Few words in the English language encapsulate as much horror, misery and doom as "plague." After all, infectious diseases have inflicted a great deal of damage throughout the centuries. They've decimated whole populations, ended blood lines, claimed higher casualties than wars and played pivotal roles in charting the course of history.

Early humans were no strangers to disease. They encountered the microbes that cause illness in drinking water, food and the environment. Occasionally an outbreak might decimate a small group, but they never encountered anything close to the widespread illnesses of the ages to follow. It wasn't until humans began gathering in larger populations that contagious diseases had the opportunity to spread to epidemic proportions. An epidemic occurs when a disease affects a disproportionally large number of people within a given population, such as a city or geographic region. If it affects even greater numbers and a wider area, these outbreaks become pandemics.

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Humans also opened themselves up to new and deadlier diseases by domesticating animals that boast their own microbes. By putting themselves in regular, close contact with formerly wild animals, early farmers gave these microbes a chance to adapt to human hosts.

As humans expanded their territory, they came into closer contact with microbes they might otherwise have never encountered. By storing food, humans attracted scavenging creatures such as rats and mice, which brought more microbes. Human expansion also resulted in the construction of more wells and ditches, which provided more standing water for disease-carrying mosquitoes. As technology allowed for wider travel and trade, new microbes could easily spread from one highly populated area to another.

Ironically, many of the pillars of modern human society paved the way for one of its greatest threats. And just as we continue to grow, so too microbes continue to evolve. In this article, we'll take a look at 10 of the worst epidemics to ever plague mankind and how each disease works.

This engraving depicts Spanish explorer Hernando Cortez's Aug. 13, 1521 capture of the Aztec capital Tenochtitlan. The weapon that ensured his victory wasn't modern firepower, but smallpox the conquistadors inadvertently introduced to the continent. Hulton Archive/Getty Images

Before European explorers, conquerors and colonists began to flood into the New World in the early 1500s, the Americas were home to an estimated 100 million native people. During the centuries that followed, epidemic diseases decreased that number to somewhere between 5 and 10 million. While these people, such as the Incas and the Aztecs, had built cities, they hadn't resided in them long enough to breed the kind of diseases Europeans had, nor had they domesticated as many animals. When the Europeans arrived to the Americas, they brought with them a host of diseases for which the native peoples had no defense or immunity.

Chief among these diseases was smallpox, caused by the variola virus. These microbes began affecting humans thousands of years ago, with the most common form of the disease boasting a 30 percent mortality rate. Smallpox causes high fevers, body aches, and a rash that develops from fluid-filled bumps and scabs to permanent, pitted scars. The disease predominantly spreads through direct contact with an infected person's skin or bodily fluids, but can also be spread though the air in close, confined environments.

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Despite the creation of a vaccine in 1796, smallpox epidemics continued to spread. Even as recently as 1967, the virus killed two million people and scared millions more across the world. That same year, the World Health Organization spearheaded an effort to eradicate the virus

through mass vaccinations. As a result, 1977 marked the last naturally occurring case of smallpox. Effectively eliminated from the natural world, the disease exists only in laboratories.

Learn how and why 1918's influenza strain killed millions of people on the next page.

Nurses care for victims of the 1918 Spanish flu epidemic outdoors amidst canvas tents in Massachusetts.Hulton Archive/Getty Images

The year was 1918. The world watched as World War I spiraled to a close. By the end of the year, the estimated death toll would reach 37 million worldwide, and millions of soldiers busied themselves with the task of returning to their homes. Then a new illness emerged. Some called it the Spanish flu, others the Great Influenza or the flu of 1918. Whatever you wanted to call it, the disease killed as many as 20 million people in a matter of months. In a year's time, the flu would run its course, but only after inflicting a staggering death toll. Global estimates range between 50 and 100 million fatalities. Many consider this the worst epidemic, and ensuing pandemic, in recorded human history.

The flu of 1918 wasn't the typical influenza virus we encounter every year. This was a new strain of flu microbe, the H1N1 avian influenza A virus. Scientists suspect the disease moved from birds to humans in the American Midwest just prior to the outbreak. It was later dubbed the Spanish flu after an epidemic in Spain killed 8 million people. Worldwide, people's immune systems were utterly unprepared for the new virus -- just as the Aztecs were unprepared for the arrival of smallpox in the 1500s. Massive troop transport and supply lines at the close of World War I allowed the virus to quickly reach pandemic proportions by spreading to other continents and countries.

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The flu of 1918 carried symptoms typical of normal influenza, including fever, nausea, aches and diarrhea. Also, patients would frequently develop black spots on their cheeks. As their lungs filled with liquid, they ran the risk of dying from lack of oxygen. Those who died effectively drowned in their own mucus.

