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Plague
Background .
• The first pandemic was believed to have started
in Africa and killed 100 million people over a
span of 60 years. plague killed approximately
one fourth of Europe's population.
• The pandemic that began in China in the 1860s
spread to Hong Kong in the 1890s and was
subsequently spread by rats transported on
ships to Africa, Asia, California, and port cities of
South America.
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Background
• In the early twentieth century, plague
epidemics accounted for about 10 million
deaths in India.
• Plague is worldwide in distribution, with
most of the human cases reported from
developing countries.
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Epidemiology
• A vector is an organism that does not cause
disease itself but that transmits infection by
conveying pathogens from one host to another,[1]
serving as a route of transmission.
• Natural reservoir, refers to the long-term host of
the pathogen of an infectious disease. It is often the
case that hosts do not get the disease carried by
the pathogen or it is carried as a subclinical
infection and so asymptomatic and non-lethal.
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Causative organism.
Yersinia pestis :
• Non motile, non–spore-forming,
pleomorphic, gram-negative
cocco-bacillus.
• The bacteria elaborate a
lipopolysaccharide endotoxin,
coagulase, and a fibrinolysin,
which are the principal factors in
the pathogenesis of this disease.
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Yersinia pestis :
Yesinia is named in
honor of Alexander
Yersin, who
successfully isolated
the bacteria in 1894
during the pandemic
that began in China in
the 1860s.
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Reservoirs :
• urban rats :
• are the most important
reservoirs for the
plague bacillus,
• but field mice, cats,
camels, chipmunks,
prairie dogs, rabbits,
and squirrels can be
important animal
reservoirs as well.
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vector for transmission .
Xenopsylla cheopis.
• It is the rat flea, which
is he most important
vector for transmission
of plague .
• Ticks and human lice
have been identified
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Pathophysiology
• When a rat flea ingests a
blood meal from an animal
infected with Y pestis, the
coagulase of the bacteria
causes the blood to clot. The
bacilli multiply in the blood clot,
• the flea inoculates thousands
of these bacilli into a host's
skin during subsequent blood
meals.
• The bacilli migrate to the
regional lymph nodes, are
phagocytosed by the
polymorphonuclear cells and
mononuclear phagocytes, and
multiply intracellularly.
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Pathophysiology
Involved lymph nodes show dense •
concentrations of plague bacilli,
destruction of the normal architecture, and •
medullary necrosis. With subsequent lysis of
the phagocytes,
bacteremia can occur and may lead to •
invasion of distant organs in the absence of
specific therapy.
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Clinical
•
•
•
•
•
History :
Travel to endemic areas.
history of a flea bite,
close contact with a potential host,
exposure to dead rodents or rabbits
should heighten consideration of a plague
diagnosis.
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History :Bubonic plague
• Patients most commonly present with this form of
plague.
• The incubation period varies but usually lasts 2-6
days.
• Patients have a sudden onset of high fever, chills,
and headache.
• Patients also experience body aches, extreme
exhaustion, weakness, abdominal pain, and/or
diarrhea.
• Painful, swollen lymph glands (buboes) arise,
usually in the groin, axilla, or neck.
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History. Meningeal plague
• Fever, headache, and nuchal rigidity
• Buboes are common with meningeal
plague.
• Axillary buboes are associated with
an increased incidence of the
meningeal form.
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History. Pharyngeal plague
• Pharyngeal plague results from
ingestion of the plague bacilli.
• Patients experience sore throat,
fever, and painful cervical lymph
nodes.
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History. Pneumonic plague
• Pneumonic plague is highly
contagious and transmitted by
aerosol droplets.
• Patients have an abrupt onset of
fever and chills, accompanied by
cough, chest pain, dyspnea, purulent
sputum, or hemoptysis.
• Buboes may or may not appear in
pneumonic plague.
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History. Septicemic plague
• Septicemic plague is observed in elderly patients
and causes a rapid onset of symptoms.
• Patients experience nausea, vomiting, abdominal
pain, and diarrhea. (Diarrhea may be the
predominant symptom.)
• Patients exhibit a toxic appearance and soon
become moribund.
• Buboes are not observed with septicemic plague.
• This form of plague is associated with a high
mortality rate.
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Physical :Bubonic plague
• Vesicles may be observed at
the site of the infected flea
bite.
• With advanced
disease pustules, carbuncles,
or papules may be observed
in areas of the skin drained by
the involved lymph nodes.
• A generalized papular rash
of the hands and feet may
be observed.
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Physical :Bubonic plague
• Buboes are unilateral, oval,
extremely tender lymph
nodes and can vary from 210 cm in size. Femoral
lymph nodes are most
commonly involved.
