AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

No disease has impacted civilization as deeply as the plague. It has been estimated that up to 200 million people have died from this disease. The first pandemic, known as the Justinian plague (AD 541-544), began in Egypt and spread throughout the Middle East and Mediterranean areas. Eventually, the entire known world was affected. By the 8th century, plague receded into scattered endemic areas. The second pandemic began in 1347, when traders from central Asia introduced plague into ports of Sicily. This became the first epidemic, known as the Black Death, which killed over one third of the population of Europe. Later, following the Great Plague of London (1665), the disease subsided. The third pandemic began in Hong Kong in 1894 and continues to the present. Alexandre Yersin discovered the plague bacillus, Yersinia pestis, and effective antibiotics were introduced in the early 1940s; however, plague remains endemic in much of the world.

Pathophysiology

The classic mode of transmission to humans is a fleabite. Alternately, broken skin serves as a portal when tissue or blood of an infected animal is handled (skinning or evisceration of infected animals). Competency of the flea to serve as vector for transmission of plague to humans depends on its willingness to feed on a human host and its tendency to regurgitate intestinal contents during a blood meal. Fleas from sylvatic rodents feed on humans only reluctantly. However, the Oriental rat flea (Xenopsylla cheopis) is an effective vector because of its tendency to regurgitate and to feed on nonrodent hosts. When the flea takes a blood meal from an infected rodent, stomach enzymes cause a clot to form, blocking the flea's proventricularis. At its next attempt to feed, unable to swallow due to the blockage, the flea regurgitates plague bacilli into the bite wound.

The organisms invade the lymphatics and travel to regional lymph nodes, causing inflammation. Large, tender lymph nodes are termed buboes and give the bubonic form of plague its name. If the infection is not contained at this site, the organisms may be further spread via the bloodstream to organs such as lungs, spleen, liver, kidneys, and meninges. Bacteremia without the appearance of buboes is considered septicemic plague. Pneumonic plague occurs when pneumonia results from either hematogenous spread (secondary pneumonic plague) or inhalation (primary pneumonic plague) of organisms transmitted from animals or other humans.

Frequency

United States

Plague is considered endemic in all western and southwestern states. Native Americans who reside on reservations are at increased risk for acquisition of the disease. Most cases of plague are acquired in rural areas. Ground squirrels and prairie dogs serve as major enzootic foci. Dogs and cats are susceptible to plague. Domestic animals, cats in particular, have been responsible for human cases. The number of cases of plague reported to the WHO has decreased this decade, with only 1 case in 2003 and 2 per year in 2001 and 2002, none of which were fatal. This decline follows an increase in plague rates in the 1990s, with a high of 14 cases reported during 1994.

International

Plague reached a worldwide maximum of 5419 cases (274 fatal) in 1997, and the incidence has declined since. In 2003, 9 countries reported 2118 cases (182 fatal) to the WHO. Algeria reported cases of human plague for the first time in 50 years. India and Indonesia also recently reported cases after a 30- to 50-year quiescent period. Occurrence is thought to be underreported.

Mortality/Morbidity

• Bubonic plague: Mortality is approximately 16%, which increases to 40-70% in untreated cases. Practitioners must maintain a high index of suspicion for plague, especially with patients exposed to animals or fleas in endemic areas. The most common complications are secondary septicemia, pneumonia, and meningitis. Polyarthritis, lung abscesses, and superinfection of lymph nodes also occur.
• Septicemic plague: Mortality ranges from 30-50% for patients with septicemic plague and increases to nearly 100% in untreated cases. This high mortality rate reflects the difficulty in diagnosis, given the disease's similarity to gram-negative bacterial sepsis. Diagnosis often is made postmortem.
• Pneumonic plague: Thankfully rare, the fatality rate of pneumonic plague approaches 100%, regardless of treatment. The last reported case of person-to-person transmission occurred during a plague epidemic in Los Angeles in 1924. Since then, cases of primary pneumonic plague have been acquired chiefly from infected cats.

Sex

• Earlier reports demonstrated a male predominance in cases. A nearly equal sex distribution has been noted in more recent reviews.

