ARTHROPOD BORNE DISEASE:

BUBONIC PLAGUE
from Yersinia pestis

It was known as the "Black Death" during the fourteenth century, causing an estimated
50 million deaths. It is an infectious disease that is caused by the bacterium Yersinia pestis and
is transmitted to humans from infected rats by the oriental rat flea (Xenopsylla cheopis) It is
named for the characteristic feature of buboes (enlarged lymph nodes) in the groin, armpits,
neck, and elsewhere. Other symptoms of bubonic plague include headache, fever, chills, and
weakness. Bubonic plague can lead to gangrene (tissue death) of the fingers, toes, and nose.

Microscopic Properties

SIZE: 0.5-0.8 Hm in width & 1-3 um in length

SHAPE: Rod- shaped or bacillus
GRAM REACTION: Gram negative
ARRANGEMENT: appears in singles, short
chains, short groups

Figure 1: Yersinia pestis

Pathophysiology

a. Transmission:
The plague bacteria can be transmitted to humans in the following ways:

● Flea bites - Plague bacteria are most often transmitted by the bite of an infected
flea. During plague epizootics, many rodents die, causing hungry fleas to seek
other sources of blood.People and animals that visit places where rodents have
recently died from plague are at risk of being infected from flea bites. Dogs and
cats may also bring plague-infected fleas into the home. Flea bite exposure may
result in primary bubonic plague.
● Contact with contaminated fluid or tissue - Humans can become infected when
handling tissue or body fluids of a plague-infected animal, for example, a hunter
skinning a rabbit or other infected animal without using proper precautions could
become infected with plague bacteria. This form of exposure most commonly
results in bubonic plague.
 Figure 2: Transmission of Bubonic Plague

b. Steps in Pathogenesis:
1. Yersinia pestis is primarily a rodent pathogen, with humans being an accidental
host when bitten by an infected rat flea. The flea draws viable Y. pestis
organisms into its intestinal tract. These organisms multiply in the flea and block
the flea's proventriculus.
2. Some Y. pestis in the flea are then regurgitated when the flea gets its next blood
meal thus transferring the infection to a new host. While growing in the flea, Y.
pestis loses its capsular layer. Most of the organisms are phagocytosed and
killed by the polymorphonuclear leukocytes in the human host. A few bacilli are
taken up by tissue macrophages. The macrophages are unable to kill Y. pestis
and provide a protected environment for the organisms to synthesize their
virulence factors.
3. The organisms then kill the macrophage and are released into the extracellular
environment, where they resist phagocytosis (YopH and YopE; Yersinia outer
membrane protein) by the polymorphs. The Y. pestis quickly spread to the
draining lymph nodes, which become hot, swollen, tender, and hemorrhagic. This
gives rise to the characteristic black buboes responsible for the name of this
disease.
4. Within hours of the initial flea bite, the infection spills out into the bloodstream,
leading to involvement of the liver, spleen, and lungs. The patient develops a
severe bacterial pneumonia, exhaling large numbers of viable organisms into the
air during coughing fits. 50 to 60 percent of untreated patients will die if
untreated. As the epidemic of bubonic plague develops (especially under
 conditions of severe overcrowding, malnutrition, and heavy flea infestation), it
eventually shifts into a predominately pneumonic form, which is far more difficult
to control and which has 100 percent mortality..

c. Virulence factors:
● Adhesion or Invasion- plasminogen activator protein of Y. pestis facilitates the
adhesion and invasion of the bacterium to the extracellular matrix of host tissues.
Plasminogen activator induces the activation of plasminogen into plasmin, which
causes proteolysis and damage to host tissues.
● Nutrient acquisition- Yersiniabactin is a siderophore that acquires iron produced
by the host. Yersiniabactin is secreted by Y. pestis to scavenge iron in the host,
and once it binds iron, it returns to the bacterial cell. Iron acquisition is a crucial
component of initial colonization via the tissues, as Yersiniabactin defective
strains cannot spread from the initial site of infection.

Diagnosis and Treatment

a. Diagnosis
The most common sign of bubonic plague is the rapid development of a swollen and
painful lymph gland called a bubo. A known flea bite or the presence of a bubo may help
a doctor to consider plague as a case of the illness. Diagnosis can also be made by
taking samples from the patient and submitting them for laboratory testing.

● Diagnostic Tests:
Specimen – If the patient has enlarged lymph nodes, aspirates of the enlarged
lymph nodes is taken for smear and culture.

