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Plague and Other Yersinia Infections

(Bubonic Plague; Pestis; Black Death)

By Larry M. Bush, MD, Affiliate Professor of Clinical Biomedical Sciences; Affiliate Associate Professor of Medicine, Charles E. Schmidt College of Medicine, Florida Atlantic University; University of Miami-Miller School of Medicine
Maria T. Perez, MD, Associate Pathologist, Department of Pathology and Laboratory Medicine, Wellington Regional Medical Center, West Palm Beach

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Plague is caused by Yersinia pestis. Symptoms are either severe pneumonia or massive lymphadenopathy with high fever, often progressing to septicemia. Diagnosis is epidemiologic and clinical, confirmed by culture and serologic testing. Treatment is with streptomycin or gentamicin; alternatives are a fluoroquinolone or doxycycline.

Yersinia (formerly Pasteurella) pestis is a short bacillus that often shows bipolar staining (especially with Giemsa stain) and may resemble a safety pin.

Plague occurs primarily in wild rodents (eg, rats, mice, squirrels, prairie dogs) and is transmitted from rodent to human by the bite of an infected rat flea vector. Plague may also be spread through contact with fluid or tissue from an infected animal. Human-to-human transmission occurs by inhaling droplets from patients with pulmonary infection (primary pneumonic plague), which is highly contagious. In endemic areas in the US, several cases may have been caused by household pets, especially cats (infected by eating infected rodents). Transmission from cats can be by bite of an infected flea or, if the cat has pneumonic plague, by inhalation of infected respiratory droplets. Pneumonic plague can also be transmitted via exposure in a laboratory or intentional aerosol spread as an act of bioterrorism.

Massive human epidemics (eg, the Black Death of the Middle Ages, an epidemic in Manchuria in 1911) have occurred. More recently, plague has occurred sporadically or in limited outbreaks. The last urban outbreak of rat-associated plague in the US occurred in Los Angeles in 1924 to 1925. Since that time, > 90% of human plague in the US has occurred in rural or semirural areas of the Southwest, especially New Mexico, Arizona, California, and Colorado.

Symptoms and Signs

There are several distinct clinical manifestations:

  • Bubonic plague (most common)

  • Pneumonic plague (primary or secondary)

  • Septicemic plague

  • Pestis minor

In bubonic plague, the most common form, the incubation period is usually 2 to 5 days but varies from a few hours to 12 days. Onset of fever of 39.5 to 41° C is abrupt, often with chills. The pulse may be rapid and thready; hypotension may occur. Lymph nodes that drain the site of inoculation by the bacteria become enlarged and tender (buboes) and appear shortly after the fever. The femoral or inguinal lymph nodes are most commonly involved, followed by axillary, cervical, or multiple nodes. Typically, the nodes are extremely tender and firm, surrounded by considerable edema. They may suppurate in the 2nd wk. The overlying skin is smooth and reddened but often not warm. A primary cutaneous lesion, varying from a small vesicle with slight local lymphangitis to an eschar, occasionally appears at the flea bite. The patient may be restless, delirious, confused, and uncoordinated. The liver and spleen may be enlarged. Because the bacteria can spread through the bloodstream to other parts of the body, bubonic plague may be complicated by hematogenous (secondary) pneumonic plague.

Primary pneumonic plague has a 2- to 3-day incubation period, followed by abrupt onset of high fever, chills, tachycardia, chest pain, and headache, often severe. Cough, not prominent initially, develops within 24 h. Sputum is mucoid at first, rapidly develops blood specks, and then becomes uniformly pink or bright red (resembling raspberry syrup) and foamy. Tachypnea and dyspnea are present, but pleuritic chest pain is not. Signs of consolidation are rare, and rales may be absent.

Secondary pneumonic plague is more common than primary and results from hematogenous dissemination of organisms from a bubo or other foci of infection.

Septicemic plague may occur with the bubonic form or without the bubonic form (called primary septicemic plague) as an acute, fulminant illness. Abdominal pain, presumably due to mesenteric lymphadenopathy, occurs in 40% of patients. Disseminated intravascular coagulopathy, gangrene of the extremities (hence, the name Black Death), and multiorgan failure eventually develop.

Pestis minor, a more benign form of bubonic plague, usually occurs only in endemic areas. Lymphadenitis, fever, headache, and prostration subside within a week.

Pharyngeal plague and plague meningitis are less common forms.

The mortality rate for untreated patients with bubonic plague is about 60%; most deaths result from septicemia in 3 to 5 days. Most untreated patients with pneumonic plague die within 48 h of symptom onset. Septicemic plague may be fatal before bubonic or pulmonary manifestations predominate.


