Debating Smallpox Strategies
Who gets vaccine a hot issue
By Laurie Garrett
August 14, 2002
Having accepted the possibility that samples of the highly contagious
and deadly smallpox virus have gotten into the wrong hands, the U.S.
government is racing to obtain millions of doses of new vaccine before
the end of this year - more than 100 million doses by Sept. 11. But
how that vaccine will be used remains a hot-button issue.
A scientific advisory panel concluded June 20 that vaccine should be
stockpiled. Only perhaps 15,000 public health workers need vaccination
before an outbreak, the panel said, and immunization could be limited
to fairly small numbers in seriously exposed areas.
But many physicians, medical organizations and political leaders are
clamoring to have vaccines now.
"I believe the threat of a smallpox attack outweighs the risks of
providing smallpox vaccinations to a well-informed public," Sen. Bill
Frist (R-Tenn.), a physician, said this week in a New York Times
article. " . . . every American should be given this option."
A Harvard University poll released June 5 found 59 percent of
Americans would get vaccinations immediately if they were available.
If smallpox surfaced somewhere in the country, 81 percent of those
surveyed said, they would want to be vaccinated immediately.
Less than three months ago, scientific experts thought they had closed
the book on the issue. Two factors seem to be key to the new debate.
First, consensus is building among national security experts that some
groups have, indeed, obtained the smallpox virus. Second, there is
disagreement about how best to control a smallpox epidemic in a
totally nonimmune population - a problem not faced for more than a
"While the threat of a smallpox attack is believed to be low, it is
indeed possible, and unfortunately, we now live in a world where we
need to be prepared ... " Health and Human Services Secretary Tommy
Thompson said June 20. "As part of that preparedness, we expect to
have in stock by the end of this year enough smallpox vaccine for
every American should it ever be needed."
Unlike the tetanus or measles vaccines, which are quite safe, smallpox
inoculation can be risky. This spring, the National Institutes of
Health administered the vaccine to 680 healthy adults born after all
U.S. vaccine programs ceased in 1972. Nine percent of those vaccinated
suffered fevers, 21 percent had muscle aches and pains, 6 percent
developed skin rashes. Twelve of the subjects suffered reactions
severe enough to warrant hospitalization.
No one knows for sure how much immunity people vaccinated before 1972
retain, but historical evidence indicates all immunity wanes within 20
Another recent NIH study showed that the key immune response elicited
by the vaccine involves so-called T cells - the kind that are depleted
in people who are infected with HIV, are undergoing cancer
chemotherapy or are elderly.
In Senate testimony May 2, Thompson estimated that "about 18
individuals out of a million would have serious repercussions from
taking the vaccine ... about two to four would die" because high-risk
groups that were not targeted for vaccination in the 1960s would be
Furthermore, the new smallpox vaccines are being made through novel
processes - not in the way used in the 1960s, when the vaccinia virus
was inoculated into cows, which in turn produced the vaccine.
"There is a risk, and everybody realizes it's possible, that the
vaccine will turn out differently from what we want," Dr. James LeDuc
of the Centers for Disease Control and Prevention in Atlanta said in
an interview. LeDuc is heading up efforts to guarantee the safety and
efficacy of the new stockpile.
If smallpox surfaced anywhere in the world, LeDuc's team would rush a
sample to the CDC's BioSafety Level-4, top security laboratory, for
analysis. Working with counterparts at VECTOR, the old bioweapons lab
in Siberia, the CDC has determined the genetic sequences of several
known strains of smallpox.
"This will give us a variable database to trace the origin of
smallpox, should it ever reappear - the pedigree," LeDuc said. "It
will also help us to rapidly identify if the genome has been
manipulated," to give the virus special powers of transmissibility or
LeDuc's task would be relatively easy. The really tough task would
fall on pediatrician Harold Margolis, also of the CDC. He would have
to decide, in the face of immense uncertainties, who should be
vaccinated first, second and further down the road.
The historical record shows that fatality rates in smallpox epidemics
were generally "around 30 percent, but could be as high as 80
percent," Margolis explained in an interview. "But those studies were
done long ago. We have much better supporting care today, so would
people who died then, live today?"
In 1972, Drs. Alfred Sommer and Stanley Foster led efforts to control
a raging smallpox epidemic in Bangladesh. In that epidemic, about 60
percent of unvaccinated people came down with smallpox, and as many as
half of those individuals died.
Nevertheless, Sommer, who is now dean of the Bloomberg School of
Public Health at Johns Hopkins University, and Foster, who is on the
faculty of Emory University in Atlanta, stopped the epidemic. They did
so by a method called ring vaccination, in which infected individuals
are identified and quarantined, and every person residing or working
within a ringed distance of that person is vaccinated.
They discovered there was no need to immunize health care workers in
advance, as the vaccine was so powerful that they were protected even
if they didn't get the vaccine before handling a dying patient.
Three recent computer models offer conflicting conclusions about the
likelihood the Sommer/Foster strategy would work in the United States
today. A Los Alamos National Laboratory study says the epidemic would
move so slowly that authorities would have ample time to respond.
LeDuc and colleagues found that the ring strategy would work, but that
4,200 people would develop smallpox with a 30 percent mortality rate,
and 40 million Americans would have to be vaccinated. Finally, a Yale
School of Public Health group calculated that the ring strategy would
leave 110,000 people dead, whereas mass vaccination would result in
only 560 lost lives.
In the end, Margolis said, "let's just hope we don't ever have to find
out the truth."
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