Culture:
● If the patient has enlarged lymph nodes, aspirates of the enlarged lymph
nodes are taken for culture.
● Specimens are cultured on blood agar, chocolate, and MacConkey agar
plates. The growth of the specimen on solid media may be slow which
requires more than 48 hours.
● Yersinia pestis usually produces non lactose-fermenting colonies on
MacConkey agar.

Smear:
● Y. pestis are small gram-negative bacilli that appear as single cells or as
pairs or short chains in clinical material.
● Wright, Giemsa, or Wayson stains may be more useful when staining
material from a suspected buboe because of the striking bipolar
appearance (safety pin shape) of the organism using these stains that is
not evident on a direct Gram stain.
b. Treatment:
● Pharmacologic
Since bubonic plague is caused by bacteria, the drug of choice is
streptomycin; if not available the gentamicin has been shown to be
effective. Alternative drugs are doxycycline and ciprofloxacin.

Table 1: Antibiotic treatment for plague for adults

Adults

Antibiotic Dose Route of Notes

administration

Streptomycin 1 g twice daily IM Not widely available in the US

Gentamicin 5 mg/kg once daily, or 2 IM or IV Not FDA approved but considered an effective
mg/kg loading dose alternative to streptomycin. Due to poor abscess
followed by 1.7 mg/kg penetration, consider alternative or dual therapy
every 8 hours for patients with bubonic disease.

Levofloxacin 500 mg once daily IV or po Bactericidal. FDA approved based on animal

studies but limited clinical experience treating
human plague. A higher dose (750 mg) may be
used if clinically indicated.

Ciprofloxacin 400 mg every 8-12 IV Bactericidal. FDA approved based on animal

hours studies but limited clinical experience
treating human plague
500-750 mg twice daily po

Doxycycline 100 mg twice daily or IV or po Bacteriostatic, but effective in a randomized trial

200 mg once daily when compared to gentamicin.

Moxifloxacin 400 mg once daily IV or po

Chloramphenicol 25 mg/kg every 6 hours IV Not widely available in the United States

Table 1: Antibiotic treatment for plague for children

Children

Antibiotic Dose Route of Notes

administration

Streptomycin 15 mg/kg twice daily IM Not widely available in the US

(maximum 2 g/day)

Gentamicin 2.5 mg/kg/dose every 8 IM or IV Not FDA approved but considered an effective
hours alternative to streptomycin. Due to poor abscess
penetration, consider alternative or dual therapy
for patients with bubonic disease.
 Levofloxacin 10 mg/kg/dose (maximum IV or po Bactericidal. FDA approved based on animal
500mg/dose) studies but limited clinical experience treating
human plague. A higher dose (750 mg) may be
used if clinically indicated.

Ciprofloxacin 15 mg/kg/dose every 12 IV Bactericidal. FDA approved based on animal

hours studies but limited clinical experience
(maximum 400 mg/dose) treating human plague

20 mg/kg/dose every 12 po
hours (maximum 500
mg/dose)

Doxycycline Weight < 45 kg: 2.2 mg/kg IV or po Bacteriostatic, but effective in a randomized trial
twice when compared to gentamicin.
daily (maximum 100
mg/dose)
Weight ≥ 45 kg: same as
adultdose

Chloramphenicol 25 mg/kg every 6h IV Not widely available in the United States

(maximum daily dose, 4 g)

Table 1: Antibiotic treatment for plague for pregnant women

Pregnant Women

Antibiotic Dose Route of Notes

administration

Gentamicin IM or IV

SAME AS ADULT SEE NOTES ABOVE

Doxycycline DOSE IV

Ciprofloxacin IV

● Non-pharmacologic
Since bubonic is from an arthropod, the source of such arthropod must be
lessen by cleaning the nesting places of rodents. Personal protective
measures such as wearing protective clothing and using insect repellent
to prevent arthropod bites.
c. Prevention:
If a person is living in an area where there’s been a case of the plague:
● Fill holes and gaps in your home to stop mice and rats from getting in
● Clean up the yard. Get rid of piles of leaves, woods, and rocks where animals
might make their homes.
● Use bug repellent to prevent flea bites when in outdoors
● Wear gloves if there is a need to touch wild animals either alive or dead
● Use flea control sprays or other treatments for pets
● Do not let outdoor pets like cats or dogs sleep in your bed.