Читать книгу The Power of Plagues - Irwin W. Sherman - Страница 44

At present, most human cases of the plague are of the bubonic form, which results from the bite of a flea, usually a flea that previously fed on an infected rodent. The bacteria spread to the lymph nodes (armpits and neck but frequently the area of the groin), which drain the site of the bite, and these swollen and tender lymph nodes give the classic sign of bubonic plague, the bubo. Three days after the buboes appear, a high fever develops, the individual becomes delirious, and hemorrhages in the skin result in black splotches. Some contend that these dark spots on the skin gave the disease the name Black Death, whereas others believe “black” is simply a mistranslation of pestis atra, meaning not “black” but rather a “terrible” or “deadly” disease.

The buboes continue to enlarge, sometimes reaching the size of a hen’s egg, and when these buboes burst, there is agonizing pain. Death can come 2 to 4 days after the onset of symptoms. In some cases, however, the bacteria enter the bloodstream. This second form of the disease, which may occur without the development of buboes, is called septicemic plague. Septicemic plague is characterized by fever, chills, headache, malaise, massive hemorrhaging, and death. Septicemic plague has a higher mortality than does bubonic plague. In still other instances, the bacteria move via the bloodstream to the alveolar spaces of the lungs, leading to a suppurating pneumonia or pneumonic plague. Pneumonic plague is the most feared form of the disease and is the only form of the disease that allows for human-to-human transmission. It is characterized by watery and sometimes bloody sputum containing live bacteria. Coughing and spitting produce airborne droplets laden with the highly infectious bacteria, and by inhalation others may become infected. Pneumonic plague is the rapidly fatal form of the disease, with a fatality rate of 100% and death occurring within 24 h of exposure.

Some have suggested that the nursery rhyme “Ring around the Rosie” refers to bubonic plague in 17th-century England.

Ring around the rosie,

A pocket full of posies,

Achoo! Achoo!

We all fall down.

The rosies are the pink body rash, posies the perfumed bunches of flowers used to ward off the stench of death, “achoo” is the coughing and sneezing, and death is signified by “we all fall down.” The first time this rhyme was suggested to be plague related was in 1961, however, and because there is no evidence of a version prior to 1881, it is unlikely that the rhyme actually relates to the plague.

Y. pestis is one of the most pathogenic bacteria: the lethal dose that will kill 50% of exposed mice is a single bacterium that is injected intravenously. Typically, Y. pestis is spread from rodent to rodent by fleas, but it can also survive for a few days in a decaying corpse and may persist in a frozen body.

The reasons for the high degree of pathogenicity of Y. pestis remain unclear, however, though some virulence factors have been identified. The genes of Y. pestis are located on one chromosome and a virulence plasmid (a circular DNA molecule). Located on this plasmid are a set of genes that are activated by body temperature and millimolar concentrations of calcium, conditions found in the mammalian host. These genes code for the T3SS (type III secretion system), containing an “injectosome,” a hypodermic-like structure, and a translocon that forms a pore across the host cell membrane. The T3SS functions to inject multiple toxic proteins, named Yops (Yersinia outer proteins), directly into the host cell cytoplasm. Once inside the cell, the Yops trigger a preprogrammed chain reaction that results in cell death. Yops also inhibit phagocytosis by macrophages and block cytokine function (see p. 97). Together this prevents the bacterium from being ingested, thereby avoiding the immune mechanisms of the host; another protein is able to degrade fibrin, a material found in the blood clot, allowing the Yersinia to move throughout the body by allowing it to escape from the clot at the site of the flea bite.

While the above description refers to the disease in humans, the disease in fleas also has a distinctive pattern. Small mammals such as urban and sylvatic (or wood) rats, as well as squirrels, prairie dogs, rabbits, voles, coyotes, and domestic cats, are the principal hosts for Y. pestis. More than 80 different species of fleas are involved as plague vectors. Fleas are blood-sucking insects (Fig. 4.7), and when a flea bites a plague-infected host (at the bacteremic/septicemic stage), it ingests the rod-shaped bacteria; these multiply in the blood clot in the proventriculus (foregut) of the flea. This bacteria-laden clot obstructs the flea’s bloodsucking apparatus, and as a consequence the flea is unable to pump blood into the midgut, where it would be digested. As a result, the flea becomes hungrier, and in this ravenous state the flea bites the host repeatedly; with each bite it regurgitates plague bacteria into the wound. In this way infection is initiated. Y. pestis can also be pathogenic for the flea, and fleas with their foregut blocked rapidly starve to death. If the mammalian host dies, its body cools down, and the fleas respond by moving off the host to seek another live warm-blooded host. If there is an extensive die-off of rodents, however, then the fleas move on to less preferred hosts such as humans, and so an epidemic may begin.