Plague facts

November 13, 2001

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Causative agent

Plague is an infectious disease of animals and humans caused by Yersinia pestis (alternatively, Yersinia pseudotuberculosis ssp. pestis), a bacterium.

Natural distribution

Plague exists in nature as a disease of wild rodents, including rats, ground squirrels, and prairie dogs. Carnivores (e.g., dogs, coyotes, raccoons, and skunks) may become infected, but with the exception of cats, they rarely develop clinical signs. Domestic cats appear to be at increased susceptibility and about 50% of those affected will eventually succumb to the disease. Wild felids are believed to be at similar risk. Natural infection of goats, sheep, and camels has also been reported. Humans may develop bubonic, primary septicemic, or pneumonic plague from the bite of infected fleas; by handling tissues of infected animals, especially rodents and rabbits; by contact with airborne droplets from human patients or household pets (especially cats) with plague pharyngitis or pneumonia; or through careless manipulation of laboratory cultures.

Geographically, enzootic plague is associated with semiarid environments. Foci exist on all continents, with the exception of Australia. In North America, plague is found in animals and their associated fleas from the Pacific Coast to the Great Plains, and from southwestern Canada to Mexico. Human cases have developed in New Mexico, Arizona, Colorado, Nevada, and California. Common characteristics of endemic areas include the availability of rodent hosts with a short natural life expectancy and high reproductive potential and vector flea activity throughout the year.

Transmission

Plague is transmitted primarily by fleas as part of an etiologic agent (Y. pestis)-arthropod vector-vertebrate host cycle with enzootic and epizootic components. Enzootic (maintenance) rodent hosts (e.g., wood rats) tend to be relatively resistant to the disease, whereas epizootic (amplifying) hosts include those species with low to moderate resistance (e.g., rock squirrels). The most resistant individuals act as hosts for fleas, which in turn infect more susceptible animals. Susceptible animals usually die, but increase the population of infected fleas through their bacteremia.

Raptors may assist in the dissemination of plague through transport of infected fleas or prey. Carnivores are effective transporters of infective fleas to other rodent populations and to humans and are most often the direct source of human infection. Infection of carnivores is most likely due to ingestion of plague-infected animals rather than fleabites. Similarly, ingestion appears to be the source of the disease in goats, sheep, and camels.

Human-to-human spread from individuals with plague pneumonia has not occurred in the United States since 1924; however, six cases of respiratory tract infection have resulted from exposure to domestic pets with plague pneumonia. Direct contact with infected human or animal blood and tissues is another route of transmission. Interhuman transmission via human ectoparasites is rare and has been observed only in heavily infested environments. Use of Y. pestis as a biological weapon would most likely involve aerosolization of the bacterial agent.

Types and clinical signs of plague in animals and humans

Plague primarily affects wild and domestic rodents. Rabbits and hares are sometimes affected. Cats are also very susceptible. Rare cases have developed in goats, sheep, and camels. The source of infection for carnivores, goats, sheep, and camels is most likely contact with or ingestion of infected animals, rather than fleabites.

Rodents—In rodents, the disease may take acute, subacute, or resolving forms. In the acute form, rodents develop hemorrhagic buboes (swollen lymph nodes) and splenomegaly, without evidence of other internal lesions, and succumb within 3 to 5 days of infection. Rodents affected by subacute plague develop necrotic buboes and necrotic nodules in the liver, spleen, and lungs, with death 6 or more days after infection. Clinical signs in the acute and subacute forms include nasal bleeding, petechia, abscess formation, and pneumonitis. The resolving form of plague is characterized by lymphadenopathy with focal purulent necrosis.

Cats—Abscesses, lymphadenopathy (especially of the submandibular and cervical lymph nodes), lethargy, and fever are typical signs in cats infected with Y. pestis. Secondary pneumonia may also be present. Pathologic lesions include necrotic nodules in the spleen and liver and evidence of suppurative pneumonia. Mortality is approximately 50% among experimentally infected cats.

Dogs—Dogs inoculated orally with Y. pestis react only with fever. All orally infected dogs have developed antibodies and recovered.

Most naturally occurring cases of plague in humans result from the bite of a plague-infected flea. Clinical signs usually develop within 2 to 8 days of the insect bite and include sudden onset of headache, fever, chills, and weakness. A bubo (an acutely swollen and painful lymph node) may develop in any regional lymph node site, but most often appears in the axillary, cervical, or inguinal regions, approximately 24 hours after the start of clinical signs. The skin overlying the bubo is frequently reddened, warm, and edematous (bubonic plague). Some individuals may develop septicemia without a bubo (primary septicemic plague) or septicemia may occur secondary to bubonic plague. Gangrene (hence the name "black death"), coagulopathies, and multiple organ failure may result from advanced plague septicemia.

