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October 9, 2008

Lessons learned in the battle against smallpox

While the international effort to eradicate smallpox ranks among the 20th century’s greatest health achievements, the road to success was quite bumpy, according to the global health expert who led the campaign.

“This was a program that almost wasn’t launched, it was soundly forecasted to fail, but it miraculously succeeded. It was a remarkable victory for international public health. But on more than one occasion, it was a very iffy situation,” said Donald (D.A.) Henderson, distinguished scholar at the Center for Biosecurity of UPMC and a professor at the Graduate School of Public Health (GSPH) and the School of Medicine.

Henderson, who has been awarded the Presidential Medal of Freedom, the National Medal of Science, the National Academy of Sciences Public Welfare Medal and the Japan Prize, among many other honors, gave the GSPH-sponsored 2008 John C. Cutler Memorial Lecture in Global Health on Sept. 23. His address, “The Eradication of Smallpox: What We Should Have Learned … but Didn’t,” traced the history of the 10-year effort to rid the planet of one of its oldest banes.

Before the World Health Organization’s (WHO) effort succeeded — the last naturally occurring case of smallpox was treated on Oct. 26, 1977 — the disease had been a scourge on humankind dating back at least to the age of the pharaohs, more than 3,500 years ago, said Henderson. The disease had claimed more than 300 million victims in the 20th century alone.

Smallpox is an acute contagious disease caused by two forms of the variola virus, variola major, which cost the lives of about 30 percent of those who were infected, and variola minor, which rarely was fatal. The disease most often was transmitted from person to person by infected air droplets spread in face-to-face contact with an infected person. The incubation period for the variola major virus usually was about two weeks, during which the disease was not contagious, followed by an onset of severe flu-like symptoms, Henderson explained.

Two to three days later, a rash appeared, typically beginning on the face, followed by lesions around the nose and mouth that progressed to pustules. A week or two after that, the pustules would form scabs, which almost always left permanent scars. Those who survived infection became permanently immune to the disease.

“Smallpox also can cause blindness. In fact it was the largest cause of blindness in India as late as 1975,” Henderson noted.

In the first half of the 20th century, international efforts to eradicate other diseases — hookworm, yellow fever, yaws and malaria — had failed for a variety of reasons, Henderson said, including lack of funding and staff. Similarly, an earlier effort by the then-fledgling WHO to eradicate smallpox failed due to a dearth of support. “In 1952, Brock Chisholm, the first director-general of the World Health Organization, said ‘Let’s get smallpox eradicated.’ It would be a world program of importance and value to every country and it would demonstrate the importance of the WHO to every member state,” Henderson said. “It seemed like a good idea. But there was prominent opposition in the United Kingdom and the United States, both of which said it was not economical and we can’t do it. So they buried it.”

In 1966, the World Health Assembly, the decision-making body for the WHO, asked Marcolino Gomes Candau of Brazil, then WHO’s director-general, to come up with a plan to launch a new effort.

Henderson, then working with the Communicable Disease Center (now the Centers for Disease Control and Prevention), was called in to draft the plan.

“We came up with a 10-year program, which the director-general said would be funded at $2.4 million a year,” Henderson said.

But many of WHO’s member states did not endorse the plan, with most citing infeasibility, he said. “Another group of primarily industrialized countries said: ‘We’ve put in enough money and that money should be going into industrialization. We will not put in any more money to accommodate smallpox.’”

The program was approved by a slim two-vote margin, the first of many hurdles in the eradication effort, Henderson said.

“The director-general, given the failure of the malaria effort, was feeling pressure that if this effort failed it would jeopardize WHO’s credibility,” he said. “So he then approached the U.S. surgeon general and said, “I want an American to run the program, because if this goes down the tubes I want it to be seen that the Americans can be held accountable.”

Henderson was persuaded by the surgeon general to lead the effort from WHO’s headquarters in Geneva.

“We were better able to estimate the state of smallpox [in 1967] by doing surveys and so forth. There were about 10 million-15 million cases and 2 million deaths. Forty-three countries reported cases. The population of endemic areas was somewhere over 1 billion people,” Henderson said.

The task to eradicate smallpox was daunting, particularly given the resources.

