Smallpox Eradication and the COVID-19 Response

Written by Leigh Henderson

On the 40th anniversary of the global eradication of smallpox, there are calls for attacking the COVID-19 pandemic as smallpox was attacked. One hallmark of smallpox eradication has been undertaken with enthusiasm—research. Scientists around the world are investigating COVID-19. Scientific journals are waiving their usual access fees to ensuring rapid and widespread communication of results.

Can smallpox eradication be a model for tackling the COVID-19 epidemic? Yes and no. Smallpox eradication could not have succeeded without its basic management, organization, and epidemiologic principles. These ‘lessons’ apply broadly and can influence the success or failure of global public health programs. 

However, the two diseases are very different. Smallpox had many characteristics that made it a viable candidate for eradication, and the strategies used took advantage of these. Confronting COVID-19 will require different strategies.

Disease Characteristics

Both smallpox and COVID-19 are caused by a virus. For smallpox, man was the only host—there were no animal reservoirs. This is not true of COVID-19

Smallpox spread almost solely by droplet inhalation over short distances. It was infectious only when the rash was present. Smallpox was easily recognizable—both the disease and successful vaccination left characteristic scars. Laboratory diagnosis was rarely necessary. It killed 20-25% or more of its victims, overwhelming the body with viral toxins. 

COVID-19 also spreads mainly by droplet inhalation over short distances. However, transmission over longer distances and by contact with virus-contaminated surfaces has not been ruled out. It can be spread by people who appear healthy, with mild or no symptoms. In addition, a symptomatic person is probably infectious before symptoms develop and after they are gone. 

COVID-19 usually attacks the respiratory system. Like influenza, pre-existing medical conditions and complications such as pneumonia contribute significantly to severe disease and death. Many people, especially the elderly, die with COVID-19 rather than directly of COVID-19. 

COVID-19’s case-fatality rate is much lower than that of smallpox—currently about 5% worldwide.1 But it can be diagnosed only by laboratory test. Tens of millions of people undoubtedly have had undiagnosed COVID-19, often with mild or no symptoms. Thus the true case-fatality rate is significantly lower than we can currently measure.

Strategies Impractical for COVID-19

Smallpox eradication was a realistic goal because of the characteristics above. In addition, there was an effective heat-stable freeze-dried vaccine that was inexpensive and easy to administer, and required only a single dose. Successful vaccination gave essentially lifelong protection. 

In 1967, when WHO’s Intensified Smallpox Eradication Program began, mass vaccination was universally accepted as the only approach to eradication. Most nations were conducting mass vaccination programs, but poor supervision and low-potency vaccine led to indifferent results. ‘Success’ was measured as the number of vaccinations given. 

The Intensified Program changed the measure of success to the number of cases of smallpox, with the goal of zero cases.

The surveillance and containment strategy

Surveillance and containment became the basic strategy in eradicating smallpox. ‘Surveillance’ is the identification of outbreaks though reporting networks and active searches. ‘Containment’ is the interruption of the person-to-person chain of transmission by localized vaccination. 

Surveillance networks were developed by improving reporting in existing health facilities. Active searches for outbreaks were conducted in schools, villages, and marketplaces. People were asked if they knew of cases of smallpox, easily recognized by its distinctive pustules. Cases were isolated while they were infectious and individuals in the areas around an outbreak were vaccinated. The source of the outbreak was traced and other outbreaks related to the source were contained.

Surveillance and containment currently has no practical application in control of COVID-19. COVID-19’s most prominent symptoms, fever and respiratory problems, are common to many diseases. Laboratory diagnosis is the only way to identify it and would be far too costly, especially on a large scale, for most nations. Contact tracing was extremely useful in smallpox eradication, where outbreaks could be easily identified and containment measures taken. But there are no practical and effective measure for identifying and containing COVID-19. A COVID-19 vaccine is probably 18 months away at best and may well be too costly for many nations to use widely.

