New studies weigh benefits and risks
Smallpox. Measles. Mumps. Polio. These words once conjured up images of people with
severe rashes, swollen jaws, or paralysis. Yet vaccines have eliminated smallpox and made
the rest of these once-common, often-debilitating diseases rare.
A child receives a vaccination.
The percentage of people vaccinated against these diseases is at an all-time high,
while death rates from them are at all-time lows. But the very success of these vaccines,
plus those for meningitis and a variety of other diseases, carries with it the germ of a
public health tumult.
As more people are vaccinated, the trauma of the original diseases becomes rarebut
harmful side effects of vaccines may garner more attention. Furthermore, inaccurate
information now spreading through the Internet exacerbates worries about vaccine safety,
public health specialists say.
Although commitment to vaccine use in the United State remains high, health
professionals worry that parents' fears of vaccine side effects may come to outweigh their
appreciation of the benefits of vaccination for their children.
Reports of side effects that she gathered from the Internet contributed to the decision
by Suzanne Walther of Murfreesboro, Tenn., to postpone giving any vaccines to her third
child, Mary Catherine. Unfortunately, her daughter developed a vaccine-preventable case of
meningitis just before her first birthday. Mary Catherine recovered fully, but children
with such an infection can become mentally retarded or die.
"These diseases weren't tangible to me [before Mary Catherine's illness], but I
saw all these horror stories about adverse reactions parents attributed to vaccines,"
Walther says. "I only wanted to vaccinate if it was the best thing for my
Several new, large studies counter some recent vaccine scares. Other work is
investigating how parents' individual decisions against vaccinating their children might
increase other children's risk of disease.
"There is no thing you can do, there is no food you can eat, there is no vaccine
you can get that is 100 percent effective and 100 percent safe," says Gregory A.
Poland of the Mayo Clinic and Foundation in Rochester, Minn. By and large, he says,
vaccines are some of the safest and most effective medical interventions in existence.
"It is legitimate to raise safety concerns," he says, "but we can't throw
these unparalleled advances away."
Rare side effects
Concerns about vaccine safety aren't new. A hundred years ago, residents in Boston
protested mandatory smallpox vaccinations. Research has linked a few vaccines to rare side
effects far more serious than the typical fever and swelling at the injection site.
About 3 in 100,000 kids given the combined vaccine for diphtheria, tetanus, and
pertussis develop breathing difficulties or seizures. Just 1 in 100,000 kids vaccinated
against measles, mumps, and rubella develop high fevers or some loss of consciousness. By
way of comparison, 11 of 100,000 pregnant women die in childbirth.
Some vaccines can on rare occasions cause problems by actually infecting a person with
a disease that the inoculation is intended to prevent. For example, in two cases over the
past 50 years of worldwide polio vaccination, outbreaks of polio have been traced to
viruses that mutated after being introduced as part of a live vaccine. In other cases,
people given the varicella, or chicken pox, vaccine as children later experienced herpes
zoster, or shingles, a painful reactivation of the virus. This complication, however,
occurs more often in people who experienced chicken pox than in those who were immunized.
In 1999, Wyeth Laboratories of Marietta, Pa., withdrew a vaccine against rotavirus
after just a year on the market. Rotavirus infection can cause diarrhea and sometimes
death, but the vaccine slightly increased the risk of potentially fatal intestinal
Some parents' worries don't focus on a specific vaccine effect. Current federal
recommendations include 20 injections in a child's first 18 months and several other
immunizations over the next 10 to 15 years to protect against 11 diseases. Despite a lack
of scientific evidence supporting their concerns, "One in four parents of children
under 6 believes their children's immune systems could be weakened by too many
vaccines," says Bruce Gellin of Vanderbilt University in Nashville, "and almost
as many believe that children get more immunizations than are good for them." Gellin,
who is also executive director of the National Network for Immunization Information in
Alexandria, Va., recently surveyed 1,600 parents with young children.
Despite their concerns, 87 percent of the parents agreed that vaccinations are
important to keeping their children healthy, Gellin reported in the Nov. 5, 2000 Pediatrics.
