Yersinia Pestis Infection

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Plague is an infectious disease of animals and humans caused by a bacterium named Yersinia pestis.

Also known as: Plague, Black Death

References

http://www.cdc.gov/ncidod/dvbid/plague/index.htm

Epidemiology and Demographics

People usually get plague from being bitten by a rodent flea that is carrying the plague bacterium or by handling an infected animal.

Wild rodents in certain areas around the world are infected with plague. Outbreaks in people still occur in rural communities or in cities. They are usually associated with infected rats and rat fleas that live in the home. In the United States, the last urban plague epidemic occurred in Los Angeles in 1924-25. Since then, human plague in the United States has occurred as mostly scattered cases in rural areas (an average of 10 to 15 persons each year). Globally, the World Health Organization reports 1,000 to 3,000 cases of plague every year. In North America, plague is found in certain animals and their fleas from the Pacific Coast to the Great Plains, and from southwestern Canada to Mexico. Most human cases in the United States occur in two regions: 1) northern New Mexico, northern Arizona, and southern Colorado; and 2) California, southern Oregon, and far western Nevada. Plague also exists in Africa, Asia, and South America (see map).

Can animals transmit plague to people?

Yes, people can get plague from an infected animal, but this is very rare. Rodents (for example, mice, rats, and squirrels) and cats are animals that can carry plague. This disease most often occurs in the southwestern part of the United States. Usually, people get plague from the bite of an infected flea. Since fleas bite both people and animals, especially cats and rodents, an infected flea can pass plague to animals or people. Sometimes, people get plague from working with an animal that is infected. People also can get infected by breathing in tiny droplets of water contaminated with Y. pestis.

References

http://www.cdc.gov/ncidod/dvbid/plague/index.htm http://www.cdc.gov/healthypets/diseases/plague.htm

Risk Factors

Outbreaks in people occur in areas where housing and sanitation conditions are poor. These outbreaks can occur in rural communities or in cities. They are usually associated with infected rats and rat fleas that live in the home.

References

http://www.cdc.gov/ncidod/dvbid/plague/qa.htm

Pathophysiology & Etiology

Fleas become infected by feeding on rodents, such as the chipmunks, prairie dogs, ground squirrels, mice, and other mammals that are infected with the bacteria Yersinia pestis. Fleas transmit the plague bacteria to humans and other mammals during the feeding process. The plague bacteria are maintained in the blood systems of rodents.

A person can get plague from another individual when the other person has plague pneumonia and coughs droplets containing the plague bacteria into air that is breathed by a non-infected person.

A person usually becomes ill with bubonic plague 2 to 6 days after being infected. When bubonic plague is left untreated, plague bacteria invade the bloodstream. When plague bacteria multiply in the bloodstream, they spread rapidly throughout the body and cause a severe and often fatal condition. Infection of the lungs with the plague bacterium causes the pneumonic form of plague, a severe respiratory illness. The infected person may experience high fever, chills, cough, and breathing difficulty, and expel bloody sputum. If plague patients are not given specific antibiotic therapy, the disease can progress rapidly to death.

References

http://www.cdc.gov/ncidod/dvbid/plague/qa.htm

Diagnosis

The typical sign of the most common form of human plague is a swollen and very tender lymph gland, accompanied by pain. The swollen gland is called a "bubo." Bubonic plague should be suspected when a person develops a swollen gland, fever, chills, headache, and extreme exhaustion, and has a history of possible exposure to infected rodents, rabbits, or fleas. A person usually becomes ill with bubonic plague 2 to 6 days after being infected.

When bubonic plague is left untreated, plague bacteria invade the bloodstream. As the plague bacteria multiply in the bloodstream, they spread rapidly throughout the body and cause a severe and often fatal condition. Infection of the lungs with the plague bacterium causes the pneumonic form of plague, a severe respiratory illness. The infected person may experience high fever, chills, cough, and breathing difficulty and may expel bloody sputum. If plague patients are not given specific antibiotic therapy, the disease can progress rapidly to death. About 14% (1 in 7) of all plague cases in the United States are fatal.

Human specimens:

Appropriate specimens should be examined for evidence of plague if a person resides in, or has a recent travel history to, plague-infected areas; has been bitten by fleas; and presents with symptoms suggestive of plague (fever, lymphadenopathy). Specimens should be obtained from appropriate sites for isolating the bacteria. The preferred specimen for microscopic examination and isolation from a bubonic case is material from the affected bubo, which should contain numerous organisms. Blood cultures should be taken whenever possible. Organisms may be seen in blood smears if the patient is septicemic, while blood smears taken from suspected bubonic plague patients are usually negative for bacteria. Bacteria may be intermittently released from affected lymph nodes into the bloodstream; therefore, a series of blood specimens taken 10-30 minutes apart may be productive in the isolation of Y. pestis. Sputum/throat smears taken from pneumonic plague patients may contain too many other organisms to be of diagnostic value if only Wayson stain is used; these smears should be stained as well with the more specific fluorescent-antibody (FA) test. Bronchial/tracheal washing should 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, e.g., in specimens taken postmortem, lymphoid tissues, lung and bone marrow samples may yield evidence of plague infection by FA test or by detection of Y. pestis DNA.

