Geographic area: Worldwide
Health condition: In 1966, there were approximately 10 million to 15 million cases of smallpox in more
than 50 countries, and 1.5 million to 2 million people died from the disease each year.
Global importance of the health condition today: Smallpox has been eradicated from the globe, with no
new cases reported since 1978. However, the threat of bioterrorism keeps the danger of smallpox alive,
and debate continues over whether strains of the disease should be retained in specified laboratories.
Intervention or program: In 1965, international efforts to eradicate smallpox were revitalized with the establishment of the Smallpox Eradication Unit at the World Health Organization and a pledge for more technical and financial support from the campaign’s largest donor, the United States. Endemic countries were
supplied with vaccines and kits for collecting and sending specimens, and the bifurcated needle made
vaccination easier. An intensified effort was led in the five remaining countries in 1973, with concentrated
surveillance and containment of outbreaks.
Cost and cost-effectiveness: The annual cost of the smallpox campaign between 1967 and 1979 was
$23 million. In total, international donors provided $98 million, while $200 million came from the endemic
countries. The United States saves the total of all its contributions every 26 days because it does not
have to vaccinate or treat the disease.
Impact: By 1977, the last endemic case of smallpox was recorded in Somalia. In May 1980, after two
years of surveillance and searching, the World Health Assembly declared that smallpox was the first disease in history to have been eradicated. The eradication of smallpox—the complete extermination of a notorious scourge—has been
heralded as one of the greatest achievements of humankind. Inspiring a generation of public
health professionals, it gave impetus to subsequent vaccination campaigns and strengthened routine immunization programs in developing countries. It continues to be a touchstone for political commitment to a health
goal—particularly pertinent in light of the United Nations’ Millennium Development Goals (MDGs).
But the smallpox experience is far from an uncomplicated story of a grand accomplishment that should (or
could) be replicated. Although the story shows howgreat global ambitions can be realized with leadership
and resources, it also illustrates the complexities andunpredictable nature of international cooperation.
The Disease Smallpox was caused by a variola virus and was transmitted between people through the air. It was usually spread by face-to-face contact with an infected person and to a The first draft of this case was prepared by Jane Seymour. lesser extent through contaminated clothes and bedding.Eradicating Smallpox Once a person contracted the disease, he or she remained apparently healthy and noninfectious for up to 17 days. But the onset of flulike symptoms heralded the
infectious stage, leading after two or three days to a reduction in fever but to the appearance of the characteristic rash—first on the face, then on the hands, forearms, and trunk. Ulcerating lesions formed in the nose and mouth, releasing large amounts of virus into the throat. Nearly one third of those who contracted the major
form died from it, and most of those who survived—up to 80 percent—were left with deeply pitted marks, especially on the face. Many were left blind. In 1700s Europe, one third of all cases of blindness were attributed to
In 1798, Edward Jenner announced success in vaccinating people against the disease and went on to claim
that his vaccine was capable of eradicating it.2Withthe development in the 1920s of an improved vaccine,
mass vaccination programs became theoretically viable.Subsequently, national programs—including the Soviet
Union’s experience in the 1930s—showed that eradication was possible. However, it wasn’t until the early
1950s that eradication became a practical goal, withthe development of a vaccine that did not require cold
storage and could be produced as a consistently potentproduct in large quantities.
In its earliest form, the idea of a global effort to eradicate smallpox was far from popular. In 1953, the World
Health Assembly (WHA)—the highest governing bodyof the WHO—rejected the notion that smallpox should
be selected for eradication. In 1958, however, the deputy health minister of the Soviet Union and delegate to the
WHA, Professor Viktor Zhdanov, proposed a 10-year campaign to eradicate the disease worldwide, based on
compulsory vaccination and revaccination—and he promised that the Soviet Union would donate 25 million
vaccine doses to initiate the program. A year later, a WHO report on the proposal suggested that eradication
could be achieved by vaccinating or revaccinating 80percent of the people in endemic areas within “four to
five years.” The Russian proposal was passed in 1959. Smallpox was a suitable candidate for eradication for
several reasons. The disease was passed directly between people, without an intervening vector, so there were no
reservoirs. Its distinctive rash made it relatively straightforward to diagnose, and survivors gained lifetime
immunity. The relatively long time between contractingit and becoming infectious meant that an epidemic took
a while to take hold—and because sufferers were likelyto take to their beds as they became infectious, due to
the severity of the symptoms, they tended to infect fewothers. Good vaccination coverage, it was reasoned,would disrupt transmission entirely; where an outbreakoccurred, the natural course of the disease gave health
workers time to isolate victims, trace contacts, and vaccinate the local population.
