Smallpox in the Medici family, Florence, 1519–1737: a historical cohort study

Abstract

Smallpox is a viral disease caused by two distinct but related viruses, Variola major and Variola minor. Both viruses only infect humans and are transmitted via the respiratory route or skin contact. Together with plague, smallpox is the infectious disease responsible for the most deaths in the history of humankind [1]. Up until the late 1950s, there were an estimated 50 million smallpox cases in the world each year [2], with a case-fatality ratio of approximately 30% for Variola major and 1% for Variola minor [3]. Smallpox is the first infectious disease for which a vaccine was developed, and it is the only human infectious disease to be eradicated to date. Despite its enormous historical importance, little is known about epidemiology of smallpox in the prevaccination era. Records of deaths from smallpox were first collected in Geneva in 1580 and in London in 1629 [2]. However, in most countries, reliable figures for reported cases only started being published in the 20th century [4], when a variable percentage of population was already vaccinated and some herd immunity was established. Here, we present the history of smallpox in the Medici family, who ruled over Tuscany in Italy between the 15th and 18th centuries. Court physicians, chroniclers and diarists recorded the clinical histories of the grand dukes of the Medici family and in most of their first-degree relatives. These histories provide information about signs and symptoms of disease, diagnosis, therapy or treatment administered and the outcome of any disease that affected members of the family. The diaries usually began at birth and were updated at any medical event of interest until death. Included in this historical, retrospective cohort are all the grand dukes of Tuscany between 1519 (date of birth of Cosimo I de’ Medici) and 1737 (date of death of Gian