Age

• Plague can occur at any age. Approximately 45% of reported cases from 1947 to 2001 occur in individuals younger than 19 years.
• Both of the deaths reported in the United States in 1996 occurred in adolescents.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Incubation period of plague is 3-4 days (range: hours to 10 days).

• Sore throat may be the only complaint of patients with plague pharyngitis.
• Bubonic plague
• • Patients complain of fever with abrupt onset and other constitutional symptoms. These symptoms usually manifest 3-6 days after contracting the organism but may appear in the first day or be delayed for longer than a week. Clinical manifestations of plague are the same for children and adults.
  • Fever with chills is virtually universal. Temperatures typically range from 38.5-40ºC.
  • Headache, malaise, and weakness are all very common.
  • An area of focal lymphadenopathy (bubo) develops. This bubo rapidly becomes very tender and can measure up to 10 cm. Over time, fluctuance develops, and the buboes often suppurate and drain. The most common site affected is the groin, followed by the axillary and cervical lymph nodes. Intra-abdominal buboes may present as an acute abdomen.
  • Nausea, vomiting, diarrhea, and abdominal pain are common. These, as well as the constitutional symptoms of headache and malaise, are thought to result from the gram-negative septicemia caused by Y pestis.
  • Patients with plague may complain of sleep disturbance, vertigo, and loss of memory. Weakness, delirium, stupor, ataxia, and speech disorders also may occur. These manifestations are due to the effects of endotoxin on the brain. Meningitis may develop. Children younger than 15 years appear to be more susceptible to meningitis.
• Septicemic plague
• • Constitutional symptoms are similar to bubonic plague. Absence of palpable buboes differentiates the 2 forms.
  • Meningitis is 4 times more common in this form of the disease than with bubonic plaque. Additionally, pneumonic plaque occurs twice as often in septicemic plaque than in the bubonic form.
  • Septicemic patients are often older than 60 years. They are usually less febrile, but mortality is higher.
  • Bacteremia may be so great that organisms can be visualized on peripheral smears.
• Pneumonic plague
• • Patients primarily manifest fever and respiratory symptoms, including cough, hemoptysis, and chest pain. Tachypnea and dyspnea are also common.
  • Thin, watery, blood-tinged sputum becomes frankly bloody and mucopurulent as the disease rapidly progresses.
  • Plague bacillus can be cultured from sputum, and disease transmission is thought to occur up to 2 meters from a coughing patient.

Physical

• Generally, patients with any form of plague are toxic in appearance. Apprehension and tachycardia are also common.
• All patients are febrile with chills.
• A large bubo is palpable in the groin, axilla, or neck of patients with bubonic plague. The mass is fixed, edematous, exquisitely tender, and often surrounded by an area of erythema.
• Intra-abdominal buboes may be accompanied by tenderness, guarding, and other peritoneal signs. Hepatomegaly can be present.
• Septicemic patients present with tachycardia, tachypnea, and hypotension. Systolic blood pressures are usually less than 100 mm Hg. Differentiation of patients with septicemic plague from patients with other types of gram-negative sepsis is often difficult due to the similarity of signs and symptoms.
• Patients with pneumonic plague manifest cough productive of bloody sputum, tachypnea, and dyspnea.
• Fever and meningismus accompany plague meningitis.
• Patients with plague pharyngitis resemble those with any other form of bacterial pharyngitis or tonsillitis. Large anterior cervical adenopathy may be appreciated.

Causes

• Bacteriology
• • Y pestis is a nonmotile, pleomorphic, gram-negative coccobacillus belonging to the family Enterobacteriaceae. Bipolar staining can be observed with Giemsa, Wayson, or Wright stains.
  • It grows at a wide range of temperatures (4-40ºC) but demonstrates optimal growth at room temperature.
  • Both an endotoxin and an exotoxin are produced, adding to the organism's pathogenicity.
• Transmission
• • Infected fleas transmit plague from animal to animal or animal to human. X cheopis, the Oriental rat flea, is the classic vector, but many other species of flea also are capable of transmitting plague. Typically, this form of transmission is common in crowded urban areas.
  • In the United States, humans are infected with plague in a more sporadic fashion. A wild animal contracts plague through infected fleas, then is handled by humans as a result of hunting or accidental discovery of the carcass. Occasionally, a domestic cat may become infected while hunting and subsequently transmit plague to its owner or veterinarian through direct contact or inhalation.
  • Person-to-person transmission occurs primarily through droplet exposure from a patient with the pneumonic form of the disease, although direct contact with body fluids also can be infectious. Flea-borne spread also can occur among humans.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Anthrax
Granuloma inguinale
Lymphogranuloma venereum
Sepsis
Surgical abdomen