The vaccine itself has characteristics that also gavereason for optimism. The freeze-dried version produced
in the early 1950s eliminated reliance on a cold chain;if stored properly, the vaccine maintains its strength for
many years. A single vaccination can prevent infectionfrom smallpox for at least a decade, and some studies
have suggested that some protection is present even 30years after vaccination. Even where vaccination failedto prevent infection, the resulting disease tended to be milder and have a lower fatality rate.1
Burden of Smallpox at the Start of the Eradication Effort In 1959, 63 countries reported a total of 77,555 cases of
smallpox.2 Acknowledged at the time to be an underestimate, it was revised to closer to 100,000, although it later
became clear that as few as 1 in 100 cases was reported. Despite well-developed health systems, some countries
only reported cases that surfaced in major urban hospitals, while others failed to report at all. Information was
also lacking from countries that were not then WHO members, such as China.
It has subsequently been estimated that in 1959 smallpox remained endemic in 59 countries containing about
60 percent of the world’s population 3In the early 1950s,there were probably around 50 million new cases each
year.1However, several countries were on the verge ofdisrupting transmission of the disease, including China,
Iraq, Thailand, and Algeria.Eradicating SmallpoxA Slow StartIn the early stages the WHO plan relied on national
campaigns for which prime responsibility in cost andhuman resources would rest with national governments.
The WHO saw itself in the role of providing technicalassistance where called for and helping out by ensuring
the production of the vaccine.In fact, in its earliest days, the smallpox eradication program was a minor concern of the WHO. The reliance on national activities and vaccine donations, and pressuresof a campaign against malaria (given the go-ahead fouryears before smallpox), gave the WHO little incentive toallot significant funds to smallpox eradication.
At the start of the campaign, around 977 million peoplewere estimated to live in endemic areas; to vaccinate
them was estimated to cost 10 cents per person, a totalof about $98 million. However, the actual amount spent
in the first half of the 1960s was around $0.5 milliona year, 0.2 percent of the WHO’s regular budget. For
several years, a medical officer and secretary were theonly full-time employees working on the program at
the WHO’s headquarters in Geneva, and until 1966only five full-time employees were assigned to field
programs.Each year the WHO’s director-general told the WHA that eradication wasn’t going as well as hoped because
of lack of funds for vehicles, supplies, and equipment.And each year the WHA pressed for more funds to be
made available. But they were not.Political and financial support was in short supply in all quarters. The smallpox effort relied heavily on themdonation of vaccines, so there was little to be donewhen supplies ran short. The problems were illustrated in India in 1963, where the WHO’s encouragement led to the announcement of a mass vaccination campaign,
only to see the campaign run into trouble when it failed to generate sufficient donations of freeze-dried vaccine.
More fundamentally, the WHO approach of relying on national campaigns and providing only limited
leadership gave those who doubted the feasibility of eradication every reason to withhold funds and political
support. An expert committee set up in 1964 realized that case reporting was running at 5 percent or less of
actual cases—indeed, it was later realized to be closerto 1 percent. This discrepancy meant that no one could
tell where progress was being made or where there was a problem. Paradoxically, because the successes in
some countries were not tracked with good monitoring systems, progress that was made could not be presented
as evidence to bolster support.The campaign mode was showing its limits in some settings. India, for example, saw vaccination programs thatconcentrated on the easiest targets to achieve 90 percent
coverage in some districts. But outbreaks were still occurring in remote villages and slums, among traveling workers, and even in the heavily vaccinated areas,mainly because of bureaucratic reporting systems and quota-driven campaign efforts. For example, schoolchildren were often revaccinated many times to fulfillquotas for numbers of vaccinations performed, while those not attending school were not vaccinated at all.Thus, in 1964, the WHO recommended that the entire
population be vaccinated to achieve eradication.At the same time, the recognition that the malaria campaign was running into difficulties exacerbated thesmallpox situation, and the malaria campaign’s shortcomings were threatening to undermine the WHO’scredibility. Overall, in the first half of the 1960s, the smallpox eradication effort hardly looked like the global success it wouldeventually prove to be.Momentum BuildsThe program’s fortunes then took a turn for the better.