The epidemic subsided within a year as the virus mutated into other, less lethal forms. Most people today have some degree of immunity to this family of H1N1 virus, inherited from those who survived the pandemic.

If you like your art dark, read on to learn how the Black Death affected the creative minds of the time.

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Carts piled high with corpses, dying families boarded up in quarantine and kings and peasants alike wailing to heaven for deliverance -- when it comes to epidemic diseases, few illnesses instill such dire images as the Black Death. Considered the first true pandemic disease, the Black Death killed half of Europe's population in 1348 and also decimated parts of China and India. This "great dying" followed paths of trade and war, decimating cities and towns and permanently altering class structure, global politics, trade and society. To learn more about the Black Death, read How the Black Death Worked.

The Black Death has long thought to have been an epidemic of plague, traveling in its bubonic form on the fleas of rats and through the air in its pneumonic form. Recent studies have called this into question. Some scientists now argue the Black Death may have been a hemorrhagic virus similar to ebola. This form of illness results in massive blood loss. Scientists continue to study the remains of suspected plague victims in hopes of uncovering genetic evidence to substantiate their theories.

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If it was plague, then the Black Death is still with us. Caused by the bacteria Yersinia pestis, the illness can still present a problem in impoverished, rat-infested areas. Modern medicine allows for easy treatment of the disease in its early stages, making it a far less lethal threat. Symptoms include swollen lymph glands, fever, cough, bloody sputum and difficulty breathing.

After you read the next page about malaria, you may feel no guilt killing the next mosquito that lands on your skin.


Malaria isn't new to the world of epidemic diseases. Records of its impact on human populations date back more than 4,000 years, when Greek writers noted its ravaging effects. Accounts of the mosquito-born illness pop up in ancient Indian and Chinese medical texts. Even then, scientists made the vital connections between the illness and the still waters where mosquitoes breed.

Malaria is caused by four species of Plasmodium microbes common to two species: mosquitoes and humans. When infected mosquitoes feed on human blood, they pass on the microbes. Once in the blood, the microbes grow inside red blood cells, destroying them in the process. Symptoms vary from mild to deadly, but typically include fever, chills, sweating, headache and muscle pains. You can read more about the disease in How Malaria Works.

­Specific figures relating to ancient malaria epidemics are difficult to come by. The past effects of the disease can best be seen in examining large-scale human undertakings in malaria-infested areas. In 1906, the United States employed more than 26,000 workers to construct the Panama Canal. Organizers hospitalized more than 21,000 of these men for malaria.

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Wartime soldiers of the past often experienced great losses to malaria. In the American Civil War alone, 1,316,000 men reportedly suffered from the illness and 10,000 died. During World War I, malaria immobilized British, French and German forces for three years. Nearly 60,000 U.S. soldiers died from the disease in Africa and the South Pacific during World War II.

At the end of World War II, the United States attempted to halt the malaria epidemic. The country initially made huge strides by using the now-banned insecticide Dichloro-diphenyl-trichlorethane (DDT), then followed up with preventive measures to keep mosquito populations low. After the Centers for Disease Control (CDC) declared malaria eradicated in the United States, the World Health Organization (WHO) set out to eradicate the illness worldwide. Results were mixed, however, and costs, war, politics, the emergence of drug-resistant strains of malaria and insecticide-resistant mosquitoes eventually led to the project's abandonment.

Today, malaria continues to pose a problem in much of the world, especially in sub-Saharan Africa, an area that was excluded from the WHO eradication campaign. Each year, between 350 and 500 million cases of malaria occur in the region. Of those cases, more than a million result in death. Even in the United States, more than a thousand cases and a handful of deaths occur each year, despite previous claims of eradication.

Next, learn about a disease that has affected mankind since the days of mummies and ancient Egypt.

A mother waits and child wait for a check-up at a free tuberculosis hospital on the outskirts of Kolkata, India. TB is a major public health problem in India, which accounts for one-fifth of the global TB incident cases.Deshakalyan Chowdhury/Associated Foreign Press/Getty Images

Tuberculosis (TB) has ravaged human populations throughout recorded history. Ancient texts detail the manner in which its victims waste away, and DNA evidence of the disease was even discovered in Egyptian mummies.

Caused by the bacteria Mycobacterium tuberculosis, TB spreads from person to person through the air. One person breathes the bacterium out and another breathes it in. The bacterium usually targets the lungs, resulting in chest pains, weakness, weight loss, fever, night sweats and fits of bloody coughing. In some cases, the bacterium also affects the brain, kidneys or spine.

