disease

disease, impairment of the normal state or functioning of the body as a whole or of any of its parts. Some diseases are acute, producing severe symptoms that terminate after a short time, e.g., pneumonia; others are chronic disorders, e.g., arthritis, that last a long time; and still others return periodically and are termed recurrent, e.g., malaria. One of the most common bases for classifying disease is according to cause. External factors that produce disease are infectious agents, including both microscopic organisms (bacteria, viruses, and protozoans) and macroscopic ones (fungi and various parasitic worms). Only infectious diseases can be transmitted—by humans, certain animals and insects, and infected objects and substances (see communicable diseases). Other external agents that can cause disease are chemical and physical agents (drugs, poisons, radiation), which can be encountered in specific work situations, deficiency of nutrients in the environment, and physical injury. Diseases that arise from internal (endogenous) causes include hereditary abnormalities (disorders inherited from one or both parents), congenital diseases (disturbances in the development of a normal embryo), allergies (hypersensitive reactions to substances in the environment), endocrine disorders (generally either overfunctioning or underfunctioning of an endocrine gland), circulatory disorders (diseases of the heart and blood vessels), and neoplasms, or tumors (masses of abnormally proliferating cells). Degenerative diseases occur as a result of the natural aging of the body tissues. Finally, a wide range of diseases are attributed to, or at least influenced by, emotional disturbances. Psychoses and neuroses result in disturbed behavior; the so-called psychosomatic diseases (certain kinds of colitis, many forms of headaches) are thought to be brought about by emotional stress. Most diseases occur as a result of a combination of both internal and external conditions, i.e., an interaction between the body and the environment. Thus a person may be hereditarily predisposed to tuberculosis, although the tubercule bacillus (the infectious agent) must be present for the disease to occur. In ancient times disease was ascribed to supernatural, spiritual, and humoral factors. The discovery by Louis Pasteur and others of the role played by microorganisms in infection and the study of cellular pathology by Rudolf Virchow in the 19th cent. were of the utmost importance in establishing the true nature of disease.

Infectious disease of warm-blooded animals, caused by Bacillus anthracis, a bacterium that, in spore form, can retain its virulence in contaminated soil or other material for many years. A disease chiefly of herbivores, the infection may be acquired by persons handling the wool, hair, hides, bones, or carcasses of affected animals. Infection may lead to death from respiratory or cardiac complications (within 1–2 days if acute), or the animal may recover. In humans, anthrax occurs as a cutaneous, pulmonary, or intestinal infection. The most common type, which occurs as an infection of the skin, may lead to fatal septicemia (blood poisoning). The pulmonary form of the disease is usually fatal. Sanitary working environments for susceptible workers are critical to preventing anthrax; early diagnosis and treatment are also of great importance. In recent decades, various countries have attempted to develop anthrax as a weapon of biological warfare; many factors, including its extreme potency (vastly greater than any chemical-warfare agent), make it the preferred biological-warfare agent. Concerns about anthrax mounted in 2001 after it was found in letters mailed to members of the U.S. government and news agencies.

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Disease transmitted primarily by direct sexual contact. STDs usually affect the reproductive system and urinary system but can be spread to the mouth or rectum by oral or anal sex. In later stages they may attack other organs and systems. The best-known are syphilis, gonorrhea, AIDS, and herpes simplex. Yeast infections (see candida) produce a thick, whitish vaginal discharge and genital irritation and itch in women and sometimes irritation of the penis in men. Crab louse infestation (see louse, human) can also be considered an STD. The incidence of STDs has been affected by such factors as antibiotics, birth-control methods, and changes in sexual behaviour. Seealso chlamydia; hepatitis; pelvic inflammatory disease; wart.

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Acute inflammation of the pelvic cavity in women, caused by bacterial infection (usually gonorrhea or chlamydia) of the reproductive system. Usually a sexually transmitted disease, it occurs mainly in sexually active women under age 25, more often in those using intrauterine devices (IUDs). PID can resemble gonorrhea, with abdominal and lower pelvic pain, chills, nausea, fever, and thick, foul-smelling vaginal discharge. Fallopian tube scarring can cause infertility and ectopic pregnancy. Treatment requires antibiotics, bed rest, pain medication, and sexual abstinence until the infection disappears. Sexual partners must also be treated to prevent reinfection.

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Illness associated with a particular occupation. The Industrial Revolution's long working hours, dim light, lack of fresh air, and dangerous machinery fostered illness and injury in general, but certain occupations (e.g., mining) carry particular risks (e.g., black lung, a type of pneumoconiosis). Twentieth-century innovations (including use of new chemicals and radioactive materials) caused an increase in certain cancers (e.g., leukemia and bone cancer in workers exposed to radiation) and injuries. So-called “sick buildings” (in which pathogens grow in air circulation systems) contribute to health problems among office workers. Occupational medicine also covers work-related emotional stresses. Seealso asbestosis; industrial medicine.

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or bovine spongiform encephalopathy (BSE)

Fatal neurodegenerative disease of cattle. Symptoms include behavioral changes (e.g., agitation), gradual loss of coordination and locomotive function, and, in advanced stages, weight loss, fine muscular contractions, and abnormal gait. Brain tissue becomes pitted with holes and spongy. Death usually follows within a year. The disease is similar to the neurodegenerative disease of sheep called scrapie. No treatment is known. A BSE epidemic in Britain that began in the mid-1980s is believed to have been caused by the use of cattle feed containing supplements made from ruminant carcasses and trimmings. Hundreds of thousands of infected cattle were slaughtered and the use of animal-derived protein supplements ended. The cause of both BSE and scrapie is attributed to an infectious aberrant protein called a prion. The unusual occurrence of Creutzfeldt-Jakob disease, another prion-related illness, in young people beginning in the mid-1990s may be linked to eating meat from cattle with BSE.

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Any of a group of relatively rare hereditary disorders of fat metabolism in which enzyme defects cause distinctive types of lipids to accumulate. They include Tay-Sachs disease, Gaucher disease, Niemann-Pick disease, and Fabry disease. Several are untreatable and cause death before age five; others occur in adulthood.

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or glandular fever

Common infection, caused by Epstein-Barr virus. It occurs most often at ages 10–35. Infected young children usually have little or no illness but become immune. Popularly called “the kissing disease,” it is spread mostly by oral contact with exchange of saliva. It usually lasts 7–14 days. The most common symptoms are malaise, sore throat, fever, and lymph-node enlargement. Liver involvement is usual but rarely severe. The spleen often enlarges and in rare cases ruptures fatally. Less frequent features include rash, pneumonia, encephalitis (sometimes fatal), meningitis, and peripheral neuritis. Relapse and second attacks are rare. Diagnosis may require blood analysis. There is no specific therapy.

