THE onslaught, when it came, was swift and merciless. It started in Crimea in 1347 before fanning out across Europe, killing terrified and defenceless people by the million. The sickness causing all this death subsided in 1351, but returned with a vengeance a few years later. By the time the second wave had passed, more than 50 million people had died.
鈥淚t was the most important, the most impactful, the worst event that ever happened in Europe,鈥� says at the Max Planck Institute for the Science of Human History in Jena, Germany. She is talking about the Black Death, a five-year outbreak of plague that, by some estimates, killed half the population of medieval Europe.
That dreaded episode is etched into our collective memory of the Middle Ages, which is perhaps why the plague feels like ancient history. But the bacterium that causes it is very much still with us, and epidemiologists are now warning that this deadliest of pathogens could yet reawaken in an even scarier guise. Far from being a spectre from the distant past, the plague could well become a disease of today, unless we start to take its threat more seriously.
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To plague historians, the Black Death was merely an early chapter 鈥� albeit a particularly gory one 鈥� in that ravaged western Eurasia and north Africa for the best part of five centuries. It wasn鈥檛 the first of its kind. That dubious honour goes to the pandemic that broke out in Constantinople (now Istanbul, Turkey) in AD 541, which spread far and wide and lasted for more than 200 years, though the severity of this pandemic has recently been called into question (see 鈥�How many people died in the Black Death in Europe?鈥�).
Nor was it the last. The little-known started in 1772 in the Chinese province of Yunnan, reached Hong Kong in 1894 and from there spread around the world on steamboats and locomotives, killing about 20 million people. All told, the plague is estimated to have caused the deaths of 200 million people.
The third pandemic eventually petered out in the 1940s, but the bacterium that caused it didn鈥檛 go away. 鈥淲e talk about the three major pandemics, but we have to remember that there鈥檚 an ongoing issue,鈥� says at Texas Southern University in Houston. 鈥淚 think it鈥檚 going to become more of a problem in the future.鈥�
The ongoing issue is that, every now and then, plague breaks cover and kills people. The bacterium that causes it, Yersinia pestis, in rodents 鈥� rats, mice, marmots, gerbils, ground squirrels and the like 鈥� and their blood-sucking parasites. These flea-bitten hordes form what are known as 鈥渮oonotic reservoirs鈥� that are abundant and widespread and hence considered impossible to eradicate.
Today, there are reservoirs on every continent except Australia. And whenever humans come into contact with them, there is a risk of plague jumping ship, either through direct contact with infected mammals or, more often, their fleas.
Sporadic cases of plague are surprisingly common, and can sometimes spark an epidemic, as was the case in in 2017. This epidemic seems to have started when an infected man got on a bus in the country鈥檚 central highlands and travelled to the eastern city of Toamasina via the capital Antananarivo. He infected dozens of fellow passengers before dying in transit. By the time the outbreak fizzled out, 2348 people had been infected and 202 of them had died. There have also been recent outbreaks in India, China and the US, and a general pattern of ever-increasing cases worldwide, according to Rosenzweig鈥檚 collaborator at the University of Texas Medical Branch in Galveston.
Plague is now considered a . One reason for that is our relentless encroachment on nature, which, as we found to our cost with covid-19, brings us into ever more regular encounters with animals carrying pathogens. 鈥淭he human population continues to grow and as we continue to develop previously underdeveloped or completely untouched lands, we come into closer contact with these zoonotic reservoirs,鈥� says Rosenzweig.
Once a human is infected, the disease鈥檚 progression is rapid, or what doctors call 鈥渇ulminant鈥�. From its entry point, typically a flea bite, the bacterium invades lymph nodes in the groin, armpit or neck and replicates wildly, causing painful swellings called buboes. This is the infamous bubonic plague, which is bad enough: after an incubation period of as little as two days, it causes a sudden attack of fever, chills, headaches, body aches, weakness, nausea and vomiting.
But it can get much worse. From its bubonic base camp, the infection can spread to the bloodstream to become septicaemic plague or to the lungs to develop into the pneumonic form. Septicaemic plague progresses to septicaemia and pneumonic to pneumonia, and from that point there is usually only one outcome. Left untreated, all varieties are highly lethal. If the infection remains bubonic, survival rates can be as high as 70 per cent. But untreated septicaemic and pneumonic plague are almost invariably fatal.
