COLLABORATIVE RESEARCH ON TROPICAL DISEASES (1985)  p. 9 of 12

G. THE SMALLPOX ERADICATION CAMPAIGN

          Thomas Jefferson in 1808 wrote to Jenner, discoverer of the smallpox vaccine, that because of his discovery “in the future the peoples of the world will learn about this disgusting smallpox disease only from ancient traditions.”  Jefferson was right, of course, but his prediction took 170 years to come true. That may not be a long time in the span of a disease known to have scarred one of the Pharaohs, but one may assume it is longer than Jefferson had in mind.

          The smallpox campaign was not primarily a research effort, although applied research was essential to its success, nor was it an American accomplishment, although D.A. Henderson and the CDC played pivotal roles. It was primarily a triumph of management, the use of scarce resources through international collaboration to accomplish an historic task. It is of interest to this study as an example of the effective use of American scientific, technological and leadership capabilities in an international context.

          The eradication campaign is not put forward as a model approach to all, or even very many, disease problems. Smallpox had several characteristics making it susceptible to eradication that are not common to many other maladies. The disease is easily diagnosed and relatively slow to spread. Protection can be conferred with a single application of an easily administered, highly stable vaccine. There are no vectors to worry about and no animal reservoirs of the virus.

          Eradication of most other diseases for which there is no natural reservoir other than man is unlikely at this time for several reasons, including the lack of a vaccine offering long-term protection with one or two injections, clinical features which make detection and diagnosis difficult, and epidemiological characteristics such as the rapidity with which measles can spread. Political commitment to eradication can be difficult to obtain when the disease in question is a relatively minor health problem in a poor country.

          A few other diseases may be susceptible to eradication efforts, according to William Foege, former head of CDC and an active participant in the smallpox campaign. Guinea worm could be gone in ten years, and it should be possible to halt the human transmission of yaws by the end of the century. The technology to get rid of polio is available, but we may lack the necessary determination.

          The biggest, most costly eradication campaign on a global scale was launched by WHO in 1955 against malaria. The discovery late in World War II of DDT gave rise to hopes that the anopheline mosquito, the main malaria vector, could be eliminated because of its tendency to rest on a vertical wall after taking a blood meal. If the walls of houses could be coated with DDT, the mosquitoes would die and transmission of the disease would be interrupted. Dramatic reductions in the disease were observed in Sardinia, Venezuela and other areas where DDT campaigns were mounted. In 1950 the Pan American Sanitary Bureau decided to undertake a regional eradication program at the urging of its director, Fred L. Soper, who turns up so often in these pages.

          WHO followed the PASB lead five years later, not because of the success achieved in the region, but because the first scattered reports of mosquito resistance to DDT began to filter in. The threat of widespread vector resistance was a goad to action, although many remained unconvinced that eradication was a feasible objective. Indeed, the campaign could not have achieved its stated objectives because WHO made no serious efforts to eradicate malaria south of the Sahara. Nevertheless, its program went on for nearly 20 years, mostly with American financing.

          WHO adopted a standard approach for 11 endemic countries, creating a separate and distinct malaria eradication service, with higher-quality and better-paid staff than others in the health services. They were to perform no duties unrelated to malaria, with the consequence that their organization, which could have been very useful in the smallpox campaign, was almost uniformly uncooperative. Funds devoted to eradication were often diverted from malaria control programs, professional efforts of long standing to curtail the spread of the disease. Research on alternative strategies was seriously neglected.

          The malaria eradication campaign set the scene for the smallpox eradication campaign. Malaria drained the reservoirs of funds and enthusiasm before they could be tapped by the smallpox effort. UNICEF, for example, contributed handsomely to the malaria campaign but very little to smallpox. Senior officials, including those at WHO, were skeptical of the smallpox campaign and concerned about another failure. Particularly after the malaria embarrassment, WHO generally opposes vertical campaigns, those shaping action around a specific disease.

