Depending on the reach and level of vaccination within Europe's various states in the 1870s, smallpox had a varied impact on various age groups. For infants below the age of one year, smallpox was responsible for between 15 and 30 percent of all deaths in the given regions, as many of these babies had not yet been vaccinated and were at a high risk of succumbing to the virus. In states where the vaccination of infants was not compulsory, such as the Netherlands, Berlin (Prussia) and Leipzig (Saxony), the share of deaths due to smallpox among young children remained high, while it was relatively low in Hesse and Scotland, who had introduced mandatory vaccination in 1815 and 1864 respectively. Great Pandemic highlights the need for revaccination As Hesse had been vaccinating on a large scale for generations, the share of smallpox deaths was relatively low among young people; however, between 1870 and 1872, over half of all deaths among those aged 30 to 60 years were due to smallpox. The reason for this was because smallpox vaccination in infancy did not guarantee lifelong protection, therefore immunity often wore off in adulthood. In the 1830s and 1840s, several German armies started to vaccinate new recruits regardless of whether they had been vaccinated in infancy or not; when scientists compared the smallpox death rates in the army with that of the civilian population during this pandemic, they noticed that it was much lower in the army, due to these revaccination policies. This discovery helped many scientists in Europe recognize the need for revaccination, which greatly contributed to the eradication of the disease across most of Europe in the early twentieth century.

The development of vaccination by Edward Jenner in 1796 is seen by many as one of the most important and world-changing medical discoveries ever made. Throughout human history, smallpox was responsible for an untold and innumerable share of fatalities, with epidemics devastating countries (and even continents) in their wake; as of 1980, the World Health Organization declared smallpox to be eliminated in nature, making it the only human disease to have been successfully eradicated. If we look at the share of smallpox deaths in England over the nineteenth century, we can see the impact that vaccination had on society during this time. Decline in Britain Within this century, the number of people dying annually from smallpox dropped from 3,000 per million people in the 1700s, to just ten people per million in the 1890s (it is also worth noting that a smallpox pandemic swept across Britain between 1891 and 1893, which caused this number to be higher than it could have been). Mandatory vaccination was not introduced in England until 1853, but by this point the number of smallpox deaths per million people had already fallen to a fraction of its eighteenth century level, and compulsory vaccination reduced these numbers even further.

Before Jenner's work made vaccination commonplace at the turn of the nineteenth century, smallpox disproportionately affected children more than adults, with the share of deaths among those aged below ten years typically above ninety percent. This number even reached one hundred percent in some epidemics, such as in Chester, England in 1775; where all 202 smallpox deaths that year occurred in children below the age of ten, and 180 of these were in children below the age of five. Following the introduction of vaccination practices, which generally had the highest rates across Britain, Germany and Scandinavia, the share of smallpox cases in those aged above and below ten years saw a significant decrease, falling as low as 3.65 percent in one sample in London in 1822. The study in Marseilles is the only case shown here where the distribution of smallpox deaths was close to the figures shown in pre-vaccination Europe; this may be due to the political instability caused by Bourbon rule in post-Napoleonic France, as French authorities typically did not promote or enforce vaccination; a factor that would contribute greatly to the outbreak of the Great Smallpox Pandemic of the 1870s.

In the history of the United States, smallpox played a pivotal role in shaping the direction of the country's development. When Europeans first arrived in the Americas, they unintentionally introduced smallpox to the continent and the disease helped to wipe out as much as 95 percent of indigenous Americans. This was one factor that allowed European settlers to colonize the continent with relative ease, although the disease remained active in the Americas until the second half of the twentieth century. The number of smallpox cases in the United States fluctuated between 1900 and 1930, with as many as 110,000 reported cases in 1920, however the number of cases fell sharply in the 1930s, and there were no cases at all in the United States from 1950 onwards. In 1980, the World Health Organization declared the disease to be successfully eradicated on a global scale, making it the first infectious disease to be wiped out by intentional human activity.

