Plague is an infectious disease of animals and humans caused by the bacterium Yersinia pestis. Y. pestis, is found in rodents and their fleas in many areas around the world.
Pneumonic plague occurs when Y. pestis infects the lungs. The first signs of illness in pneumonic plague are fever, headache, weakness, and cough productive of bloody or watery sputum. The pneumonia progresses over 2 to 4 days and may cause septic shock and, without early treatment, death.
Person-to-person transmission of pneumonic plague occurs through respiratory droplets, which can only infect those who have face-to-face contact with the ill patient.
Early treatment of pneumonic plague is essential. Several antibiotics are effective, including streptomycin, tetracycline, andchloramphenicol.
There is no vaccine against plague.
Prophylactic antibiotic treatment for 7 days will protect persons who have had face-to-face contact with infected patients.
SUMMARY (Courtesy Medical NBC Online Information Server)
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, anda bleeding diathesis. Bubonic plague incubates 2-10 days. Malaise, high fever,and tender lymph nodes (buboes); may progress spontaneously to the septicemicform, with spread to the CNS, lungs, etc.
Diagnosis: Presumptive diagnosis can be made by Gram or Wayson stainof lymph node aspirates, sputum, or CSF. Plague bacilli may also be cultured onstandard media.
Treatment: Early administration of antibiotics is very effective.Supportive therapy is required.
Prophylaxis: A licensed, killed vaccine is available. Primary seriesof an initial dose followed by a second smaller dose 1-3 months later, and athird dose 5-6 months after the second dose. Give 3 booster doses at 6 monthintervals following dose 3 of the primary series then every 1-2 years. Thisvaccine is effective against bubonic plague, but probably not against aerosolexposure.
Isolation and Decontamination: Standard Precautions for healthcareworkers exposed to bubonic plague. Droplet Precautions for healthcare workersexposed to pneumonic plague. Heat, disinfectants (2-5% hypochlorite) andexposure to sunlight renders bacteria harmless.
OVERVIEW
Yersinia pestis, a rod-shaped, non-motile, non-sporulating,gram-negative, bipolar staining, facultative anaerobic bacterium. It causesplague, normally a zoonotic disease of rodents (e.g., rats, mice, groundsquirrels). Fleas which live on the rodents can sometimes pass the bacteria tohuman beings, who then suffer from the bubonic form of plague. The pneumonicform of the disease would be seen as the primary form after purposeful aerosoldissemination of the organisms. The bubonic form would be seen after purposefuldissemination through the release of infected fleas. All human populations aresusceptible. Recovery from the disease may be followed by temporary immunity.The organism will probably remain viable in water and moist meals and grains forseveral weeks. At near freezing temperatures, it will remain alive from monthsto years but is killed by 15 minutes exposure to 72 ° C. It also remains viablefor some time in dry sputum, flea feces, and buried bodies but is killed withinseveral hours of exposure to sunlight.
HISTORY AND SIGNIFICANCE
The United States worked with Y. pestis as a potential biowarfareagent in the 1950's and 1960's before the old offensive biowarfare program wasterminated, and other countries are suspected of weaponizing this organism.During World War II, there is reported evidence that Japan investigated the useof Y. pestis as a biological weapon. It was reported that they worked ona plan for attacking enemy troops with the organism by releasing plague-infectedfleas. This bacterium could be delivered theoretically as an aerosol.
CLINICAL FEATURES
Plague normally appears in three forms in man; bubonic, primarysepticemic, and pneumonic. The buboes in the bubonic form are normally seen inthe inguinal lymph nodes as the legs are the most commonly"flea-bitten" part of the human body. Septicemia is common, as greaterthan 80 percent of blood cultures are positive for the organism in bubonicplague, although primary septicemia may occur without lymphadenopathy. Thepneumonic form is an infection of the lungs due either to inhalation of theorganisms (primary pneumonic plague), or spread to the lungs from septicemia(secondary pneumonic plague). In man, the mortality of untreated bubonic plagueis approximately 50 percent, whereas in pneumonic plague the mortality rate is100 percent.
