Bubonic Plague: Epidemiology, Treatment And History

Introduction

Humans have been experiencing the effects of Yersinia pestis since the Bronze Ages. Yersinia pestis is the bacteria responsible for the historically famous plague outbreaks, such as The Black Death. Alexandre Yersin discovered the pathogen responsible for the Plague in 1984. Alexandre identified the Plague causing pathogen was a coccobacilli, Gram-Negative Bacteria. Yersinia pestis is a zoonotic disease due to the occurrence of a unique mutation that allows fleas to survive and become vectors of the bacteria.

Historical Relevance

There were three major pandemics of the Plague, which included the Justinian Plague, The Black Death, and the Third Pandemic of 1894. Plague pandemics occurred across the globe and caused devastating mortality rates for people and animals. An article about the history of Yersinia pestis explains, “On more than one occasion plague irrevocably changed the social and economic fabric of society” (Frith).

The first of the three major plague pandemics occurred in 541CE and became known as The Plague of Justinian. The pandemic originated in Ethiopia, Africa, and spread to Egypt. Then it spread west and east to Alexandria and Gaza, and then to Jerusalem and Antioch. The disease was then spread along the Mediterranean through steamships along the trade route. The disease arrived in Constantinople in 541 and reached its peak in the spring of 542 with a death rate ranging from 5,000 to 10,000 deaths per day-eventually resulting in the death of one-third of the city’s population. Articles restate that this pandemic had drastic and permanent effects on the social fabric of the western world. One example is the disruption of food production, which was a massive contribution to the eight-year famine that followed. Major outbreaks occurred over the next 200 years throughout Europe and the Middle East. The plague outbreaks traveled to Ireland and England and continued in intermittent cycles until the mid-eighth century.

The second pandemic became famously known as The Black Death and contributes to a considerable part of history. The Black Death occurred in 1347 and originated in Asia. From Asia, it spread to Crimea, then Europe and Russia. It marked the first European outbreak of the second great plague pandemic, which occurred over the 14th and 18th centuries. Mortality rates fluctuate according to location but were overall high. For example, Florence’s mortality rates were extremely high, recording that The Black Death wiped out half the city’s population. The rapid death rates resulted in the inability to perform the proper burial, which resulted in two things. First being, the lack of Clergy available to perform burial rituals, which caused people to fear spiritual death as well as physical. And secondly, Plague infected bodies were left in homes and on the streets. At this time, people believed the Plague spread through miasma, and so remedies were limited to the inhalation of aromatic vapors such as flowers. Whole families and villages were wiped out during the second Plague pandemic, which was socially and economically influential. Crops died while travel and trade slowed down to a halt.

Along with disruption in crop production and trade, the plague's devastation heavily influenced the division between upper and lower classes. Breaking down the barriers between upper and lower classes led to the creation of a new, middle class. The Plague also inspired artworks that eventually became historically famous such as Pieter Breughel, the elder’s ‘Triumph of Death’ in 1562.

The Black Death was the second major pandemic of the Bubonic Plague. The disease was extremely contagious and had high mortality rates, reducing Europe’s population to be lower in 1430 than it had been in 1290. “In the period 1347 to 1350, the Black Death killed a quarter of the population in Europe, over 25 million people, and another 25 million in Asia and Africa” [Frith, 15]. When another Plague epidemic emerged in 1347, Venice instituted public health controls that attempted to minimize the spread of the Plague by isolating healthy populations. Quarantine stations were established to effort to stop Plague infected people from traveling from eastern to western Europe. Since The Black Death’s cause was thought to be miasma at the time, doctors wore a mask and suit to protect themselves. Doctors wore masks that resembled a beak and were filled with herbs and flowers to protect from the miasma. Patients were treated differently, as doctors attempted to avoid contact. For example, a patient’s pulse would be taken using a long stick, and incisions-of buboes- would be done using very long knives. Many ideas people had about the Plague were derived from religious beliefs. Many believed god was inflicting illness as a punishment, and therefore religious and social sigmas prevailed.

While smaller epidemics continued to occur worldwide, major outbreaks hit Europe and England, which became known as The Great Plague of London of 1665 to 1666. These major outbreaks peaked in the fall of 1665 when London’s weekly death rate reached 7,000. This major outbreak specifically involved the pneumonic Plague and resulted in the death of about one-fifth of London’s population. Following this was the Great Fire of London in 1666. Rebuilding houses is believed to have disturbed rat’s habitat and, therefore, is linked to the end of the epidemic. The false but most famous belief was that the Plague spread through miasma or ‘bad air.’ The idea of miasma is reflected in the famous English nursery rhyme ‘Ring, a-ring, o’ rosies.’ The Black Death affected several aspects of society, as it killed off a portion of the world’s population and influenced art and history.