Beginning in the 1600s, the European TB epidemic known as the Great White Plague raged for 200 years, killing approximately one out of every seven infected people. TB was a constant problem in colonial America. Even at the close of the 19th century, 10 percent of all U.S. deaths were attributed to tuberculosis.

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In 1944, doctors developed the antibiotic streptomycin with which to combat the disease. Further breakthroughs were made in the years to follow, and after 5,000 years of suffering, humankind finally had a cure for what the ancient Greeks called Phthisis, "the wasting disease."

Yet despite modern cures and treatments, TB continues to infect an estimated 8 million people annually, eventually killing an estimated 2 million. The illness made a huge comeback in the 1990s, due largely to lapsed prevention and treatment programs, global poverty, and the emergence of new, antibiotic-resistant strains of TB. Additionally, patients with HIV/AIDS experience weakened immune systems, making them more susceptible to TB infection. As AIDS spread through the world, so too did a TB resurgence.

Read the next page to learn why hydrating sports drinks and liquids may help if you've been diagnosed with cholera.

A father cradles his sick child during the cholera outbreak in 1994 that claimed thousands of lives in Goma, Zaire, after one million people fled fighting in Rwanda.Tom Stoddart/Hulton Archive/Getty Images

The people of India had lived with the dangers of cholera since ancient times, but it wasn't until the 19th century that the rest of the world experienced this disease. During this period, traders inadvertently exported the deadly virus back to cities in China, Japan, North Africa, the Middle East and Europe. Six cholera pandemics followed, killing millions.

Cholera is caused by an intestinal bacterium called Vibrio cholerae. Infections are frequently mild. Five percent of those who contract it experience severe vomiting, diarrhea and leg cramps -- leading to rapid dehydration and shock. Most immune systems can easily defeat cholera, but only if the patient remains hydrated long enough to live through it. Humans can contract the bacterium through close physical contact, but cholera mainly spreads though contaminated water and food.

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Traders introduced cholera to the cramped and squalid conditions of Europe's major cities during the industrial revolution of the 1800s. Doctors pushed for cleaner living conditions and more sanitary sewage systems, thinking "bad air" caused the epidemic. This helped matters, and when the connection was finally made to contaminated drinking water, cases greatly decreased.

For decades, it seemed cholera was a thing of the past -- just a disease of the 18th century bested by improvements in sanitation and medical science. Nevertheless, a new strain of cholera emerged in 1961 in Indonesia, and it eventually spread to much of the world. The ensuing pandemic continues to this day. In 1991, cholera sickened an estimated 300,000 people and killed 4,000 within the year.

As AIDS makes headlines on a continual basis, the disease has inspired many award-winning movies, plays, television programs and books. Read about this incurable disease on the next page.

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The emergence of AIDS in the 1980s has led to a global pandemic, killing an estimated 25 million people since 1981. According to recent statistics, 33.2 million people are currently HIV-positive, and 2.1 million people died of AIDS in 2007 alone.

AIDS (acquired immune deficiency syndrome) is caused by the human immunodeficiency virus (HIV). The virus spreads through contact with blood, semen and other bodily fluids, and it damages the human immune system. The damaged immune system opens the body up to infections, called opportunistic infections (OIs), that otherwise wouldn't pose a problem. HIV becomes AIDS if the immune system breaks down severely enough.

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Scientists believe HIV made the jump from certain species of monkey and ape to humans sometime in the mid 20th century. During the 1970s, Africa's population grew, and war, poverty and unemployment plagued urban areas. Prostitution and intravenous drug abuse rose out of the chaos, with HIV spreading easily via unprotected sex and the reuse of contaminated needles. Even in hospitals, the reuse of needles and the contaminated blood transfusions contributed to the epidemic. Since then, AIDS has moved through sub-Saharan Africa, orphaning millions of children and depleting the work force in many of the world's poorest developing nations.

Currently, there's no cure for AIDS, though certain drugs can keep HIV from developing into AIDS. Additional medications can help combat OIs. Various organizations have waged an AIDS campaign of treatment, education and prevention. As mentioned earlier, HIV is often transmitted through sexual intercourse and the use of shared needles. Doctors continue to push for the use of condoms and disposable needles. For more information about AIDS and HIV, read How AIDS Works.

Next, learn about an illness that even stopped Napoleon -- yellow fever.

Illustration of a mob attacking the Quarantine Marine Hospital in New York in 1858 because they believed that its use was responsible for numerous yellow fever epidemics.Getty Images

When Europeans began importing African slaves to the Americas, they also brought over a number of new diseases, including yellow fever. This illness, also known as "yellow jack," ripped through the colonies, decimating farms and even major cities.