New appointments to WHO in 1964 revived the conviction that smallpox was beatable and created the impetus
to set up a separate Smallpox Eradication Unit, whichprovided focused leadership for international efforts.
This coincided with the development of a better method of delivering the vaccine. And in 1965, the US government, the WHO’s largest contributor, promised more technical and material support to the campaign.The US decision to provide more support—a key factor in the program’s development—came about through a combination of serendipitous circumstances, which started with then President Lyndon B. Johnson’s search Eradicating Smallpoxfor an initiative to mark International Cooperation Yearin 1965. A combined measles control and smallpox eradication program in western and central Africa was
the favored candidate. However, some in the US Communicable Disease Center (now the US Centers for
Disease Control and Prevention, or CDC), especially Dr.D. A. Henderson, who later led the WHO’s intensifiedsmallpox program, doubted the sustainability of suchan effort, due to the high cost of the measles vaccine (atthat time more than $1 per dose), which made it unaffordable to many developing countries. An alternativesmallpox eradication plan for the region was proposed.Although this wasn’t immediately accepted, it started discussions that led to smallpox eradication being puton the US agenda for western and central Africa and,finally, US support for the global effort.Growing political and financial support from the UnitedStates, combined with the long-standing campaign fromthe Soviet Union, compelled the WHO’s directorgeneral, Dr. M. G. Candau, to reenergize the eradication plans. In 1965, at the WHA’s prompting, Dr. Candau set
out the current understanding of the global spread of smallpox and what would be needed to eradicate it. The
WHA resolved that smallpox eradication was one of theWHO’s “major objectives.”Several elements figured prominently in the directorgeneral’s proposals. First, the budget was divided sothat one part remained in the main WHO budget and
the other in a dedicated fund. This maneuver allowedcountries’ commitment to smallpox eradication to be
gauged, while at the same time safeguarding the WHO’score budget. Second, the general approach was designed
to learn from the problems with the malaria program.For example, rather than setting out a strict set of rules,
the program articulated “principles” to allow for flexibility. Indeed, the WHO handbook for the program was
written as a “draft,” leaving headquarters and nationalstaff to infer that it was not the final word and could
be updated. Third, the case reporting system was to bedeveloped right at the start of the program to guide its
progress; and fourth, research was encouraged. The proposals also made it clear that all WHO member countries would be required to participate, and their effortswould need to be coordinated.In 1966, the WHA finally agreed to back the objectiveadopted the previous year for the Intensified Smallpox Eradication Programme, which started on January 1,
1967. The budget allocation was $2.4 million, which, ifdivided among the roughly 50 countries where programs were needed, amounted to about $50,000 percountry..At that point, there were between 10 million and 15 million cases worldwide. It was estimated that 1.5 million to2 million people died of smallpox each year, and those
who survived were disfigured; some were left blind or with other disabilities. The 31 endemic countries
included many in sub-Saharan Africa, six in Asia, andthree in South America. And some of those countries
remained divided by war and famine. A Full EffortThe Smallpox Eradication Unit set to work, with minimal staff and Dr. Henderson as the chief medical officer.For most of the campaign, the staff consisted of fourmedical officers, one administrator, a technical officer,and four secretaries. With strong support from the USCDC, the team produced an epidemiological report every two to four weeks, produced training materials, anddealt with the media.
