The cocoliztli epidemic of 1576 refers to millions of deaths in the territory of New Spain in present-day Mexico in 16th century attributed to one or more illnesses collectively called cocoliztli.
The cause of the epidemic remains unknown though it might have been an indigenous viral hemorrhagic fever, perhaps exacerbated by the worst droughts to affect that region in 500 years and living conditions for indigenous peoples of Mexico in the wake of European invasion. Some historians have suggested it was typhus, measles, or smallpox, though the symptoms did not match.
1576 Cocoliztli epidemic Wikipedia
Cocoliztli epidemics usually occurred within two years of a major drought while another disease called "matlazahuatl" had appeared within two years of the rainy season.The epidemic in 1576 happened after a drought stretching from Venezuela to Canada. The correlation between the drought and the disease seems to be that in the rains that followed the drought, populations of the Vesper mouse, a carrier of viral hemorrhagic fever, increased as conditions improved. There have been 12 epidemics since thought to be of cocoliztli, with the largest being in 1545, 1576, 1736, and 1813.
The disease's name originated from the Nahuatl language word for "pest", or disease, illness, and plague.The name lost this meaning when it became associated with this unnamed disease that killed Natives and Spaniards alike when it first appeared in 1545.
According to Francisco Hernandez, a physician who witnessed the outbreak in 1576, symptoms included high fever, severe headache, vertigo, black tongue, dark urine, dysentery, severe abdominal and thoracic pain, head and neck nodules, neurologic disorders, jaundice, and profuse bleeding from the nose, eyes, and mouth; death frequently occurred in 3 to 4 days.