Epidemics cleared out huge swaths of the New World even before Europeans got there. There are numerous accounts of European explorers arriving in a village for the first time, only to find everyone dead, the houses full of rotting, pustule-covered corpses.

Historians once marveled at how Cortés, with his army of five hundred soldiers, defeated the Aztec empire of over a million people. Various ideas have been advanced: that the Spanish had crucial technological advantages in horses, swords, crossbows, cannon, and armor; that the Spanish had superior tactics honed by centuries of fighting the Moors; that the Indians held back, fearful the Spanish were gods; and that the Aztecs’ subjugation and misrule of surrounding chiefdoms had created conditions ripe for revolt. All this is true. But the real conquistador was smallpox. Cortés and his troops occupied the Aztec capital city of Tenochtitlan (the future Mexico City) in 1519, but this cannot be counted as a conquest: The uneasy Aztec emperor, Moctezuma, invited Cortés into the city, unsure if he were god or man. Eight months later, after Moctezuma was murdered under murky circumstances (perhaps by the Spanish, perhaps by his own people), the Indians rose up and handily drove the Spanish from the city, in the so-called Noche Triste, the “Night of Sorrows.” In this crushing rout, many Spanish soldiers either were killed or drowned as they fled the island on which the city was built, because they had overloaded their pockets with gold. After their flight, the Spanish encamped in Tlaxcala, thirty miles east of Tenochtitlan, licking their wounds and wondering what to do next. At that moment, smallpox invaded the Valley of Mexico.

“When the Christians were exhausted from war,” one friar wrote, “God saw fit to send the Indians smallpox.” In sixty days, smallpox carried off at least half of the inhabitants of Tenochtitlan, which had a precontact population of 300,000 or more. Smallpox also killed the very capable successor to Moctezuma, the emperor Cuitláhuac, who in his brief, forty-day rule had swiftly been building military alliances that, had he survived, would very likely have repelled Cortés. But with at least half the population dead and the city and surrounding countryside engulfed in chaos by the epidemic, Cortés was able to retake the city in 1521. The worst effect of smallpox was the complete demoralization of the Indians: They saw clearly that disease decimated them while largely sparing the Spanish, and they concluded they had been cursed and rejected by their gods, who had shifted to the side of the Spanish. As the Spanish marched into the city, one observer wrote, “The streets were so filled with dead and sick people, that our men walked over nothing but bodies.”

At the same time that smallpox was ravaging Mexico, it burned southward into the Maya realm before the Spanish arrived. While the Maya cities were no longer inhabited, the Maya people were spread out over the region and were still known for their fierceness and military prowess. The contagion paved the way for the conquest of Guatemala four years later by one of Cortés’s captains.

In the ten years following the first outbreak of smallpox in the New World, the disease had stretched deep into South America. The pandemics also felled several of the great pre-Columbian kingdoms in North America. From 1539 to 1541, explorer Hernando de Soto passed through a powerful and flourishing chiefdom called Coosa, which occupied territory encompassing parts of Tennessee, Georgia, and Alabama, and had a population of perhaps 50,000 people. But twenty years later, by the time the next European came through, Coosa had been almost entirely abandoned, the landscape littered with empty houses, the once-abundant gardens overgrown with thistles and weeds. In the Mississippi River Valley, de Soto had found forty-nine towns, but the French explorers La Salle and Joliet, a century later, encountered only seven wretched settlements, a decline of 86 percent. Most of southeastern North America had been cleared out by a massive die-off from disease.

Though the figures are hotly disputed, scholars estimate that, before Columbus’s arrival, the population of North America was about 4.4 million, Mexico around 21 million, the Caribbean 6 million, and Central America another 6 million. But by 1543, the Indian peoples of the main Caribbean islands (Cuba, Jamaica, Hispaniola, Puerto Rico) had become extinct: almost six million dead. In the smaller islands, a few shattered native populations clung to a precarious existence. The fall of Tenochtitlan, the general collapse of native populations everywhere, and the continuing waves of pandemics allowed the Spanish to quickly crush Indian resistance throughout most of Central America.

Compare this to the Spanish conquest of the Philippines, which occurred at the same time. The Spanish were just as ruthless there, but the conquest was not aided by disease: Filipinos were resistant to Old World diseases, and the islands experienced no mass die-offs or population crashes. As a result, the Spanish were forced to accommodate and adjust to coexistence with the indigenous people of the Philippines, who remained strong and retained their languages and cultures. Once the Spanish left, the Iberian influence largely faded away, along with the Spanish language, which is today spoken by few.

But did this catastrophe reach Mosquitia, and if so, how did it get into the remote interior, so far from Spanish contact? We don’t have much source material on how the 1519 smallpox epidemic affected Honduras specifically. Common sense tells us that, with smallpox raging both north and south, Honduras must have been badly afflicted. Ten years after smallpox, another dreadful pandemic swept the New World: measles. This we know ravaged Honduras with exceptional cruelty. For Europeans, measles is a far milder disease than smallpox; although easily spread, it rarely kills. But when it reached the New World it proved to be almost as deadly, killing at least 25 percent of the affected population. The conquistador Pedro de Alvarado sent a report from Guatemala to Charles V in 1532: “Throughout New Spain, there passed a sickness which they say is measles, which struck the Indians and swept the land, leaving it totally empty.” The measles pandemic coincided with epidemics of other diseases in Honduras, among them possibly typhoid, flu, and plague.