Signs and Symptoms: Pneumonic plague incubates 2-3 days. High fever, chills, headache, hemoptysis, and toxemia, progressing rapidly to dyspnea, stridor, and cyanosis. Death from respiratory failure, circulatory collapse, and a bleeding diathesis. Bubonic plague incubates 2-10 days. Malaise, high fever, and tender lymph nodes (buboes); may progress spontaneously to the septicemic form, with spread to the CNS, lungs, etc.
Diagnosis: Presumptive diagnosis can be made by Gram or Wayson stain of lymph node aspirates, sputum, or CSF. Plague bacilli may also be cultured on standard media.
Treatment: Early administration of antibiotics is very effective. Supportive therapy is required.
Prophylaxis: A licensed, killed vaccine is available. Primary series of an initial dose followed by a second smaller dose 1-3 months later, and a third dose 5-6 months after the second dose. Give 3 booster doses at 6 month intervals following dose 3 of the primary series then every 1-2 years. This vaccine is effective against bubonic plague, but probably not against aerosol exposure.
Isolation and Decontamination: Standard Precautions for healthcare workers exposed to bubonic plague. Droplet Precautions for healthcare workers exposed to pneumonic plague. Heat, disinfectants (2-5% hypochlorite) and exposure to sunlight renders bacteria harmless.
Yersinia pestis, a rod-shaped, non-motile, non-sporulating, gram-negative, bipolar staining, facultative anaerobic bacterium. It causes plague, normally a zoonotic disease of rodents (e.g., rats, mice, ground squirrels). Fleas which live on the rodents can sometimes pass the bacteria to human beings, who then suffer from the bubonic form of plague. The pneumonic form of the disease would be seen as the primary form after purposeful aerosol dissemination of the organisms. The bubonic form would be seen after purposeful dissemination through the release of infected fleas. All human populations are susceptible. Recovery from the disease may be followed by temporary immunity. The organism will probably remain viable in water and moist meals and grains for several weeks. At near freezing temperatures, it will remain alive from months to years but is killed by 15 minutes exposure to 72 ° C. It also remains viable for some time in dry sputum, flea feces, and buried bodies but is killed within several hours of exposure to sunlight.
HISTORY AND SIGNIFICANCE
The United States worked with Y. pestis as a potential biowarfare agent in the 1950's and 1960's before the old offensive biowarfare program was terminated, and other countries are suspected of weaponizing this organism. During World War II, there is reported evidence that Japan investigated the use of Y. pestis as a biological weapon. It was reported that they worked on a plan for attacking enemy troops with the organism by releasing plague-infected fleas. This bacterium could be delivered theoretically as an aerosol.
Plague normally appears in three forms in man; bubonic, primary septicemic, and pneumonic. The buboes in the bubonic form are normally seen in the inguinal lymph nodes as the legs are the most commonly "flea-bitten" part of the human body. Septicemia is common, as greater than 80 percent of blood cultures are positive for the organism in bubonic plague, although primary septicemia may occur without lymphadenopathy. The pneumonic form is an infection of the lungs due either to inhalation of the organisms (primary pneumonic plague), or spread to the lungs from septicemia (secondary pneumonic plague). In man, the mortality of untreated bubonic plague is approximately 50 percent, whereas in pneumonic plague the mortality rate is 100 percent.
After an incubation period varying from 2-3 days for primary pneumonic plague, onset is acute and often fulminant. The presentation is one of malaise, high fever, chills, headache, myalgia, cough with production of a bloody sputum, and toxemia. The chest X-ray reveals a patchy or consolidated bronchopneumonia. The pneumonia progresses rapidly, resulting in dyspnea, stridor, and cyanosis. The terminal event is one of respiratory failure, circulatory collapse, and a bleeding diathesis. In bubonic plague the incubation period ranges from 2 to 10 days with the onset also being acute and often fulminant. The presentation is one of malaise, high fever, and one or more tender lymph nodes. The liver and spleen are often tender and palpable. One quarter of patients will have various types of skin lesions. Occasionally a pustule, vesicle, eschar or papule containing leukocytes and bacteria will be apparent in the bubo distribution and presumably represents the site of the inoculating flea bite. Bubonic plague may progress spontaneously to the septicemic form with organisms spreading to the central nervous system, lungs, and elsewhere. Black necrotic and purpuric lesions caused by endotoxemia are also often present.
