Plague
is a disease that affects humans and other mammals. It is caused by the
bacterium, Yersinia pestis. Humans
usually get plague after being bitten by a rodent flea that is carrying the
plague bacterium or by handling an animal infected with plague. Plague is
infamous for killing millions of people in Europe during the Middle Ages.
The
epidemiological use of the term "plague" is currently applied to
bacterial infections that cause buboes, although historically the medical use
of the term plague has been applied to pandemic infections generally. A bubo is
a swelling of the lymph nodes. A pandemic is an epidemic (an outbreak of an
infectious disease) that spreads across a large region, such as a continent, or
even worldwide). The plague is one of the most feared of all diseases. It is
easily transmittable and has a high mortality.
HISTORY
Plague
has a remarkable place in history and has had enormous effects on the
development of modern civilization. Some scholars have even suggested that the
collapse of the Roman Empire may be linked to the spread of plague by Roman
soldiers returning home from battle in the Persian Gulf in 165 AD. For
centuries, plague represented disaster for people living in Asia, Africa and
Europe and because the cause of plague was unknown, plague outbreaks
contributed to massive panic in cities and countries where it appeared.
Numerous
references in art, literature and monuments attest to the horrors and
devastation of past plague epidemics. We now know that plague is caused by a
bacterium called Yersinia pestis that often infects small rodents (like rats,
mice, and squirrels) and is usually transmitted to humans through the bite of
an infected flea. In the past, black
rats were the most commonly infected animals and hungry rat fleas would jump
from their recently-dead rat hosts to humans, looking for a blood meal.
Pneumonic plague, a particular form of plague infection, is instead transmitted
through infected droplets in a sick person's cough.
Three Major Plague Pandemics
The Justinian Plague
The
first recorded pandemic, the Justinian Plague, was named after the 6th century
Byzantine emperor Justinian I. The Justinian Plague began in 541 AD and was
followed by frequent outbreaks over the next two hundred years that eventually
killed over 100 million people (Khan, 2004) and affected much of the
Mediterranean basin--virtually all of the known world at that time.
"Black Death" or the Great Plague
The second pandemic, widely known as the "Black Death" or the Great Plague, originated in China in 1334 and spread along the great trade routes to Constantinople and then to Europe, where it claimed an estimated 60% of the European population (Benedictow, 2008). Entire towns were wiped out. Some contemporary historians report that on occasion,there were not enough surviviors remaining to bury the dead (Gross, 1995). Despite the vast devastation caused by this pandemic, however, massive labor shortages due to high mortality rates sped up the development of many economic, social, and technical modernizations (Benedictow, 2008). It has even been considered a factor in the emergence of the Renaissance in the late14th century.Modern Plague
The
third pandemic, the Modern Plague, began in China in the 1860s and appeared in
Hong Kong by 1894. Over the next 20 years, it spread to port cities around the
world by rats on steamships. The pandemic caused approximately 10 million
deaths (Khan, 2004). During this last pandemic, scientists identified the
causative agent as a bacterium and determined that plague is spread by
infectious flea bites. Rat-associated plague was soon brought under control in
most urban areas, but the infection easily spread to local populations of ground
squirrels and other small mammals in the Americas, Africa, and Asia. These new
species of carriers have allowed plague to become endemic in many rural areas,
including the western U.S.
However,
as a bacterial disease, plague can be treated with antibiotics, and can be
prevented from spreading by prompt identification, treatment and management of
human cases. Applications of effective insecticides to control the flea vectors
also provide assistance in controlling plague.
Recent Outbreaks
The
most recent plague epidemics have been reported in India during the first half
of the 20th century, and in Vietnam during wartime in the 1960s and 1970s.
Plague is now commonly found in sub-Saharan Africa and Madagascar, areas which
now account for over 95% of reported cases (Stenseth, 2008).
