The smallpox virus is transmitted by airborne droplets or secretions from skin lesions and scabs attached to textiles or house dust [Jannetta, Epidemics]. Most outbreaks of smallpox occur in the winter and spring, because the virus can survive outside the human body for a certain length of time under cool and dry weather conditions. But human mobility—of merchants, sailors, pilgrims, and many other kinds of travelers—has always played a critical role in spreading the disease.

By the middle of the eighteenth century, the smallpox virus had become endemic in Japan. Even in remote rural regions, the virus was either circulating or frequently being reimported from outside. Under these conditions, most children would have been infected by the age of five. In the course of the Tokugawa period, travel and migration between urban and rural areas intensified and probably increased exposure to the disease. However, contemporary documentation is not detailed enough to trace the movement of the smallpox virus within and between regions.

In the nineteenth century intervals between outbreaks became shorter, and mortality from the virus appears to have decreased over time. Yet smallpox remained a major killer of young children. Because its victims were young, smallpox epidemics did not disrupt the social order in the same way as other mass outbreaks of infectious disease. But smallpox did have a significant impact on population growth. Ann Jannetta has estimated that in the case of Hida province, for which sufficient temple death records are available between 1771 and 1852, smallpox accounted for 26 percent of all deaths under age ten and claimed the lives of about ten percent of all born children. The disease more than halved the annual rate of population growth in Hida. Until the arrival of the vaccine, there was no effective prevention, let alone treatment for the infected. Although some Japanese doctors practiced variolation—controlled exposure of children to the human smallpox virus through scabs—this method was quite risky and never widely applied in Japan.