Following Edward Jenner's development of the smallpox vaccine in 1796, the death rate due to smallpox in England and Wales dropped significantly. Although Jenner's work was published in 1797, it would take over half a century for the British government to make vaccination compulsory for all infants. Between 1847 and 1853, when vaccination was optional, children under the age of five years had, by far, the largest number of deaths; the total death rate was 1.6 thousand deaths per million people, which was more than five times the overall death rate due to smallpox. When compulsory vaccination was introduced, this helped bring the smallpox death rate in this age group down by over fifty percent between 1854 and 1871. When compulsory vaccination was enforced with penalties in the wake of the Great Pandemic of the 1870s, the smallpox death rate among children under the age of five dropped to approximately fifteen percent of its optional vaccination level. Increase among adults Along with the youngest age group, children aged five to ten years also saw their death rates decrease by roughly two thirds, and the death rate among those aged ten to 15 declined by just under one third during this time. It was among adults, aged above 15 years, where the introduction of mandatory vaccination had an adverse effect on their death rates; increasing by fifty percent among young adults, and almost doubling among those aged 25 to 45. The reason for this was because, contrary to Jenner's theory, vaccination did not guarantee lifelong protection, and immunization gradually wore off making vaccinated people susceptible to the virus again in adulthood. There was some decline in the smallpox death rates among adults throughout the 1870s and 1880s, as revaccination became more common, and the enforced vaccination of children prevented smallpox from spreading as rapidly as in the pre-vaccination era. Overall trends While the introduction of mandatory vaccination saw the number of smallpox deaths increase for age groups above 15 years, the overall rate among all ages decreased, due to the huge drop in deaths among infants and children. The smallpox death rate dropped by over one quarter when compulsory vaccination was introduced, and it then fell to just over one third of it's optional-vaccination level when these measures were enforced. The development of the smallpox vaccine and the implementation of mandatory vaccination led to the eradication of the disease in Britain by 1934, and contributed greatly to the demographic developments of the twentieth century, such as the declines in fertility rate and birth rate, and the increase in life expectancy.

In Britain in the early 1890s, a smallpox epidemic spread across the country and infected thousands. While the death rate was just a fraction of the level observed during the Great Pandemic of the 1870s, the overall death rate increased from 16 deaths in 1890 to 1,456 deaths in 1893. Among all outbreaks shown here, there were more cases among those who were vaccinated and over the age of ten than in any other group, however the death rate of the infected ranged from just one to ten percent. To put this into context, the death rates among the unvaccinated over the age of ten reached as high as forty percent in Gloucester. Unvaccinated children below ten years of age had the highest death rate among infected cases, and in the second outbreak in London, there were 148 deaths in 205 cases among unvaccinated children, whereas there were no deaths in 72 cases among vaccinated children. Another development in this pandemic was that the number of cases in children below the age of ten years was much lower than those above the age of ten; this trend that did not exist in previous centuries. A century of change In the pre-vaccination era, smallpox cases among adults were rare, as the majority of adults had contracted smallpox as children and had therefore built up a tolerance to the disease. In the early nineteenth century, the number of cases among children decreased, thanks to the protection granted to them through vaccination; however vaccination did not guarantee lifelong protection, which meant that the share of smallpox cases in young adults rose until revaccination then brought this trend back down. As we can see during these epidemics in England in the 1890s, the distribution of smallpox cases was much more representative of the population's age distribution, showing the impact and development of vaccination in its first century.

In nineteenth century Belgium, smallpox vaccination was available but was never made compulsory. For this reason, the number of deaths due to smallpox fluctuated regularly (although data before 1864 is scarce*), and the Great Pandemic of the 1870s caused the number of smallpox deaths in Belgium to skyrocket to 4.2 thousand per million people in 1871. Several sources suggest that smallpox had a similar impact in the Netherlands throughout the early and mid-1800s, however the Netherlands introduced mandatory vaccination for all children who were to be enrolled in school in 1873, and following the Great Pandemic the Netherlands' death rate was much lower than that of Belgium. The last natural case of smallpox was recorded in the Netherlands in 1900 (making it the fourth country in the world to eradicate the disease on a national level), while the last endemic case of smallpox in Belgium occurred in 1926. Data for Italy and Hungary is also scarce throughout the century, however Hungary introduced mandatory vaccination and revaccination in 1887, while Italy did the same in 1888; over the next decade we can see that the average number of smallpox deaths in these countries decreased greatly, and endemic cases of smallpox were eliminated in Hungary in 1923, and in 1947 in Italy.