Plague as a Weapon of War
As a
highly contagious disease with an extremely high mortality rate if left
untreated, Yersinia pestis has been used as a weapon of biological warfare for
centuries. Some warfare strategies have included catapulting corpses over city
walls, dropping infected fleas from airplanes, and aerosolizing the bacteria
during the Cold War (Stenseth, 2008). More recently, plague raised concern as an
important national security threat because of its potential for use by
terrorists.
Signs and Symptoms
Bubonic
plague symptoms appear suddenly, usually after 2 - 5 days of exposure to the
bacteria. Symptoms include:
·
Chills
·
Fever
·
General
ill feeling (malaise)
·
Headache
·
Muscle
pain
·
Seizures
·
Smooth,
painful lymph gland swelling called a bubo commonly found in the groin, but may
occur in the armpits or neck, most often at the site of the infection (bite or
scratch) Pain may occur in the area before the swelling appears
Pneumonic
plague symptoms appear suddenly, typically 2 - 3 days after exposure. They
include:
·
Cough
·
Difficulty
breathing
·
Fever
·
Frothy,
bloody sputum
·
Pain
in the chest when you breathe deeply
·
Severe
cough
Septicemic
plague may cause death even before its symptoms occur. Symptoms can include:
·
Abdominal
pain
·
Bleeding
due to blood clotting problems
·
Diarrhea
·
Fever
·
Nausea
·
Vomiting
·
Skin
and other tissues may turn black and die, especially on fingers, toes, and the
nose.
Septicemic
plague can occur as the first symptom of plague, or may develop from untreated
bubonic plague. This form results from bites of infected fleas or from handling
an infected animal.
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Etiology
THE
CAUSE OF ALL: Yersinia Pestis
Yersinia
pestis (yer-sin'e¯-a˘ pes'tis), is a gram negative, rod-shaped, facultative anaerobic
bacterium, known for causing the plague. The plague bacillus, is normally a
pathogen of animals. This bacterium carries virulence plasmids that code for
adhesins, type III secretion systems, capsules, and antiphagocytic proteins.
Adhesins are molecules that attach pathogens to their target cells, while type
III secretion systems inject harmful proteins into the targets. Yersinia
preferentially injects antiphagocytic proteins into dendritic cells,
neutrophils, or macrophages, neutralizing their ability to mount an adaptive
immune response or to eliminate the bacterium and thus allowing bacteremia.
Y.
pestis was first discovered by a French-born Swiss bacteriologist named
Alexander Yersin in 1894. Yersin
stumbled upon this bacterium while in China studying a plague epidemic
there. However, before then, Y. pestis
has been wreaking havoc throughout human history.
The
bacteria can be transmitted from a host to a human via the bite of a vector
(usually a flea), via close contact with infected tissue or body fluids, and
via direct inhalation of aerosolized bacteria. Currently, the most common form
of transmission involves the bite of an infected flea. More than 200 different
rodents and species can serve as hosts.
The Main Vector: Xenopsylla cheopis
The
vector is usually the rat flea, Xenopsylla cheopis. Thirty different flea species
have been identified as able to carry the plague bacillus. Here a
flea is shown with a blocked proventriculus, equivalent to the gastroesophageal
region in man. In nature, this flea would develop a ravenous hunger because of
its inability to digest the fibrinoid mass of blood and bacteria. Ensuing a
biting of the nearest mammal results in clearing of the proventriculus through
regurgitation of thousands of bacteria into the bite wound.
Rodents
resistant to the infection, such as wood rats, kangaroo roots, deer mice,
grasshopper mice, and voles, form an enzootic stage that ensures the long-term
survival of the bacillus. Occasionally, fleas transfer the bacteria to animals
that are susceptible to plague such as ground squirrels (an infected squirrel
is shown in the image below), prairie dogs, and chipmunks. In the event of
large numbers of host animals dying off, hungry fleas search out new food
sources. This is known as an epizootic stage and ensures the spread of the
organism to new territory. A sylvatic stage occurs when humans are infected
from wild animals. Carnivores with the exception of cats and black-footed
ferrets have a fairly strong resistance profile, but they can be transfer
vectors. Birds and hoofed animals are seldom infected, and reptiles and fish
are resistant to plague. Virulent plague bacteria can survive dormant in soil,
animal carcasses, grains, flea feces, buried bodies, and dried sputum.