Specimens intended for culture should be taken before initiation of antibiotic treatment. Specimens are inoculated on general laboratory media and into laboratory mice for isolation; a thin smear is made from the remaining materials for examination by fluorescent microscopy. If a specimen is suspected to contain mixed flora, passage of the material through laboratory mice will increase the likelihood of recovery of a pure Y. pestis culture. Plague bacilli express a unique diagnostic envelope glycoprotein called the Fraction 1 (F1) antigen or capsular antigen at >33°C; this unique envelope antigen is the primary target antigen used for plague diagnostic FA and antibody tests. Plague bacilli are susceptible to lysis by a specific bacteriophage at both 25°C and 37°C. Plague bacilli are relatively inactive by standard enteric biochemical reactions; therefore, identification by biochemical profiles should be used as a supplemental diagnostic test. If a patient has been treated with a static antibiotic (e.g., tetracycline) for more than 4 days, bacterial cultures should be incubated for more than 5 days to give organisms a chance to recover. In case cultures yield negative results, serologic testing is advised. One serum specimen should be taken as early in the illness as possible to be followed by a second sample 1-4 months after antibiotic therapy has ceased.

Differential Diagnosis

Is pneumonic plague different from bubonic plague?

Yes. Both are caused by Yersinia pestis, but they are transmitted differently and their symptoms differ. Pneumonic plague can be transmitted from person to person; bubonic plague cannot. Pneumonic plague affects the lungs and is transmitted when a person breathes in Y. pestis particles in the air. Bubonic plague is transmitted through the bite of an infected flea or exposure to infected material through a break in the skin. Symptoms include swollen, tender lymph glands called buboes. Buboes are not present in pneumonic plague. If bubonic plague is not treated, however, the bacteria can spread through the bloodstream and infect the lungs, causing a secondary case of pneumonic plague.

References

http://www.cdc.gov/ncidod/dvbid/plague/diagnosis.htm

History and Symptoms

The typical sign of the most common form of human plague is a swollen and very tender lymph gland, accompanied by pain. The swollen gland is called a "bubo" (hence the term "bubonic plague"). Bubonic plague should be suspected when a person develops a swollen gland, fever, chills, headache, and extreme exhaustion, and has a history of possible exposure to infected rodents, rabbits, or fleas.

References

http://www.cdc.gov/ncidod/dvbid/plague/qa.htm

Laboratory Findings

SUSPECTED PLAGUE SHOULD BE CONSIDERED IF THE FOLLOWING CONDITIONS ARE MET:

Clinical symptoms that are compatible with plague, i. e., fever and lymphadenopathy in a person who resides in or recently traveled to a plague-endemic area.

If small gram-negative and/or bipolar-staining coccobacilli are seen on a smear taken from affected tissues, e.g.:

• Bubo (bubonic plague)
• Blood (septicemic plague)
• Tracheal/lung aspirate (pneumonic plague

PRESUMPTIVE PLAGUE SHOULD BE CONSIDERED WHEN ONE OR BOTH OF THE FOLLOWING CONDITIONS ARE MET:

• If immunofluorescence stain of smear or material is positive for the presence of Yersinia pestis F1 antigen.
• If only a single serum specimen is tested and the anti-F1 antigen titer by agglutination is >1:10.*

CONFIRMED PLAGUE IS DIAGNOSED IF ONE OF THE FOLLOWING CONDITIONS IS MET:

• If a culture isolated is lysed by specific bacteriophage.
• If two serum specimens demonstrate a four fold anti-F1 antigen titer difference by agglutination testing.*
• If a single serum specimen tested by agglutination has a titer of >1:128 and the patient has no known previous plague exposure or vaccination history (Agglutination testing must be shown to be specific to Y. pestis F1 antigen by hemagglutination inhibition).

References

http://www.cdc.gov/ncidod/dvbid/plague/lab-test-criteria.htm

Treatment

• A plague vaccine is not currently available for use in the United States.

