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.