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PATHOGENESIS
Three
forms of the plague exist: bubonic plague, pneumonic plague, and septicemic
plague. The bubonic form makes up approximately 80-95% of cases worldwide and
is caused by deposition of the bacillus in the skin by the bite of an infected
vector. If the vector is a flea, bacillus proliferates in the flea's esophagus,
preventing food entry into the stomach. To overcome starvation, the flea begins
a blood-sucking rampage. Between its attempts to swallow, the distended
bacillus-packed esophagus recoils, depositing the bacillus into the victim's
skin.
The
bacillus invades nearby lymphoid tissue, producing the famous bubo, an
inflamed, necrotic, and hemorrhagic lymph node. Spread occurs along the
lymphatic channels toward the thoracic duct, with eventual seeding of the
vasculature. Bacteremia and septicemia ensue. The bacillus potentially seeds
every organ, including the lungs, liver, spleen, kidneys, and rarely even the
meninges.
The most
virulent form, pneumonic plague, results from direct inhalation of the
bacillus, which occurs from close contact of infected hosts or from aerosolized
bacteria such as may occur if used as a biological weapon. A severe and rapidly
progressive multilobar bronchopneumonia ensues with subsequent bacteremia and
septicemia. Secondary pneumonic plague is caused when an infected patient seeds
his or her lungs and airways.
The
third type of plague is a primary septicemic plague. This is hypothesized to
occur when the bacillus is deposited in the vasculature, bypassing the
lymphatics. Early dissemination with sepsis occurs but without the formation of
a bubo. This usually is observed in bites to the oral, tonsillar, and
pharyngeal area and is believed to occur because of the vascularity of the
tissue and short lymphatic distance to the thoracic duct.
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PATHOPHYSIOLOGY
In general, after an incubation period of 1-6 days, the plague presents with the physical findings of severe and rapidly progressive sepsis with or without features of pneumonia. Multiple organ involvement occurs. Pneumonic plague may present only as a severe pneumonia.
- Temperature of 37-40.9°C, tachycardia, tachypnea, and hypotension, if in late septic shock
- Inguinal bubo (60%), axillary (30%), cervical (10%), or epitrochlear (10%) (Bubo is usually no greater than 5 cm, extremely tender, erythematous, and surrounded by a boggy hemorrhagic area; patient often flexes, abducts, and externally rotates the hip near an involved inguinal node to reduce pain at the site.) Children are more likely to have a cervical or submandibular bubo. Images below show a bubo and a necrotic ulcer.
A
suppurative, bubo of the femoral lymph node, shown in the image above, is the
most common site of the erythematous, tender, swollen, nodes in a plague
victim. The next most common lymph node regions involved are the inguinal,
axillary (shown here), and cervical areas. The child in this photo has an
erythematous, eroded, crusting, necrotic ulcer at the presumed primary
inoculation site on the left upper quadrant. This type of lesion is uncommonly
found in patients with plague. Bubo location is primarily a function of the
region of the body in which an infected flea inoculates plague bacilli.
Dermatologic findings
A maculopapular lesion may be found at the site of the fleabite; however, such lesions commonly are found at autopsy implying that, in the United Stated, the diagnosis often is not determined until it is too late.
Acral cyanosis, ecchymosis (shown in the image belos), petechiae, and digital gangrene are seen with Y.pestis septicimia (from disseminated intravascular coagultion [DIC]).
Ecchymoses
at the neck base of a girl with plague. Bandage is over the site of a prior
bubo aspirate. These lesions probably gave rise to the title line of the
children's nursery rhyme "Ring around the rosy."
