Bubonic

Plague
Kristie Cheng
Research

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Introduction:
Bubonic plague is a serious and deadly infection caused by the Yersinia Pestis bacteria
which is spread through fleas and rodents. This infection is zoonotic meaning it is spread by and
to animals and humans are just an accidental host of the bacteria. The bacteria grows at an
optimal temperature of 28 degrees Celsius or 82.4 degrees Fahrenheit (Roussos 2002). This
disease usually occurs in areas containing wildlife that could easily carry fleas. The bacteria can
be easily be spread if good hygiene is not practiced (Center for Disease Control and Prevention
[CDC] 2012). Bubonic plague has been, supposedly, around since biblical times and still poses a
threat to society to this day. The plague is responsible for hundreds of millions deaths throughout
history (Stenseth, Ashtabar, Begon, Belmain, Bertherat, Carniel, Gage, Liers, & Rahalison 2008;
WHO 2014).
History:
In 541 AD the first documented outbreak of bubonic plague started in Egypt and made its
way around the eastern hemisphere to North Africa, Europe, and Asia. This outbreak was known
as the Justinian plague and reduced the population of those influenced countries by 50-60%
(Roussos 2002). The second outbreak occurred in Europe in the 14th century lasting well into the
17th century in Europe. This was the best known epidemic of the plague. This outbreak also gave
the disease the name the Black Death (Stenseth et al. 2008). This epidemic caused an estimated
twenty to thirty million deaths in the span during the Black Death outbreak. The third major
outbreak took place in the mid-19th century in China and spread through the continent of Asia.
The three outbreaks resulted in an estimated two-hundred million deaths (Titball & Cleary 1998).

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The precautions taken for plague in the early fifteenth century were taken very seriously
to prevent further transmission for both the infected patient and those in contact with the infected
(Newman 2012). The house of the infected would first be tagged with a painted red cross on their
door to signal to others that the house was quarantined. Those in the house with the infected
person would be allowed to leave the house and stay quarantined in a second house is they were
fortunate enough to own one (Newman 2012). Usually only the wealthy owned a second house.
This was probably a probable cause for such a high mortality rate back then. If one was not
fortunate enough, they would stay quarantined with the infected person (Newman 2012). There
were buildings incorporated into society known as pest houses and those infected peoples or
those in contact with the infected were moved. The blueprints of the pest houses depicted two
separated buildings made with brick or stone walls, high ceilings, and large windows for optimal
airflow (Newman 2012). The buildings were tailored meticulously to the disease. If a person in a
pest house did not show symptoms of the plague within the incubation time of the plague, about
1-6 days, the person would be allowed to leave (Newman 2012). The quarantine policy in Europe
during the outbreak died out after the plague itself died out in the 17th century.
Throughout history, people have used bubonic plague as a biological warfare weapon as
early as 400 BC (Roussos 2002). Scythian archers would dip arrows in blood, feces, and tissue
from decomposing bodies and shot them at their enemies. In the medieval times, armies were
known to catapult infected dead bodies, fleas, and rats into enemy lines and cities (Roussos
2002; CDC 2012). This was also supposedly used in 1930s during World War II. The Japanese
were said to have bred and infected human fleas with the Y. pestis bacteria and released the fleas
into Chinese cities (Roussos 2002; CDC 2012).

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The appearance of bubonic plague in biblical times. Evidence is shown in the fifth
chapter of 1 Samuel where an outbreak of plague in Israel with symptoms of bubonic plague are
recorded (Griffin 2000). The text described the plague as tumors in the groin as well as the
appearance of rats before the plague broke out (Griffin 2000).
Symptoms:
When the Yersinia Bacteria first infiltrates a persons body, they travel to the lymph nodes
causing them to become swollen and tender on the first day of infection. The swollen lymph
nodes are known as buboes, hence the name bubonic plague. Other symptoms include fever,
chills, and weakness (Roussos 2002). The Y. pestis bacteria spreads to other parts of the body and
has the ability to become one of the other two types of plague, septicemic and pneumonic. If one
infected with the bubonic plague is not immediately given the antibiotics, they will develop
systemic disease within two to six days (Roussos 2002). The lesions become a rash of purple
spots due to the internal bleeding from small blood vessels resembling those of meningococcal
which is also known as meningitis. Over time, the lesions will become necrotic and kill the tissue
which will make is become black. This process is a result of gangrene and has also given
bubonic plague the nickname the Black Death (Stenseth et al. 2008; Roussos 2002).
Transmission:
This disease is transmitted via fleas to rodents such as rats and mice as well as squirrels,
rabbit, chipmunks, prairie dogs, bobcats, and cats (Roussos 2002). When a flea is infected by the
Yersinia pestis bacteria, the bacteria clogs the fleas blood and foregut disabling its ability to
swallow. The fleas inability to swallow makes it ravenous and causes it to feed more frequently
than before, which also spreads the y. pestis bacteria (Roussos 2002). When a human is bitten by