According to treatment experts, a patient diagnosed with suspected plague should be hospitalized and medically isolated. Laboratory tests should be done, including blood cultures for plague bacteria and microscopic examination of lymph gland, blood, and sputum samples. Antibiotic treatment should begin as soon as possible after laboratory specimens are taken. Streptomycin is the antibiotic of choice. Gentamicin is used when streptomycin is not available. Tetracyclines and chloramphenicol are also effective. Persons who have been in close contact with a plague patient, particularly a patient with plague pneumonia, should be identified and evaluated. The U.S. Public Health Service requires that all cases of suspected plague be reported immediately to local and state health departments and that the diagnosis be confirmed by CDC. As required by the International Health Regulations, CDC reports all U.S. plague cases to the World Health Organization.

Pharmacotherapy

Acute Pharmacotherapies

Early treatment of pneumonic plague is essential. To prevent a high risk of death, antibiotics should be given within 24 hours of the first symptoms. Several types of antibiotics are effective for curing the disease and for preventing it. Available oral medications are a tetracycline (such as doxycycline) or a fluoroquinolone (such as ciprofloxacin). For injection or intravenous use, streptomycin or gentamicin antibiotics are used. Early in the response to a bioterrorism attack, these drugs would be tested to determine which is most effective against the particular weapon that was used.

Antibiotic treatment for 7 days will protect people who have had direct, close contact with infected patients. Wearing a close-fitting surgical mask also protects against infection.

References

http://www.bt.cdc.gov/agent/plague/factsheet.asp http://www.cdc.gov/ncidod/dvbid/plague/qa.htm

Primary Prevention

Risk reduction: Attempts to eliminate fleas and wild rodents from the natural environment in plague-infected areas are impractical. However, controlling rodents and their fleas around places where people live, work, and play is very important in preventing human disease. Therefore, preventive measures are directed to home, work, and recreational settings where the risk of acquiring plague is high. A combined approach using the following methods is recommended:

environmental sanitation educating the public on ways to prevent plague exposures preventive antibiotic therapy

References

http://www.cdc.gov/ncidod/dvbid/plague/prevent.htm

Secondary Prevention

Environmental Sanitation: Effective environmental sanitation reduces the risk of persons being bitten by infectious fleas of rodents and other animals in places where people live, work, and recreate. It is important to remove food sources used by rodents and make homes, buildings, warehouses, or feed sheds rodent-proof. Applying chemicals that kill fleas and rodents is effective but should usually be done by trained professionals. Rats that inhabit ships and docks should also be controlled by trained professionals who can inspect and, if necessary, fumigate cargoes.

Public Health Education: In the western United States, where plague is widespread in wild rodents, people living, working, or playing where the infection is active face the greatest threat. Educating the general public and the medical community about how to avoid exposure to disease-bearing animals and their fleas is very important and should include the following preventive recommendations:

• Watch for plague activity in rodent populations where plague is known to occur. Report any observations of sick or dead animals to the local health department or law enforcement officials.
• Eliminate sources of food and nesting places for rodents around homes, work places, and recreation areas; remove brush, rock piles, junk, cluttered firewood, and potential-food supplies, such as pet and wild animal food. Make your home rodent-proof.
• If you anticipate being exposed to rodent fleas, apply insect repellents to clothing and skin, according to label instructions, to prevent flea bites. Wear gloves when handling potentially infected animals.
• If you live in areas where rodent plague occurs, treat pet dogs and cats for flea control regularly and not allow these animals to roam freely.
• Health authorities may use appropriate chemicals to kill fleas at selected sites during animal plague outbreaks.
• To avoid potential risk of exposure to hantavirus infection:

-Safely clean up rodent-infested areas.

-Air out infested spaces before cleanup.

-Spray areas of infestation and all excreta, nesting, and other materials with household disinfectant or 10% bleach solution then clean up, seal in bags, and dispose.

-Avoid sweeping, vacuuming, or stirring dust until the area is thoroughly wet with disinfectant;

-Wear rubber gloves; disinfect gloves before removal, and wash hands afterwards.

Prophylactic (preventive) antibiotics: Health authorities advise that antibiotics be given for a brief period to people who have been exposed to the bites of potentially infected rodent fleas (for example, during a plague outbreak) or who have handled an animal known to be infected with the plague bacterium. Such experts also recommend that antibiotics be given if a person has had close exposure to a person or an animal (for example, a house cat) with suspected plague pneumonia.

Persons who must be present in an area where a plague outbreak is occurring can protect themselves for 2 to 3 weeks by taking antibiotics. The preferred antibiotics for prophylaxis against plague are the tetracyclines or the sulfonamides.

References

http://www.cdc.gov/ncidod/dvbid/plague/prevent.htm

Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.

List of contributors:

Pilar Almonacid

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