The
medieval epithet "Black Death" is thought to have originated from the
deeply cyanotic skin, ecchymoses, and/or acral necrosis associated with
terminal septicemic and pneumonic plague.
The
initially rose-colored purpuric lesions most likely gave rise to the child's
nursery rhyme "Ring Around the Rosy."
- "Ring
around the rosy" - Rose-colored purpuric macules (may be caused by the Y
pestis enzyme that acts alternately as a plasminogen activator or coagulase at
various temperatures or may be due to DIC)
- "Pocket
full of posies" - Sweet-smelling flowers that those tending the sick would
carry to ward off the stench of disease
- "Ashes,
ashes" - Impending mortality or "A-choo, a-choo" - The sneezing
and coughing of pneumonic plague
- "All
fall down" - Death
Rare
cases of ecthyma gangrenosum–like lesions and carbuncles due to blood-borne Y
pestis have been described.
Other
findings
- Diffuse
crackles, diffuse areas of dullness to percussion (secondary to patchy
consolidation of pneumonic plague), and hemoptysis
- Diffuse
abdominal tenderness, with or without guarding, splenomegaly, hematochezia, or
heme-positive stools
- Nuchal
rigidity and diffuse muscle and joint tenderness
- Various
degrees of mental status changes, ranging from mild confusion or agitation to
delirium and coma
- Seizures
- Bleeding
from any body site or cavity (eg, hematemesis, hematochezia, hemoptysis)
- Gangrene
and necrosis (shown in the images below) of areas such as the digits, penis,
and nares (ascribed to peripheral thrombosis secondary to DIC)
Acral necrosis of nose, lips, fingers (shown
here) and toes (image below) and residual ecchymoses over both forearms in a
patient recovering from bubonic plague that disseminated to blood and lungs. At
one time, the patient's entire body was ecchymotic.
Ecchymoses
at the neck base of a girl with plague. Bandage is over the site of a prior
bubo aspirate. These lesions probably gave rise to the title line of the
children's nursery rhyme "Ring around the rosy."
The medieval epithet "Black Death" is thought to have originated from the deeply cyanotic skin, ecchymoses, and/or acral necrosis associated with terminal septicemic and pneumonic plague.
The
initially rose-colored purpuric lesions most likely gave rise to the child's
nursery rhyme "Ring Around the Rosy."
- "Ring around the rosy" - Rose-colored purpuric macules (may be caused by the Y pestis enzyme that acts alternately as a plasminogen activator or coagulase at various temperatures or may be due to DIC)
- "Pocket full of posies" - Sweet-smelling flowers that those tending the sick would carry to ward off the stench of disease
- "Ashes, ashes" - Impending mortality or "A-choo, a-choo" - The sneezing and coughing of pneumonic plague
- "All fall down" - Death
Rare
cases of ecthyma gangrenosum–like lesions and carbuncles due to blood-borne Y
pestis have been described.
Other findings
- Diffuse crackles, diffuse areas of dullness to percussion (secondary to patchy consolidation of pneumonic plague), and hemoptysis
- Diffuse abdominal tenderness, with or without guarding, splenomegaly, hematochezia, or heme-positive stools
- Nuchal rigidity and diffuse muscle and joint tenderness
- Various degrees of mental status changes, ranging from mild confusion or agitation to delirium and coma
- Seizures
- Bleeding from any body site or cavity (eg, hematemesis, hematochezia, hemoptysis)
- Gangrene and necrosis (shown in the images below) of areas such as the digits, penis, and nares (ascribed to peripheral thrombosis secondary to DIC)
____________________________________
TRANSMISSION
The
plague bacteria can be transmitted to humans in the following ways:
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
or septicemic plague.
