March 2003

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Protecting the world against smallpox - again

By Ruth SoRelle, MPH

In the 1950s, 1960s and early 1970s, virtually every child in a U.S. schoolroom was marked by a small round scar high on the upper arm or, more discreetly, on the hip. It was the outer sign that they were protected against smallpox, once a worldwide scourge.

Smallpox was declared eradicated from the world in 1980, three years after the last naturally occurring case was identified in Somalia. The last case of smallpox in the United States was in 1949, and the vaccination was not given in this country after 1971.

The current furor over smallpox vaccination raises two questions. If there is no smallpox in the world, why are health officials giving the vaccination again? And if the vaccine was given so widely in previous decades, why is everyone so upset?

Risk vs. benefit

Robert Couch, MD

The answer is one of risk and benefit. Even though there are no cases of smallpox in the world at this time, the smallpox virus is known to exist in the United States in freezers at the Centers for Disease Control and Prevention and in the former Soviet Union. According to terrorism experts and federal officials, there is the possibility that the virus may also exist in the laboratories of other countries that might put it into the hands of terrorists. The terrorists might use it as a weapon against civilian or military populations. That would mean that a disease thought eradicated from the world could become a killer once again.

“The fact that it (the virus) could be elsewhere is the reason for all this preparation,” said Robert Couch, MD, a professor of molecular virology and microbiology at Baylor College of Medicine.

It boils down to this. If there are cases of smallpox in the community that could infect you, you are going to want to be vaccinated. If there is no smallpox, you probably are not going to want to face the risks that go with the vaccine. That is the risk-benefit ratio for the public as a whole.

The death rate in previous outbreaks of smallpox has been an estimated 30 percent. Those who are infected with the virus and get the disease are left scarred. The risk-benefit balance when people are exposed to the disease is easy to figure out. The vaccine is much less risky. When there is no disease, however, the risk-benefit becomes harder to define.

Who should be vaccinated?

The controversy arises over those likely to be on the front lines – health care workers who might find themselves confronted with the first cases of the disease. Who among them should be vaccinated? When should these vaccinations begin?

In the beginning, federal health officials were concerned because the population of the United States far outstripped the supply of smallpox vaccine left from the early 1970s. However, a national study headed at Baylor by Couch demonstrated that the vaccine could be diluted five times and still protect against disease. In addition, the pharmaceutical firm Aventis found 77 million doses of vaccine they had created for the military in the late 1950s and added that to the national stockpile.

“We know today that if we had to vaccinate everyone in the country, we have the vaccine,” said Couch.

Potent vaccine

The vaccine is a live infection with vaccinia virus prepared from sheep or calf lymph. The sheep and calf material is called lymph but it is fluid from vesicles or blisters.

The immunity conferred by the smallpox vaccine is strong, as high as 97 or 98 percent effective. It lasts more than 10 years. There are some estimates that it might be effective as long as 20 or 30 years.

“It is one of the most potent vaccines ever described,” Couch said. “It will provide some protection against death if you have been vaccinated in your lifetime. You might get smallpox but it would not be severe enough to kill you.”

The vaccination is given with a bifurcated needle that looks like a tiny two-pronged fork. The “fork” picks up 2.5 microliters of vaccine, which is poked into the top layer of skin. The material is poked into the skin many times, said Couch.

If a person has never been vaccinated, the reaction starts with an itchy red pimple that becomes a little blister and then enlarges. In most cases, it eventually leaves a scar.

“The problem is that it can make you sick,” said Couch. In some people, a second area similar to the vaccination site will erupt – a so-called satellite lesion that occurs because the virus spread to that site. In some instances, it can cause lymphangitis, inflammation and infection of the systems that carries lymph; or lymphadenitis, inflammation and infection of the lymph glands.

Nine percent of individuals who have had the vaccine as part of current testing have had fever and 30 percent have reported significant symptoms. About one-quarter reported missing at least a day of school or work.

“This is an illness-producing vaccine,” said Couch.

In about half of the cases, it causes no more than redness and swelling around the vaccination site. In 25 to 30 percent of the cases, the reaction at the site of vaccination is more serious. A more significant reaction may occur in another 15 to 20 percent. Less than 1 percent has severe problems.

Photo courtesy of CDC/Arthur E. Kaye

During a primary response, a vaccinee never having been exposed to the vaccinia virus is vaccinated, stimulating the T cell population to expand in order to be able to mount a sound antibody response to a secondary inoculation to the smallpox virus.

Reactions to the vaccine

Severe issues include accidental infection, infection at another site or infection of another person. The later usually happens when the site of the vaccination was not covered.

A problem called eczema vaccinatum occurs when open skin lesions provide a portal of entry for the virus. A very rare problem is progressive vaccinia infection that cannot be contained. Couch said he has seen only one case of this in his career – a man with lymphoma who left the hospital to get vaccinated because he wanted to travel to Israel in the 1960s.

“He ended up having to have a wide area removed and skin grafts,” he said. “He should never have been vaccinated.”

All kind of rashes can occur after smallpox vaccination, but encephalitis is of greatest concern, he said. About one-half of those with the disease recover but some are left with neurologic problems.

Photo courtesy of CDC/John D. Millar

An accelerated response occurs when having previously been exposed to the smallpox virus the body reacts to a vaccination in a rapid fashion attacking the pathogen, i.e. vaccinia virus, before it can "harm" the vaccinee.

The rate of problems associated with the vaccine is much lower for people who get revaccinated, he said.

“About half of the people in the United States would be vaccinated for the first time if a mass vaccination effort got underway in response to bioterrorism. Half would be revaccinated.”

Something can be done to care for those who do have bad reactions. Immune globulin related to vaccinia is available now and there are some anti-viral drugs that have been show effective – at least in the laboratory.

Protecting the public

Protecting the entire public is a challenge. As Richard Gaston, emergency response coordinator for the Harris County Public Health and Environmental Services, noted, it is difficult to find the numbers of health care workers to vaccinate now so that they can give vaccinations later. Many have health issues that prevent them from getting vaccinated and others are hesitant. In some communities, entire hospitals have refused the vaccine.

Scheduling people in hospitals for immunizations is also difficult because vaccinating everyone in a hospital at the same time could result in staffing problems later. Many legal issues are still being considered.

After health care workers, emergency medical services and other “first responders” such as police and fire fighters will have to receive the vaccine, said Gaston. In a third phase, adult civilians who want to be vaccinated can receive the immunization on request.

It is hoped that if there is a single case, the disease can be contained by a “ring” approach. That would mean that contacts of the first smallpox patient would be vaccinated as well as their contacts and those who are suspected of being contacts.

“We would hope that this will stop it,” said Gaston.

A mass vaccination would take place only if the first wave of cases is so large it could not be managed with the ring approach, if the ring approach did not work, or if there was no decline in new cases after 30 percent of the available vaccine had been used.

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