From 1750 to 1770, the number of smallpox deaths in Berlin and Copenhagen fluctuated greatly, varying from as few as four deaths per year to over 1,000 throughout this time. In Copenhagen, the fluctuation came at regular and consistent intervals until the 1770s, when the number of smallpox deaths no longer reached more than 500 per year; this was due to the widespread adoption of inoculation practices in Scandinavia during this time. When vaccination was introduced to Copenhagen at the turn of the nineteenth century, the number of smallpox deaths per year plummeted, and following Denmark's introduction of mandatory vaccination (for all people who had never been infected) there were no more recorded cases of smallpox in Copenhagen for the remainder of the years shown. Contrast in Berlin In Berlin (which was the capital of Prussia during this time), the number of smallpox deaths continued to fluctuate throughout the remainder of the nineteenth century (at least in the years where data is available). Inoculation was not as widespread throughout the late 1800s as it was in Copenhagen, and vaccination was not made compulsory in Prussia until 1874; because of this, we can see a great discrepancy in the number of smallpox deaths, and severity of epidemics, in both cities during this time. For example, Berlin had almost four times the number of smallpox deaths than Copenhagen, while the population was just 1.7 times larger.

In the eighteenth century, before vaccination was introduced to Sweden, smallpox epidemics were much more severe and regular than in the nineteenth century. Between 1774 and 1802, epidemics in Sweden peaked roughly every five years, with the toll reaching over seven thousand deaths per million people in some years. When vaccination was introduced to Sweden in the early 1800s, it greatly decreased the total number of smallpox deaths per million people, with the number never exceeding one thousand deaths per million people in any year after 1809. In actual numbers, there were roughly two thousand smallpox deaths per year in Sweden during the pre-vaccination era; optional vaccination helped bring this average down to 623 deaths between 1802 and 1811, while the number dropped to 176 between 1857 and 1866 when compulsory vaccination was introduced. Vaccination in Sweden became enforced in 1880, where parents were punished with fines or imprisonment for failing to immunize their child, and this helped bring the average number of smallpox deaths to just two deaths per year over the next two decades. Although there were some cases and fatalities recorded in the late 1890s, naturally occurring cases of smallpox were eliminated in Sweden in 1895, which made Sweden the second country in the world (after Iceland in 1872) to successfully eradicate the disease.

The Franco-Prussian War was a ten-month-long conflict between France and the states of Northern Germany; the war itself was pivotal in creating a united German state, and establishing Germany as one of Europe's most powerful nations. One of the forgotten outcomes of the war was the last smallpox outbreak to reach pandemic levels across Europe; this pandemic would be responsible for an estimated 500,000 deaths overall, and led to much stricter vaccination laws being implemented across much of the continent. Prussian soldiers protected, but not civilians In the years leading up to the war, the smallpox death rate among the Prussian civilian population was already more than 33 times higher than it was in the army. This was due to the army's introduction of mandatory revaccination upon enlistment in 1834, and, because of this policy, the Prussian army suffered just 238* smallpox deaths during the war. In contrast to this, vaccination was encouraged but not compulsory in the rest of Prussia, which meant that a large portion of the population were vulnerable to the disease. Vaccination in France and the outbreak of the pandemic While France had been the last European country to embrace widespread inoculation in the eighteenth century, vaccination was not met with as much suspicion. In particular, religious leaders generally welcomed vaccination and promoted its use among all children in the country, however the unstable political leadership and administrations of the mid-1800s failed to make the practice mandatory. The Napoleonic regime had introduced compulsory vaccination in the army in the 1810s, but this was not enforced in the decades that followed his defeat, and vaccination coverage among new recruits in the French army had fallen below fifty percent in 1869. Between 1862 and 1872 (but not including the war), smallpox was responsible for almost one fifth of all deaths in the French army; increased mobilization allowed the disease to spread even further and faster during the Franco-Prussian War.