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or ischemic heart disease

Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis). Short-term oxygen deprivation can cause angina pectoris. Long-term, severe oxygen depletion causes a heart attack. Coronary bypass or angioplasty is needed if medication and diet do not control the disease.

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Invasion of the body by various agents—including bacteria, fungi (see fungus), protozoans, viruses, and worms—and its reaction to them or their toxins. Infections are called subclinical until they perceptibly affect health, when they become infectious diseases. Infection can be local (e.g., an abscess), confined to one body system (e.g., pneumonia in the lungs), or generalized (e.g., septicemia). Infectious agents can enter the body by inhalation, ingestion, sexual transmission, passage to a fetus during pregnancy or birth, wound contamination, or animal or insect bites. The body responds with an attack on the invader by leukocytes, production of antibodies or antitoxins, and often a rise in temperature. The antibodies may result in short-term or lifelong immunity. Despite significant progress in preventing and treating infectious diseases, they remain a major cause of illness and death, particularly in regions of poor sanitation, poor nutrition, and crowding.

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or hyaline membrane disease

Common complication in newborns, especially after premature birth. Symptoms include very laboured breathing, bluish skin tinge, and low blood oxygen levels. Insufficient surfactant in the pulmonary alveoli raises surface tension, hampering lung expansion. The alveoli collapse (see atelectasis), and a “glassy” (hyaline) membrane develops in the alveolar ducts. Once the leading cause of death in premature infants, the syndrome is now usually treated for a few days with a mechanical ventilator (see respiratory therapy), with no aftereffects. An adult respiratory distress syndrome (ARDS) can follow lung injury.

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or hoof-and-mouth disease

Highly contagious viral disease of cloven-footed mammals (including cattle), spread by ingestion and inhalation. The afflicted animal develops fever and painful blisters on the tongue, lips, other tissues of the mouth, muzzle or snout, teats, and feet. FMD is endemic in many places. Because of its rapid spread and impact on animal productivity, it is considered the most economically devastating livestock disease in the world. It is not a human health hazard. No effective treatment exists; vaccines control epidemics but have not eliminated them. Since the virus can persist, quarantine, slaughter, cremation or burial of carcasses, and decontamination must be rigorous. Strict surveillance has kept North America largely FMD-free since 1929. In early 2001 a major outbreak occurred in the United Kingdom, followed shortly by outbreaks in The Netherlands and France.

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or hemolytic disease of the newborn

Anemia in an infant, caused when a pregnant woman produces antibodies to an antigen in her fetus's red blood cells. An Rh-negative woman (see Rh blood-group system) with an Rh-positive fetus whose ABO blood group (see ABO blood-group system) matches hers is likely to have an immune reaction after the first such pregnancy, which sensitizes her when fetal red blood cells enter her bloodstream, usually during labour. If blood typing shows incompatibility, an anti-Rh antibody injection given to the mother after the birth can destroy the fetal red cells, thus preventing trouble in a future pregnancy. If amniocentesis detects products of blood destruction, Rh-negative blood transfusions to the fetus before birth or exchange transfusion after it may save the baby's life. ABO incompatibilities are more common but usually less severe.

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or glycogenosis

Any of numerous types of hereditary enzyme deficiency resulting in altered metabolism of glycogen. The problems are classified in two groups, those affecting the liver and those involving striated muscle, both primary glycogen storage sites. Symptoms in the liver group range from symptomatic hypoglycemia with ketosis to asymptomatic liver enlargement (hepatomegaly). In the muscle group, they range from weakness and cramps to fatal heart enlargement.

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Disorder characterized by frequent passage of gastric contents from the stomach back into the esophagus. Symptoms of GERD may include heartburn, coughing, frequent clearing of the throat, and difficulty in swallowing. It can be caused by relaxation of the muscle that connects the esophagus and the stomach, delayed emptying of the esophagus or stomach, hiatal hernia, obesity, or pregnancy. Treatment is with antacids or acid-inhibiting medications and lifestyle changes such as not eating before bedtime, avoiding acidic or fatty foods or beverages, cessation of smoking, and weight loss. Surgery may be necessary in severe cases.

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or osteoarthrosis or degenerative joint disease

Most common joint disorder, afflicting over 80percnt of those who reach age 70. It does not involve excessive inflammation and may have no symptoms, especially at first. Cartilage softens and wears away, and bone grows in its place, distorting the joint's surface and causing pain, stiffness, and limited movement, usually in weight-bearing joints (vertebrae, knees, hips). Treatment may include analgesics, rest, weight loss, corticosteroids, and/or physical medicine and rehabilitation or an exercise program. Hip or knee replacement or surgical removal of unhealthy tissue may be needed.

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Deformity of the heart. Examples include septal defect (opening in the septum between the sides of the heart), atresia (absence) or stenosis (narrowing) of one or more valves, tetralogy of Fallot (with four components: ventricular septal defect, pulmonary valve stenosis, right ventricular enlargement, and positioning of the aorta so that it receives blood from both ventricles), and transposition of the great vessels (so the pulmonary and systemic circulations each receive blood from the wrong side of the heart). Such defects can prevent enough oxygen from reaching the tissues, so the skin has a bluish cast. Many are fatal if not corrected surgically soon after birth—or, rarely, before birth, if detected prenatally. Abnormalities of the large vessels are usually less serious (see aorta, coarctation of; ductus arteriosus).

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A large group of disorders arising during development that cause abnormality of the human body. Most are due to genetic factors such as inherited or spontaneous mutations, whereas others are caused by environmental influences during pregnancy such as exposure to harmful chemicals. The most severe and lethal disorders arise during the first 28 days of development and include gross brain anomalies and heart defects. The mildest malformations occur in the late stages of development and are often the result of dominant inheritance, whereas complex congenital syndromes are often the result of recessive inheritance. Seealso birth defect; Down syndrome.

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or nontropical sprue

Digestive disorder in which people cannot tolerate gluten, a protein constituent of wheat, barley, malt, and rye flours. In celiac disease, gluten generates an immune response that damages the mucous lining of the small intestine; it is believed that a deficiency of gluten-digesting enzymes may underlie the disease. Poor nutrient absorption causes foul, bulky, fatty stools; malnutrition; stunting of growth; and anemia similar to pernicious anemia. It can run in families. Children begin having intermittent intestinal upset, diarrhea, and wasting at 6–21 months. In adults it usually begins after 30, with appetite loss, depression, irritability, and diarrhea. Symptoms in advanced cases stem from nutritional deficiencies and may require supportive measures. A high-protein diet low in glutens and saturated fats usually relieves symptoms.