Essential Lessons for COVID-19

Smallpox eradication depended on basic epidemiologic principles and program management that are universally applicable. Dr DA Henderson, chief of WHO’s smallpox eradication program, noted, “The limiting factor is not money, but sensible plans and intelligent management.” Regrettably, these have been conspicuously absent in the US response to the COVID-19 pandemic. 

Global participation

The most critical factor in the global eradication of smallpox was global participation. Although smallpox was no longer pandemic, it was endemic in many countries. Its introduction was a constant threat to all other countries. Epidemics occurred in non-endemic countries into the early 1970s. Smallpox vaccination was mandatory for international travelers. 

WHO provided the forum, through its World Health Assembly, to come to the international consensus that smallpox could and should be eradicated, and that WHO should take the lead role. 

The US, having decided to withhold its dues from WHO, no longer has a voice in that body. It has chosen to address COVID-19 as a national epidemic, not a global pandemic.

A single coordinating agency

WHO was the central point of coordination, contact, resource allocation, and technical assistance for the smallpox eradication program. WHO had the standing to enlist the collaboration of independent laboratories. WHO’s smallpox unit set data standards, developed surveillance networks, and compiled and analyzed data. It communicated frequent, honest, and reliable information to program participants, national health officials, and the press and public. As the coordinating agency for national programs, it maintained a vaccine bank and could quickly distribute resources when need arose. 

In the US, there is no coordinating agency. The Centers for Disease Control and Prevention (CDC) should have this role. 

A well-defined, measurable, and realistic goal

For smallpox, this was not the number of vaccinations performed or the number of lab tests administered. It was zero cases of smallpox. The intensive surveillance program provided accurate measurement of the location and number of outbreaks and cases occurring. 

The US has no defined goals, realistic or otherwise, for its COVID-19 response. There are no criteria for evaluating the effectiveness of its response.

A surveillance network

As has been noted, surveillance provided the complete and detailed data necessary to eradicate smallpox. 

In the US, reporting of COVID-19 is fragmented among states and sources. It was certain that COVID-19 would come to the US, and preparations could have been made well in advance of its arrival. CDC was ideally positioned to broaden the scope of its well-developed influenza surveillance network to accommodate COVID-19. This was not done. 

Quality control of tests and procedures by independent laboratories using a defined set of standards

For smallpox eradication, a group of independent laboratories drew up WHO standards for smallpox vaccine. At the beginning of the program, only 10% of vaccine tested met these standards. Technical assistance brought vaccine producers into compliance. WHO set up a program in which independent laboratories routinely tested vaccine samples. Laboratory diagnosis of specimens was conducted by independent laboratories. 

In the US, most COVID-19 testing uses proprietary tests developed by competing commercial laboratories who perform their own quality assurance and receive federal compensation. 

Open two-way communication at all levels

Exchange of ideas, experience, and observation among all levels led to continuous improvement in global, national, and community approaches to smallpox eradication. Communication must be frequent, open, honest, and reliable.

Defined goals and standards, roles and responsibilities

Expectations were developed and communicated for all aspects of program performance. Both performance and standards were continuously assessed, evaluated, and modified.


A collaborative research program among independent laboratories, its agenda directed by program needs, was critical to smallpox eradication. Similarly, field research by program workers was encouraged and resulted in many modifications to program tactics. Results were disseminated promptly and widely so that they could be put into action. 

Final Word

‘Sensible plans and intelligent management’ are essential for a reasonable approach to COVID-19 control. WHO has provided guidance to the global community. One can be cautiously optimistic that a consensus approach to COVID-19 will emerge, and that it can be a model for inevitable future pandemics. 

In the US, the response has suffered from lack of planning, failure to consider adverse consequences, and fractured management. Surveillance is poor and there is little meaningful communication with the public. This can change if the political will is there. 

Leigh A Henderson, Ph.D., is an epidemiologist and former director of the Behavioral Health Services Information System for the Substance Abuse and Mental Health Services Administration. She is the curator of Target Zero: The Smallpox Eradication Program Archives, which she started with her father, Dr. D.A. Henderson, Chief of WHO’s Smallpox Eradication Programme.