How Plague Works

Today, some of the illnesses that cause the most alarm are newly discovered, deadly diseases, usually spread by viruses. Scientists isolated avian flu H5N1 in 1996. Person-to-person spread is rare, but the virus has a mortality rate of about 60 percent in humans. A virus also causes Ebola, identified in 1976. Ebola has an average mortality rate of 50 percent. The first known case of HIV was reported in the 1950s. Scientists isolated the virus responsible in the 1980s. The mortality rates for this disease dropped from 16.3 per 100,000 in 1998 to just 3.7 per 100,000 in the U.S. in 2017, thanks to the availability of drugs to treat it.

In 202, the novel coronavirus (COVID-19) outbreak quickly caused a worldwide pandemic, shuttering schools, churches, businesses and society in general in an effort to limit spread of the damaging respiratory illness. The severe social distancing was forced due to the fact that the airborne COVID-19 is exceptionally contagious, and also because many people don't show symptoms at all, so they can easily and unknowingly transmit the disease to others.

People have reacted to the appearance of each of these diseases with fear and dread. A major outbreak of plague today would spark a similar reaction. But unlike many of today's newsmakers, plague comes from an old bacterium rather than a new virus. Researchers believe that Yersinia pestis diverged from the less-lethal Yersinia pseudotuberculosis about 20,000 years ago [source: Huang]. Some believe that plague lived in rats before humans existed. Descriptions of a disease resembling plague also appear in ancient texts, including the Christian Bible.

On top of being old, plague is virulent or highly infective. It generally gets the credit for three major pandemics, or massively widespread epidemics:

An infamous epidemic, the Great Plague of London, took place during the 16th century. The Great Plague killed up to a fifth of London's population, but the disease did not spread around the world. In other words, it didn't escalate from an epidemic to a pandemic.

During each of these epidemics, no one knew what caused the disease or how it spread. During the Black Death, for example, many blamed the illness on toxic miasmas, so people focused on keeping bad air away. Plague doctors, who usually had little to no medical training, wore masks stuffed with herbs to filter the air. In some cities, people blamed dogs and cats for the illness. The resulting slaughter of rats' natural predators may have encouraged the spread of the disease. In Rome, on the other hand, a large population of feral cats may have provided people with additional protection. A study of tree rings released in 2015 also suggests that, before the disease spread to Europe, the initial Asian reservoir for plague-carrying fleas may have been gerbils rather than rats.

Historical records describe a number of different symptoms during these and other outbreaks. These include rashes, nausea, sensitivity to light, diarrhea and coughing. Swollen, painful buboes appear consistently in most accounts. This is one of the reasons why plague takes the blame for so many pandemics.

The idea that bubonic plague was behind these pandemics has become part of the conventional wisdom – it's something everyone knows. However, some researchers have doubts. Next, we'll take a look at the bacterium behind plague and why some scientists believe it didn't cause the Black Death.

In 1894, researchers made a major breakthrough in plague research. Two doctors, Alexandre Yersin and Kitasato Shibasuburo, each realized that the bacterium Yersinia pestis causes plague. In 1898, another doctor, Paul-Louis Simond, discovered that fleas carry the disease from rats to people. These discoveries took place during the Third Pandemic, and they established a direct link between plague and that particular outbreak. This made it seem likely that plague had also been at the root of the Black Death, the Great Plague of London, Justinian's plague and other outbreaks.

However, the doctors practicing during the earliest pandemics didn't have the tools they needed to accurately diagnose diseases. The microscope and the idea that germs cause disease came around during the 16th century, long after many epidemics ended. There were also no accurate, standardized recordkeeping methods during most plague pandemics. For these reasons, there's not a lot of concrete evidence to prove plague was behind it all. One French team claimed to have found Yersinia pestis DNA in tooth pulp from plague-era mass graves, but other researchers haven't been able to duplicate these results.

Researchers also note a few reasons why plague may not have been the real culprit. Some claim that historical literature doesn't mention a die-off of rats, which typically happens before a plague epidemic. Others say the opposite. Some scientists claim the Black Death and other epidemics spread too far and too quickly for fleas and rats to have been the carriers.

Alternate theories for the disease behind the Black Plague and other epidemics are anthrax and a hemorrhagic virus like Ebola. Circumstantial evidence supports each of these theories. The epidemics started suddenly and seemed to end spontaneously, which is typical of some viral outbreaks. In the years before the Great Plague of London in particular, people started to rely on domestic cows for red meat instead of wild game. This made it more likely for cattle-borne anthrax to infect people. However, there's no clear indication of a massive cow die-off before the Great Plague.

Controversy surrounds these pandemics, but not everyone thinks plague wasn't the cause. As mentioned earlier, some epidemiologists claim that plague could have spread from person to person via the human flea, Pulex irritans. In this case, rats wouldn't need to carry the fleas from place to place – humans would have done all the carrying for them. Another theory is that a different type of plague infection, pneumonic plague, was responsible.

