Diagnosis Synopsis
Pneumonic plague is a severe bacterial lung infection caused by the gram-negative bacillus Yersinia pestis, which is found in rodents (e.g., prairie dogs, squirrels, rats) and their fleas and sometimes in cats. Pneumonic plague manifests in primary or secondary forms. The primary form is contracted from inhaling droplets transmitted from an infected person; this naturally occurring form is uncommon (2% of cases). Secondary pneumonic plague is a progression of bubonic or septicemic plague to the lungs, approximately 12% of cases progress to pneumonic. Bubonic and septicemic plague are rarely transmissible human to human but will become transmissible via droplets once in the pneumonic stage.

Pneumonic plague is classified as a Category A bioterrorism agent because of its ease of dissemination, contagiousness and high mortality rate. The most likely method of dispersal would be as an aerosol, but simply having an infected individual walk around infecting others is also a likely mode of dissemination. It has an incubation period of 1 to 6 days (average 2 to 4 days).

Pneumonic plague results in a severe fulminant illness with associated high fever, chills, headache, productive cough, chest pain, hemoptysis, extreme malaise, myalgias, tachypnea, tachycardia and pneumonia. GI symptoms, including nausea, vomiting, abdominal pain and diarrhea are also commonly seen. If not treated within 24 hours of onset, pneumonic plague rapidly progresses to cyanosis, respiratory failure, septicemia, circulatory collapse and death. Untreated, the mortality rate is 50 to 90%. With treatment the rate is 15%.

Plague is endemic plague to the southwestern United States (Colorado, New Mexico, Arizona, California as well as Vietnam, India, the former Soviet Union, and parts of Africa. Hikers, campers, veterinarians and owners of infected cats, especially those living or visiting endemic areas, are more at risk for contracting plague.

Currently, a plague vaccine is not available in the United States. Pneumonic plague must be reported to local and state health departments immediately.
Precautions: Strict isolation, droplet precautions and antibiotics for people with direct, close contact with infected patients.

Look For
Look for initial symptoms of fever, headache, extreme weakness and rapidly developing pneumonia with shortness of breath, chest pain and cough. Some patients' sputum may be bloody or watery. If the secondary form, look for bite sites which may appear as small ulcers.

Diagnostic Pearls
Consider plague in any sudden increase in the number of gram-negative pneumonias. Pleural effusions may be seen (50%). Primary pneumonic plague typically lacks buboes and will reveal profound lobular exudation and bacillary aggregation. Bilateral infiltrates or consolidation are common.

Differential Diagnosis & Pitfalls
Pneumonia. Pneumonic plague can be distinguished from pneumonia by mediastinal and hilar adenopathy.
Anthrax. The hemoptysis present in plague is not common in anthrax.
Tularemia
Community acquired pneumonia
Blastomycosis
Glanders
Melioidosis
Hantavirus pulmonary syndrome
Legionnaires' disease
Psittacosis
Q fever
Ricin inhalation

Best Tests
Sputum gram stain shows gram-negative bacilli. Use Wright, Giemsa or Wayson tests to look for "closed safety pin" appearing bipolar staining. Culture blood, sputum and CSF if evidence of meningitis. There may be evidence of multiorgan failure such as leukocytosis with toxic granulations, coagulation abnormalities, aminotransferase elevations, and azotemia.
Note: Warn the laboratory that you suspect plague.

Management Pearls
Begin treatment within 24 hours of initial symptoms. Identify and evaluate people who have close contact with the patient and begin preventive antibiotic therapy. Respiratory and droplet isolation is needed as well as supportive care in the ICU.

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 or 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 daily dose 1 gm).
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.

*The information contained above 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