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.

Project Tycho datasets contain case counts for reported disease conditions for countries around the world. The Project Tycho data curation team extracts these case counts from various reputable sources, typically from national or international health authorities, such as the US Centers for Disease Control or the World Health Organization. These original data sources include both open- and restricted-access sources. For restricted-access sources, the Project Tycho team has obtained permission for redistribution from data contributors. All datasets contain case count data that are identical to counts published in the original source and no counts have been modified in any way by the Project Tycho team. The Project Tycho team has pre-processed datasets by adding new variables, such as standard disease and location identifiers, that improve data interpretabilty. We also formatted the data into a standard data format.

Each Project Tycho dataset contains case counts for a specific condition (e.g. measles) and for a specific country (e.g. The United States). Case counts are reported per time interval. In addition to case counts, datsets include information about these counts (attributes), such as the location, age group, subpopulation, diagnostic certainty, place of aquisition, and the source from which we extracted case counts. One dataset can include many series of case count time intervals, such as "US measles cases as reported by CDC", or "US measles cases reported by WHO", or "US measles cases that originated abroad", etc.

Depending on the intended use of a dataset, we recommend a few data processing steps before analysis:

• Analyze missing data: Project Tycho datasets do not inlcude time intervals for which no case count was reported (for many datasets, time series of case counts are incomplete, due to incompleteness of source documents) and users will need to add time intervals for which no count value is available. Project Tycho datasets do include time intervals for which a case count value of zero was reported.
• Separate cumulative from non-cumulative time interval series. Case count time series in Project Tycho datasets can be "cumulative" or "fixed-intervals". Cumulative case count time series consist of overlapping case count intervals starting on the same date, but ending on different dates. For example, each interval in a cumulative count time series can start on January 1st, but end on January 7th, 14th, 21st, etc. It is common practice among public health agencies to report cases for cumulative time intervals. Case count series with fixed time intervals consist of mutually exxclusive time intervals that all start and end on different dates and all have identical length (day, week, month, year). Given the different nature of these two types of case count data, we indicated this with an attribute for each count value, named "PartOfCumulativeCountSeries".

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.

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.

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.

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.

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.

Project Tycho data include counts of infectious disease cases or deaths per time interval. A count is equivalent to a data point. Project Tycho level 1 data include data counts that have been standardized for a specific, published, analysis. Standardization of level 1 data included representing various types of data counts into a common format and excluding data counts that are not required for the intended analysis. In addition, external data such as population data may have been integrated with disease data to derive rates or for other applications.

Version 1.0.0 of level 1 data includes counts at the state level for smallpox, polio, measles, mumps, rubella, hepatitis A, and whooping cough and at the city level for diphtheria. The time period of data varies per disease somewhere between 1916 and 2011. This version includes cases as well as incidence rates per 100,000 population based on historical population estimates. These data have been used by investigators at the University of Pittsburgh to estimate the impact of vaccination programs in the United States, published in the New England Journal of Medicine: http://www.nejm.org/doi/full/10.1056/NEJMms1215400. See this paper for additional methods and detail about the origin of level 1 version 1.0.0 data.

Level 1 version 1.0.0 data is represented in a CSV file with 7 columns:

• epi_week: a six digit number that represents the year and epidemiological week for which disease cases or deaths were reported (yyyyww)
• state: the two digit postal code state abbreviation that represents the state for which a count has been reported
• loc: the name of a state or city for which a count has been reported, capitalized
• loc_type: the type of location (STATE or CITY) for which a count has been reported
• disease: the disease for which a count has been reported: HEPATITIS A, MEASLES, MUMPS, PERTUSSIS, POLIO, RUBELLA, SMALLPOX, or DIPHTHERIA
• cases: the number of cases reported for the specified disease, epidemiological week, and location
• incidence_per_100000: the number of cases per 100,000 people, computed using historical population counts for cities and states as reported by the US Census Bureau

