Diseases introduced to the Americas by the conquistadors had a great impact upon indigenous populations. As the Spanish were occupied with the conquest of Mexico, these diseases ran ahead of them from 1519 onwards. A smallpox epidemic swept through Guatemala in 1520–1521, and is also likely to have spread throughout the Pipil region of El Salvador. By the time the Spanish arrived in the area in 1524, it is estimated that up to 50% of the native population of El Salvador had already been eliminated by the new diseases, against which they had no immunity. It is likely that disease had significantly weakened the Pipil by the time they fielded large armies against the Spanish at Acajutla and Tacuzcalco. Further waves of epidemic diseases spread across Mesoamerica in 1545–1548, and again in 1576–1581, reducing indigenous populations to just 10% of their pre-contact levels, making successful resistance against the European colonisers extremely difficult. The deadliest of the newly introduced diseases were smallpox, malaria, measles, typhus, and yellow fever. Their introduction was catastrophic in the Americas; it is estimated that 90% of the indigenous population had been eliminated by disease within the first century of European contact.