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The Many Variables Of Smallpox Debate
Uncertainty Muddles Decision on Vaccine

By a Washington Post Staff Writer
Thursday, June 6, 2002; Page A03

Sometimes policymakers are forced to do what mathematicians would consider futile -- solve an equation in which many of the key variables and terms are missing.

Over the next three weeks, a panel of medical experts will debate whether the federal government should make smallpox vaccine widely available for the first time in 31 years. The decision -- one of many forced by last fall's episodes of biological terrorism -- will require a tricky balancing of risks and benefits in a state of great uncertainty.

The chance of a smallpox outbreak is unknown -- the disease was eradicated from the globe in 1980 -- so the most important variable can't be calculated. The risks of smallpox vaccine are also murky, because the American population is biologically different from what it was in 1971, when the substance was last used routinely.

Few doubt that paramedics, police, firefighters, physicians, nurses and epidemiologists are obvious candidates for vaccination because they would be likely to have early contact with victims of a bioterror attack. But precisely how to define the right group of "first responders" isn't clear. There's also no recent experience to guide the decision; the country's last emergency smallpox vaccination campaign was in 1947.

Beneath those large unknowns is a second order of uncertainty.

The vaccine is a live virus, vaccinia, which causes a mild infection that protects against smallpox. Although in most people vaccinia infection causes nothing more than a sore arm and low-grade fever, in those with abnormal immunity, vaccination can have serious and occasionally fatal results. The difficulty is that even some mild conditions, such as eczema, can signify that a person is at risk, and it is hard to identify all such people.

Furthermore, up to 20 percent of complications occur in people who were not themselves vaccinated, but acquired the virus from someone who was. Consequently, policymakers must consider such practical issues as whether anyone who gets the vaccine should stay off work for a week so they won't infect others.

There are also mundane uncertainties. For example, much of the existing vaccine is stored in vials containing 100 doses. How hard will it be to gather that many people together to get vaccinated at one time? How much waste should be tolerated?

"The subject is anything but clear what our recommendation will or should be," said D.A. Henderson, the chief adviser to Health and Human Services Secretary Tommy G. Thompson on biological terrorism preparedness. "It is not until you get down into the weeds that you see all the problems of trying to vaccinate any number of people."

Not least in the equation is public opinion about access to smallpox vaccine, all of which is owned by the federal government, and will continue to be for the indefinite future.

To gauge this last factor, the Centers for Disease Control and Prevention is hosting four public forums across the country. The first two will convene tonight in New York and San Francisco. The third will be Saturday in St. Louis, and the fourth on Tuesday in San Antonio. On June 15, a forum at the National Academy of Sciences in Washington will solicit the opinion of scientists and clinicians about smallpox vaccine use.

On June 19 and 20, the Advisory Committee on Immunization Practices (ACIP) -- the federal government's permanent committee that helps formulate national vaccine policy -- will meet in Atlanta and decide on a recommendation to Thompson.

Routine smallpox vaccination continued in the military through 1989. Since then, only a few people, most of them scientists and epidemiologists affiliated with CDC, have gotten the procedure, which consists of scratching a drop of vaccinia-laden liquid into the skin with a pronged needle.

The most virulent strains of smallpox -- presumably what terrorists would use -- cause death in about 30 percent of infections. Modern intensive-care treatment might reduce mortality somewhat. An antiviral drug, cidofovir, has shown promising early results in fighting viral infections similar to smallpox. Nevertheless, the virus remains one of the more dangerous ones on Earth.

The government's current strategy against a smallpox outbreak is search-and-containment, also known as "ring containment." It consists of identifying people with the infection and vaccinating everyone who has had contact with them. During the global eradication campaign (which began in 1966 and officially ended in 1980), ring containment often had literal meaning, with health workers immunizing entire villages that contained smallpox cases, and sometimes even blocking roads in and out, to prevent the virus from escaping.

But the strategy doesn't require that everyone in a geographic area be vaccinated, or that movement of large numbers of unexposed people be limited. Experts say that even in Chicago, for example, a case of smallpox caused by a bioterror attack would not require quarantining and vaccinating all Chicagoans. However, anyone having contact with the infected person would be vaccinated, isolated and observed for a fever heralding onset of the disease.

Historically, ring containment worked for smallpox for several reasons. All infections are obvious because of the disease's dramatic, bumpy rash; people don't transmit the virus until the rash appears; and, most important, if someone is vaccinated within seven days of exposure, the risk of becoming infected is reduced substantially (by as much as 70 percent, according to old studies). The disease is less contagious than some viral infections, such as measles and influenza, with data from pre-eradication outbreaks in Asia suggesting that infection usually requires days of close exposure to someone who is sick.

Numerous veterans of the global eradication campaign say scenarios of wildfire smallpox epidemics -- such as "Dark Winter," a simulation sponsored by the Center for Strategic and International Studies last year in which a three-city bioterror event caused 100,000 deaths in five weeks -- are unrealistically extreme.

But proponents of making vaccine widely available argue that ring containment may not work in highly mobile, modern America, where almost the entire population -- and certainly everyone younger than 35 -- is susceptible to the virus. Only vaccination now will lower the risk of an out-of-control outbreak, they say.

At a meeting last month of members of ACIP and a related body, the National Vaccine Advisory Committee (NVAC), there was little support for making smallpox vaccination available to anyone who wanted it. Nevertheless, there appears to be public support for just that.

Interviewers hired by the Harvard School of Public Health and the Robert Wood Johnson Foundation last month asked a sample of 3,000 Americans whether they would get a smallpox vaccination if it were offered. Fifty-nine percent said yes.

Even with "permissive" use of the vaccine, everyone agrees many people shouldn't get it. They would include people with AIDS, some cancer patients, organ transplant recipients, people with the skin condition atopic dermatitis and, in the absence of an outbreak, probably pregnant women. This comprises a large fraction of the American population, as there are an estimated 46 million people with atopic dermatitis alone in the United States.

The last mass vaccination against smallpox took place in New York City in 1947, when the disease was imported from Mexico. There were 11 cases and two deaths. About 6 million people were immunized in a month, with nine or 10 deaths from vaccine complications.