Introduction: Plague is an acute, potentially epidemic disease caused by infection with Yersinia pestis. The disease exists in natural enzootic cycles in wild rodents in Asia, Africa, extreme Southeastern Europe, and the Americas: these cycles are often unapparent, as transmission to humans is sporadic. Epidemics involving humans occur when the organisms spreads into population of rats (genus Rattus) that live near human habitation. Cases of plague must be reported to state authorities, which subsequently notify CDC. Cases confirmed by laboratory analysis are also reported to WHO.

The Organism: Y. pestis is a gram-negative coccobacillus belonging to the Enterobacteriaceae. The bacterium has several chromosomal and plasmid factors essential to virulence and survival in mammalian hosts and flea vectors.

Transmission: The most common mode is by the bite of infectious fleas (X. cheopsis in rat, but also human flea, P. irritans). Less frequently, infection is caused by direct contact with infected body fluids, or by inhalation of respiratory droplets or other aerosolized infectious material.

Clinical manifestations and epidemiology: Bubonic plague, characterized by acute regional lymphadenopathy with subcutaneous hemorrhage (bubo) typically draining the site of initial flea-bite, is the most common form of the disease, accounting for 80% to 90% of cases in the U.S. The incubation period ranges from 2 to 6 days. Without treatment the mortality rate is 50% to 60%. Septicemic plague can occur secondarily to the bubonic form, but can also develop in absence of lymphadenopathy. Approximately 10% of patients present with this form, with 50% mortality rate (treated) due to septic shock, DIC and meningitis. Pneumonic plague is the rarest but most dangerous form. It can develop secondarily to septicemia, but also as a consequence of bio-weapon use. Both the Soviet Union and U.S. researched, and likely tested the use of weaponized aerosols of Y. pestis. Signs and symptoms include severe pneumonia, high fever, dyspnea and often hemoptysis. The incubation period is 1 to 3 days. Mortality is virtually 100% if treatment does not commence within 18 hours of development of symptoms. In the U.S., 341 cases of plague were reported to CDC during 1970-1995; 80% in New Mexico, Arizona and Colorado. Pneumonic form accounted for 11% of the cases.

Laboratory diagnosis: Y. pestis is a non-motile, non-spore forming facultative anaerobe. It appears as single or short-chained, gram negative, fat rods (0.5 x 1.0 microm). The optimum growth temperature is 28 to 30 deg C at physiologic pH (7.2-7.6); however doubling time is 1.25 hours at 37 deg C. Y. pestis stained with Wayson or Wright-Giemsa show a bipolar pattern (granules at the ends of the cell), thus making the cell appear as a closed safety pin. Although characteristic, this morphology is not sufficient for definitive identification on a tissue smear (Pasteurella spp. and others look similar). Y. pestis lacks many enzymatic functions such as adenine deaminase, aspartase, ornithine decarboxylase, glucose-6-phosphate dehydrogenase and urease. It also lack the ability to ferment most carbohydrates, it primarily utilizes glucose and mannitol. It grows on sheep blood agar with little or no hemolysis, forming gray-white colonies, with "hammered copper" shiny appearance at 48 hours. The colony borders are irregular, and are often termed "fried-egg". Positive cultures showing the above characteristics are considered presumptive evidence of Y. pestis infection, are reported, and/or forwarded to state authorities for further identification and confirmation. In cases of suspected bioterrorism, FBI is also notified. Rapid diagnostic tests for the capsular antigen (F1) are available at reference laboratories.