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a flea multiple times, thousands of bacteria can enter the body. They target the lymph nodes first
causing swell up to the size of a chicken egg, become very tender, and also become sore (Titball
& Cleary 1998). These swollen lymph nodes are also known a buboes hence the name bubonic
plague (Roussos 2002; Center for Disease Control and Prevention [CDC] 2012).
Diagnosis:
Plague is diagnosed in one singular way. When a patient is infected by the bacteria,
buboes will appear and they will seek medical help in most cases. To diagnose the disease,
samples of the blood and/or swollen lymph node will be taken and sent to a laboratory for testing
(CDC 2012). Treatment must be started as soon as possible for the best survival chances.
Treatment:
When infected, the administration of antibiotics are crucial. The mortality rate without
the use of antibiotics is 30%-60%, but with antibiotics, the rate is reduced to 5% (World Health
Organization [WHO] 2014; Roussos 2002). The antibiotics to treat bubonic plague are
streptomycin, gentamicin, doxycycline, and tetracycline (Titball & Cleary 1998; Williamson
2009). If one is pregnant they should only use gentamicin and doxycycline because it because
they are not harmful to the fetus (Roussos 2002). The dosage of these drugs must be taken into
consideration as high doses are harmful to peoples bodies. Another treatment that is used is the
Killed Whole Cell Vaccine [KWCV] (Roussos 2002; Williamson 2009). This vaccine uses dead
plague cells and makes it easier for the immune system to create the necessary antibodies for the
disease. The newest treatment for the bubonic plague is the F1-V vaccine which uses a fusion
protein composed of flagellin and two protective antigens of Yersinia pestis to make a vaccine

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that increases the immunity against the plague (Mizel, Graff, Siranganathan, Ervin, Lees, Lively,
Hantgan, Thomas, Wood, & Bell 2008).
Experiment:
Parts in the Eurasian area, Africa, Southwest USA, Madagascar, and South America are
most prone to this disease currently (Titball & Cleary 1998; Alvarez, Pineyard, Crisantes,
Rigano, Pinkhasov, Walmsley, Mason, & Cardineau 2006; CDC 2012). Because this bacteria
spreads easily in dirtier environments, very poor societies are targeted most. The F1-V antigen
has been around since the discovery by Williamson, Eley, Griffin, Green, Russell, Leary, Oyston,
Easterbrook, Reddin, & Robinson in 1995. Alvarez, Pineyard, Crisantes, Rigano, Pinkhasov,
Walmsley, Mason, & Cardineau take this new antigen vaccine and strive to create a vaccine that
would be easy to administer, increase function in the immune system, be easy to create and grow,
be safe, and cost efficient (2006). The vaccine would target all forms of plague mainly the
pneumonic plague, which is the airborne strand and incurable thus far. This vaccine would be
tested for the immune system response after being administered to the mice.
Alvarez, Pineyard, Crisantes, Rigano, Pinkhasov, Walmsley, Mason, & Cardineau used
eleven mice as their test subjects. They used a tomato as the base for the vaccine due to its
impact on the immune system. The lycopene found in tomatoes is a powerful antioxidant and has
been tested positive in helping the immune system against many chronic diseases such as cancer
(Lou & Wu 2011). Alvarez et al. hoped to increase the immunogenicity of the test subjects
(2006). The F1 (Fraction 1) antigen induces phagocytosis by macrophages and the V antigen is a
protein that moves the cytotoxic effector protein from bacteria to the mammalian cells (Alvarez
et al. 2006). The tomato plant was harvested, freeze dried, and stored in bags at room
temperature. The powder was made of between 50-100 mg of young leaf or freeze-dried

