Answer: B — Smallpox
Smallpox, carried by Spanish and Portuguese conquerors, spread through America in the mid-sixteenth century, killing and decimating whole communities as native inhabitants had no immunity against it.
Source: Conquest, Disease and Trade, Chapter 3
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The passage clearly states: "the most powerful weapon of the Spanish conquerors was not a conventional military weapon at all. It was the germs such as those of smallpox." It spread deep into the continent, killing entire communities. The other options (yellow fever, malaria, cholera) are not mentioned in this context.