WORLD OF MICROBIOLOGY AND IMMUNOLOGY Bubonic plague93•
the brains of animals and humans with prion diseases. The
most alarming finding is preliminary evidence from two inde-
pendent groups that CJD patients have a ten-fold increase in
the levels of manganese in their brains. This increase is
unprecedented in any other diseases—except cases of man-
ganese poisoning—implying that high brain manganese might
be a specific hallmark of prion diseases. This has prompted
intensive work on the relationship between prion diseases and
environmental pollution. It is proposed that in regions where
manganese levels are abnormally high, the manganese may
bind to the normal brain PrPC protein and alter its structure
into the abnormal PrPSc form. Under these circumstances, the
PrPC would lose its protective antioxidant function and pre-
dispose the brain to increased oxidative damage.
Many questions concerning the connection between
metals and prion diseases remain to be answered. What is
clear is that metals can be both beneficial and malicious to
the structure and function of PrP. It is important to elucidate
the mechanisms involved in these brain metal perturbations
and their role in modulating the structure of PrP. Further-
more, it is also essential to determine the structural and func-
tional changes induced by different metals on PrP at the
molecular level and the resultant phenotypic features.
Conclusive evidence that the loss of PrPC function con-
tributes to prion diseases requires further experiments, possi-
bly with animal models. What is certain is that the next few
years will be crucial and exciting in deducing whether brain
metal abnormalities constitute a mechanism in the develop-
ment of prion disease.See alsoBSE and CJD: Socio-economic impact and ethical
issues; BSE and CJD; Slow virus and viral diseasesBBubonic plagueUBONIC PLAGUE
Bubonic plague is a disease that is typically passed from
rodents to other animals and humans via the bite of a flea. The
flea acquires the bacterium that causes the disease as it lives
on the skin of the rodent. Humans can also acquire the disease
by direct contact with infected tissue. The bacterium is called
Yersinia pestis, after one of its co-discoverers, Alexandre
Yersin.
The disease is named because of the symptoms. The
bacterial infectionproduces a painful swelling of the lymph
nodes. These are called buboes. Often the first swelling is evi-
dent in the groin. During the Middle Ages, an huge epidemic
of bubonic plague was referred to as the Black Death, because
of the blackening of the skin due to the dried blood that accu-
mulated under the skin’s surface.
The bubonic plague has been a significant cause of
misery and death throughout recorded history. The Black
Death was only one of many epidemicsof plague that extend
back to the beginning of recorded history. Biblical descrip-
tions of some disease outbreaks likely involved bubonic
plague. The first recorded outbreak of bubonic plague was in
542–543. This plague destroyed the attempts of the Roman
emperor of the day to re-establish a Roman empire in Europe.This is only one example of how bubonic plague has changed
the course of history.
The plague of London in 1665 killed over 17,000 people
(almost twenty percent of the city’s population). This outbreak
was quelled by a huge fire that destroyed most of the city.
The disease remains present to this day. In North
America, the last large epidemic occurred in Los Angeles in- With the advent of the antibiotic, era bubonic plague has
been controlled in the developed world. However, sporadic
cases (e.g., 10 to 15 cases each year) still occur in the western
United States. In less developed countries (e.g., in Africa,
Bolivia, Peru, Ecuador, Brazil) thousands of cases are reported
each year.
The infrequent outbreaks of bubonic plague does not
mean the disease disappears altogether. Rather, the disease
normally exists in what is called an enzootic state. That is, a
few individuals of a certain community (e.g., rodents) harbor
the disease. Sometimes, however, environmental conditions
cause the disease to spread through the carrier population,
causing loss of life. As the rodent populations dies, the fleas
that live on them need to find other food sources. This is when
the interaction with humans and non-rodent animals can occur.
Between outbreaks, Yersinia pestisinfects rodents without
causing much illness. Thus, the rodents become a reservoir of
the infection.
Symptoms of infection in humans begin within days
after contaminationwith the plague bacterium. The bacteria
enter the bloodstream and travels to various organs (e.g., kid-
ney, liver, spleen, lungs) as well as to the brain. Symptoms
include shivering, nausea with vomiting, headache, intoler-
ance to light, and a whitish-appearing tongue. Buboes then
appear, followed by rupture of blood vessels. The released
blood can coagulate and turn black.
If the infection is untreated, the death rate in humans
approaches 75%. Prompt treatment most often leads to full
recovery and a life-long immunityfrom further infection.
Prevention is possible, since a vaccine is available.
Unfortunately, the vaccine is protective for only a few months.
Use of the vaccine is usually reserved for those who will be at
high risk for acquiring the bacterial infection (e.g., soldiers,
travelers to an outbreak region). Antibioticssuch as tetracy-
cline or sulfonamide are used more commonly as a precaution
for those who might be exposed to the bacterium. Such use of
antibiotics should be stopped once the risk of infection is
gone, to avoid the development of resistance in other bacteria
resident in the body.
These modern day treatment and preventative measures
are a marked improvement from earlier times. In the four-
teenth century, treatments included bathing in human urine,
wearing feces, having a dead animal present in the home, and
drinking concoctions of molten gold and crushed emeralds. As
time progressed, even though the cause of the disease was still
unknown, the preventative measures became more construc-
tive. By the fifteenth century, for example, incoming ships
were required to anchor offshore for 40 days before cargo or
people could disembark. Quarantine is still practiced today as
a protective measure for some diseases.
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