American College of Physicians: Internal Medicine — Doctors for Adults ®



From the May ACP Observer, copyright 2004 by the American College of Physicians.

Plague pandemics have been recorded as early as 541 A.D. and as recently as 1855 in China. Improved living conditions, enhanced public health measures and the advent of antibiotics have helped stem the incidence of plague, which typically spreads to humans from infected fleas.

But Yersinia pestis, the gram-negative coccobacillus that causes the plague, still persists in nature, primarily in rodent reservoirs. Fewer than 20 cases of plague are reported annually in the United States, with most occurring in southwestern states.

Y. pestis can cause three different plague syndromes. The most common, bubonic plague, occurs mainly from infected fleabites. A bite is followed by the development of regional necrotizing lymphadenitis or "buboes." Bubonic plague may then progress to secondary septicemia (septicemic plague) and pulmonary involvement (primary pneumonic plague). Person-to-person transmission is possible only by respiratory droplets from patients with pulmonary involvement.

A blood smear containing Yersinia pestis plague bacteria. Note the characteristic bipolar, "safety pin"-like appearance of the Y. pestis organisms. Primary pneumonic plague from aerosol exposure is highly contagious, and it is the most likely exposure route for a bioterrorist attack. Both Soviet and U.S. scientists claim they developed aerosolized plague bacteria.

Primary pneumonic plague from aerosol exposure is highly contagious, and it is the most likely exposure route for a bioterrorist attack. As part of their bioweapons programs, Soviet and U.S. scientists claim they developed aerosolized plague bacteria.

However, other exposure routes have been used in the past. In World War II, for instance, the Japanese army reportedly dropped plague-infected fleas over areas of China, causing outbreaks of the disease.

This article will focus on pneumonic plague. For information about other plague syndromes, go here or visit the CDC's web site.

A number of clues would indicate a bioterrorist plague attack, including the following:

  • Occurrence in areas where plague is not endemic to the rodent population.
  • Absence of rodent deaths prior to the human outbreak.
  • Sudden outbreak of severe pneumonia and sepsis in people with no risk factors. Fulminant pneumonia in otherwise healthy individuals suggests pneumonic plague or inhalation anthrax.

Clinical presentation and diagnosis

Patients with pneumonic plague present with fever, cough, dyspnea, cyanosis, hemoptysis and chest pain. Common gastrointestinal symptoms can include nausea, vomiting, abdominal pain and diarrhea.

While chest radiograph findings vary, bilateral infiltrates or consolidation are common. Patients' pneumonia is fulminant and can cause respiratory failure, shock and death usually within two to six days.

Y. pestis is likely if sputum or blood samples reveal gram-negative bacilli or coccobacilli with bipolar (safety pin) staining on Wright, Giemsa or Wayson stains. Diagnosis is confirmed by culture and identification of the organism.

Under the best of circumstances, cultures are positive in 24 to 48 hours, but results may take as long as six days. Rapid tests—such as polymerase chain reaction, antigen detection and immunoassays—are available only at some state health departments, the CDC and military laboratories.

Given how rare plague infection is and the importance of containing it, the first clinical or laboratory suspicion of plague should trigger immediate notification of the hospital epidemiologist or infection control practitioner, health department and local or state health laboratory. Public health officials can rapidly arrange definitive tests through state reference laboratories or the CDC.

Differential diagnosis

Severe and rapidly progressing pneumonia with sepsis suggests pneumonic plague or inhalation anthrax. However, these signs may be overlooked, given the clinical similarity to other bacterial or viral pneumonias.

The sudden appearance of a large number of cases of fulminate pneumonia in previously healthy people suggests the possibility of a bioterrorist attack with one of these two pathogens. The additional symptom of hemoptysis makes plague more likely.


To prevent a high risk of death, antibiotics should be given within 24 hours of the appearance of the first symptoms. Do not delay treatment if plague is suspected.

There are no clinical trials to guide the treatment of pneumonic plague, although in vitro and animal studies (as well as anecdotal experience) suggest that a number of antibiotics can effectively treat plague, in addition to the few approved by the FDA.

Historically, the preferred treatment for plague has been the FDA-approved antibiotic streptomycin. But this drug is not as readily available as gentamicin, which studies suggest is as effective. Gentamicin is also inexpensive and can be given once daily.

Antibiotic resistance naturally occurs in some Y. pestis strains and may be genetically engineered into those used in a bioterrorist attack. Antibiotic susceptibility testing should be done, and results should be used to modify antibiotic prescribing. For detailed prescribing information, see "Treating pneumonic plague."

Post-exposure containment

Studies suggest that aerosolized plague bacteria survive no longer than an hour on exposed surfaces, and that the risk of re-aerosolization of Y. pestis from the contaminated clothing of exposed persons is low. Contaminated clothing and linens should be disinfected according to hospital protocol.

Isolate patients for at least the first 48 hours of antibiotic therapy, and continue isolation until clinical improvement occurs. Contacts of pneumonic plague patients require droplet isolation—use a gown, gloves, eye protection and disposable surgical facial masks—for at least the first 48 hours of antibiotic therapy and until patients improve. Unnecessary contact with patients should be avoided during this time, and patients should wear surgical-type masks when they are being transported.

The typical incubation period for pneumonic plague is two to four days, although it can be as short as a day and as long as six days. Post-exposure prophylaxis is recommended for asymptomatic members of the household, hospital or other close contacts (within two meters) of patients with untreated pneumonic plague.

These contacts should receive oral doxycycline, 100 mg BID x 7 days if they are adults, including pregnant women. Children who weigh 45 kg or more should receive the same adult oral doxycycline dosage. Children who weigh less than 45 kg should receive oral doxycycline, 2.2 mg/kg BID x 7 days.

Alternatively, ciprofloxacin can be given 500 mg, twice daily to adults or 20-30 mg per kg of body mass daily. This should be divided into two doses for children.

Any patients receiving post-exposure prophylaxis who develop fever or cough should have their antibiotic therapy upgraded to that given to pneumonic plague patients. In a community experiencing a pneumonic plague outbreak, anyone who develops a fever greater that 38.5 C (101.3 F) or new cough, or infants with tachypnea, should also receive antibiotic treatment as described above for pneumonic plague. No pneumonic plague vaccine is currently available.


Treating pneumonic plague

Adults: preferred choices

  • Streptomycin 1 g IM BID
  • 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

Adults: alternative choices

  • Doxycycline 100 mg IV BID or 200 mg IV once daily
  • Ciprofloxacin 400 mg IV BID
  • Chloramphenicol 25 mg/kg IV QID

Children: preferred choices

  • Streptomycin 15 mg/kg IM BID, maximum dose 2 g
  • Gentamicin 2.5 mg/kg IM or IV TID

Children: alternative choices

  • Doxycycline: If greater than 45 kg, give adult dose. If less than 45 kg, give 2.2 mg/kg IV BID (maximum dose 200 mg/day)
  • Ciprofloxacin 15 mg/kg IV BID
  • Chloramphenicol 25 mg/kg IV QID

Pregnant women: preferred choice

  • 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

Pregnant women: alternative choices

  • Doxycycline 100 mg IV BID or 200 mg IV once daily
  • Ciprofloxacin 400 mg IV BID

All treatments should be given for 10 days. Based on recommendations of the Center for Civilian Biodefense Studies, Johns Hopkins University Schools of Medicine.


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