• Hepatomegaly and
splenomegaly often
occur, causing
tenderness.
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Physical
• Pharyngeal plague :
• causes pharyngeal erythema and painful
and tender anterior cervical nodes.
• Pneumonic plague :
• causes fever, lymphadenopathy,
productive sputum, or hemoptysis.
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Physical
• Septicemic plague
• toxic appearance tachycardia,
tachypnea, and hypotension.
Hypothermia is common.
• Generalized purpura may be
observed and can progress to
necrosis and gangrene of the
distal extremities.
• No evidence of lymphadenitis
or bubo formation is apparent.
Patients may die from a high
level of bacteremia.
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Septicemic plague
•necrosis
and
gangrene of
the distal
extremities.
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Risk factors
•
•
•
•
•
•
•
•
Flea bite.
Contact with a patient or a potential host.
Contact with sick animals or rodents.
Residing in endemic areas of plague (eg,
southwestern United States).
Presence of a food source for rodents in the
immediate vicinity of the home.
Camping, hiking, hunting, or fishing.
Occupational exposure (eg, researchers,
veterinarians)
Direct handling or inhalation of
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contaminated tissues
or
tissue
fluids.
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Differential Diagnoses
• Acute Renal Failure
Pharyngitis, Bacterial
Anthrax
Pneumonia, Bacterial
Brucellosis
Catscratch Disease
Rocky Mountain Spotted
Fever
Cellulitis
Sepsis, Bacterial
Chancroid
Septic Shock
Dengue Fever
• Syphilis
Disseminated Intravascular
Coagulation
Lymphogranuloma
Venereum (LGV)
•
Tularemia
Lymphoma, B-Cell
Typhus
Malaria
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Laboratory Studies
• Leucocytosis with a predominance of neutrophils is
observed, Leukemoid reactions may be observed,
more commonly in children.
• Peripheral blood smear shows toxic granulations and
Dohle bodies.
• Thrombocytopenia is common, and levels of fibrin
degradation products may be elevated.
• Serum transaminase and bilirubin levels may be
elevated.
• Proteinuria may be present, and renal function test
findings may be abnormal.
• Hypoglycemia may be observed.
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Laboratory Studies
• Blood culture results are often positive for Y
pestis in patients with bubonic plague and
septicemic plague. Y pestis may be observed on a
peripheral blood smear.
• Lymph node aspirates often demonstrate Y
pestis. In patients with pharyngeal plague, Y
pestis is cultured from throat swabs.
• Cerebrospinal fluid (CSF) analysis in meningeal
plague may show pleocytosis with a predominance
of polymorphonuclear leukocytes. Gram stain of
CSF may show plague bacilli. Limulus test of CSF
demonstrates the presence of endotoxin.
• Gram stain of sputum often reveals Y pestis.
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Imaging Studies
• On chest x-ray films, patchy
infiltrates, consolidation, or a
persistent cavity is observed in
patients with pneumonic plague.
• ECG reveals sinus tachycardia
and ST-T changes.
• Obtain a CT scan of the head in
a patient with altered mental
status.
• Nuclear imaging may help in
localizing areas of lymphadenitis
and meningeal inflammation.
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Other Tests
• Direct immunofluorescence testing
of fluid or cultures may aid in rapid
diagnosis.
• A passive hemagglutination test
(performed on serum from a patient
in acute or convalescent stages) with
a 4-fold or greater increase in titer
suggests plague infection.
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Procedures
• Aspiration of lymph node (bubo)
– Inject 1 mL of sterile saline into the bubo with a 20-gauge
needle; after withdrawing several times, aspirate the
fluid. Gram stain of the aspirate reveals gram-negative
coccobacilli and polymorphonuclear leucocytes.
– Wayson stain of the aspirate shows plague bacilli as
light-blue bacilli with dark-blue polar bodies.
– Examination of the aspirate of the fluid from the inguinal
lymph nodes shows a characteristic bipolar appearance
that resembles a closed safety pin.
• Lumbar puncture for CSF analysis
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Treatment
• Medical Care :
• Precautions.
– Place all patients thought to have plague and signs of
pneumonia in strict respiratory isolation for 48-72
hours after starting antibiotic therapy.
– Report patients thought to have plague to the local
health department and to the World Health
Organization.
– Alert laboratory personnel to the possibility of the
diagnosis of plague. All fluid specimens must be
handled with gloves and mask to prevent
aerosolization of the infected fluids.
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Treatment
• Medical Care :
• Supportive therapy
– Hemodynamic monitoring and
ventilatory support are performed as
appropriate.