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also called the bends or caisson disease

Harmful effects of rapid change from a higher- to a lower-pressure environment. Small amounts of the gases in air are dissolved in body tissues. When pilots of unpressurized aircraft go to high altitudes or when divers breathing compressed air return to the surface, external pressure on the body decreases and the gases come out of solution. Rising slowly allows the gases to enter the bloodstream and be taken to the lungs and exhaled; with a quicker ascent, the gases (mostly nitrogen) form bubbles in the tissues. In the nervous system, they can cause paralysis, convulsions, motor and sensory problems, and psychological changes; in the joints, severe pain and restricted mobility (the bends); in the respiratory system, coughing and difficulty breathing. Severe cases include shock. Recompression in a hyperbaric chamber followed by gradual decompression cannot always reverse tissue damage.

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or hepatolenticular degeneration

Recessive hereditary defect (see recessiveness) that impairs one's ability to metabolize copper. In affected persons, copper accumulates in the basal ganglia (see ganglion) of the brain (involved in control of movement), causing progressive degeneration; forms a brownish ring at the margin of the cornea of the eye; and is deposited in the liver, gradually leading to cirrhosis. Other symptoms include tremor, lack of coordination, and personality changes. The disease usually appears in the person's teen years or twenties. Early diagnosis and treatment with a high-protein, low-copper diet and a substance to chelate copper can reverse the effects and prevent permanent brain and liver damage.

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Recessive hereditary metabolic disorder, mostly in Ashkenazi Jews, causing progressive mental and neurologic deterioration and death by age five. A lipid, ganglioside GM₂, accumulates in the brain (because of inadequate activity of the enzyme that breaks it down), with devastating neurological effects. Infants appear normal at birth but soon become listless and inattentive, lose motor abilities, and develop seizures. Blindness and general paralysis usually precede death. Tests can detect the disease in fetuses and the Tay-Sachs gene in carriers. There is no treatment.

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or osteitis deformans

Chronic bone disease of middle age. Named for James Paget, it is characterized by excessive bone destruction alternating with disordered bone construction (with dense, brittle bones and deformity that can compress internal structures). The long bones, vertebrae, pelvis, and skull are most often affected, more often in men. The risk of cancer, usually osteosarcoma, is high. Increased blood supply to the area of bone destruction may lead to heart or circulatory problems. Calcitonin (which regulates bone growth) and bisphosphonates (which block excessive bone breakdown) are drugs of treatment.

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Tick-borne bacterial disease. It was identified in 1975 and named for Old Lyme, Conn. It is caused by a spirochete, Borrelia burgdorferi, transmitted by ticks, which pick it up in the blood of infected animals, mostly deer. Humans can be bitten by ticks in tall grass or fallen leaves. Lyme disease has three stages: a target-shaped rash, often with flulike symptoms; migrating arthritic pain and neurological symptoms (disturbances to memory, vision, or locomotion); and crippling arthritis with symptoms like those of multiple sclerosis and sometimes with facial paralysis, meningitis, or memory loss. Most cases do not progress beyond the first stage, but those that do reach the third stage within two years. Prevention involves avoiding tick bites. Diagnosis can be difficult, especially if the initial rash is not noticed. Early antibiotic treatment can prevent progression. Advanced cases need more powerful antibiotics, and symptoms may recur.

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or Hansen disease

Chronic disease of the skin, peripheral nerves, and mucous membranes of the nose, throat, and eyes, caused by the bacterium Mycobacterium leprae. In tuberculoid leprosy, cells of the immune system crowd into infected areas of the skin, forming hard nodules, or tubercles, that spread along nerve fibres. This type of reaction commonly leads to claw hand, gross deformity of the foot, and paralysis of muscles of the face, eye, and neck. In the lepromatous type, bacilli multiply freely in deep layers of the skin and spread widely through lymphatic channels and along nerve fibres, causing thickening and corrugation of the skin, raising soft nodules on the ears, nose, and cheeks, and sometimes destroying the septum of the nose and the palate. Leprosy has a long history. Until the 20th century, infected people were ostracized from society or at best segregated and cared for in isolated leper colonies. Today the disease is entirely curable through multidrug therapy, though tissue damage caused before drug treatment cannot be reversed. Some 600,000 new cases arise every year, mostly in Asia, Africa, Central and South America, and the Pacific Islands. About 60 percent of new cases occur in India.

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Widespread disease that kills elms, originally described in The Netherlands. The disease is caused by the fungus Ophiostoma ulmi (also known as Ceratocystis ulmi). It was first identified in the U.S. in 1930, and an eradication campaign could not stop its spread into regions wherever the very susceptible American elm (Ulmus americana) grew. The leaves on one or more branches of a stricken tree suddenly wilt, turn dull green to yellow or brown, curl, and may drop early. Because symptoms are easily confused with other diseases, positive diagnosis is possible only through laboratory culturing. The fungus can spread up to 50 ft (15 m) from diseased to healthy trees by natural root grafts. Overland, the fungus normally is spread by the European elm bark beetle (Scolytus multistriatus; see bark beetle), less commonly by the American elm bark beetle (Hylurgopinus rufipes). Control involves exclusion of the beetles, usually by use of an insecticidal spray applied to the tree.

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or CJD

Rare fatal disease of the central nervous system. It destroys brain tissue, making it spongy and causing progressive loss of mental functioning and motor control. The disease commonly arises in adults between the ages of 40 and 70. Patients usually die within a year. There is no known cure. The disease is caused by a prion that builds up in neurons. Inherited or random mutation accounts for 99percnt of cases; the rest come from prion exposure during medical procedures and possibly from eating the meat of cattle with mad cow disease.

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Type of nephritis without pus formation or edema. It may or may not recur. The acute stage involves severe inflammation and back pain, deficient kidney function, swelling, and hypertension. In the subacute stage the kidney enlarges, blood does not reach its surface and red blood cells are damaged (leading to anemia), and its tissue breaks down, releasing excess blood protein into urine. In the chronic stage a small, shriveled, scarred kidney cannot filter nitrogen compounds from the blood, causing uremia. Treatment focuses on symptom relief.