Plague is a vector-borne illness, meaning it requires a living host to carry it from one animal to another. Most of the time, a specific species of flea – Xenopsylla cheopis – is the vector. Also known as the Oriental rat flea, Xenopsylla cheopsis prefers to feed on rats and other rodents, which can carry plague.

The Oriental rat flea has a physical trait that makes it very efficient at transmitting plague. Its digestive system can become blocked by a large mass of plague bacteria. When a blocked flea bites a host, it often regurgitates plague-infected blood back into the wound. Fleas that aren't prone to blockage, like the human flea, may still transmit plague by carrying bacteria on their mouthparts.

After the infected flea bites the host, the bacteria suppress the body's natural inflammatory response. They also use proteins to protect themselves from the immune system. For these reasons, it's not immediately obvious that anything is wrong.

The bacteria hitch a ride into the nearest lymph node, using white blood cells to carry them. Once the bacteria reach a lymph node, they multiply. Due to the overwhelming presence of bacteria and the endotoxins in their cell walls, the lymph node begins to swell. In a few days, the node becomes a painful, egg-sized bubo. The body's natural immune defenses kick in, causing a high fever in an attempt to kill the bacteria. Chills, muscle pain and weakness are also common.

If the infected flea bites the victim on the hand or arm, the bubo forms in the axillary lymph nodes under the arm. If it bites the foot or leg, the bubo forms in the inguinal lymph nodes in the groin. A bite to the head causes a bubo in the maxillary lymph nodes in the neck and jaw. If a flea bites the victim's torso, the bubo can form in the abdominal cavity, where doctors may not detect them.

Unless multiple plague-carrying fleas bite a person, bubonic plague generally causes only one bubo. Sometimes, it may cause a few buboes in the same cluster of lymph nodes. This is one of the reasons why some researchers doubt that bubonic plague was the culprit behind the Black Death and other pandemics. Some historical accounts describe victims as covered in buboes, which doesn't generally happen with bubonic plague.

In addition to being virulent, plague is adaptable. It can live in the bodies of rodents, cats, fleas and humans. Plague can also cause different symptoms depending on how it enters a person's body. These abilities all come from the bacterium's DNA, which carries all the instructions it needs to multiply and make people sick.

Sometimes, plague-infected material enters the body through broken skin. For example, someone might touch infected blood while skinning a dead rodent. This can lead to septicemic plague, which does not always produce buboes. Plague bacteria and toxins in the blood overwhelm the body's immune defenses. This causes a high fever, abdominal pain and exhaustion. If left untreated, or if the immune system is irreparably damaged, septicemic plague leads to multiple organ failure and death. Septicemic plague can also occur as a complication of bubonic plague.

If someone inhales droplets of moisture containing plague bacteria, the result can be primary pneumonic plague. This can happen when an infected person coughs or sneezes. Cats can contract pneumonic plague, and they can transmit the disease to humans when they cough or sneeze. As with septicemic plague, pneumonic plague can be a complication of bubonic plague – in this case, it is known as secondary pneumonic plague. Pneumonic plague causes the typical symptoms of pneumonia, including high fever and a cough that produces bloody sputum.

Generally, secondary pneumonic plague is not as contagious as the primary variety. This is because people who contract primary pneumonic plague tend to be healthy and active when they become infected. They can produce a cough that's strong enough to propel infected droplets of moisture through the air. Victims of secondary pneumonic plague, however, are usually very sick by the time the infection reaches their lungs. They can't always cough forcefully enough to expel infected particles into the air. Either way, without antibiotic treatment, pneumonic plague is almost always fatal.

Pneumonic plague is the least common form of plague, but it's the one most likely to be used as a biological weapon. This is because pneumonic plague is highly contagious, highly lethal and easy to spread. In the past, other forms of plague have also been used as weapons. According to some accounts, the Black Death started after invading forces tossed plague-ridden bodies over the walls of a besieged city. The Japanese military also reportedly dropped bombs containing infected fleas over mainland China during World War II [source: PBS].

In addition to causing pneumonic and septicemic plague, Yersinia pestis can infect other parts of the body when it comes into contact with them. If blood carries plague to the cerebrospinal fluid that surrounds the brain and spinal cord, the result can be plague meningitis. Plague can also infect the tissues of the throat, causing plague pharyngitis.

Before the discovery of antibiotics, all of these forms of plague could be fatal. But today, prompt treatment, particularly in cases of bubonic plague, makes survival much more likely. In spite of these advances, plague still thrives in many parts of the world.

Long before the development of microscopes and antibiotics, many cultures associated outbreaks of plague with rats – specifically, dead rats. This is because plague is an enzootic disease, or a disease that lives primarily in nonhuman animals. The animals that typically carry plague include prairie dogs, voles, wild gerbils and other rodents. Rats, however, are the most common.