Following the arrival of Spanish colonizers in 1519, namely Hernando Cortes and his 600 conquistadors, the indigenous population of the Mexican valley saw a dramatic decline. In the first two years of conquest, thousands of indigenous Americans perished while fighting the European invaders, including an estimated 100,000 who died of violence or starvation during Cortes' siege of the Aztec capital city, Tenochtitlan (present-day Mexico City), in 1520. However, the impact of European violence on population decline pales in comparison to the impact of Old World diseases, which saw the indigenous population of the region drop from roughly 22 million to less than two million within eight decades.. Virgin soil pandemics Almost immediately after the Spanish arrival, a wave of smallpox swept across the indigenous populations, with some estimates suggesting that five to eight million natives died in the subsequent pandemic between 1519 and 1520. This outbreak was not an isolated incident, with the entire indigenous population of the Americas dropping by roughly ninety percent in the next two centuries. The Mexican valley specifically, which was the most populous region of the pre-Columbian Americas, suffered greatly due to virgin soil pandemics (where new diseases are introduced to biologically defenseless populations). In the Middle Ages, the majority of Europeans contracted smallpox as children, which generally granted lifelong immunity. In contrast, indigenous Americans had never been exposed to these diseases, and their populations (of all ages) declined rapidly. Cocoliztli Roughly three decades after the smallpox pandemic, another pandemic swept across the valley, to a more devastating effect. This was an outbreak of cocoliztli, which almost wiped out the entire population, and was followed by a second pandemic three decades later. Until recently, historians were still unsure of the exact causes of cocoliztli, with most hypothesizing that it was a rodent-borne disease similar to plague or an extreme form of a haemorrhagic fever. In 2018, however, scientists in Jena, Germany, studied 29 sets of teeth from 16th century skeletons found in the Oaxaca region of Mexico (from a cemetery with known links to the 1545 pandemic); these tests concluded that cocoliztli was most likely an extreme and rare form of the salmonella bacterium, which caused paratyphoid fever. These pandemics coincided with some of the most extreme droughts ever recorded in North America, which exacerbates the spread and symptoms of this disease, and the symptoms described in historical texts give further credence to the claim that cocoliztli was caused by salmonella.

The child mortality rate in the United States, for children under the age of five, was 462.9 deaths per thousand births in 1800. This means that for every thousand babies born in 1800, over 46 percent did not make it to their fifth birthday. Over the course of the next 220 years, this number has dropped drastically, and the rate has dropped to its lowest point ever in 2020 where it is just seven deaths per thousand births. Although the child mortality rate has decreased greatly over this 220 year period, there were two occasions where it increased; in the 1870s, as a result of the fourth cholera pandemic, smallpox outbreaks, and yellow fever, and in the late 1910s, due to the Spanish Flu pandemic.

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.

Edward Jenner's work on smallpox, published in 1797, was the first time that any scientific findings about vaccination were presented to the wider medical community. Within a few short years of this publication, vaccination had been practiced in most European countries, and the impact was beginning to show almost immediately; particularly in countries such as Sweden and England. As vaccination practices spread, the severity and frequency of smallpox pandemics declined, and the disease ceased to be endemic in some regions. Iceland leads the way Epidemics had played a significant role in Iceland's history and development throughout the pre-vaccination era. The country's geographical location meant that viruses did not spread from other countries as frequently as they did on Europe's mainland, however, this also meant that generations would reach adulthood without developing any immunity to these diseases. When these factors were coupled with Iceland's highly concentrated population, this enabled epidemics to spread rapidly throughout the population with devastating effect. The most famous of these epidemics was between 1707 and 1709, where a ship from mainland Europe brought smallpox to Iceland, and the resulting outbreak killed over one third of the entire population.