Laboratory findings include a leukocytosis, with a total WBC count up to 20,000 cells with increased bands, and greater than 80 percent polymorphonuclear cells. One also often finds increased fibrin split products in the blood indicative of a low-grade DIC, and the ALT, AST, and bilirubin are also elevated.
A presumptive diagnosis can be made microscopically by identification of the gram-negative coccobacillus with safety-pin bipolar staining in Gram or Wayson's stained smears from a lymph node needle aspirate, sputum, or cerebrospinal fluid sample. When available, immunofluorescent staining is very useful. A definitive diagnosis can be readily made by culturing the organism from blood, sputum, and bubo aspirates. The organism grows slowly at normal incubation temperatures, and may be misidentified by automated systems because of delayed biochemical reactions. It may be cultured on blood agar, MacConkey agar or infusion broth. Most naturally occurring strains of Y. pestis produce an F1-antigen in vivo, which can be detected in serum samples by immunoassay. A four-fold rise in antibody titer in patient serum is also diagnostic.
Use Standard Precautions for healthcare workers exposed to bubonic plague and Droplet Precautions for healthcare workers exposed to pneumonic plague until the patient has been on antibiotic therapy for at least 48 hours and there has been a favorable clinical response to treatment. Streptomycin, tetracycline, chloramphenicol, and gentamicin are highly effective, especially if begun early (within 24 hours of onset of symptoms). Plague pneumonia is almost always fatal if treatment is not initiated within 24 hours of the onset of symptoms. Streptomycin remains the drug of choice and is given 30 mg/kg/day (IM) in two divided doses for ten days. Gentamicin is acceptable if streptomycin is unavailable. While the patient is typically afebrile after 3 days, the extra week of therapy prevents relapses. Intravenous doxycycline 200 mg initially, followed by 100 mg every 12 hours for 10-14 days is also effective. Results obtained from laboratory animal, but not human, experience, indicate that quinolone antibiotics, such as ofloxacin and ciprofloxacin, may also be effective. The addition of chloramphenicol is required for the treatment of plague meningitis.
Usual supportive therapy required includes IV crystalloids and hemodynamic monitoring. Although low-grade DIC may occur, clinically significant hemorrhage is uncommon as is the need to treat with heparin. Finally, buboes rarely require incision and drainage or any form of local care, but instead recede with systemic antibiotic therapy. In fact, incision and drainage may pose a risk to others in contact with the patient.
Vaccine: A licensed, killed whole cell vaccine is available for use in those considered to be at risk of exposure. The primary series consists of three doses. The initial dose of 1.0 ml IM followed by 0.2 ml IM at 1 and 6 months. Three booster doses of 0.2 ml IM are given at 6 month intervals following the third dose of the primary series and then every 1-2 years thereafter. The current vaccine offers protection against bubonic plague, but is probably not effective against aerosolized Y. pestis. Presently, 8-10 percent of inoculations result in local reactions which include erythema, induration, tenderness and edema at the site of injection. These typically resolve within 48 hours. Approximately 7-10 percent of inoculations will result in systemic symptoms including malaise, lymphadenopathy, fever and very rarely anaphylaxis, tachycardia, urticaria, or hypotension.
Antibiotics: Because of oral administration and relative lack of toxicity, the choice of antibiotic for prophylaxis or for use in face-to-face contacts of patients with pneumonic plague or after a confirmed or suspected plague BW attack is doxycycline 100 mg orally twice daily, for seven days or the duration of risk of exposure, whichever is longer. Ciprofloxacin has also shown to be effective in preventing disease in exposed mice, and may be more available in a wartime setting as it is also distributed in blister-packs for anthrax post-exposure prophylaxis.
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