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Degenerative brain disorder. It occurs in middle to late adult life, destroying neurons and connections in the cerebral cortex and resulting in significant loss of brain mass. The most common form of dementia, Alzheimer disease progresses from short-term memory impairment to further memory loss; deterioration of language, perceptual, and motor skills; mood instability; and, in advanced stages, unresponsiveness, with loss of mobility and control of body functions; death typically ensues in 5–10 years. Originally described in 1906 by the German neuropathologist Alois Alzheimer (1864–1915) with reference to a 55-year-old person and regarded as a presenile dementia, Alzheimer disease is now recognized as accounting for much of the senile dementia once thought normal with aging. The 10percnt of cases that begin before age 60 result from an inherited mutation. Neuritic plaques and neurofibrillary tangles in the brain on autopsy are the primary features used for diagnosis. No cure has been found. Most treatment targets the depression, behavioral problems, and sleeplessness that often accompany the disease.

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Disease in which gradual atrophy of the adrenal cortex causes the adrenal glands to produce insufficient quantities of the steroid hydrocortisone while causing the pituitary gland to produce excess quantities of pituitary hormones. Most of the cortex tissue is destroyed by the time symptoms (including weakness, abnormal coloration, weight loss, and hypotension) appear. Hydrocortisone-replacement therapy is often successful, usually given with other hormones to stabilize sodium levels. More than half of cases are believed to be due to an autoimmune reaction (see autoimmune disease); the remainder are caused by destruction of the adrenal gland by granuloma (e.g., tuberculosis).

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Plague is a deadly infectious disease caused by the enterobacteria Yersinia pestis (Pasteurella pestis). Plague is a zoonotic, primarily carried by rodents (most notably rats) and spread to humans via fleas. Plague is notorious throughout history, due to the unprecedented scale of death and devastation it brought. Plague is still endemic in some parts of the world.

Name

The epidemiological use of the term plague is currently applied to bacterial infections that cause buboes, although historically the medical use of the term plague has been applied to pandemic infections in general. Plague is often synonymous with "bubonic plague" but this only describes one of its manifestations. Other names have been used to describe this disease, such as "The Black Plague" and "The Black Death", the latter is now used primarily to describe the second, and most devastating pandemic of the disease.

Infection and transmission

Bubonic plague is mainly a disease in rodents and fleas (Xenopsylla cheopis). Infection in a human occurs when a person is bitten by a flea that has been infected by biting a rodent that itself has been infected by the bite of a flea carrying the disease. The bacteria multiply inside the flea, sticking together to form a plug that blocks its stomach and causes it to begin to starve. The flea then voraciously bites a host and continues to feed, even though it cannot quell its hunger, and consequently the flea vomits blood tainted with the bacteria back into the bite wound. The bubonic plague bacterium then infects a new victim, and the flea eventually dies from starvation. Serious outbreaks of plague are usually started by other disease outbreaks in rodents, or a rise in the rodent population.

In 1894, two bacteriologists, Alexandre Yersin of France and Shibasaburo Kitasato of Japan, independently isolated the bacterium in Hong Kong responsible for the Third Pandemic. Though both investigators reported their findings, a series of confusing and contradictory statements by Kitasato eventually led to the acceptance of Yersin as the primary discoverer of the organism. Yersin named it Pasteurella pestis in honor of the Pasteur Institute, where he worked, but in 1967 it was moved to a new genus, renamed Yersinia pestis in honor of Yersin. Yersin also noted that rats were affected by plague not only during plague epidemics but also often preceding such epidemics in humans, and that plague was regarded by many locals as a disease of rats: villagers in China and India asserted that, when large numbers of rats were found dead, plague outbreaks in people soon followed.

In 1898, the French scientist Paul-Louis Simond (who had also come to China to battle the Third Pandemic) established the rat-flea vector that drives the disease. He had noted that persons who became ill did not have to be in close contact with each other to acquire the disease. In Yunnan, China, inhabitants would flee from their homes as soon as they saw dead rats, and on the island of Formosa (Taiwan), residents considered handling dead rats a risk for developing plague. These observations led him to suspect that the flea might be an intermediary factor in the transmission of plague, since people acquired plague only if they were in contact with recently dead rats, but not affected if they touched rats that had been dead for more than 24 hours. In a now classic experiment, Simond demonstrated how a healthy rat died of plague after infected fleas had jumped to it from a plague-dead rat.

Pathology

Bubonic plague

When a flea bites a human and contaminates the wound with regurgitated blood, the plague carrying 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 dangerous beta-adrenergic blockade.

Y. pestis spreads through the lymphatics of the infected human until it reaches a lymph node, where it stimulates severe haemorrhagic inflammation (the root "haem" means "blood" and "haemorrhage" means to bleed) that causes the lymph nodes to expand. The expansion of lymph nodes is the cause of the characteristic "bubo" associated with the disease.

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 (DIC), causing tiny clots throughout the body and possibly ischaemic necrosis (tissue death due to lack of circulation/perfusion to that tissue) 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/haemoptysis (coughing up or vomiting of blood). 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. However, during the plague epidemics many people must have come in contact with the bacteria but survived; otherwise nearly everyone in Europe would have died. 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.

Pneumonic plague

The pneumonic plague infects the lungs, and with that infection comes the possibility of person-to-person transmission through respiratory droplets. The incubation period for pneumonic plague is usually between two and four days, but can be as little as a few hours. The initial symptoms, of headache, weakness, and coughing with hemoptysis, vomiting blood, are indistinguishable from other respiratory illnesses. Without diagnosis and treatment, the infection can be fatal in one to six days; mortality in untreated cases is 50–90%.

Other forms

There are a few other rare manifestations of plague, including asymptomatic plague and abortive plague. Cellulocutaneous plague sometimes results in infection of the skin and soft tissue, often around the bite site of a flea. Plague meningitis can occur in very rare cases of septicemic plague.

Treatments

Vladimir Havkin, a doctor of Russian-Jewish origin who worked in India, was the first to invent and test a bubonic plague vaccine, on January 10, 1897

The traditional treatments are:

• Streptomycin 30 mg/kg IM twice daily for 7 days
• Chloramphenicol 25–30 mg/kg single dose, followed by 12.5–15 mg/kg four times daily
• Tetracycline 2 g single dose, followed by 500 mg four times daily for 7–10 days (not suitable for children)

More recently,

• Gentamicin 2.5 mg/kg IV or IM twice daily for 7 days
• Doxycycline 100 mg (adults) or 2.2 mg/kg (children) orally twice daily have also been shown to be effective.