The Plague re-emerged in Yunnan, China, in 1855 as The Third Plague Pandemic of 1894. The disease spread from wild rodent reservoirs in China to Hong Kong and India, and then eventually all over the globe. After emerging in China, the disease advanced as it spread along with the tin and opium routes. The Plague reached Canton and then spread to Hong Kong in 1894, where Alexandre Yersin identified its pathogen. Then in 1898, it reached Karachi, where Paul-Louis Simond discovered rats as the primary host and fleas as the vector. These were the first scientific discoveries that accurately explained the causation of the plague outbreaks. Infected rats infected port cities, and then the disease spread throughout the city. In Australia, 12 major outbreaks of the Plague were recorded- from 1900 to 1925-causing 1371 cases and 535 deaths. Records show the increased infections within port cities such as Sydney. This pandemic lasted five decades (until 1959) and was responsible for over 15 million deaths. India was recorded to have one of the highest death rates during this pandemic. This pandemic marked the first accurate discovery of the causation of the Bubonic Plague.

Epidemiology:

Within the last 20 years, most reported cases occurred in small towns, villages, and agricultural areas rather than larger towns and cities. When first introduced to the United States, Bubonic Plague epidemics primarily occurred in port cities. Steam Ships, mainly from Asia, carried infected rats (and fleas) into the port cities of America and other countries all over the globe. The regions most affected by Yersinia pestis has changed tremendously due to the interference of progressive treatments and economic growth. With the discovery of the pathogen, host, and vector, plague pandemics were reduced. Outbreaks have immensely decreased with the introduction of vaccines and antibiotics. The Center for Disease Control reports that the last urban epidemic occurred in Los Angeles, U.S. occurred from 1924 to 1925. After that, the Plague spread from urban to rural rodents and resulted in scattered cases in rural areas.

The Center for Disease Control or CDC reports the Plague (Yersinia pestis) naturally occurs in the western United States, specifically in semi-arid grassland environments. Regions are prone to cases depending on the Plague’s natural existence in the environment. The plague foci are naturally occurring and randomly distributed across regions. Still, outbreaks tend to occur in ‘developing countries’ due to increased exposure, along with a lack of access to medical treatment. Since the 1990s, most Plague Epidemics have occurred in developing countries and regions such as Africa due to lack of medical and treatment access. The World Health Organization or WHO reports, “Currently, the three most endemic countries are the Democratic Republic of the Congo, Madagascar, and Peru” (World Health Organization).

The incidence rate of Yersinia pestis includes three major pandemics, which resulted in the estimated 200 million deaths during the 1st, 14th-17th, and 19th century. The Black Death caused an estimated incidence rate of 30% within the European population. Considering the multiple past outbreaks and progressive treatments, this is not an emerging disease. The disease is attempting to be eradicated by scientists through studies on the bacteria and testing new, more effective forms of treatment. Current vaccines and treatments are effective, but not often available or accessible to the general public in developing countries. Vaccines are mostly administered under exceptional, specific circumstances. People exposed to the infection regularly, such as animal or human doctors and people in the army, are eligible to receive the vaccine.

Etiology:

The Plague is a contagious, extremely virulent disease that uses fleas as vectors, rodents as reservoirs, and mammals (including humans) as the host. The Plague is not a hereditary disease. It is an acquired disease. The port of entry for the Bubonic Plague is through the bite of an infected flea. The Pneumonic Plague’s port of entry is the nose, eyes, or mouth through inhalation. Both versions are highly contagious through their portal of exit-which is the nose, eyes, and mouth.

There are two possible cycles, Sylvatic and Urban, which can result in the Bubonic or Pneumonic Plague in humans. The Sylvatic Cycle explains the cycle of the Plague existing in nature (wild rodents), whereas the Urban Cycle accounts for domestic rodents. The Sylvatic Cycle explains that a wild rodent is infected (with the Plague) by a flea, and then it infects fellow wild rodents and can infect humans through direct contact. The Sylvatic Cycle also explains how humans can get the disease directly from being bitten or regurgitated on by the flea vector. The Urban Cycle explains how domestic rodents may be introduced to the Plague bacteria through direct or indirect contact with a flea (from the Sylvatic Cycle). Once domestic rodents are infected, they can spread the disease to other rodents, but also to mammals or humans who come in contact with them. Both cycles may result in the spread of the Bubonic Plague to humans. These cycles are interlinked and explain the development of humans acquiring the disease. There are two modes of transmission in which humans may become infected by the Plague. The Bubonic or septicemic, version of the Plague occurs when the bacteria per flea bite infect the blood. The Pneumonic version is acquired through the inhalation of infected respiratory droplets. Pneumonic Plague has a much higher mortality rate since it directly infects the lungs. The Bubonic Plague has the potential to progress into Secondary Plague Pneumonia, which can be spread through person to person contact.