From limited records during the war, we can see a stark contrast in the impact of smallpox on both sides, with individual garrisons of French soldiers recording more smallpox deaths than the entire German Army*. While just under 2,000 deaths were recorded among French prisoners of war, the impact of these outbreaks on nearby Prussian civilians was devastating; killing over 2.4 thousand and 2.6 thousand per million people in 1871 and 1872 respectively. When the epidemic reached other countries it had a severe effect on the smallpox death rates, particularly in countries without compulsory vaccination such as Belgium and the Netherlands. This pandemic caused countries such as England and Sweden to introduce enforced vaccination, where parents would be punished for not vaccinating their children, while Germany and the Netherlands brought in compulsory vaccination. Despite the pandemic taking thousands of lives in France (the figures given by the French minister of war were seen as being well below the actual number and were quickly disregarded by most scientists), the French government was slow to react with any meaningful legislation; compulsory revaccination for all new army recruits was introduced in 1888, while vaccination was not made compulsory for all civilians until 1902.

Although vaccination was discovered in England in 1796, the practice was not made compulsory until 1853 in England and Wales, and 1864 in Scotland. For this reason, the number of smallpox deaths per million people fluctuated from year to year, often doubling or tripling from one year to the next, before the death rate for both countries settled in the late 1960s. The Great Pandemic of the 1870s, which was the last major smallpox pandemic in Europe, caused the number of smallpox deaths to soar once more, peaking at over 1,000 deaths per million people in England and Wales in 1871, and at over 820 deaths per million people in Scotland in 1872. During this pandemic, mandatory vaccination became enforced, where parents who did not vaccinate their children within the first three years of life were penalized with fines or imprisonment, and this helped the smallpox death rate to remain low and plateau in the final two decades of the nineteenth century; an estimated 11,000 of these penalties were handed out during the 1880s, which included 115 prison sentences for failure to vaccinate children. Smallpox cases in Britain were rare throughout the early twentieth century; not counting a lab accident in 1978 that infected two people (one of whom died), natural smallpox cases were eradicated in Britain in 1934.

The Great Smallpox Pandemic of 1870 to 1875 was the last major smallpox epidemic to reach pandemic level across Europe. The outbreak has its origins in the Franco-Prussian War of 1870 to 1871, where unvaccinated French prisoners of war infected the German civilian population, before the virus then spread to all corners of Europe. The death rates peaked in different years for individual countries; with the highest numbers recorded in 1871 for the German states, Belgium and the Netherlands, while death rates peaked in Austria, Scotland and Sweden in later years (the states that peaked in 1871 were closer in proximity to the frontlines of the Franco-Prussian War). Impact of compulsory vaccination The average number of deaths per million people was much higher in countries without compulsory vaccination, ranging from 953 to 1,360 in the samples given here. In comparison to this, the countries with compulsory vaccination barely reached these numbers in the years when the epidemic was at its worst, and their annual averages ranged between 314 and 361 deaths per million people during the six years shown here. Impact of the Great Pandemic Following the surge in smallpox deaths caused by the pandemic, many of the countries listed here introduced mandatory vaccination, or introduced penalties for parents who did not vaccinate their children. Germany and the Netherlands** did this in 1874, while Britain and Sweden enforced their vaccination laws with stricter penalties in 1871 and 1880 respectively. Perhaps surprisingly, Austria and Belgium, the two countries with the highest average death rate shown here, never introduced mandatory smallpox vaccination.