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tomatoes treated with liquid nitrogen and pulverized (Alvarez et al. 2006). The total soluble
proteins (TPS) started to decrease rapidly directly after the tomatos green stage of growth
[Figure 1].
The mice were each selected at birth and raised as laboratory mice. Each mouse was put
on a diet at the beginning of the trial of 2 g of freeze-dried tomato fruit powder blended with 7 g
of food mixed with a blender comprised of: two whole apples (small Washington Delicious
apples), one-half cup of mixed nuts (peanuts, cashews, almonds, halberts, brazils), two
tablespoons of honey, and one-fourth cup of water to limit the number of variables in the test
(Alvarez et al. 2006). Five of the mice were given the control tomato powder of wild/normal
tomatoes. The other six mice were given the transgenic tomato powder.
The results showed that the F1-V tomato boosted powder increase the serum and mucosal
antibodies in 100% of the mice. There was a significant boost in the number of antibodies
produced in the group given the wild type (normal/wild tomatoes) boost and those given F1-V
boost [Figure 2] (Alvarez et al. 2006). Alvarezs study did prove that the tomato engineered with
the F1-V antigen increased the antibody production of those in mice. The next step of this
experiment would be to do testing on humans until they can finally produce the tomato and
distribute it throughout the world to help eradicate the plague in the world.
Conclusion:
The bubonic plague is still a problem in the world and has not been eradicated yet. The
plague has an average of 1000 2000 cases of plague and about 200 deaths annually (Titball &
Cleary 1998; WHO 2014). Not all countries that have infected people are able to get the needed
antibiotics to fend off the disease. If the F1-V transgenic tomato vaccine were distributed to

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those countries, it would help lower the chances of infection, transmission, and potential
outbreaks in the future (Alvarez et al. 2006). The bubonic plague is able to be manipulated as
seen in the history of the disease and could become a biological weapon easily (Roussos 2002;
CDC 2012). If the disease could be eradicated completely with a definitive vaccine, the threat of
bioterrorism could be eliminated as well.

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Appendix
[1]

[2]

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List of References
Alvarez, M. L., Pineyard, H. L., Crisantes, J. D., Rigano, M. M., Pinkhasov, J., Walmsley, A. M.,
Mason, H. S., & Cardineau, G. A.(2006).Plant made submit vaccine against pneumonic
and bubonic plague is orally immunogenic in mice. Vaccine, 24, 2477-2490.
Bailey, J. R. (2015). Lycopene: Food Sources, Potential Role in Human Health and Antioxidant
Effects. Hauppauge: Nova Science Publishers, Inc.
Center for Disease Control and Prevention. (2012). Plague. http://www.cdc.gov/Plague/
Lou, C. & Wu, X. (2011). Lycopene Enhances Antioxidant Enzyme Activities and Immunity
Function in N-Methyl-N-nitro-N-nitrosoguanidineInduced Gastric Cancer Rats.
International Journal of Molecular Sciences, 12, 3340-3351.
Griffin, J.P. (2000). Bubonic Plague in Biblical Times. Journal of Royal Society of Medicine, 93,
449.
Mizel, S.B., Graff, A.H., Siranganathan, N., Ervin, S., Lees, C.J., Lively, M.O., Hantgan, R.R.,
Thomas, M.J., Wood, J., & Bell, B. (2008). Flagellin-F1-V Fusion Protein Is an Effective
Plague Vaccine in Mice and Two Species of Nonhuman Primates. Clinical and Vaccine
Immunology, 16, 21-28.
Newman, K.E.S. (2012). Shutt Up:Bubinic Plague and Quarantine in Early Modern England.
Journal of Social History, 45, 809-834.
Roussos, D. (2002). Plague. Primary Care Update for OB/GYNS, 9, 125-128.
Stenseth, N.C., Ashtabar, B.B., Begon, M., Belmain, S.R., Bertherat, E., Carniel, E., Gage, K. L.,
Liers, H., & Rahalison, L. (2008). Plague: Past, Present, and Future. PLoS Medicine, 5, 913.
Titball, R.W. & Cleary, S.E.C. (1998). Plague. British Medical Bulletin, 54, 625-633.
Williamson, E.D., Eley, S.M., Griffin, K.F., Russell, P., Leary, S.E., Oyston, P.C., Easterbrook,
T., Reddin, K.M., Robinson, A., & Titball, R. (1995). A new improved sub-unit vaccine
for plague: the basis of protection. FEMS Immunology & Medical Microbiology, 12, 223230.
Williamson, E.D. (2009). Plague. Vaccines for Biodefense, 27, D56-D60.
World Health Organization. (2013). Plague. http://www.who.int/csr/disease/plague/en/