a. Clinical Syndrome.
(1) Characteristics. Plague is a zoonotic disease caused by Yersinia pestis. Under natural conditions, humans become infected as a result of contact with rodents, and their fleas. The transmission of the gram-negative coccobacillus is by the bite of the infected flea, Xenopsylla cheopis, the oriental rat flea, or Pulex irritans, the human flea. Under natural conditions, three syndromes are recognized: bubonic, primary septicemia, or pneumonic. In a biological warfare scenario, the plague bacillus could be delivered via contaminated vectors (fleas) causing the bubonic type or, more likely, via aerosol causing the pneumonic type.
(2) Clinical Features. In bubonic plague, the incubation period ranges from 2 to 10 days. The onset is acute and often fulminant with malaise, high fever, and one or more tender lymph nodes. Inguinal lymphadenitis (bubo) predominates, but cervical and axillary lymph nodes can also be involved. The involved nodes are tender, fluctuant, and necrotic. Bubonic plague may progress spontaneously to the septicemia form with organisms spread to the central nervous system, lungs (producing pneumonic disease), and elsewhere. The mortality is 50 percent in untreated patients with the terminal event being circulatory collapse, hemorrhage, and peripheral thrombosis. In primary pneumonic plague, the incubation period is 2 to 3 days. The onset is acute and fulminant with malaise, high fever, chills, headache, myalgia, cough with production of a bloody sputum, and toxemia. The pneumonia progresses rapidly, resulting in dyspnea, strider, and cyanosis. In untreated patients, the mortality is 100 percent with the terminal event being respiratory failure, circulatory collapse, and a bleeding diathesis.
(1) Presumptive. Presumptive diagnosis can be made by identification of the gram-negative coccobacillus with safety-pin bipolar staining organisms in Giemsa or Wayson’s stained slides from a lymph node needle aspirate, sputum, or cerebrospinal fluid (CSF) samples. When available, immunofluorescent staining is very useful. Elevated levels of antibody to Y. pestis in a nonvaccinated patient may also be useful.
(2) Definitive. Yersinia pestis can be readily cultured from blood, sputum, and bubo aspirates. Most naturally occurring strains of Y. pestis produce an “F1” antigen in vivo which can be detected in serum samples by immunoassay. A fourfold rise of Y. pestis antibody levels in patient serum is also diagnostic.
(3) Differential. In cases where bubonic type is suspected, tularemia adenitis, staphylococcal or streptococcal adenitis, meningococcemia, enteric gramnegative sepsis, and rickettsiosis need to be ruled out. In pneumonic plague, tularemia, anthrax, and staphylococcal enterotoxin B (SEB) agents need to be considered. Continued deterioration without stabilization effectively rules out SEB. The presence of a widened mediastinum on chest x-ray should alert one to the diagnosis of anthrax.
c. Therapy. Plague may be spread from person to person by droplets. Strict isolation procedures for all cases are indicated. Streptomycin, tetracycline, and chloramphenicol are highly effective if begun early. Significant reduction in morbidity and mortality is possible if antibiotics are given within the first 24 hours after symptoms of pneumonic plague develop. Intravenous doxycycline (200 mg initially, followed by 100 mg every 12 hours), intramuscular streptomycin (1 g every 12 hours), or intravenous chloramphenicol (1 g every 6 hours) for 10-14 days are effective against naturally occurring strains. Supportive management of lifethreatening complications from the infection, such as shock, hyperpyrexia, convulsions, and disseminated intravascular coagulation (DIC), need to be initiated as they develop.
d. Prophylaxis. A formalin-killed Y. pestis vaccine is produced in the United States and has been extensively used. Efficacy against flea-borne plague is inferred from population studies, but the utility of this vaccine against aerosol challenge is unknown. Reactogenicity is moderately high and a measurable immune response is usually attained after a 3-dose primary series: at 0, 1, and 4-7 months. To maintain immunity, boosters every 1-2 years are required. Live-attenuated vaccines are available elsewhere but are highly reactogenic and without proven efficacy against aerosol challenge.