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Diagnosis

Plague should be considered in any patient with clinical signs of plague and a recent history of travel to the western United States or any other plague endemic area. Bubonic plague is the most common primary manifestation, with a bubo usually occurring in the groin, axilla or cervical nodes. Buboes are often so painful that patients are generally guarded and have restricted movement in the affected region. The incubation period for bubonic plague is usually 2 to 6 days.

If bubonic plague is untreated, plague bacteria invade the bloodstream and spread rapidly, causing septicemic plague, and if the lungs are seeded, secondary pneumonic plague. Septicemic and pneumonic plague may also be primary manifestations. A person with pneumonic plague may experience high fever, chills, cough, and breathing difficulty and may expel bloody sputum. If pneumonic plague patients are not given specific antibiotic therapy, the disease can progress rapidly to death.

Although the majority of patients with plague present with a bubo, some may have nonspecific symptoms. For example, septicemic plague can present with prominent gastrointestinal symptoms such as nausea, vomiting, diarrhea, and abdominal pain (MMWR, 2006). Additional rare forms of plague include pharyngeal, meningeal, and cutaneous.

Appropriate diagnostic samples include blood cultures, lymph node aspirates if possible, and/or sputum, if indicated. Drug therapy should begin as soon as possible after the laboratory specimens are taken. If plague is suspected, local and state health departments should be notified immediately. If the patient has pneumonic signs, he/she should also be isolated and placed on droplet precautions.

Diagnostic Testing

If plague is suspected, pre-treatment specimens should be taken if possible, but treatment should not be delayed. Specimens should be obtained from appropriate sites for isolating the bacteria, and depend on the clinical presentation:

  • Lymph node aspirate: An affected bubo should contain numerous organisms that can be evaluated microscopically and by culture.
  • Blood cultures: Organisms may be seen in blood smears if the patient is septicemic. Blood smears taken from suspected bubonic plague patients early in the course of illness are usually negative for bacteria by microscopic examination but may be positive by culture.
  • Sputum: Culture is possible from sputum of very ill pneumonic patients; however, blood is usually culture-positive at this time as well.
  • Bronchial/tracheal washing may be taken from suspected pneumonic plague patients; throat specimens are not ideal for isolation of plague since they often contain many other bacteria that can mask the presence of plague.
  • In cases where live organisms are unculturable (such as postmortem), lymphoid, spleen, lung, and liver tissue or bone marrow samples may yield evidence of plague infection by direct detection methods such as direct fluorescent antibody (DFA) or PCR.

Y. pestis may be identified microscopically by examination of Gram, Wright, Giemsa, or Wayson’s stained smears of peripheral blood, sputum, or lymph node specimen.Visualization of bipolar-staining, ovoid, Gram-negative organisms with a “safety pin” appearance permits a rapid presumptive diagnosis of plague.

If cultures yield negative results, and plague is still suspected, serologic testing is possible to confirm the diagnosis. One serum specimen should be taken as early in the illness as possible, followed by a convalescent sample 4-6 weeks or more after disease onset.

More information about specimen submission.

Recommended antibiotic treatment for plague

Begin appropriate IV therapy as soon as plague is suspected. Gentamicin and fluoroquinolones are typically first-line treatments in the United States. Duration of treatment is 10 to 14 days, or until 2 days after fever subsides. Oral therapy may be substituted once the patient improves.

The regimens listed below are guidelines only and may need to be adjusted depending on a patient’s age, medical history, underlying health conditions, or allergies. Please use clinical judgment.