“The $2.4 million budget wouldn’t even cover the vaccine we needed,” he said, although countries such as the United States, the Soviet Union, Indonesia, India and Brazil eventually donated vaccine to the effort.

“On the program staff in Geneva, I had three other medical officers, two administrators and three secretaries. That was the total staff, and it never got better. We had one regional adviser in each of the four WHO regions that had cases,” he said.

The total staff doing vaccinations in the field, mostly young volunteers from organizations such as the Peace Corps, topped out at 150,000.

“Most of the people we had working hard in the field were quite young, and they refused to believe you couldn’t get rid of smallpox. They were forging ahead, a small group of young people who were able to make a huge difference. That’s worth thinking about today as we look at global health issues,” Henderson said.

What the team also had going for it, he said, were certain characteristics of the disease itself. “What was unique about smallpox, and why we thought it could be eradicated, was that man was the only host. There was no animal reservoir at all. It spread in a very limited time. From the time the individual first developed a rash and then he got scabs, he would be either immune or dead. If immune, he was not a carrier after that. Also, you knew where the outbreaks were because of the rash, and if there weren’t enough people in an area for the virus to keep going, it would die out on its own,” Henderson said.

“Finally, we had a highly stable vaccine and you only needed one dose. By stable I mean you could keep it at 98 degrees [Fahrenheit] for a month. It had to pass that test, as a matter of fact, before it could be used in the field,” he added. “We found that the average vaccinator could easily vaccinate 500 people a day. That was sustained pretty much throughout the program.”

The field team’s strategic goal was to vaccinate 80 percent of the people living in areas where the smallpox was known to have occurred. “Why 80 percent? We’d seen one study of vaccinations done in Ghana where they found they could get 80 percent of the population, so we said 80 percent,” Henderson said.

“Actually, when we got going well, we discovered we could easily get 90 percent, but only if you worked with the community, if you worked with the mayor and the police chief and the school teachers and the religious leaders, then they would turn out huge numbers. That was one of the most important lessons we learned.”

The vaccinators also were aided by the development of the bifurcated needle, which had many benefits.

“We’d been vaccinating for years, usually with a drop of vaccine on the arm that’s pressed into the skin with a needle. If you pressed too deeply, [the puncture] would bleed and wash out the virus, and if you didn’t press hard enough, it wouldn’t go in and you didn’t get it to take,” Henderson explained. “But then along came one of the great discoveries: the bifurcated needle. You had two prongs and did 15 or so rapid punctures. Surprisingly, this wasn’t very painful. You only needed one-fourth as much vaccine; training time was 15 minutes, vaccination success rate was over 95 percent, the needles were easily sterilized for repeat use and the cost decreased to $5 per thousand needles.”

A key part of the overall strategy was insisting on quality control, which had been ignored in earlier disease eradication efforts, Henderson maintained. “After we vaccinated a village, we had a team of two people who would come back a week later and take a sample of the villagers and make sure they’d done 80 percent and that in 90 percent of those vaccinated they had been successful, that there was no evidence of the disease,” he said.

This method became especially important early in the program when a large batch of the vaccine was shown to be defective. “We began to realize that less than 10 percent of the vaccine met standards. In some of the vaccine we could detect no virus at all. This was a real shock,” and it meant large numbers of people had to be re-vaccinated, Henderson said.

The team also set up two labs, one in Canada and one in The Netherlands, to test the vaccine’s efficacy, another facet of quality control.

An additional important strategy to contain the disease was establishing a surveillance system for reporting new cases.

“Up until this time, every large-scale smallpox program had been simply mass vaccination. Progress was measured in terms of how many people had been vaccinated. So those figures were reported, but you had no idea how many were left with the disease. So the idea, a brand new idea, was establishing a surveillance system in the countries, so that every health center and hospital would report every week how many cases of smallpox they had.”

Henderson’s team also employed a new containment strategy, where small teams would perform a “ring vaccination.” If a village reported a new case, the team would go and vaccinate all people in the 30 closest houses.

“We found that if you could vaccinate 30 houses in the surrounding area, you could stop the spread of the disease,” Henderson said.

By 1973, of the 43 countries that had reported cases in 1967, smallpox remained in seven. “I say only seven, but that represented about 800 million people,” he said.

Some of those countries presented extra challenges, he added. For example, in 1974-75 Ethiopia went through a Marxist revolution and a civil war to add to the problems of few roads and limited staff.

In 1975, Bangladesh also was dealing with a civil war, in addition to floods and famine. “Their airport was closed, the government health service was being reorganized, the president was assassinated; it was just one thing after another,” Henderson said.

The final challenge was Somalia. “In the summer of 1977, we were within two weeks of celebrating the eradication. We had a TV crew filming what we thought was the last case, and suddenly we got a report from Somalia of two cases,” Henderson said.

“The Somalians were embarrassed that they were the last country — don’t ask me why — and they decided to suppress cases. Our people came in, did searches, but [the Somalians] were hiding all that was going on.”

Adding to the problem was the calendar, because the Muslim hajj was approaching and that meant Somalians in great numbers would be traveling to Mecca.

“But on Oct. 26, 1977, just before the hajj, a Somalian man, Ali Maalin, became the last case of naturally occurring smallpox in the world,” Henderson said.

The critical components for success of the effort were surveillance, quality control, containment and research related to the disease. Such research debunked longheld beliefs, including how smallpox spread. “The textbooks said that smallpox spreads ‘like a prairie fire.’ But our surveillance showed that it wasn’t all over a country, it was more concentrated. It kind of moves around [in close proximity], which is why our containment mechanism was so successful,” he said.

“Surveillance was really epidemiology in action,” Henderson said. “You had an indicator of how well you were doing. We stopped counting vaccinations and started to make a great effort of measuring incidence of cases. That made a huge difference. It was a brand new concept. It allowed us to identify groups or areas of risk where there were disproportionate numbers of cases, how the disease spreads. We could adapt our tactics, such as ring vaccinations, to the circumstances.”

What has been learned from the smallpox eradication effort?

“You need cooperation and commitment of the community. You need a strategy, a plan and budget. You need to be able to demonstrate efficaciousness. You need good surveillance systems and quality control systems, and you need to make research a priority,” Henderson said. “All that is what we should have learned.”

What haven’t we learned?

“In 1967, 1968 and 1969, as I went to these countries, I would find whole wards in hospitals with sick children from diseases other than smallpox — measles, diphtheria, whooping cough, polio. I asked, ‘Aren’t these children being vaccinated? There are common vaccines for these diseases.’

“We soon found that in very many countries more than 10-15 percent of the children were not receiving anything except the smallpox vaccine,” Henderson said.

“I’m also amazed: Why have public health professionals been so resistant to research? I’ll give one example, polio mellitus,” he said.

In 1988, a WHO effort to eradicate polio began, with support from UNICEF and Rotary International. “I asked, if we’re going to do this, why can’t we have a better vaccine? The answer was, the target is to eradicate polio worldwide by 2000, but it will take you 10 years to develop a better vaccine. So why bother?” he said.

While the Western Hemisphere was declared polio-free in 1994, there still are pockets of the world where it exists — more than 1,300 reported cases in 2007 — and there still isn’t a better vaccine, he noted.

On the positive side, Henderson said, the interest in global public health issues is rising rapidly among today’s best and brightest.

“There is a growing recognition that we’re one world. We have finite resources, which we have to share. We also have a great many organisms that we find we also have to share, from HIV/AIDS to West Nile virus, to possible pandemic influenza, to SARS. There’s a concern for humanitarian reasons for what’s going on in other countries, but it’s also in our own interests,” he said.

“I see in the future some changes taking place. I can see more is to be gained by cooperation, and by development and education, than we can achieve at the point of a gun. I think we’re going to see a revival of subjects, including something we haven’t said much about in the last eight years, family planning and issues of overpopulation.”

Is it time to close the book on smallpox? “I keep thinking that the subject of smallpox is closed, but [later this month] there will be a meeting at the Institute of Medicine to discuss whether we are or are not going to destroy the [stored] smallpox virus.

“We’ve only been discussing it for 20 years, so there’s no reason to think we’ll have a conclusion very soon.”

—Peter Hart

Filed under: Feature,Volume 41 Issue 4

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