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Plague Fact Sheet

Plague in Humans at CECDP

Synopsis of Plague
Plague is a zoonotic disease caused by the bacterium Yersinia pestis. Plague is transmitted primarily by fleas as part of an etiologic agent (Y. pestis)-arthropod vector-vertebrate host cycle with enzootic and epizootic components. The enzootic (maintenance) rodent hosts (e.g., wood rats) are relatively resistant to the disease, whereas epizootic (amplifying) hosts (e.g., rock squirrels, ground squirrels) tend to have low to moderate resistance. Infection also occurs in other animals. For example, infection in carnivores (e.g., dogs, cats, coyotes, mountain lions) most likely occurs as a result of ingesting plague-infected animals or flea bites. Carnivores, effective transporters of infective fleas to other rodent populations and to humans, are most often the direct source of human infection. With the exception of cats, carnivores are relatively resistant to the disease. Natural infection has also been reported in goats, sheep, and camels and also the result of ingestion or flea bites. And, infection has occurred in humans. Historically, plague has destroyed entire civilizations. In the 1300s, the “Black Death,” as it was called, killed approximately one-third (20 to 30 million) of Europe’s population. In the mid-1800s, it killed 12 million people in China. In the U.S., the last plague epidemic occurred in Los Angeles in 1924-25. Since then, human plague in the U.S. has occurred as mostly scattered cases in rural areas (10 to 15 cases per year). The highest risk groups in the U.S. includes those persons exposed to rodent fleas, wild rodents, or other susceptible animals in enzootic areas of western states (most cases occur in southwestern states of NM, AZ, CO, and CA), as well as Native Americans, hunters, veterinarians, pet owners handling infected cats, and campers or hikers entering areas with outbreaks of animal plague. Plague can be a life-threatening disease in people (fatality ratio if untreated is 30-60%) depending on the form of clinical manifestations, bubonic, septicemic and pneumonic.
  • In animals, transmission occurs via flea bites from an infective flea, inhalation of aerosol, ingestion of food or water exposed to an aerosol, or ingestion of another infected animal.
  • In humans, transmission occurs via fleas from infected rodents to humans, direct contact with infected tissues or fluids from handling sick or dead animals, and from respiratory droplets from cats and humans with pneumonic plague.
  • Basic transmission cycle: fleas become infected by feeding on rodents that are circulating the bacterium in their bloodstreams. The fleas then transmit the infection to humans or other mammals during the feeding process. Respiratory droplets of the infected person or animal can then transmit the infection to another person or animal.
  • Basic transmission cycle: fleas become infected by feeding on rodents that are circulating the bacterium in their bloodstreams. The fleas then transmit the infection to humans or other mammals during the feeding process. Respiratory droplets of the infected person or animal can then transmit the infection to another person or animal.
  • Click on the following link for a detailed description of the Y. pestis: Yersinia pestis - Etiologic Agent of Plague.1
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Clinical Signs and Symptoms
Rodents:
  • Enzootic hosts
  • Disease may take acute, subacute, or resolving forms
  • Clinical signs and symptoms for acute form:
    • Hemorrhagic buboes (swollen lymph nodes)
    • Splenomegaly
    • Nasal bleeding
    • Petechia
    • Abscess formation
    • Pneumonitis
    • Death within 3 to 5 days of infection
  • Clinical signs and symptoms for subacute form:
    • Necrotic bulboes
    • Necrotic nodules in the liver, spleen, and lungs
    • Nasal bleeding
    • Petechia
    • Abscess formation
    • Pneumonitis
    • Death in 6 or more days after infection
  • Clinical signs for resolving form:
    • Lymphadenopathy
    • Focal purulent necrosis
Dogs:
  • Relatively resistant
    • Fever
    • Development of antibodies
  • Function as transporters of infective fleas to other rodents, animals, and humans
  • May be used as sentinels by checking antibody titers
Cats:
  • Domestic cats are highly susceptible to plague and can transmit infection to humans via one of the following mechanisms:
    • Bites or scratches
    • Direct contact with infectious exudates
    • Inhalation of infectious respiratory droplets
    • Freely roaming cats can transport infective fleas into home environments
  • Cat-associated human cases were first verified in the U.S. in 1977. Since that time, approximately 25 human cases have been associated with Y. pestis-infected cats. Of these, seven occurred in veterinarians or their assistants. Cats pose a significant plague risk to owners, veterinarians, and others who handle or come into close contact with these animals.
