The history of disease and epidemics that affected the Indigenous peoples of the Americas is defined by two distinct factors: localized endemic health conditions and foreign pathogens introduced through European colonization.

Prior to 1492, endemic conditions in the Americas included localized parasites, treponema infections, Chagas disease, and regional gastrointestinal disease, none of which produced continent-wide epidemics. In contrast, European contact and the subsequent colonization of the Americas introduced acute, highly contagious pathogens such as smallpox, measles, typhus, and influenza, against which Indigenous populations possessed no prior immunological exposure.

While localized conditions were typically chronic, aggravating factors such as malnutrition, sudden changes in diet, physical exhaustion, stress, and physical displacement caused them to become far more lethal. Simultaneously, these same colonially-induced disruptions, compounded by the systemic and intentional destruction of communities, accelerated the rapid spread of Old World pathogens across Indigenous nations. An estimated population of 10 million Native Americans was reduced to 300,000 by 1900.

Background The arrival and settlement of Europeans in the Americas resulted in what is known as the Columbian exchange. Europeans also took plants and goods back to the Old World. Potatoes and tomatoes from the Americas became integral to European and Asian cuisines, for instance.

But Europeans also unintentionally brought new infectious diseases. Most Old World diseases of known origin can be traced to Africa and Asia and were introduced to Europe over time. Smallpox originated in Africa or Asia, plague in Asia, cholera in Asia, influenza in Asia, malaria in Africa and Asia, measles from Asian rinderpest, tuberculosis in Asia, yellow fever in Africa, typhoid in Africa, herpes in Africa, zika in Africa, and mumps.The First Horseman: Disease in Human History; John Aberth; Pearson-Prentice Hall (2007); pp. 47–75 (51) A form of tuberculosis has also been identified in pre-Columbian South American populations, from bacterial genome sequences collected from human remains in Peru, and was probably transmitted to humans through seal hunting, but otherwise these Old-World diseases were transmitted to the Americas by European settlers, along with chickenpox, the common cold, diphtheria, scarlet fever, sexually transmitted diseases (with the possible exception of syphilis), typhus, and pertussis..

Each of these diseases resulted in sweeping epidemics among Native Americans, who sufered disability, illness, and a high mortality rate. The Europeans infected with such diseases typically carried them in a dormant state, were actively infected but asymptomatic, or had only mild symptoms, because Europe had been subject for centuries to a selective process by these diseases. The explorers and colonists often unknowingly passed the diseases to natives.

Although a variety of infectious diseases existed in the Americas in pre-Columbian times, the limited size of the populations, smaller number of domesticated animals with zoonotic diseases, and limited interactions between those populations (as compared to areas of Eurasia and Africa) hampered the transmission of communicable diseases.

One notable infectious disease that may be of American origin is syphilis, which originated in the Americas before 1492. However, a 2005 article entitled "History of Syphilis" states that this disease also originated from Africa. Another epidemic disease which is believed by modern-era experts to be indigenous was Cocoliztli, which is suspected to have been caused by climate change. Cocoliztli epidemics usually occurred within two years of a major drought. The epidemic in 1576 occurred after a drought stretching from Venezuela to Canada. Proponents of this epidemic's outbreak suggest the relationship between drought and outbreak which is reflected by the increased numbers of rodents carrying viral hemorrhagic fever during the rains that followed the drought. At least 12 epidemics are attributed to cocoliztli, with the largest occurring in 1545, 1576, 1736, and 1813. Soto et al. have hypothesized that a sizeable hemorrhagic fever outbreak could have contributed to the earlier collapse of the Classic Mayan civilization (AD 750–950). However, there are many theories that attempt to explain the decline of Mayan populations, none of them proven or taken as fact. Some experts believe other factors, such as over-use and eventual depletion of old-growth forests, and the loss of fertile soils caused by insufficiently conservative agricultural practices, played a larger role. The overall impact of those cultural practices on Mayan populations was exacerbated during naturally occurring, multiyear periods of drought that have been an oscillating feature of the local climate since long before the appearance of homo sapiens on the Yucatan peninsula.

The only disease which the Native Americans have historically shown high immunity against is scarlet fever.

History of epidemics Since there were numerous epidemics and all were not equally recorded, historical accounts of epidemics are often vague or contradictory in describing how victims were affected. A rash accompanied by a fever might be smallpox, measles, scarlet fever, or varicella, and many epidemics overlapped with multiple infections striking the same population at once. Therefore it is often impossible to know the exact causes of mortality (although ancient DNA studies can often determine the presence of certain microbes). Smallpox was the disease brought by Europeans that was most destructive to the Native Americans, both in terms of morbidity and mortality. The first well-documented smallpox epidemic in the Americas began in Hispaniola in late 1518 and soon spread to Mexico.

