Smallpox History and Vaccination
Smallpox
Smallpox does not travel well through the air, and it is very rare for it to spread in the same way as cold or flu viruses. The variola virus (which causes smallpox) can survive for extended periods in dried scabs, pus, or blood—especially on materials like blankets or clothing used by infected individuals. While respiratory droplets from close, prolonged contact can transmit the virus, the most common route of infection is through direct contact with infectious fluids, scabs, or contaminated materials. This is why sanitation and isolation, known historically as the Leicester method, worked so well to prevent infections in the late 1800s.
The early history of smallpox vaccine is peppered with experiments and failures but it has always had something that makes it stand out from every other vaccine. It was never given by injection; it was always given through scarification of the skin. Scarification of the skin evokes a Th17 response that is essential for robust immunity which can prevent infection. Th17 cells are responsible for guarding the boundary layers of the body, skin, gut, lungs, and eyes. The boundary layers are the first point of contact for any invader and it is of the utmost importance to pre-train Th17 cells for robust immunity.
Jenner’s original vaccine, in 1796, used cowpox virus. As vaccination practices became popular and spread across Europe in the early 1800s, other vaccine producers developed their own methods to cultivate vaccine supplies, often passing the virus through different animals such as horses. By the late 1800s, a distinct virus known as vaccinia had emerged. Vaccinia is genetically distinct from both cowpox and horsepox but appears to be most closely related to horsepox. This virus does not exist in nature and has no known animal reservoir. It is a virus that originated and evolved through human activity rather than natural circulation in wild animals. Vaccinia became the standard virus used in smallpox vaccines during the 1900s.
Prior to the 1840s - smallpox caused an average of approximately 20,000 deaths per year in the UK.
In 1842, Edwin Chadwick’s landmark “Report on the Sanitary Condition of the Labouring Population of Great Britain” highlighted the link between poor sanitation and disease. This helped lay the foundation for modern public health in Britain. As public health practices advanced, smallpox mortality began to decline even before the widespread enforcement of compulsory vaccination.
1852 - UK - Compulsory vaccination against smallpox introduced.
1852 - Leicester – 800 deaths – Vaccine uptake 3,500.
1857-1859: UK - Smallpox epidemic kills 14,244 people.
1858 – Leicester – 900 deaths – vaccine uptake 4,500
1863-1865: UK - Another epidemic kills 20,059 people.
1867 - UK - Even stricter vaccination law was passed, including prosecution for those who refuse.
1871 - UK - Chief Medical Officer of England announces a vaccination rate of 97.5% has been achieved.
1872 - UK - Worst ever smallpox epidemic, 44,840 people die.
1872 - Leicester – 3,523 deaths - Vaccine uptake 5,250.
These smallpox outbreaks and deaths that seemed to be correlated with vaccine uptake numbers must have given everyone great concern because cleanliness was refocused by William Henry Corfield to included rapid case isolation, disinfection of contaminated items, and improved urban sanitation. This approach was pioneered in the Borough of Leicester and became known as the Leicester Method.
After 1874 very few deaths resulted from smallpox. Scotland in particular did better than England at implementing the strategy because they had virtually no deaths from this date forward.
Vaccine rates for Leicester dropped to almost zero, except for a couple of spikes in uptake which also correlated with an increase in deaths for those years. This is strange because vaccinia does not cause full blown smallpox. Although these diseases are distinct, vaccinia and smallpox have many similarities that may not have been fully appreciated during diagnosis of disease in those times. Plus, because the manufacturing process used live animals, there is a possibility that other viruses were being passed around at the same time by contamination. Which would explain the correlation between higher vaccine uptake and higher death rates.
1893 – Leicester – 15 deaths – vaccine uptake 250.
1902 – Leicester – 5 deaths – vaccine uptake 800.
1903 – Leicester – 21 deaths – vaccine uptake 2,000
1904 – Leicester – 4 deaths – vaccine uptake 800.
1874 – 1910 – Leicester – This 36-year period had 26 years with zero deaths.
The Leicester method illustrates that controlling smallpox is possible using sanitation and isolation, without vaccination. This understanding is also supported by modern scientific views of the dynamics of host to host spread of smallpox. Given how smallpox spreads—primarily through close contact and contaminated materials—and how visible its symptoms are, it is reasonable to consider that improved sanitation and early case detection substantially reduced its impact.
After 1910, comprehensive data on smallpox mortality in the UK becomes scarce.
1929 – UK - 39 deaths, coinciding with the Great Depression—a period during which poverty, malnutrition, and reduced sanitation likely increased vulnerability to disease. Historically, famine has been linked to higher smallpox mortality in other regions, including Cape Verde and Angola.
1930 - Freeze-drying and improved manufacturing processes are developed which allowed the vaccinia virus to be produced on a large scale and distributed widely for global vaccination campaigns.
1960s - a bifurcated needle, dipped in the vaccine, was used to puncture the skin multiple times. This was a modern, standardized version of the traditional scarification technique, designed for efficient mass vaccination. The World Health Organization (WHO) announces the global campaign to eradicate smallpox
1980 - WHO declared smallpox eradicated. This was possible because the variola virus, which causes smallpox, had no animal reservoir, it infected only humans. Once it was eliminated from the human population, the virus could no longer circulate in nature. It could not be reintroduced from animal reservoirs, unlike viruses such as coronavirus, influenza, measles, mumps, adenoviruses, enteroviruses, herpesviruses, rhabdoviruses, bunyaviruses, and arenaviruses.
If vaccinia virus had been administered by intramuscular injection instead of scarification, it would not have induced a Th17-mediated local immunity in the skin. This would have resulted in less immediate frontline defence at the boundary layers, potentially allowing mild initial infection upon exposure. The vaccine would have reduced symptoms only.
The unique combination of using a live virus vaccine delivered through a barrier site without adjuvants, together with the fact that smallpox exclusively infected humans, was critical to the success given to the smallpox vaccine.
In any case, this accolade is unjustly applied because smallpox was already controlled using modern sanitation and isolation methods.