  • Clinical Symptoms (Bubonic plague):
    • Incubation period: 2 to 3 days
    • Submandibular lymphadenitis
    • Fever
    • Lethargy
    • Anorexia
  • Clinical Symptoms (Pneumonic plague):
    • Incubation period: 3 to 4 days
    • Serious, rapidly progressing illness
    • Fever
    • Cough
    • Bloody sputum
  • Case-fatality rate (untreated) is 38%
Ungulates:
  • Y. pestis infections are rarely identified in ungulates in the U.S.; however, any ungulate that becomes seriously ill or dies under suspicious circumstances following an intentional release of plague should be examined.
Birds, Reptiles, and Fish:
  • Are considered to be completely resistant to Y. pestis infection
Humans:
  • Incubation: 2-6 days
  • Clinical Features:
    • Bubonic plague is the most common form of plague resulting from the bite of an infective flea. Plague bacillus enters the skin at from the site of the bite and travels through the lymphatic system to the nearest lymph node. The lymph node then becomes inflamed due to bacterial replication. The swollen lymph node is referred to as a "bubo" which is very painful and can become suppurated as an open sore in the advanced stages of infection. Buboes can appear in the groin, armpit, or neck region. Other clinical symptoms include the following:
      • Fever
      • Chills
      • Headache
      • Extreme exhaustion
    • Septicemic plague occurs when infection spreads directly through the bloodstream (where they multiply and spread rapidly throughout the body) without evidence of a "bubo" and may be the result of a flea bite or from direct contact with infective materials through cracks in the skin. Clinical symptoms include the following:
      • Fever
      • Chills
      • Prostration
      • Abdominal pain
      • Shock
      • Bleeding into the skin and other organs
    • Pneumonic plague is the most virulent and least common form of plague. It typically occurs as a result of a secondary spread from advanced infection or an initial bubonic form. Primary pneumonic plague results from inhalation of aerosolized infective droplets and can be transmitted from human to human without involvement of fleas or animals. Untreated pneumonic plague has a very high case-fatality ratio. Clinical symptoms include the following:
      • High fever
      • Chills
      • Cough
      • Difficulty breathing
      • Blood sputum
      • Possibly death (case-fatality rate (untreated) is 50-90% and (diagnosed/treated) is 15%)
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Diagnosis and Treatment
Diagnostic Samples:
  • In animals (ante mortem samples):
    • Lesion specimens - swabs of lesions, such as oral cavity or draining lymph nodes
    • Acute and convalescent serum samples of 0.5 ml should be collected at least 14 days apart
    • Pharyngeal swabs for suspicion of pneumonic plague
  • In animals (post mortem samples):
    • Lymph node aspirate
    • Tissue samples
      • Lymph node
      • Liver
      • Spleen
      • Lung
      • Long bones from decaying carcasses for analysis of bone marrow
      • Tissue samples should be placed in a clean container and kept chilled. Do not use formalin or alcohol.
    • Whole blood
  • In humans:
    • For bubonic cases, material form the affected bubo is the most appropriate specimen. Blood smears taken from suspected bubonic plague patients are usually negative for bacteria. However, bacteria may be intermittently released from affected lymph nodes into the bloodstream; therefore, a series of blood specimens taken 10-30 minutes apart may be productive in the isolation of Y. pestis.
    • For septicemic cases, blood samples are the most appropriate specimens.
    • For pneumonic cases, sputum/throat smears or bronchial/tracheal washings are the most appropriate specimens.
    • Post mortem samples include lymphoid tissues, lung, and bone marrow samples.
Differential Diagnosis:
  • In animals:
    • Anthrax
    • Tularemia
  • In humans, the differential diagnoses include the following:
    • For bubonic plague: appendicitis, capnocytophaga canimorsus, cellulites, lymphogranulom venereum, and non-specific infections that produce localized, unilateral lymphadenopathy, such as streptococcal or staphylococcal adenitis (Staphylococcal aureus, Staphylococcal pyogenes), tularemia (Francisella tularensis), cat scratch disease (Bartonella henselae), etc.
    • For septicemic plague: meningococcemia, septicemia caused by other gram-negative bacteria, etc.
    • For pneumonic plague: inhalation anthrax (Bacillus anthracis), tularemia (Francisella tularensis), community-acquired bacterial pneumonia, viral pneumonia, Q fever (Coxiella burnetii), etc.
Clinical Diagnosis:
  • Bubonic plague should be suspected when a person develops a swollen gland, fever, chills, headache, and extreme exhaustion, and has a history of possible exposure to infected rodents, rabbits, or fleas.
