SUMMARY
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.
OVERVIEW
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.
CLINICAL FEATURES
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.
DIAGNOSIS
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.
MEDICAL MANAGEMENT
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
(1 gm IV QID x 10-14 days) 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.
PROPHYLAXIS
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.
Copyright © : MMI Alaska Chris