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory diagnosis can be very slow. Any patient with suspected plague based on clinical or epidemiological reasons should be empirically treated with prompt appropriate antibiotic therapy after blood and tissue samples have been collected.
• Culture of Y pestis is the diagnostic criterion standard. The organism can be isolated from blood, sputum, cerebrospinal fluid, and bubo aspirates, depending on the patient's presentation. Y pestis is slow growing, but it does not require any special growth media. When attempting to culture Y pestis from a suspected case, the microbiology laboratory should be alerted to minimize the possibility of accidental transmission to personnel.
• Staining lymph node aspirates with Wright, Wayson, or Giemsa stain reveals the typical bipolar (safety pin) morphology. Blood of patients who are septicemic can also be stained to reveal organisms. A positive fluorescence antibody test on smears or cultures is presumptive evidence of infection.
• Serologic tests may be an adjunct to diagnosis. Acute and convalescent sera can be tested for fraction 1 (F1) envelope antigen and antibody by enzyme immunoassay or passive hemagglutination. A single positive hemagglutination assay or enzyme immunoassay in a patient who has not received plague vaccine nor has had previous plague is also presumptive of infection.
• Polymerase chain reaction (PCR) is available.
• Associated laboratory findings include leukocytosis, elevated liver function enzymes, and evidence of disseminated intravascular coagulopathy.
• A recently developed rapid field test has been developed but is not available in the United States.

Imaging Studies

• Pneumonic plague does not exhibit a specific chest x-ray picture. Bilateral patchy infiltrates may be seen, but unilateral consolidation is also common. Pleural effusion and hilar lymphadenopathy also can be appreciated.

TREATMENT

Section 6 of 11  

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• Follow-up
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• Multimedia
• References

Medical Care

• Initial evaluation may begin on an emergent outpatient basis. However, hospitalization generally is required to initiate therapy. Isolation of hospitalized patients varies on type of disease. Standard precautions are indicated for cases of bubonic plague. Droplet precautions are indicated for patients with pneumonic plague and for all patients until pneumonia has been excluded and treatment initiated. In patients with pneumonic plague, isolation should be continued until 48 hours of appropriate antibiotic treatment has been administered.
• Provide supportive medical care as necessary to stabilize and maintain the patient's hemodynamic and respiratory status.

Surgical Care

• Incision and drainage of buboes may be indicated. Material drained from the buboes is infectious until patient is treated appropriately.

Consultations

• Infectious disease
• Intensive care, if hemodynamic or respiratory instability is present

Diet

• No special diet is required.

Activity

• No specific activity restrictions are required.

MEDICATION

Section 7 of 11  

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Drug Category: Antibiotic agents

Few antibiotics are effective against Y pestis. Each agent is associated with toxicity, but, given the high mortality rate of the disease if untreated, treatment is preferable. New multidrug-resistant strains of Y pestis have been reported in Madagascar.

Drug Name	Gentamicin (Garamycin)
Description	Aminoglycoside used as an alternative to streptomycin and is equally effective.
Adult Dose	Loading dose: 2 mg/kg IV q8hMaintenance dose: 1-1.5 mg/kg IV q8h
Pediatric Dose	<5 years: 2.5 mg/kg/dose IV q8h >5 years: 1.5-2.5 mg/kg/dose IV q8h or 6-7.5 mg/kg/d divided q8h, not to exceed 300 mg/d
Contraindications	Documented hypersensitivity; non?dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents thus prolonged respiratory depression may occur Coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	D - Unsafe in pregnancy
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patient not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment; monitor serum levels