For these reasons, Iceland (although a dominion of Denmark at the time) became the first country in the world to introduce mandatory vaccination, in 1802. The Great Smallpox Pandemic of the 1870s was the last outbreak of the disease to reach pandemic level across Europe. Unbeknownst at the time, this would mark the last ever recorded case of naturally occurring smallpox in Iceland, in 1872. This made Iceland the first country in the world to eradicate the disease on a national level; the same factors that had allowed smallpox to be so devastating to Iceland's population in the past (i.e. distance from mainland Europe and a highly concentrated population) had become the reason why vaccination was so effective in the nineteenth century. The progress of elimination After Iceland's success, it would be another 23 years before the final smallpox cases would be recorded in any other European countries, with Sweden and Norway being the only other countries to eliminate the disease in the nineteenth century. In 1904, French Guiana was the first non-European territory to eradicate the virus, and Oceania* became the first continent to do so; with the last recorded cases in New Zealand and Australia taking place in 1914 and 1917 respectively. The United States recorded its final naturally occurring case of smallpox in 1948, and the final European case was in Portugal in 1953. Smallpox proved more difficult to eradicate in less-developed continents, due to a variety of barriers; such as dense populations and limits in infrastructure (the lack of roads made it especially difficult to combat the disease in Sub-Saharan Africa). The World Health Organization launched the Smallpox Eradication Programme in 1966, and after a number of aggressive vaccination and containment campaigns, the final case of naturally occurring smallpox was recorded in Somalia in 1977. For the next two years, scientists continued to monitor the global situation, but could find no further cases or outbreaks of the disease. On May 08. 1980, the World Health Assembly declared that smallpox had been eradicated, making it the first (and only, as of 2020) human disease to have been eradicated. This was one of the most significant and important medical developments in human history, and it has paved the way for the eradication of other communicable diseases, such as polio and measles; which are expected to be wiped out in the coming decades.

According to Edward J. Edwardes, it was in the armies of Europe where the importance of revaccination was discovered. In the pre-vaccination era, smallpox was not a serious problem in the army, as the majority of recruits had already contracted the virus during their childhood and had therefore developed an immunity to it. In the decades that followed widespread vaccination, army doctors began to notice that many servicemen were contracting smallpox in adulthood; the reason for this was that vaccination in infancy did not guarantee lifelong immunity from the virus, and the protection would wear off in adulthood. With this discovery, armies in Europe began to revaccinate all recruits upon entering the army. Britain slow to adopt revaccination When compared with the German states in the first half of the nineteenth century, Britain was much slower in adopting compulsory vaccination. The same was true in the army, as the German states began revaccinating all new recruits when the problem was first realized in the 1830s, whereas Britain did not introduce mandatory revaccination in the army until 1858. Although only Home Army figures are available in this time, we can see that the smallpox trends of the eighteenth century were repeating in the British Army, with waves of the disease coming at regular intervals. After 1858, the smallpox death rate decreases considerably in the Home Army, except during the Great Pandemic of the 1870s, and there were little-to-no deaths in the final years of the 1800s. Even slower progress in the navy and abroad While the Home Army brought its smallpox death rate down considerably by revaccinating all recruits, the impact was not as strongly felt in the Royal Navy, nor by the British Forces in India. Revaccination also applied to these armies, however their environments did not allow for the change to take hold as quickly; this was due to the nature of the navy, where recruits lived in close quarters with limited sanitation methods, and the fact that smallpox was a serious and endemic problem throughout the Indian subcontinent until the 1970s. The smallpox death rate in the British Navy was brought down considerably by the end of the century. Data suggests that the disease was likely also in decline among soldiers in India.