Additional information:

Recommended antibiotic treatment for plague [PDF – 2 pages]

1Boulanger LL, Ettestad P, Fogarty JD, Dennis DT, Romig D, Mertz G. Gentamicin and tetracyclines for the treatment of human plague: Review of 75 cases in New Mexico, 1985–1999. Clin Infect Dis. 2004 38(5):663-669.
2Mwengee W, Butler T, Mgema S, Mhina G, Almasi Y, Bradley C, Formanik JB, Rochester CG.
Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania. Clin Infect Dis. 2006 42(5):614-21.
3All recommended antibiotics for plague have relative contraindications for use in children and pregnant women; however, use is justified in life-threatening situations.
4Todd SR, Dahlgren FS, Traeger MS, Beltrán-Aguilar ED, Marianos DW, Hamilton C, McQuiston JH, Regan JJ. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain spotted fever. J Pediatr. 2015 May;166(5):1246-51.
Adults Antibiotic Dose Route of administration Notes
Streptomycin 1 g twice daily IM Not widely available in the US
Gentamicin 5 mg/kg once daily, or 2 mg/kg loading dose followed by 1.7 mg/kg every 8 hours IM or IV Not FDA approved but considered an effective alternative to streptomycin.1 Due to poor abscess penetration, consider alternative or dual therapy for patients with bubonic disease.
Levofloxacin 500 mg once daily IV or po Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague. A higher dose (750 mg) may be used if clinically indicated.
Ciprofloxacin 400 mg every 8-12 hours IV Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague.
500-750 mg twice daily po
Doxycycline 100 mg twice daily or 200 mg once daily IV or po Bacteriostatic, but effective in a randomized trial when compared to gentamicin.2
Moxifloxacin 400 mg once daily IV or po  
Chloramphenicol 25 mg/kg  every 6 hours IV Not widely available in the United States.
Children3 Streptomycin 15 mg/kg twice daily (maximum 2 g/day) IM Not widely available in the United States.
Gentamicin 2.5 mg/kg/dose every 8 hours IM or IV Not FDA approved but considered an effective alternative to streptomycin.1 Due to poor abscess penetration, consider alternative or dual therapy for patients with bubonic disease.
Levofloxacin 10 mg/kg/dose (maximum 500 mg/dose) IM or po Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague.
Ciprofloxacin 15 mg/kg/dose every 12 hours (maximum 400 mg/dose) IV Bactericidal. FDA approved based on animal studies but limited clinical experience treating human plague.
20 mg/kg/dose every 12 hours (maximum 500 mg/dose) po
Doxycycline Weight < 45 kg: 2.2 mg/kg twice daily (maximum 100 mg/dose) Weight ≥ 45 kg: same as adult dose IV or po Bacteriostatic, but FDA approved and effective in a randomized trial when compared to gentamicin.2 No tooth staining after multiple short courses.4
Chloramphenicol (for children > 2 years) 25 mg/kg every 6 h (maximum daily dose, 4 g) IV Not widely available in the United States
Pregnant women3 Gentamicin Same as adult dose IM or IV See notes above
Doxycycline Same as adult dose IV See notes above
Ciprofloxacin Same as adult dose IV See notes above

Post-exposure prophylaxis (PEP)

Post-exposure prophylaxis is indicated in persons with known exposure to plague, such as close contact with a pneumonic plague patient or direct contact with infected body fluids or tissues. Duration of post-exposure prophylaxis to prevent plague is 7 days. The recommended antibiotic regimens for PEP are as follows:

Adapted from: Inglesby TV, Dennis DT, Henderson DA, et al. Plague as a biological weapon: medical and public health management Working Group on Civilian Biodefense. JAMA. 2000 May 3;283(17):2281-90.

1Doxycycline and ciprofloxacin are pregnancy categories D and C, respectively.  PEP should be given only when the benefits outweigh the risks.
  Preferred agents Dose Route of administration
Adults Doxycycline 100 mg twice daily PO
Ciprofloxacin 500 mg twice daily PO
Children Doxycycline (for children ≥ 8 years) Weight < 45 kg: 2.2 mg/kg twice daily (maximum daily dose, 200 mg)
Weight ≥ 45 kg: same as adult dose		 PO
Ciprofloxacin 20 mg/kg twice daily (maximum daily dose, 1 g) PO
Pregnant women Doxycycline1 100 mg twice daily PO
Ciprofloxacin1 500 mg twice daily PO

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