If Europe was the periphery of the global trading system prior to 1492, where it situated by the middle of the 16th century? What had changed? What had not?

The focus shifted to America.

Explanation:

Europe was a significant trading periphery before the discovery of America in 1492. With the discovery of new trade routes and parts of the world, trade shifted to America. What remains the same is that the feeling of economic rivalry remained among European countries and even increased with the New World's discovery. During this period, the first forms of capitalism emerged, so the novelty was the exploitation of the resources of the new world like never before. The enormous amount of wealth continued to go to Europe, but the center of trade and economic activity was shifted to other parts of the world.

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the enslaved people onboard suffered from illness with some frequency