The scientific community accepts that the total number of reported smallpox cases is just a fraction of the actual number of smallpox cases in any given year. The World Health Organization (WHO) was not established by the United Nations until 1948, and did not launch their campaign to eradicate smallpox until 1967; prior to this, there was no organization responsible for collecting or correlating data relating to smallpox (or any other disease for that matter). The WHO estimates that there were approximately 50 million cases of smallpox each year in the early 1950s, while the total number of reported cases fell below 100,000 in 1953. When the WHO launched their intensified plan to eradicate smallpox in 1967, they estimate that there were between 10 and 15 million cases worldwide, although only 132,000 cases were reported in this year. For these reasons, data for reported cases should only be used to highlight trends and the distribution of outbreaks across the globe; this should also be met with some scrutiny however, as the data suggests there was a minimal number of cases in South Asia in the early-1920s, before jumping above 200,000 cases in the late 1920s. Europe, Central Asia and North America The most reliable data comes from Europe, Central Asia and North America. The number of cases in Europe and Central Asia fell from over 173,000 in 1920 to as low as 700 in 1937; apart from a brief outbreak during the Second World War, these numbers remained low until the disease's eradication. For North America, the number of cases fell significantly between 1920 and 1940, however a number of epidemics did break out between these years, which caused the decline to fluctuate. The majority of countries in Europe, North America and Oceania (where cases were rare) reported their final cases of smallpox by the middle of the century, before the WHO launched their campaign. The developing world Data for other continents is scarce, due to a combination of technological, economic and administrative limitations, however the largest concentration of cases was observed on the Indian sub-continent throughout most of the twentieth century. There were a few spikes in smallpox cases in East Asia from the mid-1940s to the mid-1960s; these years coincide with the end of the Sino-Japanese and Chinese Civil Wars, and Mao's failed Great Leap Forward, however any connection is purely speculative. The numbers of smallpox cases on other continents were much lower throughout these years, although cases did persist until the 1970s. The final naturally-occurring case of the deadly variola major strain of smallpox was observed in Bangladesh in 1975, while the last naturally occurring case of the milder variola minor strain was observed in Somalia in 1977. The WHO spent the next two years verifying the eradication of naturally occurring smallpox across the globe, before the World Health Assembly finally declared it eradicated on May 8, 1980.

Even in 2021, bubonic plague continues to exist in nature, and there are generally a few thousand human cases per year. Going back to the beginning of the 20th century, it is estimated that there were roughly one million cases per year in 1907. Within two decades, this number had fallen below one fifth of this level to 170,000 cases per year in the 1920s, and in the 1940s it was just over 20,000 per year. By the mid-20th century, it had fallen below 5,000 cases per year, but the rapid decrease in cases observed in the first half of the 1900s did not continue through the second half of the century. Even in 2019, there was one case of plague recorded in the United States. How infection occurs Yersinia pestis is the bacteria that causes the plague virus, and it is most commonly spread by rats and their fleas. The disease survives by fleas infecting rats, which in turn infect other fleas; the majority of rats survive the disease, which facilitates its spread; this is known as the "enzootic cycle ". Interestingly, the disease is usually fatal for the fleas, as it blocks their "stomachs" and causes them to starve; as the fleas get hungrier, they attempt to feed on more hosts, spreading the disease more rapidly. When the rats die, the parasitic fleas then search for a new host, which means that other animals (particularly mammals) are susceptible to this virus. While rat fleas can not survive on other hosts for very long, they can infect other (including human) fleas with the virus. The most common way for humans to contract the plague however, is when a rat flea bites its human host; during this process the flea simultaneously regurgitates Yersinia pestis bacteria into the wound, and this causes bubonic plague. Humans can then spread the disease among one another by coming into contact with the infected tissue or fluids of an infected person, or from the transfer of fleas. Continued existence of the plague Plague is extremely difficult to eradicate in nature, as rodent communities in the wild provide natural reservoirs for the disease to spread. In previous centuries, rats had much more frequent contact with humans for a variety of reasons; houses were more often made of wood (which made infestations easier), public spaces were much dirtier, and the presence of rats was tolerated more. As the understanding of epidemiology grew in the 20th century, this greatly reduced the frequency of plague in human populations. Unlike human diseases such as smallpox, which was eradicated through vaccination and other medical advancements, basic sanitation and the extermination of rats have been the driving force behind the decline of plague.

Life expectancy in the United Kingdom was below 39 years in the year 1765, and over the course of the next two and a half centuries, it is expected to have increased by more than double, to 81.1 by the year 2020. Although life expectancy has generally increased throughout the UK's history, there were several times where the rate deviated from its previous trajectory. These changes were the result of smallpox epidemics in the late eighteenth and early nineteenth centuries, new sanitary and medical advancements throughout time (such as compulsory vaccination), and the First world War and Spanish Flu epidemic in the 1910s.