– Intravenous fluids, epinephrine, and
dopamine are necessary for correction
of dehydration and hypotension.
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Treatment.
• Surgical Care
• Enlarging or fluctuant buboes require
incision and drainage.
• Consultations
• Infectious disease specialists
• Pulmonary and critical care specialists
• General surgeons
• Neurologists
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Medication :
• Streptomycin sulfate :
• is the preferred drug of choice to treat
plague.
• Dosing:
• 30 mg/kg/day (up to a total of 2 g/day) in
divided doses given IM, for a full course
of 10 days of therapy or until 3 days
after the temperature has returned to
normal .
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Medication :
• Doxycycline:
• Inhibits protein synthesis and thus
bacterial growth by binding to 30S and
possibly 50S ribosomal subunits of
susceptible bacteria.
• Dosing
• Adult
100 mg PO/IV q12h
• Pediatric
• <8 years: Not recommended
>8 years: 2-5 mg/kg/d PO/IV qd or divided
bid; not to exceed 200 mg/d
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Medication :
• Chloramphenicol :
• Binds to 50S bacterial ribosomal subunits
and inhibits bacterial growth by inhibiting
protein synthesis. Effective against gramnegative and gram-positive bacteria.
• Dosing
• Adult
• 500 mg PO/IV q6h
• Pediatric
• 50-75 mg/kg/d PO/IV divided q6h
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Medication :
• Aminoglycoside antibiotic recommended
when less potentially hazardous therapeutic
agents are ineffective or contraindicated.
• Gentamicin:
• Dosing
• Adult
• 2 mg/kg IV loading dose with normal renal
function; then, 1.7 mg/kg IV q8h for 10 d.
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Medication :
Fluoroquinolones :
such as ciprofloxacin, have been
shown to have good effect against Y.
pestis in both in vitro and animal
studies. Ciprofloxacin is bacteriocidal
and has broad spectrum activity
against most Gram-negative aerobic
bacteria,
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Medication :
• Sulfonamides :
• The combination drug trimethoprimsulfamethoxazole has been used
both in treatment and prevention of
plague.
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Prevention .
• Prophylactic antibiotic therapy.
• The CDC recommends administering
prophylactic antibiotics for a short time to :
• people who have been exposed to the bites
of potentially infected rodent fleas during a
plague outbreak.
• persons who have handled an animal
known to be infected with the plague
bacterium.
• persons who have had close exposure to a
person or an animal thought to have
pneumonic plague.
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Prevention .
• Preferred antibiotics for prophylaxis
against plague are :
• Doxycycline 100 mg PO q12h for 1421 days (for patients > 8 y) and
trimethoprim 160 mg/
sulfamethoxazole 800 mg PO q12h
for 14-21 days.
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Prevention .
• Plague vaccine
• Vaccination is of limited use and is not
mandatory for entry into any country.
• The vaccine is not effective against the
pneumonic form of plague.
• Plague vaccine is recommended for field
workers in areas endemic for plague and for
scientists and laboratory personnel who
routinely work with the plague bacterium.
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Prevention .
• Environmental sanitation
• Remove food sources used by rodents.
• Make homes, buildings, or warehouses
"rodent-proof."
• Trained professionals should apply
chemicals to kill fleas and rodents.
• Trained professionals should fumigate
cargo areas of ships and docks.
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Complications.
• Acute respiratory distress syndrome.
• Chronic lymphedema from lymphatic
scarring.
• Disseminated intravascular coagulation
• Septic shock.
• Super infections of the buboes
by Staphylococcus and Pseudomonas
species
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Prognosis
• Untreated patients with plague
have a mortality rate of
approximately 50%; however, with
appropriate therapy, the mortality
rate drops to approximately 5%.
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• Wayson stain showing
the characteristic
"safety pin"
appearance
of Yersinia pestis, the
plague bacillus
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• Fluorescence
antibody positivity is
observed as bright,
intense green
staining around the
cell wall of Yersinia
pestis, the plague
bacillus.
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• Histopathology
of lung in fatal
human plague–
fibrinopurulent
pneumonia.
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• Histopathology of
lung showing
pneumonia with
many Yersinia
pestis organisms (the
plague bacillus) on a
Giemsa stain.
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• Histopathology
of spleen in fatal
human plague
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• Histopathology
of lymph node
showing
medullary
necrosis
and Yersinia
pestis, the plague
bacillus
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• Histopathology
of liver in fatal
human plague .
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• Focal
hemorrhages in
islet of
Langerhans in
fatal human
plague.
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