Diagnosis Synopsis
Bubonic plague is a severe bacterial infection caused by the gram-negative bacillus Yersinia pestis, which can cause 3 distinct forms of illness: bubonic, septicemic and pneumonic plague. Bubonic plague may progress to both the septicemic and pneumonic forms if left untreated.

Fleas transmit the bacteria from animals (eg, prairie dogs, squirrels, chipmunks, rats, cats) to humans. Direct contact, animal bites or exposures to infected carcasses (eg, coyotes, hares, rabbits, rodents, marmots, goats) are other sources. In a bioterrorist event, plague would most likely be released as an aerosol, resulting primarily in the highly lethal and contagious pneumonic form of the disease. Bubonic plague would not immediately result, but may occur by secondary transmission by infected fleas.

Whether bubonic plague is acquired naturally or as a result of a bioterrorist attack (release of infected fleas), the onset of symptoms (after an incubation period of 4 to 7 days) is sudden and includes malaise, myalgias, high fever, headache, tachycardia and the development of large tender regional lymph nodes called buboes (usually in the inguinal area). Untreated, bubonic plague can progress to septicemic and occasionally pneumonic plague in 2 to 6 days, and death is frequent. The mortality rate of bubonic plague is low when treated early and is about 50% when untreated.

Bubonic plague cannot be transmitted person-to-person unless it develops into the pneumonic form.

Endemic plague is seen in the southwestern United States (Colorado, New Mexico, Arizona, California). About 10 cases are reported each year in the US. Elsewhere in the world, plague is seen in Vietnam, India, the former Soviet Union and parts of Africa.

People at risk for bubonic plague include hunters, hikers, abattoir workers, exotic pet owners, travelers to endemic areas and those who live in rat-infested areas.

Bubonic plague is reportable to your local health department. Precautions: Use droplet precautions (gown, gloves, handwashing, surgical mask) when treating patients with plague. If the patient has fleas, these should be treated quickly and the patient's clothes should be double bagged until they can be washed in hot water. Patients should be isolated until they are improving.

Look For
Large, painful regional lymph nodes (buboes) in the groin, axilla or neck are a hallmark of bubonic and septicemic plague. There is inflammation widely around the bubo. A petechial or purpuric eruption can develop. A papule, pustule, vesicle or bulla may be present at the site of the flea bite (up to 25% of cases).

In septicemic plague, DIC can occur, and ecthyma-like lesions and gangrene of the extremities due to vasculitis with fibrin thrombi are seen.

Diagnostic Pearls
Fever, headache and matted nodes (especially inguinal) with boggy hemorrhagic edema are diagnostic. Wright's or Wayson's stain often produces a bipolar (safety pin) appearance in the bacteria.

Differential Diagnosis & Pitfalls
Tularemia usually presents with a focal skin lesion, such as a plaque, eschar or pustule, which is present distally to the involved lymph nodes. Mycobacteria marinum usually presents with low grade or absent fever and follows an indolent course. Bacterial adenitis usually presents with a pustule or cellulitis-like skin lesion distal to the involved lymph nodes. Cat scratch disease is almost always indolent without toxicity. Lymphogranuloma venereum presents with inguinal lymphadenopathy with buboes but little signs of systemic toxicity. Chancroid presents with enlarged, painless, inguinal lymph nodes.

Best Tests
Aspirate of infected lymph nodes for gram stain and (Giemsa, Wright's or Wayson's stain) and culture. For high suspicion of plague, send to the local health department for direct fluorescent antibody (DFA). Blood cultures.

Management Pearls
Immediate gentamicin, tetracycline, doxycycline or streptomycin. Isolation and droplet precautions.

Therapy
Adult First Line:
Streptomycin 1 gm IM twice daily for 10 days (not in pregnant women) Or
Gentamicin 5 mg/kg IM or IV once daily or 2 mg/kg loading dose followed by 1.7 mg/kg IM or IV tid for 10 days. Or
Doxycycline 100 mg IV twice daily or 200 mg IV once daily for 10 days (if gentamicin not available oral antibiotics must be used). Or
Ciprofloxacin 400 mg IV bid for 10 days (or other fluoroquinolones at appropriate dosing).
Chloramphenicol (add for plague meningitis), 25 mg/kg IV 4 times daily for 10 days (concentrations should be maintained between 5 and 20 ug/ml, concentrations greater than 25 ug/ml can cause irreversible bone marrow suppression).

Child First Line:
Streptomycin 15 mg/kg IM twice daily for 10 days (maximum daily dose 2 gm).
Or
Gentamicin 2.5 mg/kg IM or IV tid for 10 days (adjust for renal function).
Or
Doxycycline:
>45 kg, give adult dosage.
<45 kg, 2.2 mg/kg IV twice daily for 10 days (maximum 200 mg/day).
Or
Ciprofloxacin 15 mg/kg IV bid for 10 days (maximum 1 gm/day).
Or
Chloramphenicol (add for plague meningitis), 25 mg/kg IV 4 times daily for 10 days (concentrations should be maintained between 5 and 20 ug/ml, concentrations greater than 25 ug/ml can cause irreversible bone marrow suppression. CONSULT SPECIALIST FOR DOSING).
NOTE: The above therapy information is partially derived from the CDC and the Center for Infectious Disease Research and Policy of the University of Minnesota. For detailed treatment and laboratory specimen collection information, please refer to: http://www.cidrap.umn.edu

Medical Disclaimer:
The information contained in this web page is intended to be an adjunct to traditional medical information sources. It is not intended to be a substitute for professional medical judgment.

Authors and Editors:
Tener Goodwin Veenema PhD, MPH, MS, CPNP