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The Plague
By Michael Brown
“The Plague,” is a commonly known, but rare disease that is usually known for its
association with the Black Death in Europe. The etiological agent, Yersinia Pestis, was
discovered and isolated by Alexandre Yersin in 1894, who combatted it using antiserum.2
The pathogen itself is transmitted commonly through fleas bites, as fleas are vectors, or
by droplet transmission after pneumonic plague, and through direct contact through eated
infected meat.1 Rodents serve as the primary reservoirs for the plague.2 Infected rodents
from ticks, carry the disease until dying, in which the infected fleas seek another food
source. Once they are infected, the cells proliferated in the flea and cause a blockage in
the stomach of the flea, and one the flea attempts to bite into a new host, it spews the
cells from the blockage into the host.2 The flea is still unable to feed, so multiple bites
usually occur, promoting likelihood of infection.2 Y. pestis is characterised as a gramnegative, nonmotile, non-spore-forming coccobacillus that is a neutrophilic, mesophilic,
facultative anaerobe.2 Some of the key tests for identifying the presence of Y. pestis are through various
techniques. A common identification is when the disease exhibits bipolar staining with
Giemsa, Wright’s, or Wayson staining.2 Other indications come from the appearance of
pinpoint colonies observed at 24 hours on Sheep’s blood agar, with a later “fried egg”
appearance.3 Other tests that conclude non-lactose fermentation, negative results for
oxidase, urease, indole, and catalase positive, with growth rate optimal at 28°C.3 Y. pestis
can also be tested for antigens of F1 in serum, with F1 being the capsule that is formed by
Y. pestis in mammalian hosts.3 Also can be identified by presence of “buboes” or swollen
lymph nodes, which is extremely characteristic of the disease.1 The plague takes three
forms depending on the type, which creates variance in the symptoms and signs. Bubonic
plague is classified due to the presence of “buboes” or swollen lymph nodes. Pneumonic
plague is where the infection is located in the lungs. This causes coughing up of water or
bloody mucus as well as similar symptoms.1 Septicemic plague is classified by infection
circulating in the blood.1 This form of plague can kill the host without any symptoms
occurring. As well, skin may turn black and die, and internal bleeding can be observed in
most cases.1 All types usually occur alongside fever, malaise, and shock.1 Multiple outbreaks throughout time with historical significance. The major three
start with the Justinian Plague. This plague occurred between the years of 541-544 AD in
Pelusium, Egypt, but led to world wide spread with estimations of up to 50-60% loss in
population from 541-700 AD.2 The second and most infamous, was labelled the “Black
Death.” It occurred between 1347- 1351, occurring in the beginning in Sicily, and
spreading to numerous European countries with a death toll of 17-28 million, which was
about 30-40% of the population.2 The third and latest was labelled the “Modern Plague.”
Beginning in 1855 in a Chinese province and spread to multiple countries forming
multiple epidemics such as India, which saw to deaths in the millions, as much 12.5
between 1898-1918.2 Y. pestis has a swath of virulence factors that give it such impact on the host as
observed in the epidemics above, with incredibly high mortality rates from sepsis. Once
the pathogen is able to bypass the skin barrier though the flea bite, and it is able to infect
macrophages. Although some are killed via neutrophils, the infected macrophages serves
a host for Y. pestis which then proliferates within and acquires phagocytic resistance.6
While proliferation occurs, the cells express an F1 protein that gives them a capsule,
which helps resist phagocytosis.6 As well, Y. pestis produces a different
lipopolysaccharide within mammalian hosts that does not stimulate TLR4, and thus
doesn’t trigger normal immune response.6 This is different than the one produced in
colder hosts, such as the flea, which would trigger normal immune response.6 The
macrophages also serve as transports to lymph nodes in which they can escape to the
extracellular compartment.6 Y. pestis is also able to form outer proteins called “Yops”
that can be used to inject into cells to inhibit immune response.6 When injected into
macrophages and neutrophils, it inhibits their ability to phagocytize and also signal to
other cells.6 NK cells are able to directly destroy Y. pestis, as well as neutrophils, so they
will eventually deplete NK cells completely and then slow secretion of necessary fluids
for NK production.6 It furthers immunosuppression with Yops in inhibiting inflammation
response from infected cells.6 Yops can also be used to lyse T-cells, and even stop the
lysed cells from use in immune response.6
Though multiple attempts to cut down on plague areas have occurred, most of the
campaigns launched by the U.S. and other countries has proven unsuccessful in
controlling outbreaks.2 The most common treatment in use of antibiotics streptomycin,
ceftriaxone, doxycycline, ciprofloxacin, and ofloxacin.5 As well gatifloxacin and
moxifloxacin, were effective in pneumonic plague.5 Antibiotics and vaccines both pose
as good forms in which to prevent plague. Antibiotic use is much more effective, ones
such as β-lactams, tetracyclines, aminoglycosides, chloramphenicol, and fluoroquinolone,
which are given in cases of contact with pneumonic plague prophylactically.5 There is a
live, attenuated vaccine, “EV76” that lacks pgm genes that has been used, but is not
available commercially.5 The vaccine itself sometimes has an adverse effect in some of
those vaccinated, and it has not proven effective at combating pneumonic plague.2 Other
forms such as subunits of F1, have also been tried, but with little success.2
The most recent epidemic of plague in the U.S. occurred in 1924 in Los Angeles,
with 30 citizens dying from pneumonic plague.7 The case led to the quarantine and rat
eradication campaign that was supposedly the reason for the disease not spreading
further.7 As well, in the United States, statistic gather between the years of 1900-2012
place a total of 1006, with new cases occurring at rate of 1-17 cases per year.1 The most
recent outbreak was in madagascar, with a total of 119 cases of plague were reported with
40 of the patients dying.4 In the world, WHO reports the number of new cases to be
between 1,000-2,000 per year.1
Sources Cited
Center of Disease Control, “Plague,” September 10, 2015, http://www.cdc.gov/plague/,
May 7, 2016
2
Perry, Robert and Jacqueline Fetherston, “ Yersinia pestis—Etiologic Agent of Plague,”
January 1997, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC172914/pdf/100035.pdf,
May 8, 2016.
3
Borio, Luciana, “Challenges to the Laboratory Diagnosis of Yersinia pestis in the
Clinical Laboratory,” December 29, 2005,
http://www.upmc-cbn.org/report_archive/2005/cbnreport_122905.html, May 8, 2016.
4
World Health Organization, “Plague – Madagascar,” November 21, 2014,
http://www.who.int/csr/don/21-november-2014-plague/en/, May 9, 2016. 5
Butler, Thomas, “Plague into the 21st Century,” January 29, 2009,
http://cid.oxfordjournals.org/content/49/5/736.full, May 9, 2016.
6
Li, Bei and Ruifu Yang, “Interaction between Yersinia pestis and the Host Immune
System,” February 4, 2008, http://iai.asm.org/content/76/5/1804.full, May 8, 2016. 7
Viseltear, Arthur, “The Pneumonic Plague Epidemic of 1924 in Los Angeles,” August
13, 1973, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2595158/pdf/yjbm001520044.pdf, May 9, 2016. 1