particularly among children, even without efficient flea-borne transmission.

The study also supports the theory that plague may have originated in Central or northeastern Asia before spreading across Eurasia through wild rodent reservoirs.

Archaeological evidence suggests that the hunter-gatherer communities studied interacted closely with marmots — large burrowing rodents that continue to carry plague today. Researchers believe the prehistoric outbreaks may have resulted from direct transmission of the disease from infected marmots to humans.

Russian incident

Meanwhile, the death of a lab worker in Russia’s Siberia region has sparked concerns over a possible plague case, the UN World Health Organization (WHO) said on Tuesday, adding that it was following the situation closely.

“A woman who worked at the laboratory in Irkutsk oblast has died, and the authorities are looking into whether pneumonic plague caused her death,” WHO spokesperson Christian Lindmeier told reporters in Geneva.

He underscored that her workplace was “an institute that studies dangerous pathogens, including plague, in a part of Siberia where plague occurs naturally in wild animals.”

No official cause of death

No cause of death has been officially confirmed to date and laboratory testing is reportedly underway,  Lindmeier said.

Sharing with reporters a message received from the Russian health authorities moments earlier on Tuesday, the WHO spokesperson said that “according to the test results, no pathogens of dangerous infectious diseases were detected among any of the contacts.”

The authorities’ message indicated that the illness “initially presented as a typical acute respiratory viral infection”.

Explaining the timeline of events, Lindmeier said that on 2 October “the internal monitoring system picked up the media reports of a suspected death from pneumonic plague in the Irkutsk oblast and started monitoring the situation.”

The next day, WHO contacted the Russian health authorities to get more information under the International Health Regulations “to verify the event, its circumstances, the laboratory tests underway and their results, the rationale for contact tracing and the health status of the contacts as well as any potential international public health implication”, Lindmeier said.