Vaccine jet injectors, kits for collecting and sendingspecimens, and training aids were stored in Geneva
and sent out on request. The effort also supplied a newbreakthrough: the bifurcated needle. The needle was a
marvel of simple technology that reduced costs (1,000needles for only $5) and made vaccinating easier. Each
needle could be boiled or flamed and reused literallyhundreds of times, and one vial provided enough vaccine for four times as many people due to the smalleramount of vaccine required. Plus, they were very easy touse. A villager could be instructed and trained in its use in 15 minutes.The quality of the international staff was important tothe program, but recruitment wasn’t easy. In 1967, few infectious disease control epidemiologists were familiar with smallpox, and the WHO was not organized to provide specialized training for new recruits.Eradicating Smallpox Despite the limits of personnel, progress was noticeable—initially in western and central Africa, where quick detection and containment of outbreaks took effect. Within two years, 17 of the 21 countries in the region were free of smallpox, despite their overall levels ofpoverty. Brazil also made spectacular progress, enablingthe Western Hemisphere to be declared free of endemicsmallpox in April 1971. Provision of enough quality.freeze-dried vaccine and the introduction of the bifurcated needle started taking effect, especially in eastern
and southern Africa.New MethodsThe following year saw major disruption to theprogram’s successful trajectory, as Bangladesh lost itssmallpox-free status to the refugees fleeing the civil warthat led to independence. Botswana was faced with anepidemic, and it became clear that Iran and Iraq wereboth endemic again. Thanks to focused campaigns,
however, all except Bangladesh were clear of the diseaseby the end of 1973. In September of that year, intensified
campaigns began in the five remaining endemic countries: Bangladesh, India, Nepal, Pakistan, and Ethiopia.
The momentum was regained as new methods andextra resources were mobilized to cope with the large
numbers of refugees from both natural and humanmade disasters. With the WHO’s persuasion, there was
a move away from concentrating on general vaccinationcampaigns to focusing on actively seeking out cases and
containing outbreaks with quarantine and vaccination/of local people. Using the surveillance and containment
strategy, teams were equipped with Jeeps and motorbikes to search villages, markets, and even houses for
cases. The approach appeared increasingly military, as motorized teams sped to an area as soon as an active case was
announced. Massive efforts were then made to isolate cases and vaccinate everyone in the area, whether or not
they had been vaccinated before. WHO staff on shortterm contracts supplemented the ranks of local health
workers. The military-like approach succeeded even in the most difficult of circumstances. By the end of 1976, tens of
thousands of health staff in search and contain mentprograms stopped smallpox transmission in Ethiopia,
a country embroiled in civil war and suffering with poverty and little infrastructure. In this final stage, large
numbers of volunteers and helicopters were used torespond to outbreaks. As smallpox was contained in
Ethiopia, war and the resulting refugees took the diseaseback into Somalia, but campaign coordinators could see
there really was an end in sight, and experienced staff and money from many countries were marshaled to
contain the outbreak. In October 1977—10 years, 9 months, and 26 days afterthe start of the intensified campaign—the last endemic case of smallpox was recorded in Somalia. National staff of tracing contacts, quarantine, and vaccination. In
May 1980, after two years of surveillance and searching, the WHA declared that smallpox finally had been
Costs of Eradication
The costs of smallpox eradication have been estimated,although the underlying data are limited. In 1967 the
main program cost was associated with vaccine, personnel, and transport. For the developing countries, this
amounted to about 10 cents per vaccination. Estimatingthat about a fifth of the 2.5 billion people living in developing countries were vaccinated each year suggests that$50 million a year was spent on vaccination. However,
the actual expenditure was much less, approximately $10million per year by the endemic countries.2
India is the only developing country that has estimated the economic loss due to smallpox. In 1976, it was estimated that the cost of caring for someone in India withsmallpox was $2.85 a patient, so the annual total costof patient care for India alone would be $12 million.3,4 Based on the proportion of the global smallpox casesthat India reported, these figures suggest that caring forpeople with smallpox cost developing countries morethan $20 million in 1967. Estimating a person’s economic productivity during his or her lifetime, it has alsobeen calculated that India lost about $700 million due todiminished economic performance each year. Assuming 1.5 million deaths due to smallpox occurred in 1967,it is reasonable to estimate that smallpox was costing Eradicating Smallpox developing countries as a whole at least $1 billion eachyear at the start of the intensified eradication campaign.2Industrialized countries, on the other hand, incurred
the cost of vaccination programs to prevent the reintroduction of the disease. In the United States, the bill
for 5.6 million primary vaccinations and 8.6 millionrevaccinations in 1968 alone was $92.8 million, about$6.50 a vaccination. Of those vaccinated, 8,024 peoplehad complications requiring medical attention, 238 werehospitalized, 9 died, and 4 were permanently disabled.With other indirect costs of the vaccination program,such as absences from work, the cost for 1968 was 75cnts per person. Even assuming that other developedcountries had lower costs, this puts the annual cost forthese countries around $350 million, based on their total population. Overall, the suggested global cost, both