When French emperor Napoleon sent an army of 33,000 to French landholdings in North America, yellow fever killed 29,000 of those soldiers. Napoleon was so shocked by the number of casualties that he decided the territory wasn't worth the risk of further losses. France sold the land to the United States in 1803; an event which would go down in history as the Louisiana Purchase.

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Yellow fever, like malaria, spreads from person to person through feeding mosquitoes. Typical symptoms include fever, chills, headache, muscle ache, backache and vomiting. Severity of symptoms ranges from mild to deadly, as severe infections can lead to bleeding, shock and kidney and liver failure. Liver failure causes jaundice or the yellowing of skin, which gives the illness its name.

Despite vaccination, improved treatment procedures and better mosquito management, epidemics of the illness persist to this day in South America and Africa.

Read the next page to find out why wartime soldiers not only had to dodge bullets, but also epidemic typhus.

A British soldier sprays a recently liberated prisoner from the squalid conditions in Bergen-Belsen concentration camp in order to combat epidemic typhus in 1945.George Rodger/Time & Life Pictures/Getty Images

Crowd enough people together in cramped, filthy conditions and you're likely to have an outbreak of body lice on your hands. Squalid cities and encamped armies throughout history have had to put up with the parasitic menace and the devastating bacteria they carry. The tiny microbe Rickettsia prowazekii causes one of the more devastating infectious diseases the world has ever known: epidemic typhus.

The disease plagued humankind for centuries, inflicting deaths by the thousands. Given its frequency among encamped armies, it was often dubbed "camp fever" or "war fever." During the course of Europe's Thirty Years War (1618-1648), typhus, plague and starvation claimed an estimated 10 million people. Occasionally, outbreaks of typhus would even dictate the outcome of entire wars.

When Spanish forces laid siege to the Moorish stronghold of Granada in 1489, an outbreak of typhus reduced the Spanish forces from 25,000 to 8,000 in a single month [source: Conlon]. Due to the ravages of typhus, it would be another century before the Spanish could drive the Moors from Spain. As recently as World War I, the disease caused several million deaths in Russia, Poland and Romania.

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Symptoms of epidemic typhus typically include headache, loss of appetite, malaise and a rapid rise in temperature. This quickly develops into a fever, accompanied by chills and nausea. If untreated, the illness affects blood circulation, resulting in spots of gangrene, pneumonia and kidney failure. Progressive heat exhaustion can eventually lead to delirium, coma and cardiac failure.

Improved treatment methods and sanitary conditions greatly reduced epidemic typhus' impact in modern times. The advent of a typhus vaccine during World War II and the widespread use of DDT on lice populations helped effectively eliminate the illness in the developed world. Outbreaks still occur in parts of South America, Africa and Asia.

Read the next page to learn why sanitation and improved living conditions left many people exposed to a (literally) crippling disease.

A 1956 operative in the Glaxo Laboratories mixes three distinct strains of killed poliovirus to prepare the final vaccine. Keystone/Getty Images

Researchers suspect polio has been an epidemic in humans for millennia, paralyzing and killing children by the thousands. As recently as 1952, there were an estimated 58,000 cases of polio in the United States alone -- one-third of the patients were paralyzed. Of these cases, more than 3,000 died.

The cause of the disease is the poliovirus poliomyelitis, which targets the human nervous system. It spreads though fecal matter, often passing on to others through contaminated food or water. Initial symptoms include fever, fatigue, headache, vomiting, stiffness and limb pains. From here, roughly one in 200 cases leads to paralysis. While this usually affects the legs, the disease sometimes spreads to the breathing muscles, usually with lethal results.

Polio occurs most frequently in children but affects adults as well. It all depends on when the person encounters the virus for the first time and develops his or her primary infection. The immune system is better prepared to fight the disease off at an early age, so the higher the age at primary infection, the greater the risk of paralyzation and death.

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Polio is an old malady for humans, circulating wildly for centuries. With increased exposure to the virus came boosted immunity, especially in children. In the 18th century, sanitation methods improved in many countries. This limited the spread of the disease, decreasing natural immunity and the chances of exposure at a very young age. As a result, more and more people encountered the virus at an older age, and the number of paralytic cases in developed nations skyrocketed.

There's no effective cure for polio, but doctors perfected a polio vaccine in the early 1950s. Since then, cases in the United States and other developed nations dropped dramatically, and only a handful of developing nations still experience polio at epidemic levels. As humans are the only known carriers of the virus, widespread vaccination almost guarantees polio's extinction. In 1988, the World Health Organization organized the Global Polio Eradication Initiative to pursue just this goal.