Sunday, February 24, 2013


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.

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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 here), 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, and cervical areas. The child in the image below 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.







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.






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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 or septicemic 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 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


  1.       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.
  2.       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.
  3.       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).
  4.       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.
  5.       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 occurred




Person 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.