direct and indirect, of smallpox in the late 1960s wasmore than $1.35 billion.2The ultimate expenditures of the intensified eradicationprogram were around $23 million per year between1967 and 1979, including $98 million from internationalcontributions and $200 million from the endemic countries.2It has since been calculated that the largest donor,the United States, saves the total of all its contributionsevery 26 days, making smallpox prevention throughvaccination one of the most cost-beneficial health interventions of the time.5Lessons LearnedObservers attribute much of the program’s success topolitical commitment and leadership, in this case fromWHO and its partner the CDC, along with specific funds, staff, and a unit with overall accountability andresponsibility for the program. The initial dismal phase
of the eradication program in the first half of the 1960sshowed how lack of that commitment and organization
undermined the efforts.For national programs, it is generally agreed that successhinged on having someone who was responsible, preferably solely, for smallpox eradication. This individualwas the main contact in the country and could be held
accountable. Best results were obtained where WHOstaff, or supervisory people, went into the field frequently to review activities and resolve problems. Theirwork showed that relatively few highly committed and knowledgeable people could motivate large numbers ofstaff successfully, even in unstable areas and the poorestof countries., No two national campaigns were alike, which points toone of the significant lessons that can be learned from smallpox eradication: the need for a flexible approach.Vaccination programs had to be adapted to differentadministrative, sociocultural, and geographical ituations, and ways of assessing the work had to be devised.Indeed, it was important that funds raised did not come with conditions that prevented their use for differentactivities in different areas.Using existing health care systems for the program bothtook advantage of established ways of working in somecountries and forced other countries to bring their services up to standard. This helped develop immunizationservices more generally—health staff helping with the
campaign received training in vaccination and searchand containment. This training was especially important
for hospital-based health systems that had no experience in setting up preventive campaigns. The knowledge gained this way then went into other campaigns,offsetting the cost of the initial campaign. This work
outside hospitals also reinforced how important it wasto seek the support of community leaders and thus theparticipation of their communities. These lessons haveed projects,including the trachoma control program (Case 10) and
the guinea worm campaign (Case 11).It was also discovered during the campaign that morethan one vaccination could be given at a time, an ideanow taken for granted. In 1970, the Smallpox Eradication Unit proposed an Expanded Programme on
Immunization to increase the number of vaccinationsadministered during a single patient interaction. The
proposal sought to add diphtheria, tetanus, pertussis,polio, and measles vaccines to the routine smallpox and
BCG (to prevent tuberculosis) vaccines. In 1974, theWHA agreed, and the United Nations Children’s Fund
(UNICEF) became a major supporter of the ExpandedProgramme on Immunization in the 1980s.
Routine immunization in the developing world underthe program may prove in the end to be the smallpox
Eradicating Smallpox.eradication effort’s greatest contribution: By 1990, 80percent of the children throughout the developing worldwere receiving vaccines against six childhood killers, compared with only 5 percent when the program
started.The importance of monitoring results is another transferable lesson. In the early 1960s, several countries relied
on measuring activity as an indicator of success—andduly reported that they had vaccinated a large number
of people. Yet the number of new cases remained high.Clearly, there was a problem with the surveillance and
program evaluation, but because the monitoring indicator was within an acceptable range, nothing changed.
From 1974, standards were established for surveillance and containment as well as for vaccination coverage.Good reporting ensures that success can be measured,but publicity of that success is essential. The messagethat the smallpox eradication campaign was workingBox 1–1The Eradication DebateSmallpox was one of only a handful of diseases considered good candidates for elimination or eradication.(Elimination refers to reducing the number of new infections to zero in a defined geographical area, withcontinued interventions required to prevent reestablishment of transmission.
Eradication means permanently reducing the number of new infections worldwide to zero, with interventions no longer needed.) Few human ailments meet the six preconditions for disease eradication:,
1. No animal reservoir for the virus is known or suspected.
2. Sensitive and specific tools are available for diagnosis and surveillance.
3. Transmission from one individual to another can be interrupted.
4. Nonlethal infection or vaccination confers lifelong immunity.
5. The burden of disease is important to international public health.
6. Political commitment to eradication efforts exists.
During the 1900s, global efforts were made to eradicate seven diseases: hookworm, yellow fever, malaria,
yaws, smallpox, guinea worm, and polio.7 Smallpox was eradicated in 1977. Today, worldwide campaigns
against polio continue, with the hope that it will become the second disease to be eradicated. Interventions against guinea worm continue in sub-Saharan Africa, the only remaining endemic area.
