A Research Paper on Bubonic Plague

Introduction

The history of medicine has come a long way, from the art of bleeding to surgeries so incomprehensibly fine that only the most trained professionals could think of conducting. The art of medicine arguably begins with the understanding of diseases, and the grasping of the fact that science trumps religion in medical terms. A disease first thought to be the will of God, the plague was nicknamed The Black Death, a bacterium responsible for the deaths of up to 60 percent of Europe’s population in the medieval ages and still thriving in many developing countries today, where sanitation is low and rat populations soar.

Overview

The bubonic plague is, in fact, the least deadly of three forms of plague caused by the same bacteria, known as Yersinia Pestis, (Y. Pestis). Bubonic plague, arguably the least deadly of the three plagues, characterized by the buboes, which are the infected lymph nodes swelling with fluid and pus from combatting the infection, often kills within eight to ten days of infection, as the body is no longer able to contain the bacteria and results to dangerous measures to contain the disease. The lymph nodes are located around the neck, armpits, groin, and other areas of the body, and the swelling and darkening of these areas are the first definite symptoms of plague. To the right is an image of a person infected with bubonic plague. The lymph nodes on their knee have been infected, and are beginning to swell.

Septicemic plague, the second form of the plague is an infection of the blood, where the death rate is roughly 95 percent within two days. Often, untreated bubonic plague will progress into septicemic plague, where the blood becomes poisoned. The third form, Pneumonic plague, is the most devastating and is the result of a lung infection from Y. Pestis, which kills the patient in as little as a day, sometimes without even showing any symptoms of infection. Unfortunately, these plagues, when at pandemic levels, have killed between 30 to 60 percent of medieval Europe, and around 75 million people worldwide.

Infection and Transmission

The bacteria Y. Pestis is most often found within a rat flea, a parasite affecting rats. When the rat is bitten by the flea, an asymptomatic carrier of the pathogen, the bacteria is transferred to the rat. This is believed to have been the cause for many of the plagues in 17th century Europe, where three plagues in 1606, 1636, and the Great Plague, 1665-1666, were noted to have seen an unprecedented amount of deaths in rats, due to their bodies also succumbing to the disease. Due to this, the fleas would find other hosts to feed, thus leading them to humans to feed off of. Once the humans die, the flea will change hosts from the dead rat to other animals, such as dogs, cats, and sometimes humans. Shown is an image of the rat flea, with the black mass within its gut, identified as Y. Pestis, responsible for the plague. When a human is bitten by the flea, the germ, which resides within the gut of the flea, is regurgitated from the flea into the human.

Once within the human, Y. Pestis will realize it is within a warm-blooded organism, as it is capable of detecting the outside temperature around its membrane. Warm blooded organisms have a body temperature between 97 and 104 degrees Fahrenheit, or roughly 36 to 40 degrees Celsius. Therefore once this temperature is met, Y. Pestis will begin the invasion of the body, knowing its location within a warm blooded organism.

Firstly, Y. Pestis will change an endotoxin found within the membrane of its composition, also known as a lipopolysaccharide. This molecule is composed of a bit of lipid (fat), and a polysaccharide, which is a mixture of carbohydrates and sugars. When the bacteria detects it is within a warm-blooded organism, it will change the composition of the molecular structure of the endotoxin, in order to disguise itself. Endotoxins are a dangerous substance to the body and are a defining trait of many harmful bacteria. Therefore, by hiding this marker, the white blood cell will no longer realize the bacteria is an enemy, and thus will leave it alone. Y. Pestis, still has a method of destroying white blood cells, as they will inject a variety of toxins into white blood cells, using a type III secretion system (T3SS) shown below in an example featuring a different form of bacteria, known as salmonella typhimurium, which uses similar injectors to inflict harm on the body. Specifically, Y. Pestis uses these to neutralize any attackers or passing white blood cells, without notice, simply to ease the journey through the body and further cripple the body’s defenses.

Y. Pestis’s goal is to reach the lymph nodes, where the first defined symptoms begin, the buboes. By traveling through the circulatory system, Y. Pestis has a route connected directly with the lymph nodes, but also many other organs, such as the lungs, which will later cause the 100 percent lethal pneumonic plague. Along this journey, Y. Pestis will need a mineral that the healthy human body has in abundance. In order to reproduce and live, Y. Pestis needs a source of iron, used in the body as a component of hemoglobin, which is found in red blood cells and is responsible for the transportation of oxygen to the various points in the body. In order to steal this iron from the body, Y. Pestis uses a molecule classified as a siderophore. Siderophores are highly attracted to iron and the kind deployed by Y. Pestis are called yersiniabactin. Yersiniabactin attacks a specific protein called transferrin, by ripping the iron out of proteins, which are busy transporting iron around the body. Transferrin is the most powerful transportation device for transporting iron across the body and to the cells, and thus contains the greatest amount of iron for Y. Pestis to take. Once yersiniabactin is able to take the iron from the body, they return to the bacteria and use the stolen iron to keep the pathogen alive and strong. In fact, this capture of iron is so massive and detrimental to health, that some of the symptoms experienced by the body are in fact symptoms of iron deficiency, brought on by the bacteria. For example, the pathogen does not directly affect the head, exempting the lymph nodes located in the face, and yet one of the defining characteristics of bubonic plague are terrible headaches and weakness. This is due to how the body has lost so much iron, that the blood is slowly losing its ability to transport oxygen, starving the brain and causing the headaches in the brain, and weakness in muscles, including the heart, once again due to the lack of oxygen in the muscle tissue.

Once arriving in the lymph nodes located around the body, Y. Pestis is safe to reproduce within the lymph nodes, effectively destroying many of the headquarters for white blood cells. With the aid of its molecularly rearranged cell membrane, Y. Pestis is allowed to hide from the enemy and destroy the lymphatic system from within. The bacteria reproduce exponentially, and when the lymphatic system eventually realizes the danger, the body fights back, creating pus and swelling at the site of infection, the lymph nodes. However, the body will be overwhelmed by the power of the bacteria and will be pushed towards a potent weapon, with enormous potential for collateral damage. Often, this kills the patient and is known as septic shock. This is when the body produces a great deal of cytokines, which are used as a beacon to bring white blood cells to a certain area to concentrate their numbers. When the white blood cells attack, however, they may also attack the tissue and organs, which leads to organ failure and massive internal and external bleeding. This septic shock is the same cause of death in Ebola patients and is also known as a cytokine storm.

Treatment, Detection, and Prevention

Luckily, with the development of modern day medicines, particularly antibiotics, which are used in many bacterial infections, Y. Pestis is curable, but only within early administration of antibiotics, specifically aminoglycosides, such as doxycycline, a powerful antibiotic used as a last ditch effort to combat bacterial pneumonia or staphylococcal infections. However, the use of antibiotics is somewhat controversial, as inappropriate use and overuse of antibiotics contributes to the growth of “super-bacteria”, which are immune to a form, or multiple forms of antibiotics. However, in scenarios where the plague or similarly dangerous infections are discovered, antibiotics are a necessity to save lives. The prevention of the plague is also an important aspect of staying safe, as it is safer to follow these procedures to prevent even the more dangerous septicemic and pneumonic plagues. A map depicting the natural possibility of finding the three forms of plague. Countries such as Argentina and China, who have large rodent infestations, especially in urban areas, where breeding grounds and food are plentiful for these rats. Thus, it is wise to be aware when travelling to these areas, especially during the spring, when animals often breed, increasing the number of rats. With a gestation period of roughly 21 days, the brown rat can have as many as 5 litters a year, as soon as 5 weeks after birth.

