Plagues and epidemics have ravaged humanity throughout its existence, often changing the course of history.

Throughout the course of history, disease outbreaks have ravaged humanity, sometimes changing the course of history and, at times, signaling the end of entire civilizations. Here are 20 of the worst epidemics and pandemics, dating from prehistoric to modern times.

1. Prehistoric epidemic: Circa 3000 B.C.

The discovery of a 5,000-year-old house in China filled with skeletons is evidence of a deadly epidemic. (Image credit: Photo courtesy Chinese Archaeology)

About 5,000 years ago, an epidemic wiped out a prehistoric village in China. The bodies of the dead were stuffed inside a house that was later burned down. No age group was spared, as the skeletons of juveniles, young adults and middle-age people were found inside the house. The archaeological site is now called "Hamin Mangha" and is one of the best-preserved prehistoric sites in northeastern China. Archaeological and anthropological study indicates that the epidemic happened quickly enough that there was no time for proper burials, and the site was not inhabited again. 

Before the discovery of Hamin Mangha, another prehistoric mass burial that dates to roughly the same time period was found at a site called Miaozigou, in northeastern China. Together, these discoveries suggest that an epidemic ravaged the entire region. 

2. Plague of Athens: 430 B.C.

Remains of the Parthenon, one of the buildings on the acropolis of Athens. The city experienced a five year pandemic around 430 B.C.  (Image credit: Shutterstock)

Around 430 B.C., not long after a war between Athens and Sparta began, an epidemic ravaged the people of Athens and lasted for five years. Some estimates put the death toll as high as 100,000 people. The Greek historian Thucydides (460-400 B.C.) wrote that "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" (translation by Richard Crawley from the book "The History of the Peloponnesian War," London Dent, 1914). 

What exactly this epidemic was has long been a source of debate among scientists; a number of diseases have been put forward as possibilities, including typhoid fever and Ebola. Many scholars believe that overcrowding caused by the war exacerbated the epidemic. Sparta's army was stronger, forcing the Athenians to take refuge behind a series of fortifications called the "long walls" that protected their city. Despite the epidemic, the war continued on, not ending until 404 B.C., when Athens was forced to capitulate to Sparta. 

3. Antonine Plague: A.D. 165-180

Roman soldiers likely brought smallpox home with them, giving rise to the Antonine Plague.  (Image credit: Shutterstock)

When soldiers returned to the Roman Empire from campaigning, they brought back more than the spoils of victory. The Antonine Plague, which may have been smallpox, laid waste to the army and may have killed over 5 million people in the Roman empire, wrote April Pudsey, a senior lecturer in Roman History at Manchester Metropolitan University, in a paper published in the book "Disability in Antiquity," Routledge, 2017). 

Many historians believe that the epidemic was first brought into the Roman Empire by soldiers returning home after a war against Parthia. The epidemic contributed to the end of the Pax Romana (the Roman Peace), a period from 27 B.C. to A.D. 180, when Rome was at the height of its power. After A.D. 180, instability grew throughout the Roman Empire, as it experienced more civil wars and invasions by "barbarian" groups. Christianity became increasingly popular in the time after the plague occurred. 

4. Plague of Cyprian: A.D. 250-271

The remains found where a bonfire incinerated many of the victims of an ancient epidemic in the city of Thebes in Egypt.  (Image credit: N.Cijan/Associazione Culturale per lo Studio dell'Egitto e del Sudan ONLUS)

Named after St. Cyprian, a bishop of Carthage (a city in Tunisia) who described the epidemic as signaling the end of the world, the Plague of Cyprian is estimated to have killed 5,000 people a day in Rome alone. In 2014, archaeologists in Luxor found what appears to be a mass burial site of plague victims. Their bodies were covered with a thick layer of lime (historically used as a disinfectant). Archaeologists found three kilns used to manufacture lime and the remains of plague victims burned in a giant bonfire. 

Experts aren't sure what disease caused the epidemic. "The bowels, relaxed into a constant flux, discharge the bodily strength [and] a fire originated in the marrow ferments into wounds of the fauces (an area of the mouth)," Cyprian wrote in Latin in a work called "De mortalitate" (translation by Philip Schaff from the book "Fathers of the Third Century: Hippolytus, Cyprian, Caius, Novatian, Appendix," Christian Classics Ethereal Library, 1885).

5. Plague of Justinian: A.D. 541-542

A mosaic of Emperor Justinian and his supporters.  (Image credit: Shutterstock)

The Byzantine Empire was ravaged by the bubonic plague, which marked the start of its decline. The plague reoccurred periodically afterward. Some estimates suggest that up to 10% of the world's population died. 

The plague is named after the Byzantine Emperor Justinian (reigned A.D. 527-565). Under his reign, the Byzantine Empire reached its greatest extent, controlling territory that stretched from the Middle East to Western Europe. Justinian constructed a great cathedral known as Hagia Sophia ("Holy Wisdom") in Constantinople (modern-day Istanbul), the empire's capital. Justinian also got sick with the plague  and survived; however, his empire gradually lost territory in the time after the plague struck. 

6. The Black Death: 1346-1353

Illustration from Liber chronicarum, 1. CCLXIIII; Skeletons are rising from the dead for the dance of death. (Image credit: Anton Koberger, 1493/Public domain)

The Black Death traveled from Asia to Europe, leaving devastation in its wake. Some estimates suggest that it wiped out over half of Europe's population. It was caused by a strain of the bacterium Yersinia pestis that is likely extinct today and was spread by fleas on infected rodents. The bodies of victims were buried in mass graves. 

The plague changed the course of Europe's history. With so many dead, labor became harder to find, bringing about better pay for workers and the end of Europe's system of serfdom. Studies suggest that surviving workers had better access to meat and higher-quality bread. The lack of cheap labor may also have contributed to technological innovation.

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