History

The earliest (though unvalidated) account describing a possible plague epidemic is found in I Samuel 5:6 of the Hebrew Bible (Tanakh). In this account, the Philistines of Ashdod were stricken with a plague for the crime of stealing the Ark of the Covenant from the Children of Israel. These events have been dated to approximately the second half of the eleventh century B.C. The word "tumors" is used in most English translations to describe the sores that came upon the Philistines. The Hebrew, however, can be interpreted as "swelling in the secret parts". The account indicates that the Philistine city and its political territory were stricken with a "ravaging of mice" and a plague, bringing death to a large segment of the population.

In the second year of the Peloponnesian War (430 B.C.), Thucydides described an epidemic disease which was said to have begun in Ethiopia, passed through Egypt and Libya, then come to the Greek world. In the Plague of Athens, the city lost possibly one third of its population, including Pericles. Modern historians disagree on whether the plague was a critical factor in the loss of the war. Although this epidemic has long been considered an outbreak of plague, many modern scholars believe that typhus, smallpox, or measles may better fit the surviving descriptions. A recent study of the DNA found in the dental pulp of plague victims, led by Manolis J. Papagrigorakis, suggests that typhoid was actually responsible. Other scientists dispute this conclusion, citing serious methodological flaws in the DNA study.

In the first century A.D., Rufus of Ephesus, a Greek anatomist, refers to an outbreak of plague in Libya, Egypt, and Syria. He records that Alexandrian doctors named Dioscorides and Posidonius described symptoms including acute fever, pain, agitation, and delirium. Buboes—large, hard, and non-suppurating—developed behind the knees, around the elbows, and "in the usual places." The death toll of those infected was very high. Rufus also wrote that similar buboes were reported by a Dionysius Curtus, who may have practiced medicine in Alexandria in the third century B.C. If this is correct, the eastern Mediterranean world may have been familiar with bubonic plague at that early date.

First Pandemic: Plague of Justinian

The Plague of Justinian in A.D. 541–542 is the first known attack on record, and marks the first firmly recorded pattern of bubonic plague. This outbreak is thought to have originated in Ethiopia. The huge city of Constantinople imported massive amounts of grain, mostly from Egypt, to feed its citizens. The grain ships were the source of contagion for the city, with massive public granaries nurturing the rat and flea population. At its peak the plague was killing 10,000 people in Constantinople every day and ultimately destroyed perhaps 40% of the city's inhabitants. It went on to destroy up to a quarter of the human population of the eastern Mediterranean.

In A.D. 588 a second major wave of plague spread through the Mediterranean into what is now France. It is estimated that the Plague of Justinian killed as many as 100 million people across the world. It caused Europe's population to drop by around 50% between 541 and 700. It also may have contributed to the success of the Arab conquests. An outbreak of it in the A.D. 560s was described in A.D. 790 as causing "swellings in the glands...in the manner of a nut or date" in the groin "and in other rather delicate places followed by an unbearable fever". While the swellings in this description have been identified by some as buboes, there is some contention as to whether the pandemic should be attributed to the bubonic plague, Yersinia pestis, known in modern times.

Second Pandemic: Black Death

From 1347 to 1351, the Black Death, a massive and deadly pandemic originated in Central Asia, swept through Asia, Europe and Africa. It may have reduced the world's population from 450 million to between 350 and 375 million. China lost around half of its population, from around 123 million to around 65 million; Europe around 1/3 of its population, from about 75 million to about 50 million; and Africa approximately 1/8th of its population, from around 80 million to 70 million (mortality rates tended to be correlated with population density so Africa, being less dense overall, had the lowest rate). This makes the Black Death the largest death toll from any known non-viral epidemic. Although accurate statistical data does not exist, it is thought that 1.4 million died in England (1/3 of England's 4.2 million people), while an even higher percentage of Italy's population was likely wiped out. On the other hand, Northeastern Germany, Bohemia, Poland and Hungary are believed to have suffered less, and there are no estimates available for Russia or the Balkans. It is conceivable that Russia may not have been as affected due to its very cold climate and large size, hence often less close contact with the contagion.

The Black Death contributed to the destruction of the feudal system in Medieval Time. As more slaves and workers died, there were fewer people to work for the nobles and they had to give higher wages to the workers willing to work on the nobles' lands. The Black Death also killed many great kings and nobles. In its aftermath, the Black Death may also have favoured the use of more advanced farming tools as a smaller workforce was available and plots grew larger as a result of the population loss.

The Black Death continued to strike parts of Europe sporadically until the 17th century, each time with reduced intensity and fatality, suggesting an increased resistance due to genetic selection. Some have also argued that changes in hygiene habits and efforts to improve public health and sanitation had a significant impact on the falling rates of infection.

Nature of the disease

In the early 20th century, following the identification by Yersin and Kitasato of the plague bacterium that caused the late 19th and early 20th century Asian bubonic plague (the Third Pandemic), most scientists and historians came to believe that the Black Death was an incidence of this plague, with a strong presence of the more contagious pneumonic and septicemic varieties increasing the pace of infection, spreading the disease deep into inland areas of the continents. It was claimed that the disease was spread mainly by black rats in Asia and that therefore there must have been black rats in north-west Europe at the time of the Black Death to spread it, although black rats are currently rare except near the Mediterranean. This led to the development of a theory that brown rats had invaded Europe, largely wiping out black rats, bringing the plagues to an end, although there is no evidence for the theory in historical records. Some historians suggest that marmots, rather than rats, were the primary carriers of the disease. The view that the Black Death was caused by Yersinia pestis has been incorporated into medical textbooks throughout the 20th century and has become part of popular culture, as illustrated by recent books, such as John Kelly's The Great Mortality.