When plague-infected rats die, their fleas look for new hosts. Fleas generally prefer to feed off of specific animals, but they will turn to other food sources when necessary. So when an outbreak of plague kills lots of rats, their fleas jump to the nearest source of blood. When people are that source, plague becomes an epizootic disease, or a disease that jumps from animals to humans. Many epizootic diseases, including avian flu, are particularly lethal to humans, who have no natural resistance.

The concept of natural resistance may be behind sudden plague outbreaks as well. When most of the rats in a particular area die of plague, the ones that survive have natural immunity. They pass this immunity to their offspring, but it becomes diluted over several generations. The rats lacking immunity then die of plague, which is usually present in the rodent population. A few rats survive, and the cycle begins again.

The fact that rats are a natural reservoir of plague is one of the reasons why the disease is less common today. In many industrialized nations, particularly in affluent areas, rats are not as common as they were before and during the Middle Ages. Better standards of living and better hygiene practices have cut down on the rat population, and with fewer rats come a smaller disease reservoir.

But the natural rat reservoir is also why plague still exists. In impoverished areas and developing nations, rats can still be prevalent. Exterminating the entire species would be almost impossible and would also affect the rest of the ecosystem.

In agricultural societies, people tend to live and work near fields and storage buildings where rats live. In addition, a mild climate and lots of sandy soil are ideal for the development of the rats' fleas. Places with both of these qualities tend to be prone to plague. Examples of such locations are the American southwest, as well as parts of South America, Africa and Asia. The three countries where the disease endures most significantly are Peru, Madagascar and the Democratic Republic of Congo. Although the Black Death and other epidemics had an enormous impact on Europe, plague is not common there today [source: WHO].

Human behavior can also affect plague outbreaks. For example, in 1989, stored food from an unusually large harvest in Botswana led to a higher-than-normal rat population. Fleas from these rats made their way to people, and plague began to spread. In Mozambique, the practice of catching and skinning rats leads to plague infections in women and children [source: Munyinyewa].

For all of these reasons, public health officials still have to focus on preventing plague and on improved tests and treatments.

Bubonic plague has a distinctive set of symptoms, but it can sometimes be difficult to diagnose. Without a visible bubo, the first symptoms simply resemble the flu. If buboes form in the abdomen, a doctor might mistake bubonic plague for appendicitis. There are also other illnesses that can cause painfully swollen lymph nodes. These include cat-scratch fever and mononucleosis. Even anthrax, which starts with similar flu-like symptoms, can provoke swelling in the lymph nodes.

Bubonic plague is a dangerous disease if left untreated. Without medical attention, pneumonic and septicemic plague are almost always fatal, and they don't generally form the buboes that can make plague easier to detect. Therefore, doctors do more than just look for buboes when making a diagnosis. They also ask about exposure to rats and other rodents, particularly in plague-prone areas. The final diagnosis often comes from examining smears of bodily fluids through a microscope. In cases of suspected bubonic plague, fluid drawn from the bubo is usually the best option, since it tends to include lots of bacteria. Doctors can also examine blood, sputum and Cerebrospinal fluid.

Without treatment, bubonic plague is up to 60 percent fatal, and pneumonic plague is almost always fatal. With prompt antibiotic treatment – within 24 hours of showing symptoms – the mortality rate drops significantly. For this reason, researchers at the Institut Pasteur have developed a new, faster test. The test uses a dipstick rather than microscopes and slides. Instead of looking for bacteria, it detects the presence of a specific molecule that is part of Yersinia pestis' cell wall. The test can confirm a diagnosis in about 15 minutes. [sources: BBC, Stephenson].

Effective treatment of plague requires antibiotics. Streptomycin is used most often, but tetracycline and gentamicin can work as well. Sometimes, doctors will prescribe antibiotics to family members or people who have been bitten by fleas in plague-prone parts of the world. Doctors may also isolate the infected person, particularly if he has contracted pneumonic plague.

Symptoms generally improve within a few days of treatment, but buboes can take weeks to return to normal. However, a drug-resistant form of the disease has emerged in Mozambique. Exactly how this strain will affect public health remains to be seen.

Since plague is a dangerous disease, doctors generally have to report suspected cases to the proper authorities. In the United States, the doctor has to notify local and state health departments. The U.S. Centers for Disease Control (CDC) confirms the diagnosis and informs the World Health Organization (WHO). In a case of biological warfare, all of these agencies would be involved in the response. Likely tactics would include quarantines and preventive doses of antibiotics, particularly in cases of pneumonic plague.

Health officials work to prevent future plague outbreaks by educating people about the disease. Officials also monitor the number of suspected cases and rat populations. For example, great gerbils living in Kazakhstan can carry plague. When these gerbils reach a certain population density, plague usually breaks out in humans two years later.

Plague can seem like a distant possibility to people who live in clean homes with few rodents nearby. However, experts disagree about whether another plague pandemic is possible. Some feel that improvements in hygiene, medical care and pest control make a worldwide outbreak almost impossible. Others believe that plague's exceptional virulence and its ability to become airborne in pneumonic cases will transcend any human efforts into stopping its spread.