The American population developed, during thousands of years, free of epidemics that had been attacking Europe, Asia and Africa. The European and African migrations, after Columbus's first trip, produced an epidemic invasion of influenza, smallpox, measles, yellow fever, malaria, diphtheria, typhus, and other diseases that attacked the immunologically virgin populations and produced a very high mortality, with a diminution of the indigenous population of more than 90% in many places. According to historical evidence, the first epidemic was influenza, produced by suine strain of virus, immediately followed by smallpox. The Spaniards mated freely with the Indians producing a mixed race called the Mestizo, who were immunologically more capable of defending themselves against various viruses, bacteria, and parasites brought over from the Old World. Marriage between the races also was sanctioned by Queen Isabella (1503) and Fernando I (1515). With these new genetic immunologic defenses against infections, the Mestizo eventually made up the majority of the population of Indians in the New World.
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