Laboratory Tests:
  • In animals:
    • Fluorescent antibody
      • Presumptive diagnosis: elevated serum antibody titer(s) to Y. pestis fraction 1 (F1) antigen without documented four-fold or greater change in a patient with no history of plague vaccination
      • Confirmatory diagnosis: a four-fold rise in antibody titer to Y. pestis fraction 1 (F1) antigen) in patient serum
    • Bacteriologic culture of peripheral blood, sputum, and bubo or cerebrospinal fluids and use of one of the following methods:
      • Specific phagocytolysis
      • Immunofluorescence
      • Agglutination
      • Phage typing
      • PCR
    • Microscopic examination (Gram, Wright, Giemsa, or Wayson's stained smears of peripheral blood, sputum, and bubo or cerebrospinal fluids)
      • Presumptive diagnosis: bipolar-staining, ovoid, Gram-negative organisms
  • In humans:
    • Fluorescent antibody
      • Presumptive diagnosis: elevated serum antibody titer(s) to Y. pestis fraction 1 (F1) antigen without documented four-fold or greater change in a patient with no history of plague vaccination
      • Confirmatory diagnosis: a four-fold rise in antibody titer to Y. pestis fraction 1 (F1) antigen) in patient serum
    • Bacteriologic culture of peripheral blood, sputum, and bubo or cerebrospinal fluids and use of one of the following methods:
      • Specific phagocytolysis
      • Immunofluorescence
      • Agglutination
      • Phage typing
      • PCR
    • Microscopic examination (Gram, Wright, Giemsa, or Wayson's stained smears of peripheral blood, sputum, lymph gland, and bubo or cerebrospinal fluids)
      • Presumptive diagnosis: bipolar-staining, ovoid, Gram-negative organisms
    • Rapid dipstick tests have been validated for field use to quickly screen for Y. pestis antigen in patients
  • Click here for more detailed information on basic protocols for laboratory identification of Y. pestis.2
Treatment:
  • In animals:
    • Antibiotic therapy:
      • Streptomycin is the treatment of choice
      • Gentamicin
      • Doxycycline
      • Tetracycline
      • Chloramphenicol
  • In humans:
    • A patient diagnosed with suspected plague should be hospitalized and medically isolated
    • Persons who have been in close contact with a plague patient should be identified and evaluated
    • Antibiotic treatment:
      • Streptomycin is the antibiotic of choice
      • Gentamicin is used when streptomycin is unavailable
      • Tetracyclines and chloramphenicol are also effective
    • Vaccination:
      • Vaccines are not recommended for immediate protection in outbreak situations.
      • Vaccines are only recommended as a prophylactic measure for high-risk groups, such as laboratory personnel who are constantly exposed to the risk of contamination.
  • Infection control:
    • Patients (animal and human) should be isolated for the first 48 to 72 hours of antibiotic treatment and until clinical improvement occurs.
    • Strict isolation protocols should be followed for patients with pneumonic plague, along with disinfection of clothing and management of contacts.
    • When treating these patients, routine barrier precautions should be followed, such as surgical gowns, gloves, eye protection, and masks.
    • Contact with remains of animal and human patients that have died following infection with Y. pestis should be handled with care by trained personnel.
    • Necropsy/autopsy procedures should not be performed due to the possible generation of aerosols.
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Economic Consequences and Disease Eradication
Economic Consequences
  • Costs associated with diagnosis and treatment
  • Costs associated with eradication efforts
Disease Prevention and Eradication:
  • All cases of suspected plague must be reported immediately to local and state health departments.
  • The diagnosis must be confirmed by the CDC and; as required by the International Health Regulations, the CDC must report all U.S. plague cases the WHO.
  • In addition, diagnostic laboratories should be informed that plague is a possible diagnosis when specimens are submitted in order to ensure that safe processing protocols are followed.
  • Basic approach:
    • Education - Inform people to be aware of the areas where zoonotic plague is active and to take precautions against flea bites and handling carcasses while in plague-endemic areas. People should also avoid having direct contact with infective tissues, or from being exposed to patients with pneumonic plague.
