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[Great oxymoron: Vaccinations are supersafe, but maybe not all at once, or for certain children]

Vaccines Get New Scrutiny

Vaccinations are supersafe, but maybe not all at once, or for certain children

By Deborah Kotz
Posted December 11, 2008

When Julie Austin decided to give her daughter the Gardasil vaccine, she desperately wanted to protect Sara, then 15, from the human papillomavirus that had caused abnormal Pap smears in other family members. A day after the shot, however, Sara complained that she was dizzy and her head was pounding. "Her doctor said the migraine­the first one Sara ever experienced­could have been caused by Gardasil, but it faded the next day, so I didn't worry," says Austin, of Westfield, Mass. But the headache struck again after Sara's second shot­and again after her third. Then, the crushing pain became constant, causing Sara to miss school, quit the soccer team, and spend weekends in bed.

Now worried. Might Gardasil be to blame for Sara Austin's severe headaches?

Her mom now wonders if she made the right decision to vaccinate, even though the Food and Drug Administration insists there's no reason to be worried about Gardasil. "We're monitoring the safety of the HPV vaccine very carefully, and the only adverse event that causes some concern is syncope or fainting," says Robert Ball, director of the FDA's office of biostatistics and epidemiology. And Gardasil's benefits can't be ignored: It protects against several dangerous HPV strains, including those responsible for the bulk of cervical cancers. But others in the medical establishment believe Gardasil's safety hasn't yet been proven and question why it's being recommended for girls as young as 9. "I certainly think it's wrong to give [Gardasil] to young teenage girls," contends pediatrician Catherine DeAngelis, editor in chief of the Journal of the American Medical Association. " What are the risks? We won't know until it's given to millions of women." Karameh Hawash, the pediatric neurologist who recently treated Sara Austin with a prescription migraine drug, says she has seen two other girls stricken by daily headaches after receiving Gardasil shots.

Such uncertainty explains the decibel level of the battle cries both defending and attacking vaccines, which has risen in recent years along with the number of immunizations children face: 38 shots against 15 diseases before kindergarten, compared with 11 shots against eight diseases 15 years ago. There's no question that vaccines have been lifesaving: If every American child followed the recommended schedule, some 33,000 lives would be saved, 14 million infections prevented, and $10 billion slashed from healthcare costs every year, according to the Centers for Disease Control and Prevention. But plenty of parents are unconvinced by the public-health mission, given other data­also from the CDC­showing that about 30,000 "adverse events" are reported every year by doctors and patients, of which 3,000 to 4,500 are serious enough to cause hospitalization, life-threatening illness, or even death. While the CDC's associate director for immunization safety, John Iskander, insists that "vaccines are extraordinarily safe medical products," he also acknowledges that the "trade-off between risks and benefits can be very difficult for parents."

Certainly, the government has taken steps through the years to make vaccines safer, replacing the live pertussis component of the diphtheria-tetanus- pertussis vaccine, which caused high fevers and seizures in some children, with the inactive virus, for example. At the same time, though, officials are targeting an ever-expanding array of diseases. Some parents, fighting against the more-is-better philosophy, have gone so far as to organize chickenpox parties in the belief that infecting their kids the "natural way" is safer than vaccination with a weakened form of the virus; others, fearful that vaccines have led to the rise in autism, choose not to vaccinate at all. Alarmed, the American Academy of Pediatrics in September formed an "immunization alliance" with other medical groups to push for kids to get all recommended vaccines on time. Public schools are pushing harder, too; one Maryland school district threatened to bring criminal charges against noncompliant parents.

Call for study. Far more quietly, the government is acknowledging that, at the moment, science doesn't know much about how many shots a kid can safely get at once and which children will be harmed. Last March, the family of 9-year-old Hannah Poling won a claim in the federal Vaccine Court (created to protect manufacturers from ruinous lawsuits) that the autism she developed as a toddler was most likely triggered by receiving five shots against nine diseases in one day; all told, the government has paid out more than $900 million for vaccine injuries over the past two decades. Since the Poling verdict, the government has called for new safety studies­to evaluate, say, whether gene variations may make some kids more susceptible to vaccine injury. "If we can show that individuals of a certain genetic profile have a greater propensity for developing adverse events, we may want to screen everyone prior to vaccination," says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, a key partner in the new initiative.