Once these animals or their fleas bite a human, the plague infects them. However, like septicemic plague, infection from other humans is in fact, rare. The greatest possibility of contracting the plague is through the flea. The urban rat flea thrives in areas of high rat populations, thus incubating and potentially causing outbreaks. The plague is also found in the wild, amongst the population of wild rats, and is able to reproduce freely and without human interference. Luckily, if we remain vigilant about the dangerous number of potentially infected rats, the chances of infections are reduced significantly. However, unlike other forms of plague, pneumonic plague is very contagious, and coupled with the fact that the incubation period for this disease is a mere 24 hours, containing an outbreak would prove very difficult, as those who don’t show symptoms may further spread the outbreak further. While treatment is readily available in developed countries, prevention is also necessary to prevent outbreaks from taking place. Vaccines are readily available but are also not recommended by WHO, as the chances of plague in developed countries are very low, and thus are unnecessary. However, for those often in contact with the disease, it is important to be vaccinated to this disease, as even the slight contact with those with pneumonic plague could result in an outbreak or death. It is also important to remember not to kill rodents before the fleas are eliminated. Since the rodents are mostly the vessel that fleas use to move between victims, culling of the rodents will result in the fleas spreading to new hosts, which could mean humans would be under risk of infection. Chemicals that target fleas should be used for the best effect on clearing the plague.

History

Y. Pestis has an infamous and massively known history, with pandemic levels reaching a high of roughly 75 million dead, or around 30 to 60 percent of medieval Europe. The most prominent outbreaks of the plague occurred in England, well known as one of the most extensive empires. They had many trade routes amongst their colonies and other empires. During the second plague pandemic, the plague came from ships returning from Sicily, and entered ports. Unfortunately, due to the rate of infectivity of the plague, rats and their respective parasites were successful in infecting much of London, causing one of the most devastating impacts towards a prospering kingdom. During the late 17th century, and the reign of King Charles the Second, the Great Plague of London, of 1665 to 1666 had spread to England. This plague alone was responsible for around 100,000 deaths within 18 months. To put this into perspective, roughly 5 thousand people died every month. Interestingly, this plague was one of a much smaller scale compared to earlier pandemics, but is remembered as “The Great Plague”, as the last global plague period. During this age of death, a number of solutions were put up in order to slow infectivity. A solution to kill pets, thought to be transmitters of the plague, was correct, but due to the already record number of rats in population centers, this went unnoticed and ultimately played a very minor role in preventing infection. Furthermore, carriers of the plague were often isolated, much like our quarantine facilities found in airports to prevent infection. Although this would mean a nearly guaranteed death for the patient, this was effective to some degree for preventing outbreaks. When the outbreak had not yet reached London, ships were ordered to moor in Hole Haven for a period of 30 days, which was extended to 40 days as the plague worsened. Ships who passed this quarantine were given a certificate of health, and permitted to travel upstream through the Thames, which passes through London, the heart of the English kingdom. It was not uncommon for the rich to flee, as King Charles, the courts, and much of Parliament, once the plague hit London, leaving the poor to suffer from this disease.

Unfortunately, the plague is still a common occurrence within many developing countries. According to the WHO, by 1990, most outbreaks of the plague were in Africa, with other common areas being Asia, and South America. Currently, the most endemic countries, are the Democratic Republic of the Congo, Peru, and Madagascar. Madagascar’s natives constantly suffer from the plague, such as the 2017 outbreak, where 221 people died of bubonic and pneumonic plagues, beginning with a 31 year old man traveling in a crowded minibus. Naturally, this unfortunate encounter meant a rapid spread of disease, first to the occupants of the minibus, but further to anyone within contact with those infected. These occurrences have been the subject of many in the World Health Organization, which have dispatched doctors and medical aid to Madagascar to help prevent the plague, which was prevented before truly becoming an unstoppable force of desolation. Unfortunately, this plague, ever since being brought from India, is a seasonal occurrence associated with the springtime, where rats and their fleas breed, thus causing a swell in plague occurrences.

Conclusion

The plague is a disease capable of dangerous pandemics and yet is perfectly preventable. With the proper equipment and information, this disease, much like many other conquered diseases, can be eradicated. However, without global knowledge and active prevention, it is unlikely we will be able to destroy the plague, since it does exist in the wild, away from human interference. Hopefully, we will learn from the past and will identify and eradicate this disease from claiming any more lives than it should.