DIAGNOSIS
After an incubation period varying from 2-3 days for primary pneumonicplague, 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 ableeding diathesis. In bubonic plague the incubation period ranges from 2 to 10days with the onset also being acute and often fulminant. The presentation isone of malaise, high fever, and one or more tender lymph nodes. The liver andspleen are often tender and palpable. One quarter of patients will have varioustypes of skin lesions. Occasionally a pustule, vesicle, eschar or papulecontaining leukocytes and bacteria will be apparent in the bubo distribution andpresumably represents the site of the inoculating flea bite. Bubonic plague mayprogress spontaneously to the septicemic form with organisms spreading to thecentral nervous system, lungs, and elsewhere. Black necrotic and purpuriclesions caused by endotoxemia are also often present.
Laboratory findings include a leukocytosis, with a total WBC count up to20,000 cells with increased bands, and greater than 80 percent polymorphonuclearcells. One also often finds increased fibrin split products in the bloodindicative of a low-grade DIC, and the ALT, AST, and bilirubin are alsoelevated.
A presumptive diagnosis can be made microscopically by identification of thegram-negative coccobacillus with safety-pin bipolar staining in Gram or Wayson'sstained smears from a lymph node needle aspirate, sputum, or cerebrospinal fluidsample. When available, immunofluorescent staining is very useful. A definitivediagnosis can be readily made by culturing the organism from blood, sputum, andbubo aspirates. The organism grows slowly at normal incubation temperatures, andmay be misidentified by automated systems because of delayed biochemicalreactions. It may be cultured on blood agar, MacConkey agar or infusion broth.Most naturally occurring strains of Y. pestis produce an F1-antigen invivo, which can be detected in serum samples by immunoassay. A four-foldrise in antibody titer in patient serum is also diagnostic.
MEDICAL MANAGEMENT
Use Standard Precautions for healthcare workers exposed to bubonic plague andDroplet Precautions for healthcare workers exposed to pneumonic plague until thepatient has been on antibiotic therapy for at least 48 hours and there has beena 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 fatalif 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 twodivided doses for ten days. Gentamicin is acceptable if streptomycin isunavailable. While the patient is typically afebrile after 3 days, the extraweek of therapy prevents relapses. Intravenous doxycycline 200 mg initially,followed by 100 mg every 12 hours for 10-14 days is also effective. Resultsobtained from laboratory animal, but not human, experience, indicate thatquinolone antibiotics, such as ofloxacin and ciprofloxacin, may also beeffective. The addition of chloramphenicol is required for the treatment ofplague meningitis.
Usual supportive therapy required includes IV crystalloids and hemodynamicmonitoring. Although low-grade DIC may occur, clinically significant hemorrhageis uncommon as is the need to treat with heparin. Finally, buboes rarely requireincision and drainage or any form of local care, but instead recede withsystemic antibiotic therapy. In fact, incision and drainage may pose a risk toothers in contact with the patient.
PROPHYLAXIS
Vaccine: A licensed, killed whole cell vaccine is available for use inthose considered to be at risk of exposure. The primary series consists of threedoses. 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 thethird dose of the primary series and then every 1-2 years thereafter. Thecurrent vaccine offers protection against bubonic plague, but is probably noteffective against aerosolized Y. pestis. Presently, 8-10 percent ofinoculations result in local reactions which include erythema, induration,tenderness and edema at the site of injection. These typically resolve within 48hours. Approximately 7-10 percent of inoculations will result in systemicsymptoms including malaise, lymphadenopathy, fever and very rarely anaphylaxis,tachycardia, urticaria, or hypotension.
Antibiotics: Because of oral administration and relative lack oftoxicity, the choice of antibiotic for prophylaxis or for use in face-to-facecontacts of patients with pneumonic plague or after a confirmed or suspectedplague BW attack is doxycycline 100 mg orally twice daily, for seven days or theduration of risk of exposure, whichever is longer. Ciprofloxacin has also shownto be effective in preventing disease in exposed mice, and may be more availablein a wartime setting as it is also distributed in blister-packs for anthraxpost-exposure prophylaxis.
