PLAGUE

• Caused by Yersinia pestis, a rod shaped, gram-negative coccobacillus.

• Transmission to humans usually occurs through the bites of infected rodent fleas, by handling infected animal carcasses, or by respiratory droplets from animals to humans and from humans to humans.

• Plague is endemic in the western regions of the United States, but extremely rare in Washington State.

• Naturally occurring plague in humans has three clinical forms:  bubonic, pneumonic and septicemic. 

• Pneumonic plague would be the most likely outcome of an intentional (bioterrorist) aerosol dissemination.  The bubonic form would arise if plague is inoculated through the skin. Septicemic plague can arise secondarily either from pneumonic or bubonic forms of the disease or as the primary manifestation of infection.  

• Person-to-person transmission CAN occur with primary pneumonic plague.

PNEUMONIC PLAGUE 

Incubation: 2-3 days

Clinical Presentation: Typically a fulminant presentation.

• Presenting symptoms include:  malaise, high fever, chills, headache, myalgia, cough with production of bloody sputum and toxemia. 

• CXR shows patchy or consolidated bronchopneumonia, mediastinitis, and/or pleural effusions (there are no specific CXR findings for plague).

• Rapidly progressing pneumonia results in dypsnea, stridor and cyanosis. 

• Terminal illness is characterized by respiratory failure, circulatory collapse, and a bleeding diathesis.

• Mortality of untreated pneumonic plague is approximately 100%

Laboratory Clues to Y. pestis:

• Gram stain and Wayson’s stain:  Gram-negative coccobacillus with “safety pin” bipolar staining in smears from respiratory secretions, lymph node aspirates, or cerebrospinal fluid are presumptively diagnostic.

• Microbiology: Definitive diagnosis: isolation of Y. pestis from blood, sputum or lymph node.  Y. pestis grows slowly at normal incubation temperatures and may be misidentified by automated readers.

• Immunology:  A four-fold rise in antibody titer is diagnostic.  F1 antigen detection by immunofluorescent assay is presumptively diagnostic.

Laboratory Confirmation of Diagnosis:

• Testing should be performed by the Department of Health Public Health Laboratories or the CDC.

• Appropriate clinical samples for testing at Public Health Laboratories include blood, sputum or tracheal washings, needle aspirate(s) from swollen lymph nodes, or CSF.

• Coordinate transport and packaging of clinical specimens with local and state health departments.

• Public Health Laboratories have the capacity to report preliminary results within four hours while laboratory confirmation may take days.

BUBONIC PLAGUE

Incubation: 2-10 days.

• Bacteria are transmitted through the bite of an infected flea or by direct inoculation of contaminated material through the skin.

Clinical presentation:

• Presenting signs and symptoms include malaise, high fever and one or more tender lymph nodes.  The liver and spleen may be palpable.

• A pustule or ulcer may develop at the site of inoculation as well as large, tender regional lymph nodes called buboes.

• In naturally occurring bubonic plague, buboes most often involve inguinal or axillary lymph nodes as extremities are the most common areas bitten by fleas.

• Bacteremia is common, with greater than 80% of blood cultures being positive for the organism in bubonic plague.

• Mortality of untreated bubonic plague is approximately 50%.

SEPTICEMIC PLAGUE

• Most often occurs due to dissemination from bubonic or pneumonic plague infections though may occur as primary presentation of the disease.

• Blood cultures are positive for the organism.

• May occur without lymphadenopathy.

• May spread to lungs causing secondary pneumonic plague.  Mediastinitis or pleural effusion may develop.

• Bloodstream dissemination of the organism may infect various parts of the body including the meninges, causing meningitis.

• Endotoxic shock and disseminated intravascular coagulation may occur without localizing signs of infection.

TREATMENT OF PLAGUE

• Treatment of all forms of the disease is most effective when started within 24 hours of initial symptoms.

• Plague pneumonia is often fatal if treatment is not initiated within 24 hours of the onset of symptoms.

• Physicians may be asked to obtain informed consent for administration of certain medications supplied by the National Pharmaceutical Stockpile (NPS).

POST-EXPOSURE PROPHYLAXIS

• An exposed person is defined as a person who has been exposed to aerosolized Y. pestis or has been in close contact with a confirmed pneumonic plague patient:

• Close contact with a case patient is defined as less than two meters during a period when a case was symptomatic and before the case had received 48-72 hours of antibiotics.

• Household contacts and healthcare worker contacts should be considered exposed and should receive prophylaxis.

• All antibiotic therapy should continue for 7 days after the last exposure to the case.

• Decisions on antibiotic therapy should be guided by susceptibility testing.

• Physicians may be asked to obtain informed consent for administration of certain medications supplied by the National Pharmaceutical Stockpile (NPS).

RECOMMENDATIONS FOR THE TREATMENT OF PATIENTS WITH PNEUMONIC PLAGUE IN THE CONTAINED AND MASS CASUALTY SETTINGS AND FOR POST EXPOSURE PROPHYLAXIS^{1, 2}    

Contained Casualty Setting

Mass Casualty Setting and Postexposure Prophylaxis⁸

1.        These are consensus recommendations of the Working Group on Civilian Biodefense and are not necessarily approved by the Food and Drug Administration.  In non-bioterrorism response situations, routine treatment guidelines should be followed.  Please refer to original publication (Ingelsby TV, Dennis DT, Henderson, DA, et al. Plague as a biological weapon: Medical and public health management. JAMA. 2000;283:2281-2290) for explanations and further discussion.

2.        One antimicrobial agent should be selected.  Therapy should be continued for 10 days. Oral therapy should be substituted when patient’s condition improves. 

3.        Aminoglycosides must be adjusted according to renal function.  Evidence suggests that gentamicin, 5 mg/kg IM or IV once daily, would be efficacious in children, although this is not yet widely accepted in clinical practice.  Neonates up to 1 week of age and premature infants should receive gentamicin, 2.5 mg/kg IV twice daily. 

4.        Other fluoroquinolones can be substituted at doses appropriate for age. 

5.        Serum concentration should be maintained between 5 and 20 mg/mL.  Concentrations greater than 25 mg/mL can cause reversible bone marrow suppression. 

6.        Refer to “Management of Special Groups” in the source article for details. Children younger than 2 years should not receive chloramphenicol.

7.        Refer to “Management of Special Groups” in the source article for details and discussion of breastfeeding women.  Alternatives to breastfeeding may be required while mother is taking certain antibiotics. See specific antibiotic package insert for information on breastfeeding

8.        Duration of treatment of plague in mass casualty settings is 10 days.  Duration of postexposure prophylaxis to prevent plague infection is 7 days.

9.        Children younger than 2 years should not receive chloramphenicol.  Oral formulation available only outside the United States.

10.     Tetracycline may be substituted for doxycycline.

* Indicates medications which will be supplied as part of the NPS maintained at the CDC

INFECTION CONTROL

• Pneumonic plague can be spread from person-to-person by respiratory droplet transmission (coughing, sneezing).

• Multiple patients with pneumonic plague may be isolated together as long as all patients are receiving appropriate therapy.

• Patients with pneumonic plague should be placed on Droplet Precautions until 48 hours after the administration of appropriate antibiotics and clinical improvement has been demonstrated.

• Standard (Universal) Precautions for care and transport of patients and during post-mortem care.

• Contact Precautions should be followed if skin lesions are present as transmission can occur from plague skin lesions (such as draining buboes or abscesses).

Plague Vaccine

A plague vaccine is no longer manufactured or available in the United States.