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The Black Death
The Black Death originated in marmots and migrated to fleas and black rats and eventually to humans. This plague began in Central Asia or China and traveled to South Eastern Europe, channeled through soldiers and merchants. From here, it spread to Northern Africa and Western Europe. It's major occurences were in Italy, London, Seville, Vienna, Marseille, and Russia, all at varying times. It is estimated to have been part in 75 million deaths.
The Black Death had a lasting effect on Europe, not only physically, but also culturally. The Roman Catholic Church was severely weakened due to the plague and widespread death, which led to them further oppresion of the Jews and other smaller ethnic groups. Also, people lived with more risk, due to their uncertainty about whether or not they would live another day.
The Black Death was believed to be caused by Gods anger, which led to mass killings of Jews and Jewish communities. Monarchs worldwide set massive government regulations, which limited production of grain and prohibited inport of grain. This weakened Englands grain market.