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Virgin soil epidemic is a term coined by Alfred Crosby, who defined it as epidemics "in which the populations at risk have had no previous contact with the diseases that strike them and are therefore immunologically almost defenseless." His concept is related to that developed by William McNeill, who connected the development of agriculture and more sedentary life with the emergence of new diseases as microbes moved from domestic animals to humans. Virgin soil epidemics have occurred with European colonization, particularly when European explorers and colonists brought diseases to lands they conquered in the Americas, Australia and Pacific Islands.

The concept would later be adopted wholesale by Jared Diamond as a central theme in his popular book Guns, Germs and Steel as an explanation for successful European expansion.

When a population has not had contact with a particular pathogen, individuals in that population have not built up any immunity to that organism and so have not received immunity passed from mother to child. The epidemiologist Francis Black has suggested that some isolated populations may not have mixed enough to become as genetically heterogeneous as their colonizers, which would also have affected their natural immunity. That can happen also when such a considerable amount of time has passed between disease outbreaks that no one in a particular community has ever experienced the disease to gain immunity. Consequently, when a previously unknown disease is introduced to such a population, there is an increase in the morbidity and mortality rates. Historically, that increase has been often devastating and always noticeable.

Diseases introduced to the Americas by European colonizers and the African people they enslaved include smallpox, yellow fever, measles and malaria as well as new strains of typhus and influenza.

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