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Variolation has been brought up in some circles nowadays as a proposal to deal with the Covid-19 crisis (sometimes by invoking the glorious/revolutionary American past).

Looking at the aforementioned Wikipedia page, which indeed confirms that (historically) variolation was widely accepted in the US at some point, I can't seem to find any scientific analyses of its effectiveness listed there. So, have such studies been conducted, either in terms of analyzing the historical data through a (counterfactual) epidemiological lens (iffy I suppose), or at least in contemporary animal studies?

(Obviously, the practice was abandoned once a vaccine was developed.)

Variolation served as a natural precursor to the discovery of vaccination. The major differences between the two were that in vaccination, material from cowpox, an animal disease, was used, but particularly that it was safe to those vaccinated and was not transmitted to their contacts. Vaccination offered the public a less-harmful method of preventing smallpox. Vaccination would revolutionize the control of smallpox, leading to its eventual eradication.

I see there's a University of Colorado page that says:

During the smallpox epidemic that swept across North America from 1775 to 1782, Revolutionary War soldiers took an unusual approach to protecting themselves from the virus known as Variola major. In a process known as variolation (a.k.a. inoculation), they took virus-loaded material from an infected person’s smallpox pustule, carved an incision into the flesh of a healthy solder, and rubbed it in.

Recipients of variolation invariably got the disease, so were quarantined. About 5% died. But most got a mild version of the smallpox disease.

“There is no question that it worked,” says Fenn. “Assuming you lived through it, you would garner immunity and go about the world without worrying about smallpox.” [...]

Fast forward to today, and variolation has come full circle, as researchers explore the idea of using “convalescent plasma” (survivor blood believed to contain antibodies to COVID-19) as a treatment.

So apparently some (historical, at least) studies might have been conducted, but they're not clearly listed there. (I think the whole page is based on an interview with "CU Boulder history Professor Elizabeth Fenn, a Pulitizer Prize winning writer, scholar of epidemics and author of Pox Americana: The Great Smallpox Epidemic of 1775-82.")

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    What is wrong with this question? – Fizz Apr 13 at 7:14
  • Are you asking what papers were published 200+ years ago on a practice that is in some countries outlawed? – Graham Chiu Apr 13 at 23:32
  • @GrahamChiu: there is such thing as a retrospective epidemiological study. – Fizz Apr 21 at 16:09
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On page 465 of a 1983 paper on the history of smallpox, Abbas M. Behbehani reports the following data about the variolation experience of Zabdiel Boylston (a non-physician) of Brookline, Massachusetts during the 1721 smallpox outbreak in Boston.

“Boylston subsequently reported that by February 1722 he had variolated 242 individuals from Boston and its suburbs, of whom 6 died, which gave a mortality rate of 2.5% as compared with 15% among persons with naturally occurring smallpox during the same epidemic period (849 deaths among 5,889 cases).”

https://pubmed.ncbi.nlm.nih.gov/6319980/

The paper does not document the source of the Boylston data.

A National Library of Medicine History of Medicine exhibition about smallpox states the following:

“In Asia, practitioners developed the technique of variolation—the deliberate infection with smallpox. Dried smallpox scabs were blown into the nose of an individual who then contracted a mild form of the disease. Upon recovery, the individual was immune to smallpox. Between 1% to 2% of those variolated died as compared to 30% who died when they contracted the disease naturally.”

https://www.nlm.nih.gov/exhibition/smallpox/sp_variolation.html

No source is given for the 1%-2% estimate of death after variolation. The estimate of 30% case fatality rate for variola major is widely cited.

Behbehani AM. The smallpox story: life and death of an old disease. Microbiol Rev. 1983 Dec;47(4):455-509. PMID: 6319980; PMCID: PMC281588.

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