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  • Writer's pictureP.K. Peterson

Smallpox Is Gone, but the Lessons Learned Live On

“I hope that some day the practice of producing cowpox in human beings will spread over the world - when that day comes, there will be no more smallpox.”

Edward Jenner

“It always seems impossible until it’s done.”

Nelson Mandela

Every day we are inundated with new COVID-19 data. Just this past week, it was reported that the number of cases worldwide has topped 31 million and deaths have exceeded 1 million. I don’t know about you, but I needed some relief from the constant barrage of COVID-19 information and misinformation confronting me, so I took a busman’s holiday and read Smallpox: the Death of a Disease (Prometheus Books, 2009) by Dr. Donald A. Henderson. Henderson was the physician and epidemiologist who led the World Health Organization’s (WHO) Smallpox Eradication Unit. His book tells the incredible story of what is, in my opinion, the most momentous medical achievement of all time, the eradication of the greatest contagious disease scourge in human history. And, it offers us some important lessons that can be applied to the COVID-19 pandemic.

Eradication, elimination and control: what each means. To understand the magnitude of the accomplishment of smallpox eradication, it’s helpful to reiterate several definitions from past Germ Gem posts. According to public health experts, the term eradication refers to a “permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts, and intervention measures are no longer needed.” Variola major, the virus that caused smallpox, is the singular example of an infectious agent of humans that has been eradicated due to an effective vaccine. (Rinderpest virus, the cause of rinderpest or cattle plague, is the only example of an animal virus that has been eradicated, also due to an effective vaccine.)

As discussed in a Germ Gem post last year, the world is still awaiting with hope and anticipation for the eradication of a second human pathogen: poliovirus. On August 28, 2020, a major achievement on the path to this goal was announced by WHO, which declared that polio was finally eliminated in Africa. Elimination means “a reduction to zero of the incidence of a specified disease in a defined geographical area as a result of deliberate efforts; continued intervention measures are required.” Because of highly effective vaccines, a number of other pathogens have been eliminated from many areas of the world, including rubeola virus, the cause of measles. (Largely because of anti-vaxxers, however, cases of measles have surged in the United States and elsewhere in recent years.)

Finally, while not eradicated or eliminated, many infectious diseases are considered controlled, that is, “a reduction of disease incidence, prevalence, morbidity or mortality to a locally acceptable level as a result of deliberate efforts; continued intervention measures are required to maintain the reduction.” Influenza is an example of an infection that is considered controlled, in part because of a vaccine. Another example are foodborne infections, most of which are controlled through various public health measures. With the aid of a safe and effective vaccine, the control and possibly even the eventual elimination of COVID-19 could be reasonable goals.

Smallpox: it was the worst of times. Things are bad now with COVID-19, but they were worse in the past. By the time the WHO declared smallpox eradicated in May 1980, it had killed more people than all wars combined. In the 20th century alone, smallpox claimed the lives of more people than influenza (including the 1918-19 pandemic that killed more than 50 million), HIV/AIDS, and tuberculosis all together. In the early 1950s, 150 years after smallpox vaccination was introduced by William Jenner, there were still some 50 million cases per year globally. By 1967, when Dr. Henderson assumed leadership of the WHO’s Smallpox Eradication Campaign, that figure had fallen to about 10-15 million cases a year. With an infection fatality rate (IFR) of about 30%, smallpox killed an estimated 3.5 million people that year worldwide. (By comparison, the IFR of COVID-19 is about 1%.)

How was the eradication of smallpox achieved? It took almost two centuries to eradicate smallpox from the face of the earth. Three factors were required to give smallpox the final boot from our planet: a vaccine; a surveillance-containment strategy; and last, but not least, leadership.

