• Disease Overview
  • Synonyms
  • Subdivisions
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report
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Plague

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Last updated: 6/15/2023
Years published: 1987, 1988, 1989, 1998, 2001, 2009, 2010, 2013, 2016, 2019, 2023


Acknowledgment

NORD gratefully acknowledges the Centers for Disease Control and Prevention, Division of Vector-Borne Diseases, for assistance in the preparation of this report.


Disease Overview

Plague is an acute, severe infectious disease caused by the bacterium Yersinia pestis. The bacterium is found in fleas and wild rodents such as rats, squirrels, chipmunks or prairie dogs. Plague is a zoonotic disease, which means it can be transmitted to humans through animals, most often through the bites of fleas or through direct contact with infected animal tissue. The disease is most common in parts of Africa, Asia and South America, but it also occurs in some areas of the western United States. Symptoms can include an abrupt onset of chills, fever, and enlarged, painful lymph nodes (buboes). Most cases of plague resolve with effective treatment, though treatment must be started immediately to avoid life-threatening complications. Although plague is extremely rare in the United States, interest in the infection has heightened in recent years because of its potential use as an agent of biological warfare.

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Synonyms

  • Black Death
  • La Peste
  • pestilential fever
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Subdivisions

  • bubonic plague
  • pneumonic plague
  • septicemic plague
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Signs & Symptoms

The symptoms of plague vary greatly depending upon the specific form that develops. The main clinical forms of plague are bubonic, septicemic, and pneumonic.

Bubonic Plague
Bubonic plague is the most common form of the disease. Symptoms usually develop 2-6 days after exposure to the bacterium and include the sudden onset of fever, chills, weakness, headaches, muscle pain and a general feeling of discomfort or ill health (malaise). An infected individual develops a bubo – a tender, inflamed swelling of a lymph node. Buboes are firm and often very painful. The lymph nodes of the groin, armpit (axilla) or neck are most often involved.

If untreated, the bacteria can spread from the affected lymph node to the bloodstream (septicemia) and the lungs (pneumonia) and cause toxicity, shock, and other life-threatening complications.

Septicemic Plague
This form of plague is characterized by massive growth of bacteria in the blood. It can occur as bacteria in the lymph nodes (bubonic plague) spread to the bloodstream, or as a primary infection (no swollen lymph nodes). Affected individuals may develop prominent gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain. Other general symptoms may include high fever, chills, exhaustion, headache and muscle pain (myalgia). Septicemic plague progresses rapidly and can quickly cause life-threatening complications if not diagnosed and treated promptly.

Pneumonic Plague
Pneumonic plague is infection of the lungs by the Yersinia pestis bacterium. It can occur as a complication of bubonic or septicemic plague in which the bacteria spread to the lungs through the bloodstream, or as a primary infection in which the bacterium is inhaled directly into the lungs. If inhaled, disease develops rapidly, usually within 1-3 days Affected individuals can develop a wide variety of symptoms including fever, chills, a rapid heartbeat, difficulty breathing, cough, chest pain, severe headaches and the coughing up of bloody sputum (hemoptysis). If untreated within the first 24-36 hours, this form of plague can rapidly progress to multiple organ failure, adult respiratory distress syndrome and ultimately death.

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Causes

Plague is caused by infection with the bacterium Yersinia pestis. This bacterium is found in wild rodents and their fleas. Some of the most commonly infected rodents are rats, squirrels, chipmunks or prairie dogs. Rabbits and hares (lagomorphs) may also carry the bacteria. The disease is most often transmitted to humans by the bite of infected fleas. Less frequently, direct contact with infectious animal tissue can also result in infection.

Pneumonic plague is the only manifestation of plague that can be transmitted from one person to another. This transmission occurs when a person breathes in (inhales) droplets from a coughing pneumonic plague patient. However, human-to-human transmission is extremely rare and has not been demonstrated in the United States since 1924. Domestic cats and dogs can become ill with pneumonic plague and transmit the infection to their owners or attending veterinarians in the same manner. The source of a recent human plague outbreak in Colorado was a dog with pneumonic plague.