Concerns over safety
Gregg Burgess, a parent of two in Sterling, Va., hasn't immunized his two boys. He
feels that the number of vaccines given kids these days can cause their immune systems to
get "screwed up," perhaps resulting in autism and autoimmune disorders like
diabetes. Burgess is a board member of the National Vaccine Information Center, an
antivaccine group that claims there isn't enough evidence to demonstrate the safety of
If parents' fears over vaccine safety rise, public health officials worry that
immunization rates will drop. Such a decline would naturally lead to more cases of disease
among the unvaccinated children. Because most vaccines don't provide complete protection
against disease in every child, however, even vaccinated children would become more
vulnerable if vaccination rates drop, scientists predict.
In Colorado, an unusually large contingent of parents holds religious or philosophical
objections to vaccination. Among that state's school-age kids, 1.4 percenttwice the
national averageremain unvaccinated. A study in the Dec. 27, 2000 Journal of the
American Medical Association reported that unvaccinated children were more than 20
times as likely as vaccinated children to develop measles and almost 6 times as likely to
develop pertussis, also known as whooping cough.
In addition, vaccinated children living in areas with high percentages of unvaccinated
children were significantly more likely to get one of these infectious diseases than were
children in more highly vaccinated areas, says Robert T. Chen of the Centers for Disease
Control and Prevention (CDC) in Atlanta, an author of the study. For each 1 percent of
kids that go unvaccinated in a county, the researchers calculated that the risk of measles
among vaccinated children rose by 60 percent and the risk of pertussis rose by 90 percent.
Other researchers have looked at the effects of widespread vaccine-safety scares in
different countries. Eugene J. Gangarosa of Emory University in Atlanta and his colleagues
showed that vaccination rates for pertussis in the 1970s and 1980s dropped in European
countries that had strong antivaccine campaigns in reaction to concerns about seizures and
brain damage. Soon thereafter, he found, the rates of pertussis in these countries rose to
levels 10 to 100 times as high as those in countries where antivaccine movements hadn't
affected immunization programs.
"There's no question these movements undermine, collectively and individually, the
benefits of vaccination," Gangarosa says.
Some vaccination side effects have been well documented, and vaccine makers have
changed their products to reduce these effects. In other cases, however, scientists have
been unable to confirm anecdotal links between vaccines and diseases.
Federal guidelines now recommend a pertussis vaccine that uses only part of, instead of
entire, killed pertussis bacterium and is safer than the earlier version. Walther says,
however, that this change to the so-called acellular vaccine is not immediately apparent
to parents looking for safety information on the Internet.
Another recent switch in the United States, effective last year, provides injected
polio vaccine instead of the oral version. Despite the advantages of avoiding shots, the
small chance of developing polioabout 1 case per 750,000 oral vaccinationswas
deemed greater than the chance of catching polio from another person in this country.
Oral polio vaccines continue to be widely used in developing countries, where polio is
more common and health officials believe the ease and safety of administering oral
vaccines outweigh any risks.
New formulations for many vaccines will soon reach pediatric offices. Thimerosol, a
mercury compound, is an ingredient that prevents bacteria and fungi from contaminating
vaccines. Although no research indicates a problem, public health officials feared that
with the increasing number of vaccines that each baby receives, low-birth-weight babies
might be exposed to too much mercury. At high doses, the chemical can cause kidney and
The new formulations will contain alternative preservatives to thimerosol or be
provided in single-use vials that don't require a preservative. Researchers and public
health officials plan to examine large databases of health-care and vaccination records to
see whether they can link the mercury of the traditional vaccines to health problems.
A recent set of widely reported vaccine-safety concerns suggested a link between the
measles, mumps, and rubella (MMR) vaccine and autism, a developmental disorder
characterized by a person's difficulty connecting with others. These concerns were sparked
in part by a report published in 1998 in The Lancet, a British medical journal.
There, researchers described 12 children who developed autism and similar behavioral
problems soon after vaccination with MMR.
