Plague

Prophylaxis

Vaccine. No vaccine is currently available for prophylaxis of plague. A licensed, killed whole-cell vaccine was available in the U.S. from 1946 until November 1998. It offered protection against bubonic plague, but was not effective against aerosolized Y. pestis. Presently, an F1-V antigen (fusion protein) vaccine is in development at USAMRIID. It protected mice for a year against an inhalational challenge, and is now being tested in primates.

Immunoprophylaxis. There is no passive immunoprophylaxis (i.e., immune globulin) available for pre- or postexposure management of plague.

Preexposure prophylaxis: No antibiotics are licensed by the FDA for use before exposure to plague. However, chemoprophylaxis with doxycycline (or ciprofloxacin) may protect against plague based upon in vitro susceptibilities.

Postexposure prophylaxis: Face-to-face contacts (within 2 meters) of patients with pneumonic plague or persons possibly exposed to a plague aerosol (i.e., in a plague BW attack) should be given antibiotic prophylaxis for 7 days or the duration of risk of exposure plus 7 days. If fever or cough occurs in these individuals, a full treatment course with antibiotics should be started.

Preferred empiric prophylaxis:

  • Doxycycline 100 mg po bid for adults and children >=45 kg (for children <45 kg use 2.2 mg / kg po bid), or

Alternatives

  • Ciprofloxacin 500 mg po bid for adults (20 mg/kg po bid (up to 1 g/day) for children)
  • Chloramphenicol, 25mg/kg po qid

Other tetracyclines and fluoroquinolones antibiotics could potentially be substituted for doxycycline and ciprofloxacin, respectively. Trimethoprim-sulfamethoxazole may represent a second-line alternative, should susceptibilities allow. Chemoprophylaxis is generally not recommended after contact with bubonic or septicemic plague patients; however, individuals making such contacts, especially if sharing the same environment in which the patient received a natural exposure, should be observed for symptoms for a week. If symptoms occur, start treatment antibiotics while awaiting results of diagnostic studies.

Postexposure Prophylaxis for Pneumonic Plague

Antibiotic prophylaxis (with tetracycline, doxycycline, or trimethoprim-sulfamethoxazole) following exposure to a person with primary or secondary pneumonic plague has been recommended as a public health control measure (see References: ACIP/CDC 1996). Prophylaxsis also is recommended for laboratory workers who may have been exposed to an infectious aerosol via a laboratory accident (see References: Worsham 2007). Tetracycline and doxycycline are approved by the FDA for this indication. Clinical experience with the fluoroquinolones for prophylaxis against pneumonic plague is limited; however, animal studies have suggested efficacy in this setting (see References: Russell 1996).

Few data are available on the efficacy of postexposure prophylaxis in this setting; however, according to a CDC report published in 1984, more than 2,000 persons had been placed on prophylactic antibiotics, and no cases of person-to-person transmission had been reported (see References: CDC 1984). In fact, the CDC has not received any reports of person-to-person Y pestis transmission in the United States since the last US outbreak of pneumonic plague in Los Angeles in the 1920s.

The Working Group on Civilian Biodefense developed consensus-based recommendations in 2000 for treatment and postexposure prophylaxis of pneumonic plague during a bioterrorist attack (see References: Inglesby 2000). The working group made the following recommendations:

  • Any potentially exposed persons in the affected community in whom a temperature of 38.5°C or higher or a new cough develops should be evaluated and placed on appropriate parenteral therapy (if available) for presumptive pneumonic plague. (Note: the working group did not recommend mass use of antibiotic prophylaxis for the entire population in the affected community in response to a release of Y pestis organisms.)
  • Persons who have close contact with a patient with pneumonic plague who has not received at least 48 hours of appropriate antibiotic therapy should receive antibiotic postexposure prophylaxis, as outlined in the table below. Since transmission occurs through respiratory droplets, close contact is defined as contact at less than 2 meters.
  • Persons who develop fever or cough while receiving antibiotic prophylaxis should be evaluated immediately for pneumonic plague and treated appropriately if plague is suspected.

Recommendations from the Working Group on Civilian Biodefense for Antib iotic Postexposure Prophylaxis During an Outbreak of Pneumonic Plague Following a Bioterrorism Event

Choices by Patient Category

Therapy Recommendationsa

Adults: Preferred choices

Doxycycline: 100 mg PO twice daily for 7 daysb,c
or
Ciprofloxacin: 500 mg PO twice daily for 7 daysc,d

Adults: Alternative choicee

Chloramphenicol: 25 mg/kg PO 4 times daily for 7 daysf

Children: Preferred choices

Doxycycline:
    >45 kg: same as adult
   <45 kg: 2.2 mg/kg PO twice daily for 7 daysb
or
Ciprofloxacin: 20 mg/kg PO twice daily for 7 days (maximum daily dose, 1 g)d

Children: Alternative choicee

Chloramphenicol: 25 mg/kg PO 4 times daily for 7 days (maximum daily dose, 4 g)f,g

Abbreviation: PO, orally.

aRecommendations were reached by consensus of the Working Group on Civilian Biodefense and may not necessarily be approved by the Food and Drug Administration. Although these recommendations are intended for postexposure prophylaxis, they also can be used for treatment of plague cases in the mass-casualty setting where the number of patients is too great for all patients to receive intravenous antibiotics and oral antibiotics must be substituted (except that treatment should be continued for 10 days instead of 7 days as for prophylaxis).
bTetracycline can be substituted for doxycycline at a dose of 10-25 mg/kg/day divided into 2-4 doses.
cAcceptable for pregnant women. Although fetal toxicity may occur with doxycycline use and toxic effects on the liver in pregnancy have been noted with the tetracycline class, the working group recommended doxycycline or ciprofloxacin for postexposure prophylaxis of pregnant women or for treatment of infection in the mass-casualty setting.
dOther fluoroquinolones may be substituted at dosages appropriate for age.
eTrimethoprim-sulfamethoxazole (40 mg sulfa/kg/day administered orally in 2 divided doses for 7 days) has been recommended for postexposure prophylaxis in children younger than 8 years old and pregnant women (see References: AAP 2006, McGovern 1997).
fConcentration should be maintained between 5 and 20 mcg/mL; concentrations >25 mcg/mL can cause reversible bone marrow suppression. The oral formulation is available only outside the United States.
gAccording to the working group, children younger than 2 years of age should not receive chloramphenicol.

Adapted from Inglesby 2000 (see References).

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