A pandemic is an epidemic of infectious disease that has spread through human populations across a large region, multiple continents, or even worldwide. The World Health Organization (WHO) produced a six-stage classification that describes the process by which a novel influenza virus moves from the first few infections in humans through to a pandemic. This starts with the virus mostly infecting animals, with a few cases where animals infect people, then moves through the stage where the virus begins to spread directly between people, and ends with a pandemic when infections from the new virus have spread worldwide.
A disease or condition is not a pandemic merely because it is widespread or kills many people; it must also be infectious. For instance, 
cancer is responsible for many deaths but is not considered a pandemic because the disease is not infectious or contagious. Further, flu pandemics generally exclude recurrences of seasonal flu. Throughout history there have been a number of pandemics, such as smallpox and tuberculosis, and more recent pandemics include the HIV pandemic and the H1N1 pandemics of 1918 and 2009.
Fortunately for humans, pandemics are relatively rare. In fact, there were only three in the last one hundred years, and they varied in severity. The 1918 Spanish Flu was the most severe. It is estimated that approximately 20 to 40 percent of the worldwide population became ill and that over 50 million people died. Between September 1918 and April 1919, approximately 675,000 deaths from the flu occurred in the U.S. alone. One of the most unusual aspects of the Spanish flu was its ability to kill young adults. It was later determined that the 1918 pandemic was caused by an avian influenza.
Here’s a quick summary of the 5 deadliest pandemics in history:
1. The Peloponnesian War Pestilence
The very first pandemic in recorded history was described by Thucydides. In 430 BC, during the Peloponnesian war between Athens and Sparta, the Greek historian told of a great pestilence that wiped out over 30,000 of the citizens of Athens (roughly one to two thirds of all Athenians died).
Thucydides described the disease as such “People in good health were all of a sudden attacked by violent heats in the head, and redness and inflammation in the eyes, the inward parts, such as the throat or tongue, becoming bloody and emitting an unnatural and fetid breath.” Next came coughing, diarrhea, spasms, and skin ulcers. A handful survived, but often without their fingers, sights, and even genitals
Until today, the disease that decimated ancient Athens has yet to be identified.
2. The Antonine Plague
In 165 AD, Greek physician Galen described an ancient pandemic, now thought to be smallpox, that was brought to Rome by soldiers returning from Mesopotamia. The disease was named after Marcus Aurelius Antoninus, one of two Roman emperors who died from it.
At its height, the disease killed some 5,000 people a day in Rome. By the time the disease ran its course some 15 years later, a total of 5 million people were dead.
3. The Plague of Justinian
In 541-542 AD, there was an outbreak of a deadly disease in the Byzantine Empire. At the height of the infection, the disease, named the Plague of Justinian after the reigning emperor Justinian I, killed 10,000 people in Constantinople every day. With no room nor time to bury them, bodies were left stacked in the open. By the end of the outbreak, nearly half of the inhabitants of the city were dead. Historians believe that this outbreak decimated up to a quarter of human population in the eastern Mediterranean.
What was the culprit? It was the bubonic plague, caused by the bacterium Yersinia pestis. This outbreak, the first known bubonic plague pandemic in recorded human history, marked the first of many outbreaks of plague – a disease that claimed as many as 200 million lives throughout history.
4. The Black Death
After the Plague of Justinian, there were many sporadic oubreaks of the plague, but none as severe as the Black Death of the 14th century. While no one knows for certain where the disease came from (it was thought that merchants and soldiers carried it over caravan trading routes), the Black Death took a heavy toll on Europe. The fatality was recorded at over 25 million people or one-fourth of the entire population.
It’s interesting to note that the Black Death actually came in three forms:
- The bubonic plague was the most common: people with this disease have buboes or enlarged lymphatic glands that turn black (caused by decaying of the skin while the person is still alive). Without treatment, bubonic plague kills about half of those infected within 3 to 7 days.
- In pneumonic plague, droplets of aerosolized Y. pestis bacteria are transmitted from human to human by coughing. Unless treated with antibiotics in the first 24 hours, almost 100% of people with this form of infection die in 2 to 4 days.
- The septicemic plague happens when the bacteria enter the blood from the lymphatic or respiratory system. Patients with septicemic plague develop gangrenes in their fingers and toes, which turn the skin black (which gives the disease its moniker). Though rare, this form of the disease is almost always fatal – often killing its victims the same day the symptoms appear.
We haven’t heard the last of the bubonic plague. In 1855, another bubonic plague epidemic (named the Third Epidemic) hit the world – this time, the initial outbreak was in Yunnan Province, China. Human migration, trade and wars helped the disease spread from China to India, Africa, and the Americas. All in all, this pandemic lasted about 100 years (it officially ended in 1959) and claimed over 12 million people in India and China alone.
5. The Spanish Flu
In March 1918, in the last months of World War I, an unusually virulent and deadly flu virus was identified in a US military camp in Kansas. Just 6 months later, the flu had become a worldwide pandemic in all continents.
When the Spanish Flu pandemic was over, about 1 billion people or half the world’s population had contracted it. It is perhaps the most lethal pandemic in the history of humankind: between 20 and 100 million people were killed, more the number killed in the war itself.
The Spanish Flu actually didn’t originate in Spain – it got its name because at the time, Spain wasn’t involved in the war and had not imposed wartime censorship, thus it received great press attention there.
Recently, scientists were able to ”resurrect” the virus from a well-preserved corpse buried in the permafrost of Alaska.
Sources:
http://www.solanocounty.com/depts/ph/flu/history_of_pandemics.asp
http://en.wikipedia.org/wiki/Pandemic
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