A fluorescent image of a human body louse with Yersinia pestis infection — that’s the cause of the plague — depicted in orange/red in the glands.

National Institute of Allergy and Infectious Diseases/National Institute of Allergy and Infectious Diseases

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National Institute of Allergy and Infectious Diseases/National Institute of Allergy and Infectious Diseases

The plague — which in the mid-14th century was also known as the Black Death — devastated swaths of Europe, killing millions in under a decade.

One of the puzzles surrounding this ancient pandemic was how it spread so quickly.

The common wisdom is that rat fleas were the big spreaders. But now a new paper is making a second parasite look like it may have helped play a role in plague transmission — the lowly human body louse.

The disease is caused by a bacterium called Yersinia pestis. Once the bacteria enters the skin, they travel to a nearby lymph node — in your armpit, groin or neck, say — and multiply. The lymph node swells and inflames, becoming what’s called a bubo (hence the term “bubonic plague”).

From there, the bacteria usually break out into the bloodstream where they cause severe infection. “And that’s always life-threatening,” says Joe Hinnebusch, a microbiologist now retired from the NIH’s National Institute of Allergy and Infectious Diseases. Sometimes, “plague can spread from the bloodstream and infect the lungs, causing pneumonia.” This form develops rapidly and is usually fatal. It can also be transmitted between people when someone coughs or spews infected droplets.

The classical route of infection for this disease, which still circulates in 2024, was and remains rat fleas — small biting parasites that transfer the bacteria from wild rodents to people.

“A lot of these rodents are quite susceptible to plague,” says Hinnebusch. “So the rodent population can die off, leaving all these hungry fleas.” The fleas aren’t picky, so when their “rat hosts are unavailable, they will feed on other small animals — as well as humans.”

“The rat fleas aren’t gonna start biting humans until all of their preferred hosts — the rats — are gone,” says Abigail Agresta, a medieval historian at George Washington University.

“That’s how these human outbreaks and epidemics start,” says Hinnebusch. Even just a few flea bites can transmit enough bacteria to infect a single human.

Maybe the rat fleas had some help

But some researchers have suggested that rat fleas alone couldn’t have triggered one of the fastest spreading pandemics in human history.

Hinnebusch and his colleagues wondered whether human body lice might have provided the bacteria with an additional transmission route. They can transmit other infections (like relapsing fever whose 40% mortality rate drops to 2-5% for those who receive treatment) and would have likely been common in the Middle Ages when hygiene was poorer.

It’s a question of considerable controversy among scholars of the period. For instance, Hinnebusch says that the plague surged in the summer and fall when fleas tend to be abundant, and “not in winter when people probably wore layers of clothing for long periods, which would increase exposure to lice. It’s of surprising interest to medical and medieval historians and sometimes a hotly debated topic,” says Hinnebusch.

Now, in research published in the journal PLOS Biology, Hinnenbusch and his colleagues demonstrate that human body lice are indeed more efficient transmitters of plague than previously thought. Hinnebusch isn’t sure how large a role they may have played in the Middle Ages; he speculates that rat fleas made up the lion’s share of transmission. “But in certain ecological situations,” he caveats, “the lice could have played some role in some cases, sometimes in some areas.”

These findings aren’t just of historical interest. The disease remains a public health concern in certain parts of the world, from Madagascar to northern New Mexico and Arizona. “Plague is still out there,” says Hinnebusch, though today rapid treatment with antibiotics stops it in its tracks. He recommends that “people living in areas where plague is present in rodent populations should be vigilant.” The main worry remains infected fleas. But “if hygienic conditions collapse due to war or in refugee camps,” transmission via body lice may become more likely.

Being nice to lice

The hardest part of the whole experiment was figuring out how to raise human body lice in the lab. “They’re not an easy insect to work with,” admits Hinnebusch.

The breakthrough came from a collaboration with a lab at the University of Massachusetts Amherst that had successfully reared colonies of lice. The insects were kept in what were essentially Dixie cups. “There’s a tuft of artificial hair at the bottom and they like to cling to that,” says Hinnebusch.

Then, the researchers ordered human blood to feed to the lice. “We’d pick up that tuft of hair that all the lice were clinging to,” he explains, and allow them to feed on the blood.

The lice were high-maintenance guests. “They don’t tolerate a day off from feeding,” he says, which means keeping the colony going was time consuming. Feeding “has to be done every day, seven days a week. People had to come in every day on weekends, holidays.”

Once the system was up and running, Hinnebusch and his colleagues spiked the blood with the plague bacteria to mimic an infection. “Inevitably, since they were feeding on the blood,” he says, “they would ingest bacteria along with their blood meal.”

Of guts and glands

The researchers attached a red fluorescent protein to the bacteria to make them light up — verifying that they stayed alive in the lice and where they ended up in the little critters. The results were clear — the plague bacteria found their way into the louse’s gut. More surprisingly, they also showed up in a pair of salivary glands in the head.

“Nobody had described anything like that,” says Hinnebusch. In the case of one kind of typhus fever, for example, lice excrete the pathogen in their feces. When people scratch the resulting itch, they scratch the infected feces right into their skin. “All the other louse-born diseases are like that,” he says. “So this was something brand new.”

When Hinnebusch and his colleagues let the lice with the plague feed on sterile blood, they were able to transfer the infection to the blood.

These results suggest to Hinnebusch an efficient way for lice to transmit plague to and between people — by biting them. That is, he says, “Lice have more potential to transmit plague directly from one human plague patient to another human than has been appreciated.”

“This seems to be the most convincing case so far that body lice could have been involved,” says Agresta, who wasn’t involved in the research. If you were to think of the Black Death as a movie, “this is introducing a new protagonist right into that story — the body louse — which would also mean a new plot line when it comes to transmission,” she says. “For historians who don’t get very many perspectives usually, [it’s] super interesting.”

Still, she acknowledges the lack of direct proof. “We don’t necessarily know how likely it is,” she says. However, “it would be very hard to get that kind of evidence.”

As for Hinnebusch, he admits there’s more work to do to demonstrate this phenomenon outside of the laboratory in the real world. But he won’t be the one to do it. He’s recently retired. He says he’s pleased that this turned out to be his final scientific publication. “It’s kind of a nice one to end up on,” he chuckles.