Many modern researchers have argued that the disease was more likely to have been viral (that is, not bubonic plague), pointing to the absence of rats from some parts of Europe that were badly affected and to the conviction of people at the time that the disease was spread by direct human contact. According to the accounts of the time the black death was extremely virulent, unlike the 19th and early 20th century bubonic plague. Samuel K. Cohn has made a comprehensive attempt to rebut the bubonic plague theory. In the Encyclopedia of Population, he points to five major weaknesses in this theory:

• very different transmission speeds — the Black Death was reported to have spread 385 km in 91 days in 664, compared to 12-15 km a year for the modern Bubonic Plague, with the assistance of trains and cars
• difficulties with the attempt to explain the rapid spread of the Black Death by arguing that it was spread by the rare pneumonic form of the disease — in fact this form killed less than 0.3% of the infected population in its worst outbreak (Manchuria in 1911)
• different seasonality — the modern plague can only be sustained at temperatures between 50 and 78 °F (10 and 26 °C) and requires high humidity, while the Black Death occurred even in Norway in the middle of the winter and in the Mediterranean in the middle of hot dry summers
• very different death rates — in several places (including Florence in 1348) over 75% of the population appears to have died; in contrast the highest mortality for the modern Bubonic Plague was 3% in Mumbai in 1903
• the cycles and trends of infection were very different between the diseases — humans did not develop resistance to the modern disease, but resistance to the Black Death rose sharply, so that eventually it became mainly a childhood disease

Cohn also points out that while the identification of the disease as having buboes relies on accounts of Boccaccio and others, they described buboes, abscesses, rashes and carbuncles occurring all over the body, the neck or behind the ears. In contrast, the modern disease rarely has more than one bubo, most commonly in the groin, and is not characterised by abscesses, rashes and carbuncles.

Researchers have offered a mathematical model based on the changing demography of Europe from 1000 to 1800 AD demonstrating how plague epidemics, 1347 to 1670, could have provided the selection pressure that raised the frequency of a mutation to the level seen today that prevent HIV from entering macrophages that carry the mutation (the average frequency of this allele is 10% in European populations). It is suggested that the original single mutation appeared over 2,500 years ago and that persistent epidemics of a haemorrhagic fever struck at the early classical civilizations.

Third Pandemic

The Third Pandemic began in China in 1855, spreading plague to all inhabited continents and ultimately killing more than 12 million people in India and China alone. Casualty patterns indicate that waves of this pandemic may have come from two different sources. The first was primarily bubonic and was carried around the world through ocean-going trade, transporting infected persons, rats, and cargos harboring fleas. The second, more virulent strain was primarily pneumonic in character, with a strong person-to-person contagion. This strain was largely confined to Manchuria and Mongolia. Researchers during the "Third Pandemic" identified plague vectors and the plague bacterium (see above), leading in time to modern treatment methods.

Plague occurred in Russia in 1877–1889 in rural areas near the Ural Mountains and the Caspian Sea. Efforts in hygiene and patient isolation reduced the spread of the disease, with approximately 420 deaths in the region. Significantly, the region of Vetlianka in this area is near a population of the bobak marmot, a small rodent considered a very dangerous plague reservoir. The last significant Russian outbreak of Plague was in Siberia in 1910 after sudden demand for Marmot skins (a substitute for Sable) increased the price by 400 percent. The traditional hunters would not hunt a sick Marmot and it was taboo to eat the fat from under the arm (the axillary lymphatic gland that often harboured the plague) so outbreaks tended to be confined to single individuals. The price increase, however, attracted thousands of Chinese hunters from Manchuria who not only caught the sick animals but ate the fat which was considered a delicacy. The plague spread from the hunting grounds to the terminus of the Chinese Eastern Railway and then followed the track for 2,700 km. The plague lasted 7 months and killed 60,000 people.

The bubonic plague continued to circulate through different ports globally for the next fifty years; however, it was primarily found in Southeast Asia. An epidemic in Hong Kong in 1894 had particularly high death rates, 90% . As late as 1897, medical authorities in the European powers organized a conference in Venice, seeking ways to keep the plague out of Europe. The disease reached the Republic of Hawaii in December of 1899, and the Board of Health’s decision to initiate controlled burns of select buildings in Honolulu’s Chinatown turned into an uncontrolled fire which led to the inadvertent burning of most of Chinatown on January 20, 1900 according to the Star Bulletin's Feature on the Great Chinatown Fire Plague finally reached the United States later that year in San Francisco.

Although the outbreak that began in China in 1855 is conventionally known as the Third Pandemic, (the First being the Plague of Justinian and the second being the Black Death), it is unclear whether there have been fewer, or more, than three major outbreaks of bubonic plague. Most modern outbreaks of bubonic plague amongst humans have been preceded by a striking, high mortality amongst rats, yet this phenomenon is absent from descriptions of some earlier plagues, especially the Black Death. The buboes, or swellings in the groin, that are especially characteristic of bubonic plague, are a feature of other diseases as well.

Plague as a biological weapon

Plague has a long history as a biological weapon. Historical accounts from ancient China and medieval Europe detail the use of infected animal carcasses, such as cows or horses, and human carcasses, by the Xiongnu/Huns, Mongols, Turks, and other groups, to contaminate enemy water supplies. Han Dynasty General Huo Qubing is recorded to have died of such a contamination while engaging in warfare against the Xiongnu. Plague victims were also reported to have been tossed by catapult into cities under siege.

During World War II, the Japanese Army developed weaponised plague, based on the breeding and release of large numbers of fleas. During the Japanese occupation of Manchuria, Unit 731 deliberately infected Chinese, Korean, and Manchurian civilians and prisoners of war with the plague bacterium. These subjects, termed "maruta", or "logs", were then studied by dissection, others by vivisection while still conscious. Members of the unit such as Shiro Ishii were exonerated from the Tokyo tribunal by Douglas MacArthur but twelve of them were prosecuted in the Khabarovsk War Crime Trials in 1949 during which some admitted having spread Bubonic plague within a 36-km radius around the city of Changde.

After World War II, both the United States and the Soviet Union developed means of weaponising pneumonic plague. Experiments included various delivery methods, vacuum drying, sizing the bacterium, developing strains resistant to antibiotics, combining the bacterium with other diseases (such as diphtheria), and genetic engineering. Scientists who worked in USSR bio-weapons programs have stated that the Soviet effort was formidable and that large stocks of weaponised plague bacteria were produced. Information on many of the Soviet projects is largely unavailable. Aerosolized pneumonic plague remains the most significant threat. The plague can be easily treated with antibiotics, thus a widespread epidemic is highly unlikely in developed countries.

1994 Epidemic in Surat, India

In 1994, there was a pneumonic plague epidemic in Surat, India that resulted in 52 deaths and in a large internal migration of about 300,000 residents, who fled fearing quarantine .

A combination of heavy monsoon rain and clogged sewers led to massive flooding which resulted in unhygienic conditions and a number of uncleared animal carcasses. It is believed that this situation precipitated the epidemic.. There was widespread fear that the flood of refugees might spread the epidemic to other parts of India and the world, but that scenario was averted, probably as a result of effective public health response mounted by the Indian health authorities .