Drug Name	Kanamycin (Kantrex)
Description	Aminoglycoside used as an alternative to streptomycin or gentamicin.
Adult Dose	15 mg/kg/d IV divided q8-12h
Pediatric Dose	15-30 mg/kg/d IV divided q8-12h
Contraindications	Documented hypersensitivity; non?dialysis-dependent renal insufficiency
Interactions	Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents thus prolonged respiratory depression may occur Coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	D - Unsafe in pregnancy
Precautions	Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patient not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment; monitor serum levels

Drug Name	Tetracycline (Sumycin)
Description	Frequently used for prophylaxis as well as treatment. Usually is substituted for streptomycin after a few days of therapy to minimize toxicity. Inhibits bacterial protein synthesis by binding with 30S and, possibly, 50S ribosomal subunits.
Adult Dose	250-500 mg PO q6h
Pediatric Dose	<8 years: Not recommended >8 years: 25-50 mg/kg/d PO divided qid
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Doxycycline (Doxy, Vibramycin)
Description	Used as an alternative for tetracycline. Inhibits protein synthesis and thus bacterial growth by binding to 30S and, possibly, 50S ribosomal subunits.
Adult Dose	100 mg IV q12h
Pediatric Dose	<8 years: Not recommended >8 years: 2-4 mg/kg/d IV divided q12h, not to exceed 200 mg/d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last half of pregnancy through age 8 years) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Chloramphenicol (Chloromycetin)
Description	DOC for plague meningitis. The PO form is not available in the United States, but the IV formulation can be obtained. Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis.
Adult Dose	50 mg/kg/d IV divided q6h, not to exceed 4 g/d
Pediatric Dose	50-100 mg/kg/d IV divided q6h
Contraindications	Documented hypersensitivity
Interactions	Concurrently with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Avoid in pregnancy at term or during labor because of potential toxic effects on fetus (gray baby syndrome); serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur; evaluate baseline and perform periodic blood studies approximately every 2 d while in therapy; discontinue on appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction

FOLLOW-UP

Section 8 of 11  

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• Follow-up
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• Multimedia
• References

Further Inpatient Care

• Admit for antibiotic therapy and isolation.

Further Outpatient Care

• Patient may be discharged on oral tetracycline or doxycycline after 48 hours if hemodynamically stable and symptoms are resolving.
• Follow up closely for potential relapse.

In/Out Patient Meds

• Antibiotics include streptomycin, tetracycline, doxycycline, and chloramphenicol. Y pestis is often susceptible in vitro to ampicillin, but this antibiotic is rarely effective in vivo. Gentamicin is equally as effective as streptomycin. Kanamycin can sometimes be useful.
• Antipyretics are useful for patient comfort.

Transfer

• Transfer may be required for further hemodynamic and respiratory monitoring and isolation.

Deterrence/Prevention

• Identifying the source of infection is vital in preventing outbreaks. If an urban area is involved, rodent control should be undertaken. In rural plague-endemic areas, the public must be instructed to avoid handling sick or dead animals and to avoid places where wild animals live. Pets should be kept free of fleas.
• Contacts of pneumonic plague victims should receive antibiotic prophylaxis. Tetracycline or streptomycin typically is used. Trimethoprim-sulfamethoxazole also has been effective for prophylaxis. Contacts of those with bubonic or septicemic plague have no need for prophylaxis.
• Plague vaccine is no longer available in the United States. Vaccine development is in progress.

Complications

• Polyarthritis
• Lung abscesses
• Suppuration or superinfection of buboes
• Meningitis
• Death

Prognosis

• Mortality rate for untreated plague is 40-70%.
• Pneumonic plague is nearly 100% fatal.
• From 1947-1996, reported mortality rate in the United States was 15%.
• Because plague is often a difficult disease to consider in the differential diagnosis, many patients who succumb to it have previously sought medical care.

