Vaccine Verity.

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.

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 rare--but 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 child."

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."

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 blockages.

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 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.

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 anti-vaccine group that claims there isn't enough evidence to demonstrate the safety of vaccines.

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 percent--twice the national average--remain 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 polio--about 1 case per 750,000 oral vaccinations--was 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 neurologic damage.

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. committees--one assembled by the Institute of Medicine (IOM), a federal advisory agency, and another by the American Academy of Pediatrics--concluded 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 JURNAL 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.

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 worried parent.

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 again."