Much like the Black Death that spread through medieval Europe, some questions still remain unanswered about the 1994 epidemic in Surat.

Initial questions about whether it was an epidemic of plague arose because the Indian health authorities were unable to culture Yersinia pestis, but this could have been due to poor laboratory procedures. Yet, there are several lines of evidence strongly suggesting that it was a plague epidemic: blood tests for Yersinia were positive, a number of individuals showed antibodies against Yersinia and the clinical symptoms displayed by the affected were all consistent with the disease being plague .

Other Contemporary cases

Two non-plague Yersinia - Yersinia pseudotuberculosis and Yersinia enterocolitica - still exist in fruit and vegetables from the Caucasus Mountains east across southern Russia and Siberia, to Kazakhstan, Mongolia, and parts of China; in Southwest and Southeast Asia, Southern and East Africa (including the island of Madagascar); in North America, from the Pacific Coast eastward to the western Great Plains, and from British Columbia south to Mexico; and in South America in two areas: the Andes mountains and Brazil. There is no plague-infected animal population in Europe or Australia.

• On August 31, 1984, the Centers for Disease Control and Prevention reported a case of pneumonic plague in Claremont, California. The CDC believes that the patient, a veterinarian, contracted plague from a stray cat. This could not be confirmed since the cat was destroyed prior to the onset of symptoms.
• From 1995 to 1998, annual outbreaks of plague were witnessed in Mahajanga, Madagascar as per a study done by Pascal Boisier and other scientists and publish in Emerging Infectious Diseases journal in March 2002.
• In the U.S., about half of all food cases of plague since 1970 have occurred in New Mexico. There were 2 plague deaths in the state in 2006, the first fatalities in 12 years.
• In Fall of 2002, a New Mexico couple contracted the disease, just prior to a visit to New York City. They both were treated by antibiotics, but the male required amputation of both feet to fully recover, due to the lack of blood flow to his feet, cut off by the bacteria.
• On April 19, 2006, CNN News and others reported a case of plague in Los Angeles, California, lab technician Nirvana Kowlessar, the first reported case in that city since 1984.
• In May 2006, KSL Newsradio reported a case of plague found in dead field mice and chipmunks at Natural Bridges about west of Blanding in San Juan County, Utah.
• In May 2006, AZ Central reported a case of plague found in a cat.
• One hundred deaths resulting from pneumonic plague were reported in Ituri district of the eastern Democratic Republic of the Congo in June 2006. Control of the plague was proving difficult due to the ongoing conflict.
• It was reported in September 2006 that three mice infected with Yersinia pestis apparently disappeared from a laboratory belonging to the Public Health Research Institute, located on the campus of the University of Medicine and Dentistry of New Jersey, which conducts anti-bioterrorism research for the United States government.
• On May 16, 2007, an 8-year-old hooded capuchin monkey in the Denver Zoo died of the bubonic plague. Five squirrels and a rabbit were also found dead on zoo grounds and tested positive for the disease.
• On June 5, 2007 in Scotland, UK a 68 year old woman developed bubonic plague, which progressed to pneumonic plague.
• On November 2, 2007, Eric York, a 37 year old wildlife biologist for the National Park Service's and The Felidae Conservation Fund, was found dead in his home at Grand Canyon National Park. On October 27, York performed a necropsy on a mountain lion that had likely perished from the disease and three days afterward York complained of flu-like symptoms and called in sick from work. He was treated at a local clinic but was not diagnosed with any serious ailment. The discovery of his death sparked a minor health scare, with officials stating he likely died of either plague or hantavirus, and 49 people who had come in to contact with York were given aggressive antibiotic treatments. None of them fell ill. Autopsy results released on November 9th, confirmed the presence of Y. pestis in his body, confirming plague as a likely cause of death.

Literary and popular culture references

• The Decameron by Giovanni Boccaccio (1350). Takes place in Florence in 1348, during the outbreak of the Black Death.
• Romeo and Juliet (1597) Friar John was unable to go to Mantua and deliver a letter to Romeo because of Bubonic Plague quarantine.
• A Journal of the Plague Year by Daniel Defoe (1722). A fictional first hand account of the London outbreak of 1665. Probably based on the experiences of Defoe's uncle.
• "The Masque of the Red Death" (1842) by Edgar Allan Poe includes a vivid description of pestilence that some scholars have interpreted to be septicemic plague.
• I Promessi Sposi (The Betrothed) (1842) by Alessandro Manzoni set in early 17th century in Northern Italy, is one of the most read and better known classical novels in Italian literature. Contains a detailed and vivid account of society during the plague outbreak in its time.
• Narcissus and Goldmund by Hermann Hesse (1930). A fictional account in which the main character ends up witnessing the effects of the plague first-hand.
• The Plague by Albert Camus (1947) depicts an outbreak of plague at the Algerian city of Oran. The disease, often interpreted as a metaphor for the German occupation of France in World War II, serves as a means for the author to examine his characters' responses to hardship, suffering and death.
• Panic in the Streets (1950) by Elia Kazan. A murder victim is found to be infected with pneumonic plague. To prevent a catastrophic epidemic, the police must find and inoculate the killers and their associates.
• (Don't Fear) The Reaper (1976) by Blue Öyster Cult. The line "40,000 men and women everyday... Like Romeo and Juliet - 40,000 men and women everyday... Redefine happiness - Another 40,000 coming everyday... We can be like they are" is a reference to the number of people dying daily during ''The Black Plague"
• The Plague Dogs (1977), by Richard Adams. A fictional story in which two dogs, Rowf and Snitter, escape from a British government research laboratory and are hunted down by the government as potential carriers of the plague.
• Doomsday Book by Connie Willis (1992). A Hugo award and Nebula award-winning historical science fiction novel, in which a time-traveler inadvertently ends up in the plague-ridden England of 1348.
• King of Shadows (1999), by Susan Cooper. Nathan Field, an actor, is infected with the bubonic plague while staying in London, which sends him back in time to the Elizabethan ages.
• Confessions of an Ugly Stepsister (1999), a novel by Gregory Maguire, takes place in 17th Century Haarlem, Netherlands, where a resurgence of the plague occurred.
• Year of Wonders by Geraldine Brooks (2001), a fictional story of an historical event in which the small Derbyshire village of Eyam quarantines themselves once infected with the plague.
• The Years of Rice and Salt by Kim Stanley Robinson (2002). Presents an alternate history of the world where the population of Europe is obliterated by the Black Death setting the stage for a world without Europeans and Christianity.
• In Dies the Fire by S. M. Stirling in (2004), an epidemic of the Black Death is described around the city of Portland, Oregon.
• Episode 18 of the second season of American television show House features the bubonic plague.
• In the season one episode of Torchwood, "End of Days", a woman from the 14th century infected by the plague falls through the rift into Cardiff, causing an infection of dozens of people in a local hospital.
• Third Watch In the third episode of the fifth season, a number of illegal immigrants are discovered in the back of a truck and brought to hospital where they are diagnosed with the plague. The situation is complicated by the fact one of the immigrants managed to flee.
• In The Keys to the Kingdom by Garth Nix, Suzy Turquoise Blue, one of the Piper's children, was led to the House by the Piper from London during the Great Plague of London.
• Grey's Anatomy In the first episode of the third season, a couple comes into the hospital because of flu symptoms, but get in a car crash along the way because the woman passed out while driving. Different rooms in the hospital are quarantined, and the woman in the crash dies after surgery, due to complications from the plague.
• In Grand Theft Auto Advance, Liberty City is said to be affected by Bubonic plague.
• The band Modest Mouse references "the rats and the fleas" that caused the disease to spread to humans in their song March into the Sea.
• An episode of the TV show Wire in the Blood features a strain of bubonic plague as a biological weapon.
• In Spooks Series 6 (episodes one and two) a fictional virus that causes symptoms mimicking pneumonic plague is accidentally released in London.
• Lux perpetua (2006) by Andrzej Sapkowski. One of the main characters is murdered by magically induced septicemic plague.
• World Without End (2007) by Ken Follett. The plague's spread throughout Europe in the 14th century is an integral part of the book's storyline.
• The Shifting Tide (2004) by Anne Perry. The plague enters England via a ship transporting ivory.
• In an episode of the TV show NCIS, SWAK, a team member gets infected with an engineered variant of pneumonic plague after opening a contaminated envelope.
• In the television series The Marvelous Misadventures of Flapjack, the Plague makes people's faces hideously swelled and deformed. The only person it does not affect is Flapjack, whose blood is needed to make a cure. Bubbie does not get the Plague either, all though it is unknown if she is immune or not.
• The Return of the Black Death, an album by the Christian Black Metal band Antestor, deals with the second outbreak of the Plague epidemic in Norway and the country's subsequent Christianization.

