IOTL smallpox decimated the population of the Americas, killing between 50-90% of the natives showing chaos and resentment against the authorities that helped the Spanish immensely. But small pox was a fast burning disease, the transmission of which was only possible due to repeated high volumes of slaves brought from Africa to Caribbean plantations and a bit of luck. So my question is: suppose the Spanish jumped the gun and tried to conquer the natives before smallpox was present how would it go?