    • Vector control - control rodent and flea populations
      • Flea control products: fipronil or pyrethrin
    • Pets should be regularly defleaed
    • Environmental sanitation
    • Avoid flea bites by using insecticides and repellents
    • Rat-proof buildings, store food appropriately, and dispose of garbage
    • Wear protective clothing, such as gloves, when hunting or handling wildlife
    • Preventive antibiotic therapy
  • Infection control for pet owners:
    • Owners of cats with suspected plague should be advised to consult their physician and local or state health department
    • Confine pets as much as possible to reduce the risk of transporting infected fleas into homes
    • Cats and other mammalian pets should not share sleeping areas with family members
    • All ill animals, especially cats, should be seen by a veterinarian
  • Case recognition, medical intervention, and field investigation:
    • Identify the most likely source of infection in the area where the human case(s) was exposed, typically looking for clustered areas with large numbers of small animal die-offs. Institute appropriate sanitation and control measures to stop the exposure source.
    • Ensure dissemination of information concerning areas with active plague transmission, the clinical features of plague and the case definitions to health workers.
    • Verify that patients have been placed on appropriate antibiotic treatment and that local supplies of antibiotics are adequate to handle further cases.
    • Isolate pneumonic plague patients.
    • Obtain specimens for laboratory confirmation.
    • Active long-term surveillance of zoonotic foci and rapid response to reduce exposure during epizootic outbreaks have been successful in reducing human plague.
  • To access the CDC Plague training module, click on the following link: http://www.bt.cdc.gov/agent/plague/trainingmodule/.
  • Viability:
    • Sensitive to sunlight and heat
    • Will not survive for long periods outside a host
    • Household bleach solution, with a contact time of 30 minutes, may be used effectively for decontamination prior to normal cleaning
      • If organic material is present (quickly denatures bleach solutions), cleaning should precede decontamination
Plague and Bioterrorism:
  • Y. pestis is widely available in microbiology banks around the world, can be produced in large quantities, and can be disseminated as an aerosol.
  • NIAID research:
    • Identifying genes in the Y. pestis bacterium that infect the digestive tract of fleas and researching how the bacterium is transferred to humans
    • Studying the disease-causing proteins and genes of Y. pestis that allow the bacterium to grow in humans and how they function in human lungs
    • NIAID is also working with the U.S. Department of Defense, the Centers for Disease Control and Prevention, and the Department of Energy to
      • Develop a vaccine that protects against inhalationally-acquired pneumonic plague
      • Develop promising antibiotics and intervention strategies to prevent and treat plague infection
  • Click on one of the following links for more information on the use of plague as a biological weapon:
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Outbreaks
  • Historically, plague has destroyed entire civilizations. In the 1300s, the "Black Death," as it was called, killed approximately one-third (20 to 30 million) of Europe's population. In the mid-1800s, it killed 12 million people in China.
  • In the U.S., the last urban plague epidemic occurred in Los Angeles in 1924-1925. Since then, human plague in the U.S. has occurred as mostly scattered cases in rural areas (an average of 10 to 15 persons each year. Most human cases in the U.S. occur in two regions: 1. northern New Mexico, northern Arizona, and southern Colorado; and 2. California, southern Oregon, and far western Nevada.
  • Cat-associated human cases were first verified in the U.S. in 1977. Since that time, approximately 25 human cases have been associated with Y. pestis-infected cats. Of these, seven occurred in veterinarians or their assistants.
  • Globally, the World Health Organization reports 1,000 to 3,000 cases of plague each year. Plague exists in Africa, Asia, and South America. In 2003, nine countries reported about 2,000 human cases and about 180 deaths. According to WHO, 98.7% of those cases and 98.9% of those deaths were reported from Africa.
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Sources and Related Articles
Sources:
Related Articles:
  1. Perry, R. D. and J. D. Fetherston, January 1997. Yersinia pestis - Etiologic Agent of Plague. Clinical Microbiology Reviews. 10(1):35-66. Available at http://cmr.asm.org/cgi/reprint/10/1/35.pdf.←
  2. Chu, M. C., S. E. Sharp, and M. A. Saubolle, April 22, 2002. Basic Protocols for Level A Laboratories: For the Presumptive Identification of Yersinia pestis. Published by the CDC in collaboration with the American Society for Microbiology and the Association of Public Health Laboratories. Available at http://www.asm.org/ASM/files/LEFTMARGINHEADERLIST/DOWNLOADFILENAME/....←
  3. Inglesby, T. V., D. T. Dennis, D. A. Henderson, J. G. Bartlett, M. S. Ascher, et. al., May 3, 2000. Plague as a Biological Weapon. JAMA. 283(17):2281-2290. Available at http://jama.ama-assn.org/cgi/reprint/283/17/.←
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