References

Notes

Bibliography

• Weatherford 2004: 242-250
• Benedictow, Ole J. The Black Death 1346-1353: The Complete History. DS Brewer, 2006. ISBN 978-1843832140.
• Biraben, Jean-Noel. Les Hommes et la Peste The Hague 1975.
• Buckler, John and Bennet D. Hill and John P. McKay. "A History of Western Society, 5th Edition." New York: Houghton Mifflin Co., 1995.
• Cantor, Norman F., In the Wake of the Plague: the Black Death and the World It Made New York: Harper Perennial, 2002. ISBN 978-0060014346.
• de Carvalho, Raimundo Wilson; Serra-Freire, Nicolau Maués; Linardi, Pedro Marcos; de Almeida, Adilson Benedito; and da Costa, Jeronimo Nunes (2001). Small Rodents Fleas from the Bubonic Plague Focus Located in the Serra dos Órgãos Mountain Range, State of Rio de Janeiro, Brazil Memórias do Instituto Oswaldo Cruz 96(5), 603–609. PMID 11500756. this manuscript reports a census of potential plague vectors (rodents and fleas) in a Brazilian focus region (i.e. region associated with cases of disease); free PDF download Retrieved 2005-03-02
• Chase, Marilyn. The Barbary Plague: The Black Death in Victorian San Francisco. New York: Random House Trade Paperbacks, 2004. ISBN 978-0375757082.
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• Gregg, Charles T. Plague!: The shocking story of a dread disease in America today. New York, NY: Scribner, 1978, ISBN 0-684-15372-6.
• Ernest Jawetz, et al. Medical Microbiology. 18th ed. United States: Prentice-Hall International Inc., 1989. ISBN 0-8385-6238-8
• Kelly, John. The Great Mortality: An Intimate History of the Black Death, the Most Devastating Plague of All Time. New York: HarperCollins Publishers Inc., 2005. ISBN 0-06-000692-7.
• McNeill, William H. Plagues and People. New York: Anchor Books, 1976. ISBN 0-385-12122-9. Reprinted with new preface 1998.
• Mohr, James C. Plague and Fire: Battling Black Death and the 1900 Burning of Honolulu's Chinatown. New York, NY: Oxford University Press, 2005, ISBN 0-19-516231-5.
• Moote, A. Lloyd, and Dorothy C. Moote. The Great Plague: The Story of London's Most Deadly Year. Baltimore, MD: Johns Hopkins University Press, 2004. ISBN 978-0801877834.
• Orent, Wendy. Plague: The Mysterious Past and Terrifying Future of the World's Most Dangerous Disease. New York: Free Press, 2004. ISBN 0-7432-3685-8.
• Papagrigorakis, Manolis J., Christos Yapijakis, Philippos N. Synodinos, and Effie Baziotopoulou-Valavani. "DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens," International Journal of Infectious Diseases 10 (2006): 206-214. ISSN 1201-9712.
• Patrick, Adam. "Disease in Antiquity: Ancient Greece and Rome," in Diseases in Antiquity, editors: Don Brothwell and A. T. Sandison. Springfield, Illinois; Charles C. Thomas, 1967.
• Platt, Colin. King Death: The Black Death and its Aftermath in Late-Medieval England Toronto University Press, 1997.
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• Simpson, W. J. A Treatise on Plague. Cambridge, England: Cambridge University Press, 1905.
• Spielvogel, Jackson J. Western Civilization: A Brief History Vol. 1: to 1715. Belmont, Calif.: West/Wadsworth, 1999, Ch. 3, p. 56, paragraph 2. ISBN 0-534-56062-8.

External links

• World Health Organization
• Health topic
• Communicable Disease Surveillance & Response - Impact of plague & Information resources
• Centers for Disease Control and Prevention
• CDC Plague map world distribution, publications, information on bioterrorism preparedness and response regarding plague
• Infectious Disease Information more links including travelers' health
• Symptoms, causes, pictures of bubonic plague
• Secrets of the Dead . Mystery of the Black Death PBS
• Researchers sound the alarm: the multidrug resistance of the plague bacillus could spread
• Plague - LoveToKnow 1911
• Genome information is available from the NIAID Enteropathogen Resource Integration Center (ERIC)