First, and foremost, was the development of an effective smallpox vaccine. For that we have to thank Edward Jenner. As discussed in the May 27th Germ Gem post, in 1796 Jenner observed that milkmaids who became infected with cowpox (a relatively benign disease but an occupational hazard for milkmaids) became resistant to small pox. He hypothesized that something in cowpox lesions could be used to cross-protect against smallpox. (This was particularly insightful given that, at that time, no one knew of the germ theory of disease.) And, he had the brilliant idea that material scraped from cowpox scabs of milkmaids could be inoculated into people to protect them from smallpox. (The word vaccine is derived from the Latin word vacca for “cow.”) Jenner became recognized as the father of vaccinology (although recent research suggests his vaccine was more likely developed from horsepox, not cowpox).

A second factor that played a critical role in the eradication of smallpox was a surveillance-containment strategy. One of Henderson’s key colleagues, Dr. William Foege, was largely in charge of this strategy, in which infected individuals and their families and neighbors would be immediately isolated and vaccinated to prevent further transmission of smallpox. Their emphasis on active searches and detection and the containment of outbreaks was essential to eliminate infection centers, or foci.

Leadership was the third factor that was crucial in eradicating variola major. Drs. Henderson and Foege, along with other colleagues at the WHO as well as at the Center for Disease Control and Prevention (CDC), pulled off what seemed like a miracle. How did they accomplish this? Perseverance (in the face of a number of powerful naysayers), imagination, courage, a refusal to let bureaucracy stop them, teamwork, and above all, establishing trust. In the final chapter of his book, Henderson concludes, “I believe that the important longer-term contribution of smallpox eradication to world health was its demonstration of how much could be achieved through community-wide vaccination programs.”

Lessons learned: what the world needs now. As was necessary for smallpox, an effective vaccine is needed to control and possibly eliminate COVID-19. One or more vaccines against SARS-COVID-19 may be released within the next six months. This will be the lynchpin in the campaign against this disease.

But as the history of smallpox eradication makes clear: while a vaccine is necessary, it, by itself, is not sufficient. A surveillance-containment strategy is also necessary. The strategy used in the eradication of smallpox appears to be similar to today’s self-help measures used to help control the spread of COVID-19, namely, social distancing and self-quarantining practices.

Of note, there is no mention of the use of masks in the smallpox surveillance-containment strategy even though transmission of variola virus like SARS-CoV-2 is airborne. Proper use of masks is now known to play a crucial role in controlling the spread of SARS-CoV-2. The thinking about the effectiveness of surgical masks in protection against SARS-CoV-2 has evolved considerably since the early months of the pandemic. At the beginning of the pandemic, the CDC recommended wearing a surgical mask only if you had COVID-19 to protect others from the airborne spread of the virus. (Mea culpa, this was also my recommendation in my March 3 Germ Gem post.) But, in a House Select Subcommittee hearing on COVID-19 in July, Dr. Robert Redfield, the director of the CDC, suggested that masks may offer better coronavirus protection than a vaccine.

The current stance on the importance of wearing a mask to protect oneself against SARS-CoV-2 represents a remarkable change in the understanding of this virus since the early months of the pandemic. This turnabout in thinking, however, is based on new scientific evidence, as is discussed by Dr. Rossi A. Hassad in an August 3 article in Medpage Today, “No RCT for Masks? No Problem: Other forms of evidence are available to judge effectiveness of this and other interventions.”

The importance of mask-wearing is taken one step further by Drs. Monica Gandhi and George Rutherford in an article in the New England Journal of Medicine on September 8, “Facial Masking for Covid-19 — Potential for “Variolation” as We Await a Vaccine.” They hypothesize that widespread population masking may act as a sort of “variolation” by exposing individuals to a smaller amount of viral particles that could produce an immune response thereby fostering herd (community) immunity.

Finally, we need leadership. Thus, when a vaccine appears, we all need to hope that another D.A. Henderson and a coordinated worldwide “COVID-19 Elimination Campaign” will also emerge. There is no question in my mind that such leaders exist and with support of coordinated global, science-based public health policies the battle against SARS-CoV-2 will be won.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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