MISCELLANEOUS

Section 9 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to consider plague in the differential diagnosis
• Failure to take adequate precautions in patients with pneumonic plague against transmission to others
• Failure to differentiate septicemic plague from gram-negative bacterial sepsis

Special Concerns

• Disease reporting
• • By law, cases of suspected plague must be reported to the state or local health department. The health department then alerts the CDC. Both organizations investigate all suspected cases.
  • Confirmed cases are reported to the WHO.
• Bioterrorism
• • Y pestis has been used as a bioweapon, notably by the Japanese during World War II. In addition, in the midst of the Cold War, the former Soviet Union weaponized the plague bacillus. Today, the use of plague as a biological weapon has clear advantages for terrorists.
  • Plague is endemic in many parts of the world and is easily found in nature. Only a small inoculum of fewer than 500 organisms needs to be inhaled to result in pneumonic plague, which is then very contagious to individuals within a 2-m radius. Mortality is high if patients are not treated rapidly. The 3-4 day incubation period, coupled with modern transportation systems, allows for swift widespread expansion of disease. Initial symptoms are clinically indistinguishable from various common illnesses, especially during the winter season.
  • A high index of suspicion is required to discern plague from community-acquired pneumonia or numerous viral illnesses.

MULTIMEDIA

Section 10 of 11  

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• Miscellaneous
• Multimedia
• References

Media file 1:  Bioterrorist agents: signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/bioterrorism.html.
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Media type:  Image

Media file 2:  Wright stain peripheral blood smear of patient with septicemic plague demonstrating bipolar, safety pin staining of Yersinia pestis. While Wright stain often demonstrates this characteristic appearance, Giemsa and Wayson stains most consistently highlight this pattern. Courtesy of Jack Poland, PhD, CDC, Fort Collins, CO.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Centers for Disease Control and Prevention. Fatal human plague--Arizona and Colorado, 1996. MMWR; Can Commun Dis Rep. 1997;46:617-620. [Medline].
• Cleri DJ, Vernaleo JR, Lombardi LJ, et al. Plague pneumonia disease caused by Yersinia pestis. Semin Respir Infect. Mar 1997;12(1):12-23. [Medline].
• Crook LD, Tempest B. Plague. A clinical review of 27 cases. Arch Intern Med. Jun 1992;152(6):1253-6. [Medline].
• Dattwyler RJ. Community-acquired pneumonia in the age of bio-terrorism. Allergy and Asthma Proc. 2005;26:191-194.
• Dennis DT, Chow CC. Plague. Pediatric Infectious Disease Journal. 2004;23(1):69-71.
• Galimand M, Guiyoule A, Gerbaud G, et al. Multidrug resistance in Yersinia pestis mediated by a transferable plasmid. N Engl J Med. Sep 4 1997;337(10):677-80. [Medline].
• Goldstein MD. Plague (Yersinia pestis). Textbook of Pediatric Infectious Diseases. 1998;1334-1339.
• Hoyle JD Jr, White LJ. Treatment of pediatric and adolescent mental health emergencies in the United States: current practices, models, barriers, and potential solutions. Prehosp Emerg Care. Jan-Mar 2003;7(1):66-73. [Medline].
• Josko D. Yersinia pestis: Still a plague in the 21st century. Clin Lab Sci. 2004;17(1):25-29.
• Perry RD, Fetherston JD. Yersinia pestis--etiologic agent of plague. Clin Microbiol Rev. Jan 1997;10(1):35-66. [Medline].
• Russell P, Nelson M, Whittington D, et al. Laboratory diagnosis of plague. Br J Biomed Sci. Dec 1997;54(4):231-6. [Medline].
• Smego RA, Frean J, Koornhof HJ. Yersiniosis I: microbiological and clinicoepidemiological aspects of plague and non-plague Yersinia infections. Eur J Clin Microbiol Infect Dis. Jan 1999;18(1):1-15. [Medline].
• Solomon T. Hong Kong, 1894: the role of James A Lowson in the controversial discovery of the plague bacillus. Lancet. Jul 5 1997;350(9070):59-62. [Medline].
• Taketomo CK, Hodding JH, Kraus DM. Plague. In: Pediatric Dosage Handbook. 1998.
• Titball RW, Leary SE. Plague. Br Med Bull. 1998;54(3):625-33. [Medline].
• Weir E. Plague: a continuing threat. CMAJ. 2005;172(12):1555.
• World Health Organization. Human plague in 1996. Wkly Epidemiol Rec. Nov 20 1998;73(47):366-9. [Medline].
• World Health Organization. Human plague in 2002 and 2003. Wkly Epidemiol Rec. 2004;79(33):301-306.

Article Last Updated: May 15, 2006