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PLAGUE
Updated 9/2001
Agent: Plague is an acute febrile zoonotic disease caused by Yersinia pestis, a nonmotile microaerophilic bacillus (sometimes coccobacillus) of the family Enterobacteriaceae. There are three common forms of plague: bubonic (most common), pneumonic (most rapid and most frequently fatal), and septicemic. The latter two are either primary or secondary to metastatic spread. BW using plague would produce primarily pneumonic plague. Plague has a high mortality rate (>50%, with pneumonic having a higher rate) and over history has caused approximately 200 million deaths in pandemics in various parts of the world.
The most recent pandemic was in the late 19th and early 20th centuries and resulted in estimated 12,000,000 deaths. In recent years (1970s-1990s), most cases have been reported in Africa, Asia, and the Americas (Chin, 2000; Heddurshetti, Pumpradit, & Lutwick, 2001; Inglesby, Dennis, Henderson, Bartlett, Ascher, Eitzen, Fine, Friedlander, Hauer, Koerner, Layton, McDade, Osterholm, O'Toole, Parker, Perl, Russell, Schoch-Spana, & Tonat, 2000).
Routes of Infection: In a BW context, Y. pestis would be delivered in an aerosol and the inhaled organisms would cause primary pneumonic plague, with significant numbers of septicemic cases. Secondary pneumonic cases would occur from contact with patients with pneumonic plague. The bacillus may remain viable for as long as an hour after an attack (Heddurshetti, Pumpradit, & Lutwick, 2001; Inglesby et al, 2000).
As a naturally occurring zoonosis, plague is endemic among more than 200 rodents and is spread among them and transmitted to humans primarily by flea bite (resulting in bubonic plague), but also from direct inoculation through handling infected mammal carcasses or person-to-person via the respiratory route from infected droplets from a patient with pneumonic plague (Chin, 2000).
Incubation: The incubation period (with aerosolized Y. pestis) is usually 2-4 days with a range of 1-6 days.
CLINICAL FINDINGS & TREATMENT
Signs & Symptoms: Patients with pneumonic plague following an attack would present with acute fulminate pneumonia with high fever, malaise, dyspnea, and cough (sometimes productive of watery blood-tinged sputum; and less commonly, purulent sputum). Cutaneous manifestations (terminal stage) include livid cyanosis and large ecchymosis. Acral (digits, nose) necrosis may also occur. Gastrointestinal symptoms might occur, including abdominal pain, nausea, vomiting, and diarrhea. Buboes would seldom be present (in contrast to bubonic or secondary pneumonic plague, in which buboes are common). Sepsis would develop rapidly, with progression including dyspnea, stridor, cyanosis, shock, and respiratory failure (see septicemic plague below). Common radiographic finding would be bilateral alveolar infiltrates and consolidation (Heddurshetti, Pumpradit, & Lutwick, 2001; Inglesby et al, 2000; McGovern, Christopher, & Eitzen, 1999).
Naturally occurring plague is manifested by abrupt onset of high fever, severe headache, severe myalgias, prostration, and in some cases, delirium. The incubation period is 2-10 days. An ulcer may develop at the inoculation site. Lymphadenitis is followed by painful, draining bubo(s). Hematogenous spread or septicemic plague is characterized by rapid decline, disseminated intravascular coagulation, purpura, and coma (Chin, 2000; Titball & Leary, 1998).
Diagnosis: Delayed diagnosis virtually guarantees death. A presumptive diagnosis can be made on the basis of acute fulminating pneumonia with Gram-negative bacilli or coccobacilli and bipolar "safety-pin" staining organisms in sputum, peripheral blood, lymph node needle aspirate, or other specimens. The sudden appearance of large numbers of otherwise healthy individuals with severe pneumonia and sepsis indicates either plague or anthrax.
Differential Diagnosis: Large numbers of patients with severe pneumonia and sepsis indicates either plague or anthrax; and if there is hemoptysis, plague is the more likely. A single case might be one of several pneumonias. Diagnosis is confirmed by culture, antigen detection, IgM enzyme, immunostaining, and polymerase chain reaction (Heddurshetti, Pumpradit, & Lutwick, 2001; Inglesby et al, 2000).
Treatment: Treatment must begin within 24 hours of the onset of symptoms and preferably before. There is a lack of experience in treating (especially primary pneumonic) plague in humans, hence some therapies discussed below have not been adequately studied and are not FDA approved.
Mass casualties and
post-exposure (treat at least seven days):
Adults: Ciprofloxacin 500 mg po every 12 hours OR doxycycline 100 mg
(po or IV) every 12 hours. An alternative for adults is chloramphenicol 25
mg/kg po four times daily. All are given for at least seven days.
Children: Doxycycline is the preferred choice and if weight is 45 kg
or more, give adult dose and if less than 45 kg, give 2.2 mg/kg po every 12
hours (maximum 200 mg/24 hours) OR ciprofloxacin 20 mg/kg po every 12 hours
(up to adult dose). An alternative for children more than two years is chloramphenicol
25 mg/kg po four times daily. All are given for at least seven days.
Contained casualties
(treat 10 days):
Adults: Streptomycin 1 gram IM twice daily OR gentamicin 5mg/kg IM
or IV once daily (gentamicin is the choice for pregnant women). Alternatives
are doxycycline 100 mg IV twice daily OR doxycycline 200 mg IV once daily
OR ciprofloxacin 400 mg IV twice daily OR chloramphenicol 25 mg/kg IV 4 times
daily.
Children: Streptomycin 15 mg/kg IM twice daily (maximum dose 2 grams)
OR gentamicin 2.5mg/kg IM or IV 3 times daily. Alternatives include doxycycline:
if 45 kg or greater, give adult dose and if less than 45 kg, give 2.2 mg/kg
IV twice daily (maximum 200 mg/24 hours) OR ciprofloxacin 15 mg/kg IV twice
daily OR chloramphenicol 25 mg/kg IV 4 times daily if two years or older.
There is not currently a plague vaccine available in the U.S. (Heddurshetti, Pumpradit, & Lutwick, 2001; Inglesby et al, 2000).
Protection: Patients
should be isolated for the first 48 hours of antibiotic treatment and until
there is improvement; and unnecessary contact with others avoided. Close contacts
should receive prophylactic treatment. Isolation of close contacts who refuse
prophylaxis is not recommended; but such persons should be closely monitored
for fever or cough for the first seven days after exposure and treatment started
if either occurs. Patients and others in contact should wear disposable surgical
masks. Rooms of patients with pneumonic plague should be terminally cleaned
and contaminated linens disinfected according to hospital protocol. Plague
aerosol would likely be infectious for as long as one hour after release,
hence later environmental danger is minimal (Inglesby et al, 2000).
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