Great epidemics decimated the European population several times throughout history. In ancient times, it was the plague and leprosy. The population of Italy dropped from more than 7 million in the first century to 4 million in 500 AD to 2.5 million in 650 following the Plague of Justinian in 543. The great plagues, which spread due to troop movements and trading, acted on individuals’ immune systems, all the more susceptible due to malnutrition and poor hygiene.

The European population grew slowly from 26 million in the eighth century to 80 million by the beginning of the fourteenth century, but this growth was interrupted by the Black Death in the mid-fourteenth century, which reduced the population by more than 25%. Growth in the sixteen century was halted by the Thirty Year War and by two great plague epidemics, the Great Plague of Milan of 1630 described by Manzoni and the other of 1664. Together with smallpox and epidemic typhus, these cataclysms resulted in a drastic population decline, which was only reversed in the late seventeenth century with the improvement of nutrition and disappearance of the plague from Europe. It went from 140 million in 1750 to 250 million in 1845 (Fenner p. 229).

Epidemics were an unintentional arm in the conquest of the Americas through extermination. "The most effective killers were the germs carried by the Europeans to which the natives had never been exposed and to which they had no type of immune or genetic resistance" (Diamond p. 163). Due to smallpox, for example, the inhabitants of Pre-Columbian Mexico went from 20 million to just over a million and a half in one century.