HISTORICAL REVIEW Megadrought and Megadeath in 16th Centur y Mexico Rodolfo Acuna-Soto,* David W. Stahle,† Malcolm K. Cleaveland,† and Matthew D. Therrell† The native population collapse in 16th century Mexico was a demographic catastrophe with one of the highest death rates in history. Recently developed tree-ring evidence has allowed the levels of precipita- tion to be reconstructed for north central Mexico, adding to the growing body of epidemiologic evidence and indicating that the 1545 and 1576 epidemics of cocoliztli (Nahuatl for "pest”) were indigenous hemor- rhagic fevers transmitted by rodent hosts and aggravated by extreme drought conditions. T ease in the wake of European conquest (Figure 1), begin- he native people of Mexico experienced an epidemic dis- ning with the smallpox epidemic of 1519 to 1520 when 5 million to 8 million people perished. The catastrophic epidem- ics that began in 1545 and 1576 subsequently killed an addi- tional 7 million to 17 million people in the highlands of Mexico (1-3). Recent epidemiologic research suggests that the events in 1545 and 1576, associated with a high death rate and referred to as cocoliztli (Nahuatl for “pest”), may have been due to indigenous hemorrhagic fevers (4,5). Tree-ring evi- dence, allowing reconstructions of the levels of precipitation, indicate that the worst drought to afflict North America in the past 500 years also occurred in the mid-16th century, when severe drought extended at times from Mexico to the boreal forest and from the Pacific to Atlantic coasts (6). These droughts appear to have interacted with ecologic and socio- logic conditions, magnifying the human impact of infectious disease in 16th-century Mexico. The epidemic of cocoliztli from1545 to 1548 killed an esti- mated 5 million to 15 million people, or up to 80% of the native population of Mexico (Figure 1). In absolute and rela- tive terms the 1545 epidemic was one of the worst demo- graphic catastrophes in human history, approaching even the Black Death of bubonic plague, which killed approximately 25 million in western Europe from 1347 to 1351 or about 50% of the regional population. The cocoliztli epidemic from 1576 to 1578 killed an addi- tional 2 to 2.5 million people, or about 50% of the remaining native population. Newly introduced European and African diseases such as smallpox, measles, and typhus have long been the suspected cause of the population collapse in both 1545 and 1576 because both epidemics preferentially killed native people. But careful reanalysis of the 1545 and 1576 epidemics now indicates that they were probably hemorrhagic fevers, likely caused by an indigenous virus and carried by a rodent host. These infections appear to have been aggravated by the extreme climatic conditions of the time and by the poor living conditions and harsh treatment of the native people under the *Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Mexico and † University of Arkansas, Fayetteville, Arkansas, USA encomienda system of New Spain. The Mexican natives in the encomienda system were treated as virtual slaves, were poorly fed and clothed, and were greatly overworked as farm and mine laborers. This harsh treatment appears to have left them particularly vulnerable to epidemic disease. Cocoliztli was a swift and highly lethal disease. Francisco Hernandez, the Proto-Medico of New Spain, former personal physician of King Phillip II and one of the most qualified phy- sicians of the day, witnessed the symptoms of the 1576 cocoliztli infections. Hernandez described the gruesome cocoliztli symptoms with clinical accuracy (4,5). The symp- toms included high fever, severe headache, vertigo, black tongue, dark urine, dysentery, severe abdominal and thoracic pain, large nodules behind the ears that often invaded the neck and face, acute neurologic disorders, and profuse bleeding from the nose, eyes, and mouth with death frequently occur- ring in 3 to 4 days. These symptoms are not consistent with known European or African diseases present in Mexico during the 16th century. Figure 1. The 16th-century population collapse in Mexico, based on estimates of Cook and Simpson (1). The 1545 and 1576 cocoliztli epi- demics appear to have been hemorrhagic fevers caused by an indige- nous viral agent and aggravated by unusual climatic conditions. The Mexican population did not recover to pre-Hispanic levels until the 20th century. 360 Emerging Infectious Diseases • Vol. 8, No. 4, April 2002