          Under the circumstances, it is not surprising that the smallpox eradication campaign got off to a slow start after it was adopted at the 1958 World Health Assembly (WHA). It was a Russian initiative, the Americans being firmly behind the malaria effort and contributing 95% of its voluntary contributions. The Soviets, having just returned to WHO in 1957, were not involved in the malaria effort, so they may have wanted a cause to call their own. They themselves had reported no cases of smallpox since 1938, having rid their country of the disease by making vaccination compulsory beginning in 1919. Sharing a long common border with endemic countries such as China, Afghanistan, and Iran, it was greatly in their interest to eradicate the disease at least from their region. In addition to proposing the resolution for WHO commitment to eradication, they pledged to release 25 million doses of freeze-dried vaccine for the campaign.

          The Assembly adopted the Soviet resolution, which called for the vaccination or revaccination of 80% of the population within five years. The primary responsibility for implementing this objective was to rest with the individual countries, however. WHO budgeted only for one fulltime medical officer, with 18 months’ consultant time, an international conference, two training courses, and the distribution of donated vaccines.

          Five years later, the campaign appeared to have achieved very little. Many countries lacked the administrative structure to execute a massive vaccination program. Some found smallpox a low priority in terms of the health status of their populations and refused to devote resources to it. There were shortages of reliable vaccine supplies, and WHO itself was not pushing the campaign.

          In fact, individual countries had achieved more than was recognized, especially China, where the last case of smallpox occurred in 1960, a record not known or properly documented until 1978, five years after China joined WHO. Vietnam, Kampuchea, Laos, Iraq, Saudi Arabia, Democratic Yemen and Iran halted transmission through vaccination campaigns during this period, but pilgrims and laborers from southern Asia repeatedly reintroduced smallpox to the Middle East. In the Western Hemisphere, Ecuador and Bolivia succeeded in interrupting transmission, but Peru became again endemic from the spread of the disease from the Amazon area of Brazil. Brazil itself made little effort to eradicate the disease, in part because the disease was the mild form of smallpox with a death rate of no more than one per cent.

          Despite progress in some areas, the information system of WHO was so unreliable that not more than 5% of all cases were being reported, according to later estimates. In Africa, then in the midst of the process of independence, health problems were receiving little attention, and smallpox was seldom a priority.

          By 1965, pressure was building within the WHA for WHO to take a more active role in smallpox eradication. The Soviet Union was impatient with the lack of progress on a campaign they had initiated, and two other developments added to US interest in the idea. These were the development of a jet injector for smallpox vaccinations, and the commitment by AID to support a smallpox eradication program in eighteen west and central African countries.

          The jet injector, as originally conceived, would not serve a smallpox vaccination campaign in the field because it was electric-powered, and delivered inoculations subcutaneously rather than intradermally as required. In 1962, Aaron Ismich of the US Army developed a special nozzle that permitted intradermal inoculation and a hydraulic power system operated by a foot pedal. CDC demonstrated the efficacy of the modified device, which could vaccinate as many as 1,000 persons per hour at one-third the cost of conventional methods.

          The African smallpox program grew out of a faltering AID measles vaccination program launched in Upper Volta and neighboring countries in 1961. Logistical and technical problems arose, and AID requested CDC to assist by providing medical officers to ten countries for six months. CDC had doubts about the long-term value of the measles program because the vaccine cost more than $1.00 per dose, and the host governments would not have the resources to continue the program after the anticipated four years of AID support. Measles spreads rapidly in western Africa, and three years after the vaccination program ceased it could be expected that 90% of children under three years of age would again experience the disease. CDC proposed smallpox vaccination along with measles vaccination, because that could have permanent results, and eventually 20 countries participated in the program.

          With the support of the USA and the USSR, as well as many developing countries, the WHA decided in 1966 on an intensified global eradication program to be supported, in part, by an allocation of $2.4 million from the regular budget of WHO.

          The campaign plan differed from that of malaria eradication in three ways. The campaign in each country would consider available resources, local conditions and the epidemiological situation, rather than follow a set format; it would develop a reporting system for cases at the inception of a campaign rather than after the attack phase was completed; and it would encourage research. The plan retained the basic strategy of reliance on freeze-dried vaccine, augmented by the concept of surveillance.