Infectious droplets. When a person has plague
pneumonia, they may cough droplets containing the plague bacteria into air. If
these bacteria-containing droplets are breathed in by another person they can
cause pneumonic plague. Typically this requires direct and close contact with
the person with pneumonic plague. Transmission of these droplets is the only
way that plague can spread between people. This type of spread has not been
documented in the United States since 1924, but still occurs with some
frequency in developing countries. Cats are particularly susceptible to plague,
and can be infected by eating infected rodents. Sick cats pose a risk of
transmitting infectious plague droplets to their owners or to veterinarians. Several
cases of human plague have occurred in the United States in recent decades as a
result of contact with infected cats.
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DIAGNOSIS
In order to make a plague diagnosis, the doctor will ask a number of questions about a person's medical history, including questions about:
· Medical conditions
· Medications
· History of possible exposure to infected rodents, rabbits, or fleas
· Recent travel history.
The doctor will also perform a physical exam. During the exam, the doctor will look at the skin and listen to the lungs for signs of plague. If the doctor has a high suspicion that a person has plague, he or she will recommend doing laboratory tests. If plague is suspected, pre-treatment specimens should be taken if possible, but treatment should not be delayed. Specimens should be obtained from appropriate sites for isolating the bacteria, and depend on the clinical presentation:
- · Lymph node aspirate: An affected bubo should contain numerous organisms that can be evaluated microscopically and by culture.
- · Blood cultures: Organisms may be seen in blood smears if the patient is septicemic. Blood smears taken from suspected bubonic plague patients early in the course of illness are usually negative for bacteria by microscopic examination but may be positive by culture.
- · Sputum: Culture is possible from sputum of very ill pneumonic patients; however, blood is usually culture-positive at this time as well.
- · Bronchial/tracheal washing may be taken from suspected pneumonic plague patients; throat specimens are not ideal for isolation of plague since they often contain many other bacteria that can mask the presence of plague.
- · In cases where live organisms are unculturable (such as postmortem), lymphoid, spleen, lung, and liver tissue or bone marrow samples may yield evidence of plague infection by direct detection methods such as direct fluorescent antibody (DFA) or PCR.
Y. pestis may be identified microscopically by examination of Gram, Wright, Giemsa, or Wayson's stained smears of peripheral blood, sputum, or lymph node specimen. Visualization of bipolar-staining, ovoid, Gram-negative organisms with a "safety pin" appearance permits a rapid presumptive diagnosis of plague.
If cultures yield negative results, and plague is still suspected, serologic testing is possible to confirm the diagnosis. One serum specimen should be taken as early in the illness as possible, followed by a convalescent sample 4-6 weeks or more after disease onset.
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Treatment
An Indian doctor, Vladimir Havkin, was the first to invent and test a plague antibiotic.
The traditional treatments are:
· Streptomycin 30 mg/kg intramuscular twice daily for 7 days
· Chloramphenicol 25–30 mg/kg single dose, followed by 12.5–15 mg/kg four times daily
· Tetracycline 2 g single dose, followed by 500 mg four times daily for 7–10 days (not suitable for children)
More recently,
· Gentamicin 2.5 mg/kg intravenous or intramuscular twice daily for 7 days
· Doxycycline 100 mg (adults) or 2.2 mg/kg (children) orally twice daily have also been shown to be effective.
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EPIDEMIOLOGY
Frequency
United States
An average of 10-15 cases per year have been reported during the last few decades. One of the largest animal foci of the plague worldwide is found west of the 100th parallel, in states such as New Mexico, Arizona, Colorado, Utah, and California. Only one case of imported plague has been reported since 1926. Most cases occur during the wet, warmer months of the year. In 2006, 13 human plague cases were reported in the United States, the most since 1994.
Plague cases in the United States, 1900–2010. In 1907, an outbreak of plague followed in the aftermath of the San Francisco earthquake. Since the mid–20th century, plague in the United States has typically occurred in the rural West.
