The disease, which spread quickly throughout cities for centuries, is actually a bacterial infection.

Plague is a bacterial infection found mainly in rodents and their fleas. But via those fleas it can sometimes leap to humans. When it does, the outcome can be horrific, making plague outbreaks the most notorious disease episodes in history.

The Black Death

Most infamous of all was the Black Death, a medieval pandemic that swept through Asia and Europe. It reached Europe in the late 1340s, killing an estimated 25 million people. The Black Death lingered on for centuries, particularly in cities. Outbreaks included the Great Plague of London (1665-66), in which one in five residents died.

The first well-documented pandemic was the Plague of Justinian, which began in 541 A.D. Named after the Byzantine emperor Justinian I, it killed up to 10,000 people a day in Constantinople (modern-day Istanbul, Turkey), according to ancient historians. Modern estimates suggest half of Europe's population was wiped out before the plague disappeared in the 700s.

The cause of plague wasn't discovered until the most recent global outbreak, which started in China in 1855 and didn't officially end until 1959. The first breakthrough came in Hong Kong in 1894 when researchers isolated the rod-shaped bacillus responsible—Yersinia pestis. A few years later, in China, doctors noticed that rats showed very similar plague symptoms to people, and that human victims often had fleabites.

The animal reservoir for plague includes mice, camels, chipmunks, prairie dogs, rabbits, and squirrels, but the most dangerous for humans are rats, especially the urban sort. The disease is usually transmitted by the rat flea, Xenopsylla cheopis.

Types of Plague

Bubonic plague, the disease's most common form, refers to telltale buboes—painfully swollen lymph nodes—that appear around the groin, armpit, or neck. Septicemic plague, which spreads in the bloodstream, comes either via fleas or from contact with plague-infected body matter. Pneumonic plague, the most infectious type, is an advanced stage of bubonic plague when the disease starts being passed directly, person to person, through airborne droplets coughed from the lungs. If left untreated, bubonic plague kills about 50 percent of those it infects. The other two forms are almost invariably fatal without antibiotics.

Yersinia pestis is extraordinarily virulent, even when compared with closely related bacteria. This is because it's a mutant variety, handicapped both by not being able to survive outside the animals it infects and by an inability to penetrate and hide in its host's body cells. To compensate, Y. pestis needs strength in numbers and the ability to disable its victim's immune system. It does this by injecting toxins into defense cells such as macrophages that are tasked with detecting bacterial infections. Once these cells are knocked out, the bacteria can multiply unhindered.

Victims are so overwhelmed that they're more or less poisoned to death as the bacilli gather in thick clots under the skin, where a passing flea might pick them up. Other grim side effects can include gangrene, erupting pus-filled glands, and lungs that literally dissolve.

Plague Today

Plague still exists in various parts of the world. In 2003, more than 2,100 human cases and 180 deaths were recorded, nearly all of them in Africa. The last reported serious outbreak was in 2006 in the Democratic Republic of the Congo, when at least 50 people died. The United States, China, India, Vietnam, and Mongolia are among the other countries that have confirmed human plague cases in recent years.

Most people survive if they're given the correct antibiotics in time. Good sanitation and pest control help prevent plague outbreaks since they need crowded, dirty, rat-infested conditions to really get going.

There are fears that plague bacteria possibly could be used for a bioterror attack if released in aerosol form.