          Surveillance techniques developed and refined by Alexander Langmuir at CDC had been applied domestically but never before internationally. As applied to smallpox, they involved a systematic approach to detecting possible cases and investigating the source and site of acquisition of the disease. The discovery of the means of transmission was to be followed by an intensive vaccination program in the immediate area. In highly endemic countries, surveillance might have to be deferred until a vaccination campaign in the areas most infected was completed, but could not be delayed until the countrywide vaccination campaign was complete. This strategy, which emerged from experience, proved important to the success of the campaign.

          The need for continuing research in epidemiology and virology was seen as unnecessary by most health officials, including those at WHO, who insisted that the disease and how to combat it were well known; all that was needed was the mobilization of resources and administration of the program. Eventually, agreement was reached to leave research in the plan, but less than $50,000 was allocated for this purpose.

          Overall, an expenditure of $180 million was foreseen, of which $48.5 million would be from international sources. Although the estimates were rough and did not take inflation into account, they were not far off. Between 1967 and 1980, international support in the amount of $110 million was required.

          The timing of the initiation of the AID/CDC western Africa program was fortuitous. By the end of 1966, agreements had been signed with most of the 18 countries, a staff of 50 recruited and trained at CDC, operations manuals developed, and supplies and equipment ordered. The draft manuals for field operations and for the operation and maintenance of the jet injectors were a boost to the WHO campaign. They were soon revised to meet WHO needs and translated into French and Portuguese for use in Brazil and Zaire.

          The eradication campaign as it evolved could be a Cecil B. DeMille epic. It involved 150,000 people working in 50 countries, guided and supported by a WHO headquarters unit of six professionals and between five and ten professional staff at each participating regional office. The story deserves detailed telling, and fortunately it will have it. D.A. Henderson already has a major book in draft, from two of whose chapters most of the information in this document is taken. Here we can attend only to some of the organizational and informational elements of the campaign, and to the role of research.

We need first to understand why many public health officials, including senior WHO staff, remained unenthusiastic about the campaign. They did not think the objective was attainable, believing, as a WHO Expert Committee affirmed in 1964, that eradication required the vaccination of everyone. Given the fact that smallpox was then endemic in many of the most primitive arid remote areas of the world, eradication seemed an unattainable goal.

          Secondly, the malaria eradication campaign was already in trouble in 1966, and was deeply resented by the regular health services. Proponents of the malaria campaign had argued that it would contribute to the development of the basic health services, but in most countries it remained an autonomous authority. There seemed no reason to believe the smallpox enthusiasts would have different results, despite their intention of relying on existing health service personnel for the execution of the campaign. WHO officials perceived that international resources could become subject to faddish campaigns against particular diseases, one after another, with the result that the basic health infrastructure in many countries would never satisfactorily develop.

          In some countries, the governments were reluctant to participate. Such reluctance on the part of governments could be explained, before the intensified campaign got underway in 1967, by local priorities for the use of scarce resources. After that date, however, the availability of funds in the WHO budget meant that for most countries, particularly in Africa, it was no more costly to participate in the eradication program than to continue control programs. WHO was able to supply vaccine, vaccination instruments, supplies and technical assistance, and a limited number of vehicles.

          Staff quality is key to the success of any venture. At the outset of the intensified campaign, in 1967, the international staff consisted of 15 in WHO and the 50 CDC personnel in western Africa. Gradually the international cadre grew in size and quality. Emphasis was on youth and vigor as well as technical competence, because duties frequently involved travel into the interior on foot or mule back. The number of international staff never exceeded 100 at any one time, but nearly 700 took part at one time or another. An esprit de corps developed among them that still opens doors when veterans of the eradication campaign encounter one another.

          The sources of able staff were varied and sometimes surprising. A Soviet Vice-Minister of Health, for example, identified a group of able epidemiologists from his ministry and permitted Henderson to interview and select five to join the program. Able contingents also came from the High Institute for Public Health in Alexandria and from OXFAM, a British voluntary organization. The CDC offered five full-time staff when an unexpected smallpox outbreak occurred in Bangladesh, and was ready on short notice to meet specialized staffing needs. National programs themselves were valuable reservoirs of experienced staff that could be tapped for international service. Outstanding people were recruited from Afghanistan, Bangladesh, Brazil, India, Indonesia, Nepal, Sudan and Togo. As time went on, the smallpox group came to be known as among the best and most dedicated of any in international service. They were kept that way by careful selection and the easing out of those who wearied of extensive travel and heavy responsibilities.