Septicaemic plague recycles the pathogen back into parasites, while pneumonic plague can spread from person to person via infected respiratory droplets inhaled from the air or picked up from surfaces. That is also why outbreaks can spread so rapidly.
All three forms of plague can be cured with antibiotics. But the Madagascan outbreak had a , despite being thrown at it. More than 75 per cent of cases were pneumonic, which has a much shorter window for treatment than the bubonic form. If antibiotics aren鈥檛 initiated within 24 hours of symptoms appearing 鈥� which, for pneumonic plague, can be within a day of exposure 鈥� .
In a place like rural Madagascar, access to treatment is often limited. But higher-income nations can鈥檛 rest on their laurels. In 2015, 15 people caught plague in the US. Four died, a mortality rate of more than 25 per cent.
There is also the diabolical prospect of Y. pestis acquiring antibiotic resistance, which would render our best treatments useless. It could gain that resistance from other bacteria through a process called horizontal gene transfer, which is probably how it evolved its lethal virulence in the first place when it diverged from the much less dangerous stomach bug Yersinia pseudotuberculosis. This is a theoretical threat posed by all bacterial pathogens and a very real one when it comes to plague. Resistance to various antibiotics has been observed in Y. pestis samples taken from wild animals, and to every drug recommended for treatment. 鈥淢ost infections are still fairly treatable, but if a drug-resistant strain becomes an issue, not just locally but even globally, that scenario could potentially be grim,鈥� says Rosenzweig.
Another frightening possibility is that plague could be turned into a bioweapon. Alongside anthrax, Y. pestis is considered the most readily weaponisable human pathogen, says Rosenzweig.
Given these threats, by far the best option is vaccination. Existing vaccines have proven effective in the past, but they are showing their age. In 2018, the World 午夜福利1000集合 Organization (WHO) said it with these old vaccines.
Vaccine push
The most widely used were 鈥渓ive attenuated鈥� vaccines, based on a living strain of Y. pestis rendered harmless by mutations but still capable of provoking an immune response. The first was developed from a bacterium isolated from a Malagasy child who died of plague in 1926, and first used in Madagascar in 1934.
It was later distributed to other countries on the front line of the third plague pandemic, including China, Brazil and the USSR. Another vaccine used in this pandemic consisted of corpses of Y. pestis killed by formaldehyde.
These vaccines and helped to halt the pandemic, says Andrey Anisimov at the State Research Center for Applied Microbiology and Biotechnology in Obolensk, Russia.
However, they have major drawbacks. The killed vaccine produces only short-lived immunity and is ineffective against pneumonic plague. The attenuated vaccines can lead to side effects including rashes, inflammation and abscesses, and there is the ever-present danger of reversion, where the bacterium remutates back to its virulent form. That hasn鈥檛 happened yet, but in 2009 a researcher died of septicaemic plague in Chicago after coming into contact with an attenuated strain in the lab. He turned out to have a genetic condition that essentially rearmed the bacterium, but the condition is common enough in white people that some researchers have said attenuated vaccines are .
After the 2017 Madagascan outbreak, the WHO said there was an urgent need to develop new plague vaccines. There are now more than 20 in the pipeline. Rosenzweig is part of a group working on better attenuated vaccines and an using technology similar to the Oxford/AstraZeneca covid-19 jab, while Anisimov鈥檚 group is developing a , which consists of the bacterial cell wall emptied of its contents. Other teams are also exploring various vaccine technologies, including edible vaccines designed to suppress the rodent reservoirs. But none has yet fulfilled the WHO鈥檚 criteria for a successful vaccine.
Progress is slow. 鈥淔unds are limited; resources are limited,鈥� says Rosenzweig. 鈥淟ike other pathogens that could become an issue, pestis is not a pressing issue all the time. It breaks onto the scene, does some damage, scares people, disappears, and then people tend to forget about it.鈥�
We would do well to remember. The next pandemic might be another novel zoonotic virus 鈥� or it might be an old foe resurgent. The world is unlikely to endure a cataclysm on the scale of the Black Death again, and yet it is worth bearing in mind that even with vaccines and antibiotics at our disposal, plague still kills 10 per cent of the people it infects. For comparison, the prevaccine death rate from covid-19 was just 1 per cent, and that brought entire countries to a standstill. So if plague does get even more deadly, all bets are off, says Rosenzweig. 鈥淵ou have to prepare for the worst.鈥�
