House on Fire

by William H. Foege

  There were several reasons why the WHO program had a good chance of succeeding. First, key technological advances made it possible to standardize the quality and stability of the smallpox vaccine worldwide. Up to this time, the production of the vaccine had remained almost a cottage industry in many countries. This meant that while the vaccinia virus—somewhat modified over the years from Jenner’s original cowpox virus—was a great vaccine, it wasn’t consistently great. The potency varied widely. The production process was crude, involving shaving calves, scarifying the exposed skin (scratching or lacerating the skin to make it raw), and painting this raw surface with a substance containing vaccinia virus. The virus would grow on the scarified tissue and then be harvested by raking off the pustular material. The resulting matter was cleaned of extraneous bits of hair and flesh to provide high concentrations of vaccinia virus. It looked as unappetizing as it sounds.

  Much of the resulting vaccine was kept in a liquid form that required refrigeration to remain viable—yet high temperatures were the norm in most smallpox-endemic areas. It was possible to launch effective programs with liquid vaccine, as many areas had shown over 160 years, but it was very difficult. Early in the twentieth century a method was developed for freeze-drying vaccines, permitting them to be stored at room temperature for extended periods. However, there remained the problem of how to convert all the vaccinia manufacturers around the world to this new technology.

  Early in the eradication program, WHO, under the leadership of D. A. Henderson, assembled a panel of experts who came up with a global standard for the vaccine and created a detailed manual for its production as well as how to convert to freeze-drying the vaccine. Consultants were sent out to help countries convert to the new system. Reference centers for testing vaccines were established in Canada and the Netherlands. To fill the gap while all areas of the world were catching up, two dozen countries already producing vaccine of satisfactory quality donated vaccine where it was needed. By 1969, all vaccine used in the smallpox-endemic countries met WHO standards, and by 1973 more than 80 percent of the vaccine in use was being produced by the developing countries themselves.

  A simplified and improved vaccination technique, in the form of the jet injector, also increased the odds of success for the global eradication effort. Up to the mid-twentieth century, most areas of the world were still using the multiple pressure vaccination technique, in which a vaccinator repeatedly pressed a needle, at an angle, through a drop of vaccine placed on the vaccinee’s skin. The needle nicked the skin on the upstroke, created a small injured area where the vaccine could begin multiplying. The procedure is simple but difficult to teach, which meant that take rates varied according to the vaccinator’s skill and even for the same vaccinator under different conditions. The method also required cleaning the skin before vaccination, which meant that vaccinators were encumbered with bottles of alcohol, acetone, or soap and cotton swabs.

  Another method still used in some countries, including India, was the rotary lancet. This brutal instrument consisted of a quarter-inch-diameter wheel with tines attached to a long axle. The wheel was placed on the vaccinee’s skin and the axle was rotated by the vaccinator’s fingers, causing cuts as the tines rotated through a drop of vaccine, giving the vaccine access to underlying tissue. The result, once the vaccine took and the lesion healed, was a large vaccination scar. Many vaccinators would do two or three vaccinations on the vaccinee’s forearm or upper arm to increase the chances that one would take. In fact, if the vaccine was not potent, none of the attempts would provide a take; if it was potent, the person was likely to end up with more than one hot, angry vaccination lesion developing at the same time.

  Figure 3. Rotary lancet, a vaccination device used in India until the early 1970s. CDC/Bruce Weniger; James Gathany

  In 1960, Aaron Ismach, working with the U.S. Army, had developed a foot-operated jet injector, called the Ped-O-Jet, that was an efficient work of art. It consisted of a hydraulic foot pedal that, with a single step, depressed a piston releasing just enough pressure for one vaccination. The vaccinator placed the pistol-like portion of the jet injector against the vaccinee’s skin and pulled the trigger, releasing a plunger that delivered the vaccine intradermally, between the layers of the skin. No needle was involved. A 50 cc bottle attached to the injector could provide five hundred doses of 0.1 cc smallpox vaccine.

  The jet injector’s tidy and reliable delivery of a packet of virus allowed for uniform take rates (approaching 100 percent) even with different vaccinators. The technique was simple and quickly learned, and because there was so little wastage, the Ped-O-Jet was economical. The 1964 Tonga study I had participated in had determined an effective dilution rate for the vaccine, which meant additional savings.

  Figure 4. Ped-O-Jet, the delivery instrument for millions of vaccinations in Africa in the 1960s. CDC/Susan Lindsley

  The Ped-O-Jet, introduced into the West Africa program in late 1966, made it possible to vaccinate one thousand people in an hour. On one occasion, while vaccinating in a large prison where the prisoners moved past the injector in a highly disciplined way, we were able to deliver six hundred vaccinations in less than thirty minutes. During one very long day in Enugu, I did 11,600 vaccinations.

  The Ped-O-Jet’s speed offered little advantage if vaccinators moved house to house. Instead, arrangements were made with a village ahead of time, and on the designated day, the vaccinators would arrive and set up the site. People often milled around the site watching the procedure before committing to participate. Even after their own vaccination, they would stay around to watch others go through the line, pressing in to the point where we could no longer move people past the injector. Crowd control was essential. If the site was under a tree, we delineated the route people should take with ropes wrapped around three-foot metal stakes. If it was in a church or school, the vaccinator would be positioned immediately inside the doorway so only one person at a time could pass by.

  In addition to these technological advances, the new world order that had emerged after World War II, particularly the development of the United Nations and WHO, made it practical to consider and carry out global objectives. The idea of a global perspective was not new. The Greek historian Polybius understood two thousand years ago that nothing happens in isolation. He said the world must be seen as an organic whole, and he provided examples of events in Africa impacting Athens. By the mid-twentieth century, a global view could truly include the entire world. The UN and WHO made it possible, for the first time in history, to select a global health objective, organize to reach that objective, and apply the greatest resources to the largest problems.

  A global perspective is essential to dealing with infectious diseases, since diseases have no regard for national boundaries. And, it turns out, what’s good for the global community is good for the individual country. For the United States, which had been smallpox-free since 1949, the investment in global smallpox eradication amounted to just onequarter of the annual expense of vaccinating U.S. children and maintaining a program to check the vaccination status of people coming into the country.

  A less tangible yet no less important ingredient in smallpox eradication was simply the belief that it could be done. In fact, in retrospect, the belief that it could be done seems like the most important factor in the global eradication effort. The technology and the infrastructure were necessary, but the planning and hard work required to use them to full effect rested on the faith that eradication was possible. We all know the adage that some things have to be seen to be believed. In fact, the opposite is often true: some things have to be believed to be seen.

  The fact of smallpox was so ingrained in human experience that we had our work cut out for us to convince people that eradication was not a wishful fantasy. The shift from doubt to belief was not unlike a religious conversion; it involved not just facts, but emotion, too. A person suddenly transformed by the vision of what was possible could not be stopped. One dramatic examp
le was Dr. George Glokpur, head of the smallpox eradication program for Togo. In 1967, he attended a three-week course on smallpox eradication held at the CDC in Atlanta. After the first week, he decided to go home. By then, he was convinced he could do it and did not want to wait an additional two weeks before getting started.

  As more geographic areas became free of smallpox, it became easier to transmit this belief. Like a communicable disease, the belief in smallpox eradication was infectious, with an incubation period, various degrees of susceptibility, and an increasing rate of spread that finally infected many who came in its path. Once this condition was shared by a critical mass of people, no barrier was insurmountable.

  Even though we were setting out to do something never accomplished before, we believed, from the beginning, that eradication of this disease was possible. What we did not know was that we yet lacked a key ingredient: a more effective primary strategy. This final element was fortuitously discovered at the very outset of the program.

  CHANGING THE PRIMARY STRATEGY

  As the CDC smallpox eradication teams established programs in West and Central Africa in late 1966 and into 1967, they followed the same plan that vaccinators had followed for seventeen decades: to vaccinate as many people as possible. This method provided direct protection for the person vaccinated and aimed to accomplish “herd immunity”—indirect protection for unvaccinated persons who would have acquired smallpox if the vaccinated person had become sick. There is no question that mass vaccination could work, as was demonstrated early on in Ceylon (now Sri Lanka) and later in Bolivia, China, and in many countries of the industrialized world.

  The problem with mass vaccination is that an exceedingly obsessive program is required to make inroads into the last 20 percent of any population. The segments of the population most difficult to reach with vaccine—the drifters, the marginalized populations, beggars, itinerant workers—are often the ones most at risk of both getting and spreading the disease. Therefore, surveillance and containment of outbreaks was seen as the next step after mass vaccination. Add to this the high population densities in urban areas and it becomes clear that herd immunity is easy in theory but not fully effective in practice. Even with a good program, a critical mass of unprotected persons can accumulate, and the vulnerability of such unvaccinated pockets often leads to an explosive outbreak when the smallpox virus is reintroduced. This problem is well recognized in public health. Yet at the time it was the best plan anyone had. My CDC colleagues and I working in Eastern Nigeria embraced this strategy, and during the final months of 1966 began making plans to pursue it with determination.

  Serendipity provided a chance for us to rethink the eradication strategy before the year ended. On December 4, 1966, Hector Ottemüller, a longtime missionary in the Ogoja area, contacted me by radio. There was an outbreak of smallpox in the village of Ovirpua, in the Alifokpa area of Ogoja province, some ninety miles northeast of Enugu, and Hector was asking if the smallpox unit could help. Ottemüller was a minister by training, with a patriarchal bearing enhanced by striking white hair and a white beard. His consuming interest lay in improving the lives of the people in his rural area. He was involved in agriculture and water supply schemes, although the people also called upon him for health advice. Thus it was not surprising that he was the first to receive the report of a rash disease feared by all in his area.

  The village of Ovirpua was some miles from a road, but Dave Thompson and I managed to get hold of two Solex motorbikes, which were ideal for this work. Made in France, they are essentially sturdy bicycles with a small motor that engages directly on the rubber of the front tire, and they are lightweight enough to be carried under one arm across logs spanning creeks. We arrived at Ovirpua in mid-afternoon. The first person I examined was a young man in his twenties, and there was no question about the diagnosis. We examined and questioned four other people who had the disease. We vaccinated the patients’ family members and other villagers in immediate contact with them.

  Figure 5. First smallpox patient seen in Ogoja, Nigeria, outbreak, December 4, 1966

  That night, Thompson and I and several missionaries assembled around kerosene lamps in the house of a missionary who lived in the area. We talked through the problem while educating the missionaries about the sobering situation we were facing. We knew this was smallpox but we did not know its extent. How many villages were involved? How many people were sick and how many were in the incubation period? Had it just been introduced to the area, or had it been smoldering for some time?

  The standard response was to vaccinate everyone within a certain radius while attempting to determine the extent of the outbreak. However, we did not have enough vaccine to do this. The program was so new that supplies had not yet arrived in quantity, and there was no likelihood of quickly receiving more. How could we most efficiently use the limited amount of vaccine we had on hand?

  It was tempting to consider diluting the vaccine so we could vaccinate more people. However, history showed that this was a risk that should not be taken. In 1962, Dr. Robert Hingson, founder of the Brother’s Brother Foundation, committed to vaccinate Liberia’s population of about 1.3 million people against smallpox. A massive campaign was undertaken, but the program organizers found that they had underestimated their vaccine needs, so they diluted the vaccine fifteen-fold. A subsequent assessment by WHO indicated that only 60 to 70 percent of the population had successful primary vaccinations, and 325 cases of smallpox were reported in Liberia the same year, after the campaign ended.3 Some people who had been vaccinated subsequently got smallpox, probably because of the vaccine dilution. If we now did the same thing, we could be leaving unprotected an unknown number of people who were directly in the viral path.

  Forced to look for another solution, we raised the question: if we were smallpox viruses bent on immortality, what would we do to extend our family tree? The answer of course was to find the nearest susceptible person in which to continue reproduction. Our task, then, was not to vaccinate everyone within a certain range but rather to identify and protect the nearest susceptible people before the virus could reach them.

  What we knew about the virus’s behavior also figured into our strategy. The smallpox virus poses little risk to people other than its host during the incubation period. It is only when the characteristic sores form on the skin and mucous membranes that the virus can escape the host and seek new victims. Spread is also easiest during the early days of rash, when the number of virus particles on the body’s surfaces is large and people may not yet recognize the disease. The potential for spread decreases as people become wary, and as the host’s immune mechanisms respond and the number of viruses on the patient’s exterior declines. Spread is most likely within the first week of clinical symptoms and is probably rare after three weeks.

  We discussed the risks of spread. The highest spread potential was obviously in the home, but early in the illness the patients might also have been in contact with visiting relatives or might have attended one of the region’s markets. We could use the missionaries’ knowledge of market patterns and family patterns to make predictions about high-risk areas for spread, but first we needed to know where the virus was at that moment.

  Acquiring this type of intelligence would be difficult even in a country like the United States. It seemed absolutely impossible in rural Africa. However, the missionary community’s own support system offered an answer. There were no telephones, so every night at 7 P.M., the missionaries turned on their shortwave radios and checked in to make sure that no one was in need of assistance.

  We weren’t that hopeful, but it was worth a try. That night we got on the radio with missionaries up to some thirty or more miles distant, explained the situation, and, with maps in front of us, divided up the area. We asked each missionary to send runners to every village in his assigned area to ask if anyone had seen cases of smallpox.

  The following night Thompson and the local missionaries and I again got on the radio,
and to our joy and amazement were given the precise information we needed. Only four villages had smallpox cases at that moment. The rest were free of the disease.

  Our plan was straightforward. First, we vaccinated the currently infected villages, where some people were probably already infected even if they had not yet developed symptoms. For those recently exposed, vaccination would greatly reduce the disease’s impact, if not prevent it. Those exposed even two weeks earlier would still get smallpox, but they would be surrounded by vaccinated people, making further transmission of the virus very difficult. If we were fortunate, it might even stop transmission totally.

  Second, based on the missionaries’ knowledge of where the patients and their families usually traveled, we made some informed guesses regarding other places where the virus was most likely incubating. We identified three, all within a fifteen-mile radius, and decided to use the remaining vaccine there. We could not know as we vaccinated these three additional areas that smallpox was already incubating in two of them. By the time clinical cases were detected in these two places, the remaining population was already protected—and smallpox was stopped in its tracks. The outcome was the complete cessation of this outbreak.

  Figure 6. Patient outside the infectious disease hut near Abakaliki, Nigeria, 1967