  • Staining, cultures, and serologic testing

Rapid diagnosis is important because mortality increases significantly the longer treatment is delayed.

Diagnosis is made by stain and culture of the organism, typically by needle aspiration of a bubo (surgical drainage may disseminate the organism); blood and sputum cultures should also be obtained. Other tests include immunofluorescent staining and serology; a titer of > 1:16 or a 4-fold rise between acute and convalescent titers is positive. PCR testing, if available, is diagnostic.

Prior vaccination does not exclude plague; clinical illness may occur in vaccinated people.

Patients with pulmonary symptoms or signs should have a chest x-ray, which shows a rapidly progressing pneumonia in pneumonic plague. The WBC count is usually 10,000 to 20,000/μL with numerous immature neutrophils.


  • Streptomycin or gentamicin

  • Alternatively, doxycycline, ciprofloxacin, levofloxacin, or chloramphenicol

Immediate treatment reduces mortality to < 5%.

In septicemic or pneumonic plague, treatment must begin within 24 h with streptomycin 15 mg/kg (up to 1 g) IM bid or gentamicin 5 mg/kg IM or IV once/day (or 2 mg/kg loading dose followed by 1.7 mg/kg q 8 h) if renal function is normal; the drug is given for 10 days or until 3 days after temperature has returned to normal. Doxycycline 100 mg IV or po q 12 h is an alternative. Ciprofloxacin, levofloxacin, and chloramphenicol are also effective.

Chloramphenicol is preferred for patients with infection of tissue spaces into which other drugs pass poorly (eg, plague meningitis, endophthalmitis). Chloramphenicol should be given in a loading dose of 25 mg/kg IV, followed by 12.5 mg/kg IV or po q 6 h.

Routine isolation precautions are adequate for patients with bubonic plague. Those with primary or secondary pneumonic plague require strict respiratory isolation and droplet precautions (see the Centers for Disease Control and Prevention's Resources for Clinicians).


All pneumonic plague contacts should be under medical surveillance. Temperature should be taken q 4 h for 6 days. They and others in close contact with patients who have plague pneumonia or in direct contact with infected body fluids or tissues should receive prophylaxis for 7 days with

  • Doxycycline 100 mg po q 12 h

  • Ciprofloxacin 500 mg po q 12 h

  • For children < 8 yr, trimethoprim/sulfamethoxazole [TMP/SMX] 20 mg/kg [of the SMX component] q 12 h

Levofloxacin taken for 7 days is an alternative.

Travelers should be given prophylaxis with doxycycline 100 mg po q 12 h during exposure periods.

Plague vaccine is no longer available in the US.

Rodents should be controlled and repellents used to minimize flea bites.

Key Points

  • Plague is a highly contagious, life-threatening infection now present in the US mainly in rural or semirural areas of the Southwest.

  • Plague may cause massive, often suppurative lymphadenopathy (buboes), severe pulmonary infection, and/or septicemia.

  • Rapid diagnosis using stain and culture of the organism is important because mortality increases significantly the longer treatment is delayed.

  • Place patients with pneumonic plague in strict respiratory isolation; routine isolation is adequate for those with other forms.

  • Treat with streptomycin or gentamicin; acceptable alternatives include doxycycline, ciprofloxacin, levofloxacin, and chloramphenicol.

  • Monitor close contacts carefully, and treat them prophylactically with doxycycline, ciprofloxacin, or levofloxacin, and treat children with TMP/SMX; plague vaccine is no longer available in the US.

Other Yersinia Infections

Yersinia enterocolitica and Y. pseudotuberculosis are zoonoses acquired by ingestion of contaminated food or water; they occur worldwide.

Y. enterocolitica is a common cause of diarrheal disease and mesenteric adenitis that clinically mimics appendicitis. Y. pseudotuberculosis most commonly causes mesenteric adenitis and has been suspected in cases of interstitial nephritis, hemolytic-uremic syndrome, and a scarlet fever–like illness. Both species can cause pharyngitis, septicemia, focal infections in multiple organs, and postinfectious erythema nodosum and reactive arthritis. In patients with chronic liver disease or iron overload, mortality from septicemia may be as high as 50%, even with treatment.

The organisms can be identified in standard cultures from normally sterile sites. Selective culture methods are required for nonsterile specimens. Serologic assays are available but difficult and not standardized. Diagnosis, particularly of reactive arthritis, requires a high index of suspicion and close communication with the clinical laboratory.

Treatment of diarrhea is supportive because the disease is self-limited. Septic complications require beta-lactamase–resistant antibiotics guided by susceptibility testing. Third-generation cephalosporins, fluoroquinolones, and TMP/SMX are preferred.

Prevention focuses on food handling and preparation, household pets, and epidemiology of suspected outbreaks.

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