Yersinia pestis, the causative agent of plague, is a gram-negative, facultatively anaerobic, intracellular rod (Fig. 1; Gram stain). When stained, the organism has a bipolar staining pattern (Fig. 2; Giemsa stain of blood smear) due to the ends of the bacterium taking up more stain than the center of the organism. Y. pestis is endemic to rodents and is transmitted through the bite of the infected flea. Humans are susceptible and may contract the disease in this manner.

The disease has two major cycles: the sylvatic cycle and the urban cycle (Fig. 3). The sylvatic cycle is carried out in wild rodents. If these wild rodents come into contact with domestic city rats, fleas can transmit the bacteria to the domestic rats. As this population succumbs to disease and dies, the fleas will then search out humans as a food source and transmit Y. pestis to the human population. Sylvatic plague is common in Southeast Asia and exists on most continents, with the exception of Australia. Y. pestis is found in squirrels and prairie dogs in the southwestern United States.

Plague may manifest itself in one of two clinical forms: bubonic plague or pneumonic plague. In the bubonic form, a painful bubo (swelling of the lymph node) develops within 2 to 7 days after the flea bite, usually in the groin area (Fig. 4). A fever accompanies the bubo and gangrene in the extremities may be seen (Fig. 5), giving the disease the nickname "The Black Death." Without treatment bacteremia and death from gram-negative shock will follow in 50% to 75% of cases. The pneumonic form has an incubation period of 2 to 3 days and the first symptoms are fever, malaise, and a tightness in the chest. Cough, production of sputum, cyanosis, and then death follow in 100% of untreated cases. Streptomycin is the treatment of choice and lowers mortality rates to 10% to 20%. Positive identification of the bacillus may be facilitated through the application of direct fluorescent antibody stain and its affinity for the Y. pestis' capsular antigen (Fig. 6; photo credit: Larry Stauffer, Oregon State Public Health Laboratory).

Plague, with its almost certain death in untreated cases, wiped out a quarter of the population of Europe, 25 million people, during an epidemic in the Middle Ages and killed 10 million people in a later outbreak in China and India. Due to its high mortality rate and easy human-to-human transmissibility, plague is considered by the Centers for Disease Control and Prevention to be a likely candidate for weaponization and use in bioterrorism and biological warfare.