May 8, 2002
By Lisa Ellis
InteliHealth News Service
Should most Americans be vaccinated against smallpox? Even after Sept. 11 and the bioterror attacks using anthrax bacteria, the question seldom was raised seriously. After all, the disease had been declared eradicated in 1980, two years after the last known case. Moreover, the only known supplies of the virus were in secure government laboratories in the United States and Russia.
Besides, inoculation itself kills about one person out of a million. And there wasn't enough vaccine anyway.
Now, suddenly, there's enough vaccine. And the U.S. government is asking the public to join a debate about whether a nationwide vaccination campaign is a good idea.
In late March, a study found that the existing supply of 15.4 million doses could be effective if diluted fivefold, and the vaccine maker Aventis Pharma announced it had located 85 million doses in storage and would donate them to the U.S. government. By the time a U.S. order for 209 million doses is filled at the end of 2002, there should be more than enough to vaccinate the whole population. (The U.S. Census Bureau estimates that there are now nearly 287 million people in the United States.)
The debate about vaccination policy was launched in recent weeks in medical journals, including an editorial by a U.S. health official calling for a public dialogue.
That official dialogue begins this week, as a panel commissioned to make recommendations to the U.S. Centers for Disease Control and Prevention (CDC) holds its first meeting May 8 and 9 in Atlanta.
The principal question is this: Should we inoculate millions of people with a vaccine that can cause serious complications or death in order to prevent a disease with a mortality rate of about 30 percent?
Matthew M. Davis, M.D, a researcher at the University of Michigan, believes we should consider it seriously.
According to studies presented by Dr. Davis and colleague Alex Kemper, M.D., at a medical conference May 7, vaccinating most Americans under 30 against smallpox would cost $430 million. But if an outbreak occurred, this pre-vaccination strategy could save about 1,800 lives, the researchers say.
This figure compares the likely death rate from vaccination and a subsequent smallpox attack with the number of potential smallpox deaths if the United States retains its current policy of vaccinating people only after an outbreak begins. This is known as a ring-vaccination policy because it would concentrate on vaccinating the ring of close contacts around those who contract the virus. According to the CDC, people exposed to smallpox can have less a severe case or even avoid getting sick if they are vaccinated within four days after exposure.
"I think that as long as the public recognizes the risks and accepts them with open eyes, a mass vaccination campaign may be an appropriate policy to follow," says Dr. Davis. He is presenting the research to the Pediatric Academic Societies in Baltimore.
But to Gregory Evans, Ph.D., director of the Center for Study of Bioterrorism and Emerging Infections at St. Louis University, the risks of mass vaccination are too great.
"We're in the process of developing a newer version of the vaccine and hopefully that will have fewer side effects," he says. "Then, at that point, it might be worth vaccinating the whole population, but until that time I just don't think it's warranted."
Smallpox is caused by the variola virus. The risks of inoculation include death resulting from reactions to the vaccine, which produces immunity to smallpox by giving a live dose of vaccinia, a similar virus. In the past, about one of every million people vaccinated has died from the resulting infection or from vaccine-caused encephalitis. People who have the skin disease eczema or weakened immune systems are especially vulnerable.
Doctors Davis and Kemper estimated that one-quarter of the population could not be vaccinated because of being at high risk of complications or in close contact with a high-risk person.
They concluded that vaccinating 75 percent of all people ages 1 to 29 would cause 86 deaths. They said a smallpox outbreak after the vaccination campaign would cause another 158 deaths, for a total of 244.
In contrast, they estimate there would be 2,160 deaths if an attack occurred and the ring-vaccination strategy was followed.
The study assumed that people who got vaccinations before the United States stopped offering them in 1972 would no longer be immune. There is disagreement in the medical community about how much immunity this group has. The study nevertheless focused on younger people because they definitely are not immune.
Dr. Davis says it's unclear whether the public will favor vaccination, especially in a time when many parents have questioned the safety of certain routine vaccinations for their children. Some surveys have found that that at least half of U.S. adults are willing to be vaccinated.
"The smallpox vaccine is potentially more deadly than any (other vaccine) we currently use," he says. "Whether the public is willing to accept that depends on whether the sentiment about vaccines has changed in the post-Sept. 11 world."
John F. Modlin, M.D., co-chairman of the CDC working group on smallpox vaccination, has questioned some of the assumptions made by Davis and Kemper in a related study, which was published in April 2002 in the journal Effective Clinical Practice.
In an editorial in the journal, Dr. Modlin says the researchers may have underestimated the number of high-risk people. He also questions whether the public would be willing to accept dozens or hundreds of deaths from vaccination.
To find out what the public thinks, the CDC will sponsor forums around the country this summer. "A major part of our plan is to make sure the issue is adequately aired," says Dr. Modlin, who is chairman of pediatrics at Dartmouth Medical School.
Another important consideration is whether any terrorist group actually has obtained a supply of the smallpox virus and is willing to use it.
Anthony S. Fauci, M.D., director of the U.S. government's National Institute of Allergy and Infectious Diseases, raises the issue in the April 25, 2002, issue of the New England Journal of Medicine:
"Some samples may have fallen into the hands of rogue governments or potential bioterrorists," he writes. "Therefore, we must assume that the threat of a deliberate release of smallpox as an agent of bioterrorism is real."
In the editorial, Dr. Fauci calls for a public dialogue about smallpox vaccination.
Still, nobody knows if the virus is in dangerous hands, says Dr. Modlin. "We don't have any better information of what the threat may be than anyone else, and that's one of the things that makes the task so difficult." He says it is unclear how much U.S. intelligence information will be made available to the committee.
But such evidence is crucial, says Evans, of St. Louis University.
"If we don't see any imminent threat, I would be very hesitant to vaccinate the whole population," he says. "I personally would be very hesitant to recommend that my family be vaccinated unless I know there is evidence that this is a bioterror weapon that is likely to be used in the near future."
William Bicknell, M.D., M.P.H., a professor of public health at Boston University, disagrees, saying that the potential death toll of smallpox justifies a mass voluntary vaccination effort.
Not only does the virus kill one out of three people, but "smallpox is unbelievably infectious," he says. Furthermore, most of the population has no immunity or only partial immunity. "That argues for pre-exposure vaccination because this disease kills a lot of people."
In an editorial in the New England Journal of Medicine, Dr. Bicknell also questions how well health officials could implement the ring-vaccination strategy in a crisis.
The same issue includes studies that demonstrate smallpox vaccine could be diluted and Dr. Fauci's editorial. All were early-released by the journal March 28.
Referring to a 2001 exercise that simulated a smallpox outbreak to test the existing system, Dr. Bicknell writes that it produced "logistic havoc." He adds, "Pre-exposure vaccination does not pose the logistic difficulties of vaccination during an outbreak and, if pre-exposure vaccination is limited to persons over 5 or even 10 years of age, complications and deaths from vaccination are greatly reduced."
Evans says the current system should not be replaced, but improved, as the federal government is trying to do now in cooperation with the states.
Dr. Modlin says the ability of the system to function in an outbreak may depend on many factors, including whether an attack occurs in multiple locations at once.
Still, he says, "we believe that once contacts [with infected people] are identified, our means of preventing additional cases are very good."
Much information must be gathered before it's possible to say whether current policy needs changes, Dr. Modlin says. "I honestly don't know how this is going to turn out. I think it's important that we do this in a careful, deliberate manner and consider all the scientific data available."