From 1629 to 1881, the number of smallpox deaths each year in London fluctuated greatly, with the number generally increasing and then decreasing year-on-year, or every two years; the first case of an increase or decrease over three consecutive years was not observed until the 1780s. The lowest number of smallpox deaths in any of the years given was in 1666; this was the year after the Great Plague of London, and the same year as the Great Fire of London, therefore the actual number of smallpox deaths in this year was likely to be much higher. The highest number of deaths recorded was in 1871, where it reached almost 8,000 deaths during the Great Epidemic of the 1870s. Smallpox in Glasgow In the final decade of the eighteenth century, the population of Glasgow was estimated to be around 75,000, and smallpox was responsible for just under nineteen percent of all deaths. When compared with London, smallpox was responsible for just over nine percent of all deaths in the same decade. Scientists do not have a concrete explanation why smallpox was responsible for almost one fifth of all deaths in pre-vaccination Glasgow, whereas it caused just under one tenth of the deaths in London during the same period (as both cities had similar overall death rates).

As Sweden was one of the first countries to implement smallpox vaccination on a large scale, and the second country in the world to successfully eradicate the disease, it is important to understand the role that smallpox had played Sweden's demographic development. In the late eighteenth century, smallpox epidemics swept across the Scandinavian country with relative regularity, peaking in four or five year intervals. In 1779 and 1784, smallpox epidemics were responsible for one quarter and one fifth of all Swedish deaths respectively; in other terms, this meant that roughly 0.7 percent and 0.6 percent of the entire population died due to smallpox in these years. While data for this time is scarce in other continents, when compared with other countries or cities in Europe, we can see that the trends observed here were not unique to Sweden; thus highlighting the devastating toll that smallpox pandemics took on Europe's population in the pre-vaccination era.

In human history, smallpox has been one of the most widespread and lethal diseases to occur in nature, taking hundreds of millions of lives across the globe before it was successfully eradicated in the twentieth century. Although an effective smallpox vaccine was first developed in England in 1796, it would take over a century for the vaccine to be understood and implemented across Europe. While the vaccine was discovered in England, it was in Germany where the practice of vaccination first took off on a large scale, and where the importance of revaccination was discovered. Bavaria leads in vaccination development The state of Bavaria was the first in Germany (and second in the world, after Iceland) to introduce mandatory smallpox vaccination for newborns. This was reflected in them generally having the lowest number of smallpox deaths in Europe in the mid-1800s. Before the vaccination era, infants and children were generally the most at risk of dying from smallpox infection; vaccination caused these death rates to plummet, however it then presented microbiologists with a new challenge. As the century progressed, the smallpox death rate among young adults increased and it became apparent that vaccination in infancy would not last until adulthood, thus the need for revaccination emerged, with Bavaria again at the forefront. The German Vaccination Law of 1874 It was during the great pandemic of the 1870s The German Vaccination Law of April 8, 1874 was passed; where all children under the age of two, and any unvaccinated child under the age of twelve had to be vaccinated by law. From this year we can see a sharp decrease in the death rate due to smallpox, where it remains consistently low for the remainder of the century. The introduction of this law brought the smallpox death rates in all German states in line with those of Bavaria, with the death rate in Württemberg dropping even below that of Bavaria. In contrast to Germany, mandatory smallpox vaccination was never introduced in Austria, and we can see that the death rate due to smallpox in Austria remained much higher than in Germany for the remainder of the century.