          The headquarters unit in Geneva had responsibility for global strategy and coordination, mobilizing international resources, and stimulating needed research. They traveled at least a third of the time, and sometimes spent 50-70% of their time outside Geneva. Although four additional medical officers were later authorized, conditions in Ethiopia and Pakistan at the time required their full-time assignment there.

          Rapid and effective communications are essential to a global scientific enterprise such as this. Campaign workers in all participating countries needed to be kept abreast of progress, not only for morale purposes but in order to learn of field observations elsewhere, successful innovations and failures, and the results of research that could benefit their programs. The surveillance system, new to international practice, was founded on the notion of rapid and accurate communication of knowledge about the origins and incidence of the disease. National policy-makers, WHA delegates and the public at large needed to know about the campaign and its prospects in order to generate the necessary support. The energy and ingenuity required to generate these information flows in an international agency are exceptional.

          The unit began in late 1967 to issue quarterly surveillance reports, mimeographed documents sent to all international staff and national program directors dealing with smallpox. After 1968 it was agreed that a brief report might be inserted periodically into the Weekly Epidemiological Record (WER) a publication in which all quarantinable diseases are to be listed based on telegraphic reports from national authorities. This proved to be a boon for the smallpox unit because WER is printed rather than mimeographed and is distributed to 5000 health officials and others throughout the world.

          Information in the WER was limited to epidemiological data, and the campaign needed access to additional information, such as research results from laboratories, the conclusions of expert committees, and so on. For that purpose, the Geneva unit packaged and mailed information on a bi-weekly basis to 150 persons in the campaign.

          As a policy, the smallpox unit cultivated the mass media. Reasoning that voluntary donors, governments and policy-makers in endemic countries were more likely to be responsive if the program were widely known, the unit took every opportunity to interest the media in the campaign. They even arranged trans-Atlantic press conferences, with correspondents in New York, Washington, London, Geneva and Delhi interviewing Henderson in Geneva. One particularly helpful newspaper series, written by Lawrence Altman for the New York Times, was based on an extended tour though India and Bangladesh in 1974. Correspondents from the Soviet news agency TASS, Japan, and the United Kingdom covered the program closely.

          In addition to the printed word, communication was advanced by frequent staff travel from headquarters and some regional offices and by annual conferences. The conferences began as sessions where national reports on progress were read, but soon the format was changed to focus on specific findings and strategies employed in particular national programs. The events were important means for sharing experience and building the program’s momentum.

          In addition to good communications, the keys to success were found in imaginative management, improved technology, and applied research. Managerial improvisation characterized the program. As an example of the campaign’s flexibility, the operations manual never got beyond the draft stage. Changes were made as conditions required, but nothing was cast in concrete.

          This flexibility did not imply carelessness in conducting the campaigns. Accurate reporting, rigorous surveillance, and prompt response to outbreaks were essential to ensuring that the disease was actually eradicated rather than temporarily set back. Over the years, the campaign solved many logistical and resource problems (almost from the beginning it was short of funds and vaccines), but the recounting of these must await publication of Henderson’s book. Enough has been said here to reveal that this program was no ordinary UN or WHO activity. It was characterized by a high level of resourcefulness, imagination and a certain irreverence concerning standard operating procedures.

          One of the principles of the campaign was that no endemic country should be constrained by a shortage of vaccine or vaccination devices. This was a difficult rule to live up to because of another principle that no vaccine should be purchased by the program. Originally it was thought that the 25 million doses annually donated by the USSR, plus vaccine supplied bilaterally as in western Africa, would suffice.

          An investigation in 1967 and 1968 of the source and quality of vaccine available revealed that few labs were producing vaccine of acceptable standards, most did not test their vaccine for stability, and some assessed potency simply by vaccinating a group of young children.