This bar graph shows the number of plague cases by year, but can be interpreted in two separate time frames. From 1900 to 1942, plague occurred in mostly urban areas, particularly in port cities. The disease was sporadic in nature--characterized by epidemics, followed by years without cases. Since 1942, the number of plague cases has become more uniform in nature, with cases occurring nearly every year and with fewer large outbreaks. Since 1942, plague has primarily occurred in rural and suburban areas, and over time, has begun to resemble that of a low level endemic disease.
International
From 1987-2001, the World Health Organization has reported an annual average of 38,876 cases of the plague with 2847 deaths worldwide. The number of actual cases is probably much higher, given the failure of many countries to diagnose and report the plague. Most cases occur in the developing countries of Africa and Asia. Recent outbreaks of the plague have occurred in Vietnam, India, Algeria, Madagascar, and the northeastern part of the Democratic Republic of the Congo. During 2000-2001, 95% of the world's cases occurred in Africa.
Mortality/Morbidity
Bubonic plague has a 1-15% mortality rate in treated cases and a 40-60% mortality rate in untreated cases.
Septicemic plague (primary or secondary) has a 40% mortality rate in treated cases and 100% mortality rate in untreated cases.
Pneumonic plague (primary or secondary) has 100% mortality rate if not treated within the first 24 hours of infection.
Sex
More than 50% of cases of plague occur in males.
Age
Approximately 50% of cases occur in persons younger than 20 years.
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PREVENTION
- Reduce rodent habitat around your home, work place, and recreational areas. Remove brush, rock piles, junk, cluttered firewood, and possible rodent food supplies, such as pet and wild animal food. Make your home and outbuildings rodent-proof.
- Wear gloves if you are handling or skinning potentially infected animals to prevent contact between your skin and the plague bacteria. Contact your local heath department if you have questions about disposal of dead animals.
- Use repellent if you think you could be exposed to rodent fleas during activities such as camping, hiking, or working outdoors. Products containing DEET can be applied to the skin as well as clothing and products containing permethrin can be applied to clothing (always follow instructions on the label).
- Keep fleas off of your pets by applying flea control products. Animals that roam freely are more likely to come in contact with plague infected animals or fleas and could bring them into homes. If your pet becomes sick, seek care from a veterinarian as soon as possible.
- Do not allow dogs or cats that roam free in endemic areas to sleep on your bed.
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NURSING INTERVENTIONS
Pre-hospital Care
Provide
supportive care. Crystalloid infusion to maintain normal vital signs and
clinical hydration state may be necessary. Administer oxygen via nasal cannula,
nonrebreather mask, or intubation as determined by the respiratory distress of
the patient. Use pulse oximetry to monitor the degree of respiratory
compromise.
Assume
universal precautions, including goggles, gloves, and gown, when dealing with
any patient with an infectious disease presentation. Masks should be worn if
respiratory involvement is possible.
Emergency Department Care
Depending
on the stage of presentation, supportive care varies. Early presentation may
require only crystalloid administration with monitoring of vital signs, clinical
state, and urine output.
Septic
shock requires invasive hemodynamic monitoring with crystalloid and vasopressor
agents. Airway management may require intubation and mechanical ventilation
with positive end-expiratory pressure (PEEP).
Empiric
antibiotic coverage is discussed in Medication.
Use strict isolation
precautions. If respiratory symptoms are present, institute universal
precautions with strict respiratory isolation for the first 96 hours of
therapy.If no respiratory symptoms are present, only 48 hours of isolation or
isolation until purulent drainage from the bubo ceases is required. Incinerate
or autoclave all contaminated material. Inform the laboratory of the
possibility of handling plague infected material. Cases of laboratory-acquired
plague have occurredPerson wearing a hat, a mask suggestive of a bird beak, goggles or glasses, and a long gown. The clothing identifies the person as a "plague doctor" and is intended as protection. Descriptions indicate that the gown was made from heavy fabric or leather and was usually waxed. The beak contained pungent substances like herbs or perfumes, thought at the time to purify the air and helpful in relieving the stench. The person also carries a pointer or rod to keep patients at a distance.