From the 1630s to the 1830s, the annual number of smallpox deaths in each decade fluctuated greatly in London. The population of London in 1650 is estimated to have stood at 350,000 inhabitants, with an average annual death toll of roughly 680 people during this time. As London's population grew over the next hundred years, the number of smallpox deaths also increased at varying rates in each decade. Scientific advancements flatten the curve The average number of annual smallpox deaths was between 1.7 and 2.5 thousand in each decade between 1710 and 1799, as the introduction of inoculation (i.e. using a mild dose of smallpox to develop some immunity to the virus) helped to lower the smallpox death rate to some extent. Following Jenner's discovery of vaccination in 1796 (which provided a much safer and more reliable method of protection), the death rate decreases further. London's population at this time was just under one million people, and the average number of deaths in the first decade of the 1800s was 1.4 thousand per year (or 1.4 deaths per thousand inhabitants). Vaccination brought this number down even further in the next quarter century, despite the fact that mandatory vaccination was not implemented by the British government until 1853. Smallpox death rate in other capitals While there is little reliable data for other major cities in the seventeenth or early-eighteenth century, London's death rate can be compared with that of Berlin or Copenhagen at the turn of the nineteenth century, during a time of increased urbanization and industrialization. In 1800, Berlin was estimated to have a population of roughly 170,000 people, and Copenhagen's was 100,000. This gave Berlin a smallpox of death rate of roughly 2.7 deaths per thousand in the first decade of the 1800s, and Copenhagen's was 0.67 deaths per thousand. Berlin's smallpox death rate was consistent between 1770 and 1809, while Copenhagen and London's both decrease after vaccination was introduced (Denmark made it mandatory in 1810). Unfortunately, a lack of information from this time makes it difficult to draw further conclusions about the spread of smallpox in urban centers in these years.

Between 1783 and 1800 in Glasgow, smallpox was responsible for an average of nineteen percent of all deaths per year. Relatively severe epidemics were responsible for over a quarter of all deaths in 1784 and 1791, and, as is usually the case following an epidemic, the share of smallpox deaths dropped significantly the following year. When compared with another major British city, such as London, the death rate due to smallpox was almost doubled in Glasgow during these years; scientists are not sure if this was actually the case, or if the recorded data was inaccurate in Glasgow or in the other cities (or in both).

The story of smallpox in Stuttgart is a clear example of how vaccination can make a significant impact. In the first 25 years shown here, the number of smallpox deaths averaged at 224 deaths per year, before a slight increase over the next five years to 274 deaths per annum. With the introduction of vaccination practices to Europe at the turn of the nineteenth century, a clear decrease can be observed in the next decade, dropping to 154 deaths per year between 1802 and 1806, and falling again to just two deaths per year between 1801 and 1811. In two of the next three five-year periods, the average number of smallpox deaths per year was zero. The state of Württemberg (of which Stuttgart was the capital) was one of the first in Europe to make vaccination compulsory, doing so in 1818; joining its south-German neighbors of Bavaria and Baden at the forefront of the fight to eradicate smallpox.

The World Health Organization (WHO) estimates that there were millions of smallpox cases every year until the 1970s, when the WHO's eradication program then successfully eliminated the disease in nature. Some academic estimates place smallpox's death toll at 300 million in the twentieth century, and 500 million in its final hundred years of existence. The development of the smallpox vaccination, which was the first successfully developed vaccine (the word vaccination comes from the Latin word for cow;"vacca", as cowpox was used to develop the smallpox vaccine), greatly contributed to the significant decline in infant and child mortality across the globe, and the boom in population growth during the twentieth century. Reported cases In spite of these large numbers, the figures for reported cases was only a tiny fraction of this; for example, the WHO estimates that there were fifty million cases in 1950, however less than one percent of these cases were recorded. In spite of this, the data is still useful for showing how smallpox developed and spread throughout the world; we know that the majority of these cases were recorded in the Indian sub-continent, and that epidemics across Asia drove the number of recorded cases up in the middle of the century. The final naturally-occurring cases were observed in 1977, while the two cases in 1978 were due to a lab accident in England, which resulted in one fatality.

In the pre-vaccination era in Sweden, smallpox was responsible for a considerable number of deaths annually, with over 92 percent* of these deaths occurring in children below the age of ten. Between 1774 and 1798, records show that smallpox was responsible for an average of 4,131 deaths annually, with 2,370 (over 57 percent) of these occurring in children below the age of three. When compared with similar studies from Switzerland and Scotland during this time period, we can see that the proportion of deaths among infants and children was even lower in Sweden than in other areas; highlighting the devastating impact that smallpox had on Europe's infant and child mortality rates before vaccination became available.