Since the 1998 report, several larger studies including tens of thousands of children
have found no link between MMR vaccination and autism, and researchers haven't yet
demonstrated a plausible biological mechanism for such a link. Earlier this year, two U.S.
committeesone assembled by the Institute of Medicine (IOM), a federal advisory
agency, and another by the American Academy of Pediatricsconcluded that the vaccine
wasn't behind a decade-long rise in the number of U.S. children diagnosed with autism.
"There is simply no evidence to support an association between MMR and
autism," says Marie McCormick of the Harvard School of Public Health in Boston, who
chaired the IOM committee.
Another widely reported concern is that the hepatitis B vaccine leads to multiple
sclerosis, a disease that causes nerve degeneration and muscle weakness. In the Feb. 1 New
England Journal of Medicine, two research teams concluded that this vaccination
doesn't appear to either cause multiple sclerosis or exacerbate the course of the disease.
One researcher reported that when given to young infants, the vaccine for the
meningitis-causing bacterium Haemophilus influenzae B might trigger diabetes. So
far, however, no study has confirmed that link, says Heather McPhillips of the University
of Washington School of Medicine in Seattle. Nor is there research support for the idea
that the hepatitis B vaccine increases the risk of sudden infant death syndrome.
Conflicting safety claims
It's easy to understand why parents might associate a vaccine with a disease whose
cause is unknown. Since the administration of vaccines is so common, the chances are good
that disease onset will follow vaccination in some people, Chen says. The early signs of
developmental disorders tend to show up in the first few years of life, a time when
healthy kids are getting vaccinated often, so conditions such as autism may seem linked to
an immunization even when they are not. Sifting through conflicting safety claims can be
difficult, says Chen.
Many vaccine scares are hard to quell because scientific studies can never prove that a
vaccine doesn't underlie a particular disease, only that the chances of it being the cause
are very low, Poland says. That might reassure a scientist, but it may not comfort a
Moreover, extremely rare side effects of any new vaccine can't be reliably detected
until the vaccine has entered the market and been given to millions of people. Vaccines
then get a lot of publicity. For example, Wyeth Laboratories tested the rotavirus vaccine
on 10,000 infants before it received governmental approval. In the March 21 Vaccine,
Gregory A. Poland of the Mayo Clinic in Rochester, Minn., and his colleagues show that the
bowel problems associated with the rotavirus vaccine couldn't have been detected unless
more than 100,000 infants had been studied.
The risk associated with the rotavirus vaccine's side effects is lower than the risk of
injury associated with most car trips and some antibiotics given to treat children with
infections, Poland says. However, because so many healthy infants are vaccinated, even
infrequent side effects can be important.
The critical next step for public health professionals is to develop better ways to
identify which kids are most likely to suffer adverse effects, says Poland. Researchers
are currently tracking vaccinations and health problems in more than 2.5 percent of the
U.S. population, and CDC plans to expand the effort.
"It's a good thing when there's a lot of scrutiny and accountability about
safety," says Poland.
Such large national databases are going to be increasingly important tools for
monitoring rare side effects, says Chen. "Until recently, the paradigm for
vaccination has been that once the disease has been effectively eliminated, we'll stop
immunizing, thus eliminating vaccine side effects," he says. Disease elimination
needs to be worldwide because the incubation period for most infectious diseases is longer
than the time required for a jet flight halfway around the globe. The only vaccine success
on this scale is the fight against smallpox.
Chen has reservations about ending any vaccination programs against deadly diseases.
"In this world of potential bioterrorism, any disease worth eliminating is also a
perfect target for bioterrorists," he says.
"That means we no longer have the luxury of ignoring even very rare adverse
events," Chen concludes. "We are never going to be able to stop immunizing
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Robert T. Chen
Centers for Disease Control and Prevention
1600 Clifton Road
Atlanta, GA 30333
Eugene J. Gangarosa
5305 Greencastle Way
Stone Mountain, GA 30087-1427
Bruce G. Gellin
Department of Preventive Medicine
Vanderbilt University Medical Center
Nashville, TN 37232-2637
Marie C. McCormick
Harvard School of Public Health
677 Huntington Avenue
Kresge Maternal and Child Health
Boston, MA 02115
Gregory A. Poland
Department of Medicine
Vaccine Research Group
Mayo Medical School
Rochester, MN 55905