Benefits of Elimination and Eradication
The most obvious benefits of disease eradication are that no illness or death from that disease will ever
occur again.8 Control programs are no longer needed, and this allows resources, both monetary and otherwise, to be redirected. These benefits result from the two basic objectives of eradication programs: to
eradicate the disease and to strengthen and further develop the health system.9
The monetary benefits of elimination and eradication can be substantial. One study estimated that if measles were eradicated by 2010, and vaccination could be discontinued, the United States could save $500
million to $4.5 billion.10 Another study estimated that seven industrialized countries (Canada, Denmark,
Finland, the Netherlands, Spain, Sweden, and the United Kingdom) would save between $10 million and
$623 million if measles were eradicated, even assuming that measles vaccination would continue.11
(continued on next page)
Other benefits of elimination and eradication relate to the campaigns themselves. Surveillance, logistics,
and administrative support are invigorated to achieve a higher standard of performance. If designed with
system strengthening in mind, elimination and eradication programs that benefit from high political visibility and financial support can improve the quantity and quality of health workers, bolster health infrastructure, foster coordination among donors, and contribute to other improvements in the backbone of public
Potential Pitfalls of Elimination and Eradication Campaigns
Efforts to eliminate or eradicate disease also can inadvertently cause major problems. The near-term risk
is that the focused efforts to deal with one ailment detract from a health system’s ability to deal with many
other causes of human suffering. Particularly in global eradication programs, where large outlays may be
required to reach populations in which the disease in question is of relatively small importance (compared
with other illnesses), the diversion of resources can be detrimental; local political commitment can waver
in the face of pressures to address higher-priority health concerns. This risk can be—but is not always—
countered by explicit attention to how the eradication campaigns can strengthen the basic functions of the
health system, such as surveillance, human resource development, management, and others. The longerterm risk is that it may be impossible to obtain all the promised benefits because vaccination (or other
preventive actions) must continue, even if the program is successful in reducing to zero the incidence of a
disease. As the US Institute of Medicine’s Forum on Emerging Infections put it, even in developed countries where infections have been eradicated or nearly eradicated, mass vaccinations will probably have to
be maintained at very high levels for an extended time in order to protect against reintroduction from areas
where poverty, civil unrest, or lack of political will impede high vaccination coverage and sustain endemicity.6 In fact, without continued preventive measures, eradication can put the world’s population at risk if
there are changes in the natural history of the disease, if the scientific community is wrong about the effectiveness of immunization or other preventive measures, or if bioterrorism is a threat.
Being prepared for outbreaks of long-gone diseases comes at a price. In 1997, for example, the US
Department of Defense contracted with BioReliance to deliver 300,000 doses of an improved smallpox
vaccine for $22.4 million (about $70 per dose), and in 2000, the CDC contracted OraVax to manufacture
40 million doses of smallpox vaccine beginning in 2004 and continuing through 2020 at a cost of $8 per
dose, though this schedule was altered after the 2002 anthrax outbreak. By the end of 2002, the Bush
administration had set aside $500 million to procure 300 million doses of smallpox vaccine.12 As of January 31, 2003, some 291,000 doses were released by the CDC to vaccinate first responders in the United
States against smallpox, and $42 million was appropriated to establish the Smallpox Vaccine Injury Compensation Program, even though smallpox was eradicated almost 30 years ago.13
The Eradication Debate (continued)
really spread among donors only in 1974, when just fiveendemic countries remained, thus triggering large donations and more funds.Impact of EradicationThe eradication of smallpox continues to inspire andhighlights the importance of cooperation, national commitment, leadership, reliable epidemiologic information,and appropriate technology. The particular features ofsmallpox, both in terms of the disease and the vaccine,which made the disease a prime candidate for eradication, may not be found in other diseases. And recentevents have highlighted the potential of an eradicateddisease becoming a bioweapon (see Box 1–1).nbe adapte to other circumstances. The lasting legacyto public health of the smallpox eradication campaignis the demonstration of how the combination of goodscience, outstanding organization, focused monitoring,and international commi