Variolation was replaced at the end of the eighteenth century by a safer form of inoculation with pus from the smallpox vaccine. The discovery was made in 1796 by Edward Jenner (1749-1823), and the Library of Pharmaceutical and Pharmacological Sciences of the University of Padova has the 1799 edition with colour plates (digital copy). Jenner had observed that farmers infected with the smallpox vaccine, a milder form of the disease contracted from milking when they were exposed to the pustules on cow udders, developed immunity to smallpox. The success and safety of the new practice quickly spread throughout Europe, drastically reducing the contagion. In Sweden, deaths decreased from about 5,000 in the nineteenth century to around 500 after vaccination (Fenner p. 272). There were some relapses, with outbreaks in 1824-1829 and from 1837-1840, for various reasons. In part, because there were fewer inoculations at the same time that there were fewer cases of the disease; in part, follow-up systems needed to be improved, i.e. successive vaccinations to guarantee complete immunity; in part, the Franco-Prussian War helped spread the disease through the movement of the armies. All of these factors led States to implement mandatory vaccination policies, including the Prussian army from 1833. Efficiency increased: in Germany, the approximately 1,000 deaths in 1871 to less than ten a few years after vaccinations were made obligatory (Fenner p. 273).

In the public notice about the antidote, or the smallpox preventive treatment published in 1801 (digital copy), the doctor, Alessandro Moreschi, attributes "the success of such an interesting operation" (p. 5) to what he learned about it in Vienna during the 1800 epidemic which resulted in "around 14 victims each day" (p. 4). "It was under the auspices of the learned doctor, Mr Francesco Aglietti, that I first engrafted the 15-month-old child of Nobleman Mr Giuseppe Albrizzi Patrizio Veneto" (p. 5). Moretti hopes that "all Governments can follow the example of the English and French Nations, which expressly established institutes in the respective Capitals to administer this engraftment under the immediate patronage of the most worshipful persons of their States" (p. 53). As a guarantee of quality, the author proposed to buy from him the "vaccine material" (p. 55) and, based on the foreign model, recommended the presence of an apothecary in the institute for the vaccination (p. 66). He attached the London institute’s 1799 register for vaccine inoculation, that is, the card for recording of clinical results following the vaccination.

The immediate success even in the local area was recorded in Memoria storica e ragionata sopra l'innesto del vajuolo vaccino di Francesco Fanzago Letta all'Accademia di Padova nel febbrajo del 1801 (digital copy).
The Treatise on children’s diseases by the Swiss physician Christoph Girtanner (1760-1800) was translated and published in Venice in two volumes, in 1802 and in 1803 (digital copy). It is interesting to note how the first volume dealt only with inoculation while the second was attached to the Treatise on the vaccine by the doctor Gio. Enrico Lavather, with a chronological table of progress of the vaccine in Europe reproduced here.
The Prospectus of results from the medical clinic of the I.R. University of Padova for the 1824-1825 academic year from… Valeriano-Luigi Brera… with special notes on the vajuolo de’ vaccinati detto varioloide... (digital copy) four cases of smallpox infection at the Civil Hospital of Padua in 1825 are described of which two patients had been vaccinated and two had not been: the disease was weaker in those vaccinated. "All of these observations… far from destroying the current doctrine about the virtue of the smallpox vaccine, they are instead dispensing new arguments to confirm it" (p. 121).

There were, however, some detractors for this discovery. Locally, there was Iacopo Penada (1748-1828), an engraver at the Anatomical Institute of Padua and vice archiater of the city who, in 1801, published Riflessi sull'innesto della vaccina (Reflections on engrafting the vaccine), held in the Library of Pharmaceutical and Pharmacological Sciences of the University of Padova , in which he proposed isolation for prevention of the infection and complained about the lack of critical civic spirit in enthusiastically adopting the "vaccine" without fully evaluating the risks and, citing Azzoguidi, he suspects a lack of objectivity in the analysis of the contraindications and, tout court, the data: "They should not look for excuses and theories to favourably interpret these fatal accidents linked to the Vaccine, and upon scrupulously observed phenomena, they should not speak about it simply and naïvely!" (p. 14). Responding to this appeal for data, he attached a necrology table/plate/illustration of smallpox deaths in Padua during the entire eighteenth century, reproduced here. In the 1790s, there was an increase of smallpox deaths, which the author links to the introduction of the practice of vaccination (p. 13).

From Variolation...