In recent years, plague has regained notoriety as a potential agent of bioterrorism. Most researchers believe that if used in such a manner, the bacteria would most likely be released as an aerosol with the intent of causing an outbreak of pneumonic plague.

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Affected populations

Plague affects both males and females of all ages; however, historically it is slightly more common among men. Men may be more likely to become infected with plague because they are more likely to engage in outdoor activities that put them at risk (https://www.cdc.gov/plague/maps/index.html). Seven human plague cases are reported on average in the United States each year. Most cases in the United States occur in the Western and Southwestern part of the country, especially in New Mexico, Colorado, Arizona and California (https://www.cdc.gov/plague/maps/index.html). Plague has a scattered worldwide distribution. Most cases occur in sub-Saharan Africa, but plague still occurs on most continents. Historically, plague has caused massive pandemics most notably the Black Death of the Middle Ages.

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Diagnosis

The diagnosis of plague may be confirmed by specialized laboratory tests in addition to characteristic clinical findings. Yersinia pestis can be identified in blood samples, tissue taken from enlarged lymph nodes (buboes) and sputum. All suspected cases of plague in the United States must be reported to the appropriate local and/or state health department, which in turn notifies the Centers for Disease Control and Prevention (CDC).

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Standard Therapies

Treatment

The treatment of plague must begin as soon as possible to avoid serious life-threatening complications.
Doxycycline (and other tetracyclines) and fluoroquinolones levofloxacin, ciprofloxacin, and moxifloxacin are approved by the U.S. Food and Drug Administration (FDA) to treat plague. Gentamicin is not FDA approved for this purpose, but has been used successfully to treat plague, and is recommended therapy. Streptomycin is FDA approved and highly effective, but rarely available in many countries. In addition, doxycycline, ciprofloxacin, levofloxacin and moxifloxacin are approved by the FDA to prevent plague in exposed individuals (https://www.cdc.gov/plague/healthcare/clinicians.html).

When pneumonia has developed, droplet precautions should be taken by health care providers to prevent transmission. There is no commercially available vaccine against plague in the United States.

Individuals living in plague endemic areas should take preventive measures such as avoiding contact with rodents and fleas.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/news-patient-recruitment/

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

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References

JOURNAL ARTICLES
Kugeler K, Staples E, Hinckley A, Gage K, Mead P. Epidemiology of Human Plague in the United States. Emerging Infectious Diseases. 2015; 21(1):16-22.

Kwit N, Nelson C, Kugeler K, Petersen J,… and Mead P.. Human Plague – United States, 2015. MMWR. 2015: 918-919.

Runfola J, House J, Miller L, Colton L, Hite D, Hawley A, . . . Pabilonia K. Outbreak of Human Pneumonic Plague with Dog-to-Human and Possible Human-to-Human Transmission — Colorado, June–July 2014. MMWR. 2015;64(16):429-434.

Maher S, Ellis C, Gage K, Enscore R, and Peterson AT. Range-wide Determinants of Plague Distribution in North America. Am J Trop Med Hyg 2010; 83: 736-42.

Inglesby T, Dennis D, Henderson D, Bartlett J. Ascher M. Eitzen E., . . . Tonat K. Plague as a Biological Weapon: Medical and Public Health Management. JAMA; 2000:283(17):2281-2290.

INTERNET
Minnaganti VR, Jackson RL, Bronze MS, Minnaganti VR. Plague. Medscape. Updated: Aug 13, 2021. Available at: https://www.emedicine.com/MED/topic3381.htm Accessed June 14, 2023.

Centers for Disease Control and Prevention. Page last reviewed:Aug 6, 2021. Available at: https://www.cdc.gov/plague Accessed June 14, 2023.

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Programs & Resources

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NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

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NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

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Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations


National Organization for Rare Disorders