The outbreak of swine flu, first in Mexico then cases all over the world, has gotten a lot of people worried. And for a very good reason: despite the existence of scarier diseases caused by exotic viruses like Hantavirus and Ebola, influenza still reigns as the number one infectious killer in modern times.

Unlike regular seasonal epidemics of the flu, there are also rare but deadly pandemics, i.e. cases of influenza that spread on a worldwide scale and infect a large proportion of the human population.

While it's important not to panic (the swine flu appears to be highly treatable with conventional antiviral drugs), a review of past pandemics will elucidate why authorities are responding quickly to this outbreak. 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 (Source)

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. (source)

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. (source)

It's interesting to note that the Black Death actually came in three forms: the bubonic, pneumonic, and septicemic plague. The first, 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 last form, 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. (Photo and Source: Insecta-Inspecta)

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



Emergency military hospital at Camp Funston, Kansas (Image: National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington D.C.) via PLoS Biology

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 (Source)

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.