|
By Susan Okie
Federal health officials, spurred by last
month's terrorist attacks and by the recent dissemination
of anthrax spores through the mail, are mounting an unprecedented
effort to produce enough smallpox vaccine for every American
by the end of next year.
The smallpox virus, which some experts fear may be in the
arsenal of rogue nations and terrorist organizations, is the
most dreaded potential biological weapon.
Smallpox can't be cured with current drugs, kills about one-third
of victims and spreads easily from person to person. Because
most Americans have no immunity to the virus, isolating those
infected and vaccinating everyone who came into contact with
them would offer the only hope of halting a potentially devastating
epidemic.
But the crash program is raising some questions: Should some
medical workers be vaccinated immediately? And will the decision
to produce so many doses of the vaccine fuel public demand
for a hazardous mass immunization campaign?
The vaccine's rare but serious side effects make it far too
risky to administer preventively in a national immunization
campaign. When all US infants were vaccinated routinely, a
practice that ended in 1971, about five children died of vaccine-related
complications for every 1 million immunized. The risk of death
is lower, but still present, in adults.
"This is a vaccine that has real, known adverse reactions,
and that's why it's not to be given out lightly en masse,"
said Myron M. Levine, director of the Center for Vaccine Development
at the University of Maryland School of Medicine.
"I hope we'll never get back to having to use it in large
numbers of people again."
The frequency of serious complications with the old smallpox
vaccine was higher than for any vaccine now on the market,
and vaccine experts assume the risks will be similar with
the new version, which contains the same live virus -- called
vaccinia or cowpox -- but is made by a different process.
In a child with eczema,
for example, the virus in the vaccine can spread quickly to
produce a life-threatening rash.
In rare instances, especially in people with weakened immune
systems, it can cause encephalitis (brain inflammation) or
can spread from the vaccination site to involve the entire
arm, the bloodstream or other areas of the body.
If the frequency of serious complications from the new vaccine
is similar to that seen in the 1960s with the old vaccine,
a national immunization campaign would be expected to kill
more than 300 people.
But the vaccine's risks
could be considerably greater today than in the 1960s because
more Americans are living with weakened immune systems,
said John F. Modlin, chief of pediatrics at Dartmouth Medical
School and chairman of the Advisory Committee on Immunization
Practices for the federal Centers for Disease Control and
Prevention.
"Thirty and 40 years ago, we weren't treating patients
with leukemia, we weren't doing kidney and liver transplants,
we didn't have HIV infection," Modlin said.
Because of those risks, experts are divided even on the question
of whether to recommend that emergency room personnel and
hospital staff should be vaccinated unless there is an imminent
threat of smallpox.
A newly vaccinated health care worker could spread live vaccinia
virus to others, thereby posing a threat to hospital patients
whose immune systems were compromised, Henderson said.
"Trying to vaccinate your health care workers in advance,
we don't think it's a great idea," said Henderson, who
was recently named chairman of a new HHS advisory committee
on bioterrorism.
Most of the approximately 300 million doses that federal officials
say are needed would come from a new version of the smallpox
vaccine that has not yet been tested in humans. An estimated
75 million doses would come from the existing stock of 15
million doses of an old vaccine, which health officials hope
to dilute to make it go farther.
The smallpox vaccine formerly used in the United States was
made by growing large quantities of vaccinia virus on the
abdominal skin of live calves. It is no longer manufactured,
and the process used to produce it is outmoded.
So when Henderson and other health experts warned the Clinton
administration in the late 1990s that smallpox vaccine stocks
should be expanded, government officials had to seek a new
manufacturer to produce a vaccine using modern methods.
Last fall, the federal government contracted with a US company
called Oravax (subsequently bought by British drugmaker Acambis
PLC) to make a new smallpox vaccine. It contains vaccinia
virus that has been grown in cultured human fibroblasts (connective
tissue cells) inside large sterile containers called bioreactors,
said Anthony S. Fauci, director of the National Institute
of Allergy and Infectious Diseases.
The contract originally called for delivery of 40 million
doses by 2004, but the company recently agreed to provide
50 million doses by the end of 2002.
The new vaccine has yet
to be tested in people.
Health officials assume it will be effective because it contains
the same type of vaccinia virus that was used successfully
in the old vaccine. Pilot lots of the new vaccine for testing
in human volunteers should be available in January, Fauci
said.
Because volunteers can't be infected with smallpox virus to
test the vaccine's protective effect, researchers will have
to use skin tests, antibody tests and other measures to see
whether it produces an immune response, Levine said.
"We don't know for sure what the mediators of protection
[against smallpox] are," he said. "If there was
a big difference between a new vaccine and the old vaccine,
that would be a potential problem."
The Food and Drug Administration, which regulates vaccines,
has agreed to act quickly on the new smallpox vaccines, officials
said. "We're committed to doing everything we can to
speed development of these products . . . without shortcutting
FDA standards for safety and effectiveness," said FDA
spokeswoman Lenore Gelb.
Meanwhile, health officials hope to stretch the existing stock
of 15 million doses of the old vaccine by diluting it. Fauci
said that a preliminary study in 60 people found that even
when diluted to one-tenth of its original concentration, the
vaccine produces a characteristic skin reaction indicating
an immune response in 70 percent of recipients.
The National Institutes of Health and other research centers,
including the University of Maryland, are recruiting volunteers
for a similar study in 650 people, comparing undiluted vaccine
with 5 to 1 and 10 to 1 dilutions.
Fauci predicted the vaccine will be about 90 percent effective
when diluted to one-fifth the original concentration, allowing
current stocks to be diluted to make 75 million doses.
Experts emphasized that control of any potential smallpox
outbreak will depend as much on doctors' ability to recognize
cases of the disease when they see it as on health officials'
ability to deliver the vaccine.
Few US doctors practicing today have ever seen a case of smallpox.
Henderson said that despite warnings from bioterrorism experts
urging training for doctors, little training has been provided
until recently.
Washington
Post October 28, 2001; Page A18
|
