Portal de Periódicos da CAPES

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

2015; Elsevier BV; Volume: 21; Issue: 8 Linguagem: Inglês

10.1016/j.cmi.2015.01.021

1469-0691

Donatella Lippi, J.P. D'Elios, Saverio Caini,

Zoonotic diseases and public health

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]Grmek M.D. History of AIDS: emergence and origin of a modern pandemic. Princeton University Press, Princeton1990Google Scholar]. Up until the late 1950s, there were an estimated 50 million smallpox cases in the world each year [[2]Fenner F. Henderson D.A. Arita I. Jezek Z. Ladnyi I.D. Smallpox and its eradication. World Health Organization, Geneva1988Google Scholar], with a case-fatality ratio of approximately 30% for Variola major and 1% for Variola minor [[3]Heymann D.L. Control of communicable disease manual. 19th ed. American Public Health Association (APHA), Washington, DC2008Google Scholar]. 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]Fenner F. Henderson D.A. Arita I. Jezek Z. Ladnyi I.D. Smallpox and its eradication. World Health Organization, Geneva1988Google Scholar]. However, in most countries, reliable figures for reported cases only started being published in the 20th century [[4]Rusnock A. The weight of evidence and the burden of authority: case histories, medical statistics and smallpox inoculation.Clio Med. 1995; 29: 289-315PubMed Google Scholar], 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 Gastone de' Medici, the last descendant of the Medici family reigning over Tuscany), together with their first-degree relatives (parents, siblings and children) for whom clinical histories were available. The clinical diaries were reviewed to identify all smallpox cases, and all available details on the clinical course of diseases (date of onset, signs and symptoms, outcome—recovered or died) were recorded. We calculated the risk and incidence of smallpox and the median age at onset of symptoms, overall and after stratifying by gender and century of birth (16th vs. 17th). Clinical diaries were available for 46 members of the Medici family, including the seven reigning grand dukes and 39 of 43 potentially eligible first-degree relatives. Thirty (15 male and 15 female subjects) and 16 (10 male and 6 female subjects) of them were born in the 16th and 17th centuries, respectively. Twenty-three smallpox cases were observed during 904 person-years with an overall risk of 50% and an overall incidence of 25 cases per 1000 person-years. The incidence of smallpox was higher in male subjects compared to female subjects (32 vs. 19 cases per 1000 person-years, p 0.07). The 14 male subjects with smallpox became infected at a median age of 14 years, and none of them died from the disease. Four of nine female subjects infected with smallpox died from it, and the median age at infection—33 years—was higher among female compared to male subjects (p 0.03). Differences were also observed after stratifying by century of birth. Both the risk (33% vs. 81%) and incidence (16 vs. 46 cases per 1000 person-years) were significantly (p 0.01) higher among the Medici family members that were born in the 17th compared to the 16th century. All four deaths were observed among female subjects born in the 16th century. A cluster of smallpox cases suggestive of intrafamilial transmission was observed in autumn in Florence in 1626. Between September and December 1626, five members of the Medici family were struck by the disease. Among them was Ferdinando II (1610–1670), who had become grand duke of Tuscany in 1621. The course of the disease was masterfully illustrated by the court painter of the Medici family, Justus Sustermans (1597–1681), who portrayed the young Ferdinando II at his seventh and ninth day of smallpox infection (Fig. 1). To our knowledge, this is the first report on the epidemiological aspects of smallpox in a fully susceptible population. The members of our study group were part of a ruling dynasty, and the study is spread over a period of over two centuries; therefore, our results cannot be considered representative of the general population of Tuscany during the same period. Despite its lack of generalizability, our study may, however, anecdotally add to the evidence that smallpox has represented one of most terrible scourges in the history of humankind. The gradual increase of population density during the 16th and 17th centuries (the number of people living in cities with more than 10 000 inhabitants increased by 50% between 1500 and 1600 in Tuscany) probably contributed to facilitate the gradual spread of smallpox and to make it a leading cause of death during that period. For instance, smallpox was responsible for an average 10% of all deaths in London between 1650 and 1750 [[5]Duncan S.R. Scott S. Duncan C.J. The dynamics of smallpox epidemics in Britain, 1550–1800.Demography. 1993; 30: 405-423Crossref PubMed Scopus (37) Google Scholar]. Despite the introduction of variolization in Europe in 1721 by Lady Montagu, it was necessary to wait until Edward Jenner's cowpox vaccine became available in the early 19th century for the first key step towards the eradication of smallpox to be taken. All authors report no conflicts of interest relevant to this article. We thank M. Caini for his valuable support for preparing the artwork. We also thank O. Wojcik, O. Kacelnik and A. Donachie for their valuable suggestions.