Secondary pneumonic plague develops in about 10 to 15% of patients with bubonic or primary septicemic plague by hematogenous spread of Y. pestis to the lungs. Clinical signs in patients with pneumonic plague include cough, chest pain, bronchopneumonia, and hemoptysis. Primary pneumonic plague caused by inhalation of Y. pestis is rare, but has been reported after handling of cats with pneumonic plague. In addition to respiratory disease, patients with pneumonic plague often show gastrointestinal signs such as nausea, abdominal pain, vomiting, and diarrhea. Other types of plague in humans include plague meningitis and plague pharyngitis. The case fatality rate for untreated bubonic plague in humans is about 50%. Untreated primary septicemic plague and pneumonic plague are invariably fatal. Modern therapy has markedly reduced fatalities from bubonic plague. Pneumonic and septicemic plague also respond if recognized and treated early.

Diagnosis

Y. pestis may be identified microscopically by examination of Gram, Wright, Giemsa, or Wayson's stained smears of peripheral blood, sputum, and bubo or cerebrospinal fluids. Finding bipolar-staining, ovoid, Gram-negative organisms permits a rapid presumptive diagnosis of plague. Organisms may also be identified through bacteriologic culture of these same fluids in appropriate media and use of specific phagocytolysis, immunofluorescence, agglutination, phage typing, or PCR tests. A four-fold rise in antibody titer in patient serum is also diagnostic.

Prevention

Prevention of plague is based on control of rodents and vectors. In areas where natural foci exist, continued surveillance for plague cases and epizootic plague activity is important. Resistant species, such as dogs and coyotes, may be used as sentinels by checking antibody titers. Insecticides should be used to control insect populations, and these should be applied prior to or simultaneously with methods to eradicate rodent reservoir populations. Preventing contact between domestic hosts and wild rodent sources of infection is also important. Cats and dogs should be kept indoors and food and shelter should be denied to rats or wild rodents around residences and recreational areas. Pets should be regularly defleaed.

A US-licensed vaccine was discontinued in 1999 and is no longer available. In other parts of the world killed vaccines and live, attenuated plague vaccines are available. Seven days of postexposure prophylaxis (doxycycline, ciprofloxacin, or chloramphenicol) is recommended for asymptomatic individuals having close (less than 2 meters) contact with plague victims.

Treatment

Historically, the treatment of choice for bubonic, septicemic, and pneumonic plague has been streptomycin; however, this drug is no longer readily available. Alternatives include gentamicin, doxycycline, ciprofloxacin, and chloramphenicol.

Infection control

For animals and humans, plague is a reportable disease in the United States. Local and state health departments, federal animal health officials, and the CDC's National Center for Infectious Diseases, Meningitis and Special Pathogens Branch should immediately be notified of any suspected cases. In addition, diagnostic laboratories should be informed that plague is a possible diagnosis when specimens are submitted, to ensure that safe processing protocols are followed.

Patients should be isolated during the first 48 to 72 hours of antibiotic treatment and until clinical improvement occurs. Strict isolation precautions should be followed for patients with pneumonic plague, along with disinfection of clothing, and management of contacts. Available evidence suggests that human-to-human transmission of plague occurs via respiratory droplets; therefore, routine barrier precautions (surgical gowns, gloves, eye protection, and masks) should be followed.

Bodies of animal and human patients that have died following infection with Y. pestis should also be handled with care. Contact with remains should be limited to trained personnel, and necropsy or autopsy procedures that are likely to generate aerosols (such as bone sawing) should not be performed.

Decontamination

Y. pestis is sensitive to sunlight and heat and does not survive for long periods outside a host. A household bleach solution, with a contact time of 30 minutes, may be used effectively for decontamination prior to normal cleaning. Organic material will quickly denature a bleach solution; therefore, if organic material is present, cleaning should precede decontamination.

Use of plague as a biological weapon

Plague resulting from aerosolization of Y. pestis is of most concern when considering the use of plague as a biological weapon. The first indication of an attack would most likely be a sudden outbreak of severe pneumonia and sepsis. The presence of hemoptysis in previously healthy patients with fever, cough, shortness of breath, chest pain, and rapid death would suggest the possibility of plague.


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