Anti-Infectives

Plague is caused by Yersinia pestis, a gram-negative coccobacillus. It is a zoonotic disease, and rodents, prairie dogs, and squirrels are the primary reservoirs. In a bioterrorist event, intentional dissemination of plague would most likely be delivered as an aerosol of Y. pestis, resulting in cases of primary pneumonic plague.

Pathogenesis
Plague is usually transmitted to humans by the bites of infected fleas. This results in inoculation of thousands of Y. pestis organisms into a patient’s skin. The bacteria migrate to regional lymph nodes and multiply, causing destruction of lymph node architecture and subsequent bacteremia.
Human infection can also be acquired by inhalation of plague bacilli via droplet nuclei. After inhalation, the bacteria migrate to mediastinal lymph nodes, multiply, and subsequently disseminate into the bloodstream. Plague rarely occurs after ingestion of infected meat or handling of contaminated tissue.

Clinical Manifestations
There are three clinical syndromes of plague infection:
Bubonic plague typically occurs 2 to 8 days after a flea bite. It is characterized by the sudden onset of fever, chills, and fatigue. This is followed by the development of a bubo, an acutely warm, tender, swollen regional lymph node (usually in the groin, axilla, or cervical region). Buboes are non-fluctuant and often associated with considerable edema. Despite treatment, bubonic plague carries a 14% case-fatality rate.
Septicemic plague develops in a small fraction of people infected by fleas. Buboes may or may not be present. Septicemic plague may lead to disseminated intravascular coagulation, plague meningitis, or gangrene of the digits or nose (thus the name “Black Death”). It carries a case-fatality rate of approximately 22% despite therapy.
Pneumonic plague may be primary or secondary. Secondary pneumonic plague develops via hematogenous spread in a small number of patients with bubonic or septicemic plague. Patients experience dyspnea, chest pain, and hemoptysis. Primary plague pneumonia is most likely in the event of a bioterrorist attack. It occurs 2 to 4 days after an exposure and manifests with symptoms similar to those of secondary pneumonic plague. Abdominal pain, nausea, and vomiting are also prominent. This syndrome rapidly progresses to sepsis and respiratory failure and is invariably fatal if therapy is delayed for more than 24 hours.

Diagnosis
The diagnosis of plague requires a high index of suspicion. Fever, cough, dyspnea, chest discomfort, and a fulminant course should immediately suggest the possibility of pneumonic plague or inhalational anthrax. The presence of hemoptysis in this setting suggests plague.
A Gram stain of infected blood or sputum may reveal safety pin-like gram-negative bacilli or coccobacilli. Cultures of sputum, blood, or lymph node aspirates are important in the diagnosis of the disease. Rapid diagnostic tests are not widely available. Direct antigen detection in urine, serologic tests, immunohistochemical staining of tissue, and PCR are available but usually are performed only in reference laboratories.

Treatment and Postexposure Prophylaxis
Postexposure prophylaxis for asymptomatic close contacts (less than 2 m) of patients with pneumonia consist of either oral doxycycline (100 mg twice daily) or ciprofloxacin (500 mg twice daily) for a total of 7 days. Fever or cough in a close contact warrants immediate isolation.

Infection Control
All patients with suspected pneumonic plague should be isolated to avoid person-to-person spread, and droplet precautions should be maintained during the first 48 hours of antibiotic treatment. Persons living or working in close contact with patients with confirmed or suspected pneumonic plague should use surgical masks to prevent disease transmission.
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ANTI-INFECTIVES