The Center for Disease Control or the CDC reports domestic animals in areas where Yersinia pestis exists naturally are at risk, and so are their owners. Domestic animals can contract the Plague by coming in contact with an infected flea or rodent, putting owners at risk. Interestingly enough, CDC mentions that cats are more symptomatic carriers than dogs. Cats often become very ill and die, whereas dogs can be almost asymptomatic for periods. Transmission of the Plague from domestic animals to humans should be avoided by educating the public. In places that Yersinia pestis occurs naturally, domestic animals should not interact with rodents or wild animals, and humans should take precautions when handling wild rodents due to their possible infectious state.

Pathology and Pathophysiology:

The Plague is caused by bacteria called Yersinia pestis, which transports itself by utilizing the protein called LcrV. This protein suppresses the immune system during the event of an infection. In an article by the University of Chicago Medical Institute, Scheewind explains LcrV is secreted-using the type-III pathway- in mass amounts during the state of infection. Without it, the bacteria would be relatively harmless to mammals. Yersinia pestis has revealed itself as a gram-negative bacteria, plague pathogen, and category an agent of bioterrorism. This bacterium can overcome the innate immune system with the assistance of LcrV.

In a Peer-Reviewed Journal titled, “Imaging Early Pathogenesis of Bubonic Plague,” researchers focused on the bacteria and immune cell’s interaction, and results suggest the Yersinia pestis infection may prevent neutrophils from activation. Researchers noticed the bacteria interacting mostly with neutrophils. Studies may even indicate the infection (Yersinia pestis) of neutrophils to cause them to return to circulation and migration to distal sites.

The Plague’s pathogen, Yersinia pestis, has mutated to create a unique stage of life for itself. Yersinia pestis’ pathogen is exceptional, especially in terms of its mutation. The pathogen forms a layer of bacteria biofilm while in the arthropod’s gut. This bacteria biofilm is surrounded by a complex extracellular polymeric substance which localized then adheres to the flea’s foregut. For this arthro-borne pathogen, “Localization and adherence of the biofilm to the flea foregut is essential for transmission” (Sun 1).

Symptoms:

Fleas are asymptomatic vectors of Plague, causing bacteria, Yersinia pestis. Humans are not asymptomatic carriers, and symptoms vary depending on the mode of transmission. The Bubonic/Septicemic Plague’s symptoms include a 2-6 day latency period, whereas the Pneumonic Plague’s latency period is only 1-2 days after infection. Symptoms of the Bubonic Plague include the formation of buboes and or blackened inflammation in the groin and armpits. Pneumonic Plague symptoms include fever and edema, which lead to much higher mortality rates. Once within the mammal host’s system, Yersinia pestis travels to the lymphatic system where it multiplies. In the lymphocytes, Yersinia pestis grows logarithmically and then spreads, systematically, to various parts of the body. The multiplication of bacteria in the lymphocytes causes the buboes to be prevalent in areas of infection (lymphocytes).

Treatments:

The Plague is treatable, but early diagnosis is essential for the most effective treatments. Antibiotics are used to treat the symptoms and cure the body of the bacteria. The Pneumonic version of the Plague is more difficult to treat using antibiotics. Since the disease develops at an extremely rapid rate, the treatment must be administered during the early stages of the infection to increase successful treatment outcomes. Unfortunately, developing countries are over-exposed to and under-treated for the Bubonic Plague. When treatment is not accessible at the early stages of Yersinia pestis infections, mortality rates rise.

Effective Plague Vaccination via Oral Delivery of Plant Cells Expressing F1-V Antigens in Chloroplasts was written in August of 2008. This text explains an alternative to fermentation-based systems used in the production of vaccine biopharmaceuticals and antigens. This alternative plus oral booster doses proved to be successful at eliciting an immune response to Yersinia pestis. Improving and adjusting treatments is essential for the disease’s eradication. This study reports, “.. this is the first report of a plant-derived oral vaccine that protected animals from live Yersinia pestis, bringing the likelihood of lower-cost vaccines closer to reality” (Arlen 2008). Similar reports indicate scientists’ and researchers’ intent for future eradication. There are fewer than 2,000 cases a year worldwide, including 10 to 20 each year in the western United States. By studying the interaction of the bacteria with the host’s immune system, scientists hope to develop a more useful and accessible form of treatment and prevention.

Relevance to Human Society:

The Encyclopedia of the Black Death explains the ravaging social, cultural, and religious effects (especially on the Christian and western Islamic worlds) of the Black Deaths because it was responsible for about 40 percent of the population’s death (Byrne 2012). As societies were ravaged, there was an increased desire to understand the underlying causation of the brutal plague outbreaks. The pandemic plague outbreaks have had effects on several aspects of human life, knowledge, and interaction. The major plague outbreaks caused an increase in efforts to understand the cause of the disease. Therefore, the intense outbreaks promoted scientific progress and increased science, medical, and public desire for a better understanding (and to find a cure).

Vaccines and antibiotics are being created, adapted, and tested (on mice) with the intent of discovering alternative treatment options. Treatments must be tailored to become more convenient and accessible to developing countries. Regions that are prone to Yersinia pestis bacteria should create public awareness and reinforce a general understanding of the disease’s mode of transmission and dangers.