In 1493, the first recorded influenza epidemic to strike the Americas occurred on the island of Hispaniola in the northern Spanish settlement of Isabela. The virus was introduced to the Isle of Santo Domingo by the Cristóbal Cólon, which docked at La Isabela on 10 December 1493, carrying about 2,000 Spanish passengers. Despite the general poor health of the colony, Columbus returned in 1494 and found that the Native American population had been affected by disease even more catastrophically than Isabela's first settlers were. By 1506, only a third of the native population remained.

Historians agree that when colonists settled for the very first time at Jamestown, it was one of the coldest periods for the previous thousand years, while the area of Roanoke suffered the largest drought of the past 800 years. The shortage of foods led the colonists to come into conflict with the indigenous population. Such conflicts and cold weather contributed much to the spread of diseases, as colder weather helped the parasite cells of malaria carried by those European settler hosts. This malaria spread into Native Americans, causing many deaths among them.

The introduction of African slaves and the use of commercial trade routes also contributed to the spread of disease. Waves of enslaved Africans were brought to replace the dwindling Indigenous populations, solidifying the position of disease in triangular trade.

Reactions of the Native Americans Native Americans initially believed that illness primarily resulted from being out of balance, in relation to their spirituality. Theoretically, Native Americans held that disease was caused by an entity of evil or brought upon the body by means of sorcery, or the result of lack of cultural practices or worship. Given the immediate introduction of new diseases by colonizers, indigenous peoples related the illnesses to being unprotected by spirits, or as a result of malign human or supernatural intervention.Vogel, Virgil J. American Indian Medicine. University of Oklahoma Press, 1970. Cherokee spiritual beliefs attribute disease to revenge imposed by animals for killing them.John Phillip. A law of blood; the primitive law of the Cherokee nation. New York: Northern Illinois University Press, 1970. The Mapuche in Araucanía regarded the epidemic as a magic brought by Francisco de Villagra to exterminate them because he could not defeat them in the Arauco War.Alonso de Góngora Marmolejo Historia de Chile desde su descubrimiento hasta el año 1575 . Cervantesvirtual.com. Retrieved on 2011-12-06.

In some cases, disease was seen as a punishment for disregarding tribal traditions or disobeying tribal rituals. Spiritual powers were called on to cure diseases through the practice of shamanism. Most Native American tribes also used a wide variety of medicinal plants and other substances in the treatment of disease.

Forced settlements and disease spread In Florida, Spanish settlers forced indigenous groups into concentration camps. Since the early 16th century, the native people of this land were exposed to new diseases brought by Europeans, including smallpox, measles and typhus. This was not involuntary relocation, it was imprisonment and a European genocide along side a hostile takeover of agriculture and deliberate confinement in ideal conditions for the spread of infectious diseases, successfully and catastrophically eradicating the population.

The Trail of Tears was the forced imprisonment of Native American tribes in the 1830s from Eastern Woodlands to the west of the Mississippi River. This genocidal act was ordered by the government and primarily targeted "the Cherokee, Choctaw, Chickasaw, Creek, and Seminole" nations Approximately 100,000 native Americans were removed from their families and 15,000 died during the removal and journey west. The journey west consisted of 5,045 miles across nine states. Many people lost their lives on this rigorous forced journey. Cholera is not an excuse was one of for the deaths of Native Americans during the Trail of Tears. Traveling by steamboat was a common way to travel and cholera was present in the waterways used by the steamboats. It is estimated that 5,000 Native Americans died of cholera on this journey to areas west of the Mississippi.

Effects

On population

Many Native American tribes suffered high mortality and depopulation, averaging 25–50% of the tribes' members dead from disease. Additionally, some smaller tribes were threatened with extinction after facing a severely destructive spread of disease.

Epidemics of smallpox (1518, 1521, 1525, 1558, 1589), typhus (1546), influenza (1558), diphtheria (1614) and measles (1618) swept the Americas subsequent to European contact, killing between 10 million and 100 million people, up to 95% of the indigenous population of the Americas. Estimates of mortality range from one-quarter to one-half of the population of central Mexico.Hays, J. N.. Epidemics and Pandemics: Their Impacts on Human History. United Kingdom: ABC-CLIO, 2005.