The Plague


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Diagram of plague transmission. The sylvantic rodent-flea cycle is when rodents (such as squirrels and chipmunks) and fleas transmit the pathogen to each other. Fleas and rodents can also transmit the pathogen to birds, which can carry the pathogen long distances. Fleas can also transmit to cows, which can then transmit to humans. Fleas can also transmit to rodents,  which are involved in long-distance transport if the travel on a boat. The urban rodent-flea cycle is when urban rodents (such as mice) and fleas transmit the pathogen to each other. Fleas can infect humans. Pneumonic transmission in humans is when one human transmits to another via the airborne route. Humans can carry the pathogen long distances when they travel. The squirrels and chipmunks in the sylvatic cycle can also transmit to humans; or they can transmit to cats which can then transmit to humans.
Yersinia pestis, the causative agent of plague, has numerous modes of transmission. The modes are divided into two ecological classes: urban and sylvatic (i.e., forest or rural). The urban cycle primarily involves transmission from infected urban mammals (rats) to humans by flea vectors (brown arrows). The disease may travel between urban centers (purple arrow) if infected rats find their way onto ships or trains. The sylvatic cycle involves mammals more common in nonurban environments. Sylvatic birds and mammals (including humans) may become infected after eating infected mammals (pink arrows) or by flea vectors. Pneumonic transmission occurs between humans or between humans and infected animals through the inhalation of Y. pestis in aerosols. (credit “diagram”: modification of work by Stenseth NC, Atshabar BB, Begon M, Belmain SR, Bertherat E, Carniel E, Gage KL, Leirs H, and Rahalison L; credit “cat”: modification of work by “KaCey97078”/Flickr)

The gram-negative bacillus Yersinia pestis causes the zoonotic infection plague. This bacterium causes acute febrile disease in animals, usually rodents or other small mammals, and humans. The disease is associated with a high mortality rate if left untreated. Historically, Y. pestis has been responsible for several devastating pandemics, resulting in millions of deaths. There are three forms of plague: bubonic plague (the most common form, accounting for about 80% of cases), pneumonic plague, and septicemic plague. These forms are differentiated by the mode of transmission and the initial site of infection.

In bubonic plague, Y. pestis is transferred by the bite of infected fleas. Since most flea bites occur on the legs and ankles, Y. pestis is often introduced into the tissues and blood circulation in the lower extremities. After a 2- to 6-day incubation period, patients experience an abrupt onset fever (39.5–41 °C [103.1–105.8 °F]), headache, hypotension, and chills. The pathogen localizes in lymph nodes, where it causes inflammation, swelling, and hemorrhaging that results in purple buboes. Buboes often form in lymph nodes of the groin first because these are the nodes associated with the lower limbs; eventually, through circulation in the blood and lymph, lymph nodes throughout the body become infected and form buboes. The average mortality rate for bubonic plague is about 55% if untreated and about 10% with antibiotic treatment.

Septicemic plague occurs when Y. pestis is directly introduced into the bloodstream through a cut or wound and circulates through the body. The incubation period for septicemic plague is 1 to 3 days, after which patients develop fever, chills, extreme weakness, abdominal pain, and shock. Disseminated intravascular coagulation (DIC) can also occur, resulting in the formation of thrombi that obstruct blood vessels and promote ischemia and necrosis in surrounding tissues. Necrosis occurs most commonly in extremities such as fingers and toes, which become blackened. Septicemic plague can quickly lead to death, with a mortality rate near 100% when it is untreated. Even with antibiotic treatment, the mortality rate is about 50%.

Pneumonic plague occurs when Y. pestis causes an infection of the lungs. This can occur through inhalation of aerosolized droplets from an infected individual or when the infection spreads to the lungs from elsewhere in the body in patients with bubonic or septicemic plague. After an incubation period of 1 to 3 days, signs and symptoms include fever, headache, weakness, and a rapidly developing pneumonia with shortness of breath, chest pain, and cough producing bloody or watery mucus. The pneumonia may result in rapid respiratory failure and shock. Pneumonic plague is the only form of plague that can be spread from person to person by infectious aerosol droplet. If untreated, the mortality rate is near 100%; with antibiotic treatment, the mortality rate is about 50%.

part a shows the upper leg of a person with a large red bump near the groin. Part b is a photo of blackened toes.
 (a) Yersinia pestis infection can cause inflamed and swollen lymph nodes (buboes), like these in the groin of an infected patient. (b) Septicemic plague caused necrotic toes in this patient. Vascular damage at the extremities causes ischemia and tissue death. (credit a: modification of work by American Society for Microbiology; credit b: modification of work by Centers for Disease Control and Prevention)

The high mortality rate for the plague is, in part, a consequence of it being unusually well equipped with virulence factors. To date, there are at least 15 different major virulence factors that have been identified from Y. pestis and, of these, eight are involved with adherence to host cells. In addition, the F1 component of the Y. pestis capsule is a virulence factor that allows the bacterium to avoid phagocytosis. F1 is produced in large quantities during mammalian infection and is the most immunogenic component.13 Successful use of virulence factors allows the bacilli to disseminate from the area of the bite to regional lymph nodes and eventually the entire blood and lymphatic systems.

Culturing and direct microscopic examination of a sample of fluid from a bubo, blood, or sputum is the best way to identify Y. pestis and confirm a presumptive diagnosis of plague. Specimens may be stained using either a Gram, Giemsa, Wright, or Wayson’s staining technique. The bacteria show a characteristic bipolar staining pattern, resembling safety pins, that facilitates presumptive identification. Direct fluorescent antibody tests (rapid test of outer-membrane antigens) and serological tests like ELISA can be used to confirm the diagnosis. The confirmatory method for identifying Y. pestis isolates in the US is bacteriophage lysis.

Prompt antibiotic therapy can resolve most cases of bubonic plague, but septicemic and pneumonic plague are more difficult to treat because of their shorter incubation stages. Survival often depends on an early and accurate diagnosis and an appropriate choice of antibiotic therapy. In the US, the most common antibiotics used to treat patients with plague are gentamicin, fluoroquinolones, streptomycin, levofloxacin, ciprofloxacin, and doxycycline.

A micrograph showing small rod shaped purple cells in between larger human cells. The purple bacterial cells have a small clear circle in the center.
This Wright’s stain of a blood sample from a patient with plague shows the characteristic “safety pin” appearance of Yersinia pestis. (credit: modification of work by Centers for Disease Control and Prevention)


Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at: