541 A.D.: Justinian Plague
First appearing in Egypt, the Justinian plague spread through Palestine and the Byzantine Empire, and then throughout the Mediterranean.
The plague changed the course of the empire, squelching Emperor Justinian's plans to bring the Roman Empire back together and causing massive economic struggle. It is also credited with creating an apocalyptic atmosphere that spurred the rapid spread of Christianity.
Recurrences over the next two centuries eventually killed about 50 million people, 26 percent of the world population. It is believed to be the first significant appearance of the bubonic plague, which features enlarged lymphatic gland and is carried by rats and spread by fleas.
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