          To ensure the availability of adequate supplies of effective vaccines, the programs provided assistance to production laboratories in endemic countries, developed vaccination devices requiring less vaccine than conventional devices, and actively solicited contributions from producer countries.

          The conventional scarification technique of vaccination, familiar to those of us with dime-sized indentations on our upper arms, used a whole drop of vaccine. A vial of 0.25 ml contained enough vaccine for 20-25 persons. The jet injectors used only a third of that amount. Jet injectors proved to be of limited value outside of western Africa, Zaire and Brazil, however, because of problems of maintenance and repair. In Asia, where vaccination house to house was common, jet injectors were impractical. A new bifurcated needle that could hold a tiny amount of vaccine by capillary action between its tines was becoming available in the U.S. Field trials in Kenya, Egypt and Bangladesh demonstrated that it could be used effectively to vaccinate 100 or more persons with a single 0.25 ml vial.

          The research dimensions of the campaign are of particular interest to us. In 1966, many in WHO and outside it did not believe further research was necessary, yet Henderson says without doubt that the campaign would not have succeeded without the adaptations of strategy made possible by research.

          The research agenda was by no means clear in 1967, except for the critically important problem of ensuring that there was no animal reservoir of the variola virus, the unexpected factor that wrecked Rockefeller Foundation plans for yellow fever eradication in the l930s.  Research on this problem continued for many years, revealing that smallpox was dependent on a human host, but also discovering and characterizing monkeypox, a disease that cannot be sustained by human transmission alone.

          Other research accomplishments included refinement in the epidemiology of smallpox that necessitated changes in campaign strategy. It turned out that even in highly endemic areas, the disease was not usually so widely disseminated as supposed, nor did it spread as rapidly. The most elegant and comprehensive epidemiological studies, incidentally, were conducted in 1965-66 by the University of Maryland ICMR in Lahore. These findings were not utilized by the eradication campaign, however, until campaign researchers rediscovered them later.

          Other accomplishments included improved techniques for sample survey assessment, better vaccine production and testing procedures, the adaptation of vaccination technology, and genetic mapping of variola and vaccinia viruses, which provided new insights into the relationship of different viruses. The vaccination of newborn children was demonstrated to be effective, altering concepts of the efficacy and duration of vaccinal immunity.

          For the most part, it was operational research, learning and adapting procedures and technology while pursuing the campaign. Everyone was part of it, in the sense that improved procedures originated from the national programs as well as from laboratories with research titles. Important contributions were made by CDC, the Institute for Virus Preparations in Moscow, the National Institute of Health in Japan, the Department of Virology of St. Mary’s Hospital School of Medicine in London, the Rijks Institute in the Netherlands, Wyeth Laboratories in the U.S., the Public Health Institute in Bangladesh, and the Pakistan Medical Research Center in Lahore, home of the Maryland ICMR. Most of these contributions were funded from sources other than WHO, but frequently were in response to problems posed by the campaign.

Assessment

          The collaborative framework we used in discussing other models of programs for research on tropical diseases is of limited utility here. The program, being global in nature and achieving total eradication of a disease, is of course the ultimate in collaborative effort and in results.

          The results of the campaign in terms of capacity building for dealing with smallpox is not an issue, but a related question is central to a continuing debate on international health assistance strategies. Is the mobilization of a national health service to carry out a campaign against one or several diseases an effective way to improve the overall competence of the system?  Quite possibly the designation of measurable health objectives, as is possible in well-designed campaigns, is a valuable tool for capacity building.

          The history of the smallpox campaign offers some insight on the usefulness and limitations of WHO as a channel for U.S. funds to combat tropical diseases. It appears from the account that Henderson and his colleagues were successful in spite of WHO, rather than because of it. Yet the campaign itself would not have been possible without WHO.

          The annual World Health Assemblies were invaluable for developing consensus on the need for a global campaign. Standards set by WHO for vaccine became universally accepted. The movement of biological and other materials across national borders is greatly facilitated by WHO procedures. Multilateral pressures on governments to participate in a global effort may be more acceptable than bilateral pressures. WHO involvement seems to represent a necessary, but not sufficient condition, for the success of a global campaign.