Plague. Plague is an infectious disease caused by the bacterium Yersinia pestis. Symptoms include fever, weakness and headache. Usually this begins one to seven days after exposure. In the bubonic form there is also swelling of lymph nodes, while in the septicemic form tissues may turn black and die, and in the pneumonic form shortness of breath, cough and chest pain may occur. Bubonic and septicemic plague are generally spread by flea bites or handling an infected animal. The pneumonic form is generally spread between people through the air via infectious droplets. Diagnosis is typically by finding the bacterium in fluid from a lymph node, blood or sputum. Those at high risk may be vaccinated. Those exposed to a case of pneumonic plague may be treated with preventive medication. If infected, treatment is with antibiotics and supportive care. Typically antibiotics include a combination of gentamicin and a fluoroquinolone. The risk of death with treatment is about 10% while without it is about 70%. Globally, about 600 cases are reported a year. In 2017, the countries with the most cases include the Democratic Republic of the Congo, Madagascar and Peru. In the United States, infections occasionally occur in rural areas, where the bacteria are believed to circulate among rodents. It has historically occurred in large outbreaks, with the best known being the Black Death in the 14th century, which resulted in more than 50 million deaths. When a flea bites a human and contaminates the wound with regurgitated blood, the plague-causing bacteria are passed into the tissue. Y. pestis can reproduce inside cells, so even if phagocytosed, they can still survive. Once in the body, the bacteria can enter the lymphatic system, which drains interstitial fluid. Plague bacteria secrete several toxins, one of which is known to cause beta-adrenergic blockade. Y. pestis spreads through the lymphatic vessels of the infected human until it reaches a lymph node, where it causes acute lymphadenitis. The swollen lymph nodes form the characteristic buboes associated with the disease, and autopsies of these buboes have revealed them to be mostly hemorrhagic or necrotic. If the lymph node is overwhelmed, the infection can pass into the bloodstream, causing secondary septicemic plague and if the lungs are seeded, it can cause secondary pneumonic plague. Main article: Septicemic plague Lymphatics ultimately drain into the bloodstream, so the plague bacteria may enter the blood and travel to almost any part of the body. In septicemic plague, bacterial endotoxins cause disseminated intravascular coagulation, causing tiny clots throughout the body and possibly ischemic necrosis from the clots. DIC results in depletion of the body's clotting resources, so that it can no longer control bleeding. Consequently, there is bleeding into the skin and other organs, which can cause red and/or black patchy rash and hemoptysis/hematemesis. There are bumps on the skin that look somewhat like insect bites; these are usually red, and sometimes white in the center. Untreated, septicemic plague is usually fatal. Early treatment with antibiotics reduces the mortality rate to between 4 and 15 percent. People who die from this form of plague often die on the same day symptoms first appear. Main article: Pneumonic plague The pneumonic form of plague arises from infection of the lungs. It causes coughing and thereby produces airborne droplets that contain bacterial cells and are likely to infect anyone inhaling them. The incubation period for pneumonic plague is short, usually two to four days, but sometimes just a few hours. The initial signs are indistinguishable from several other respiratory illnesses; they include headache, weakness and spitting or vomiting of blood. The course of the disease is rapid; unless diagnosed and treated soon enough, typically within a few hours, death may follow in one to six days; in untreated cases mortality is nearly 100%. Transmission of Y. pestis to an uninfected individual is possible by any of the following means. droplet contact-coughing or sneezing on another person. direct physical contact-touching an infected person, including sexual contact. indirect contact-usually by touching soil contamination or a contaminated surface. airborne transmission-if the microorganism can remain in the air for long periods.