The concern that vaccines might trigger autism was first sparked a decade ago by a British study­since refuted­showing that the measles part of the measles-mumps-rubella shot caused intestinal inflammation and allowed toxins to enter the bloodstream and attack the central nervous system. Other experts speculated that thimerosal, a preservative containing mercury, was the culprit, and it was removed from children's vaccines in 2001 ( though most flu vaccines still contain it). The CDC is currently conducting a study of 1,200 children to see whether a thimerosal-autism link really does exist, while some scientists wonder whether a small percentage of cases are, like Hannah Poling's, triggered by multiple vaccinations. Poling was found to have mitochondrial disease, a nerve disorder causing autismlike symptoms that appeared to be brought on by her immunizations. "Mitochondrial disease often occurs in the later stages of a viral illness, and it's proper reasoning to think that vaccines could do what viruses do," in terms of immune reactions, says neurologist Bruce Cohen, a mitochondrial disease expert at the Cleveland Clinic.

A search for markers. The answer could lie in gene studies. "We'd like to know if there are particular markers that signal undetectable diseases like a subclinical mitochrondrial disorder," says Fauci. A 2007 study already found that certain mutations affect a person's susceptibility to fevers after smallpox vaccination; the researchers say they may also predict other responses, like febrile seizures linked to the MMR vaccine.

It's important to keep the risks in perspective: More than 95 percent of kids sail through their shots with, at most, a little fussiness, according to Renee Jenkins, president of the American Academy of Pediatrics. A small percentage experience an overactive immune response like redness, swelling, or pain at the injection site, high fever, or extreme irritability, but severe complications like anaphylactic shock are extremely rare ( see graphic). Still, how to account for the fact that once familiar diseases like measles and mumps have become nearly as rare as the adverse reactions?

"It's one thing to take a risk [with a medication] if you actually have a disease, but taking a risk when the goal is prevention of a very rare disease is less tolerable," says Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania. Menactra, for example, protects against bacterial meningitis, which strikes about 1 in 100,000 people per year and kills about 1 in a million. But it also may cause Guillain-Barré syndrome, a temporary but severe paralysis triggered by an overactive immune system, in 1 to 2 teens per million who are vaccinated, according to Iskander.

New vaccines like Menactra and Gardasil pose unknown safety risks because, like any drug submitted for FDA approval, they only need to be tested in several thousand people. "These trials simply aren't big enough to detect rare events that only come to light after 1 million or more doses are distributed," says Iskander. The original vaccine against rotavirus, which causes severe diarrhea and dehydration in infants, was tested on fewer than 1,300 American infants before it was approved in 1998; a year later, after being given to 1.5 million babies, RotaShield was pulled from the market because 13 reported cases of severe intestinal blockages were attributed to the vaccine. The meningitis vaccine Menactra was studied in just over 7,500 people before it was approved in 2005 for adults and kids over age 11. It wasn't until last February, after 15 million doses had been administered, that the CDC announced a "small increased risk" of Guillain-Barré that needs to be studied further.

Hit or miss. The CDC's current system of detecting rare problems is hit or miss. Perhaps the crudest tool is the Vaccine Adverse Event Reporting system, which relies on doctors and patients to file a report if they suspect symptoms have been caused by a vaccine. Many problems filed with VAERS have nothing to do with vaccinations; real adverse events often go unreported. A better monitoring system, the agency's Vaccine Safety Datalink, regularly scans 5.5 million anonymous health records provided by managed care organizations to see whether new vaccines are associated with a spike in certain conditions. Still, even the Datalink database doesn't hold enough teens to definitively prove a causal link between Guillain-Barré and Menactra, says Harvard Medical School professor and vaccine researcher Richard Platt. He and his colleagues recently established a surveillance system that includes 50 million people and are using it to check for Menactra-related Guillain-Barré cases in more than 9 million young people ages 11 to 21. Platt expects to publish results sometime in 2009.

This larger surveillance system could also help determine whether there's a limit to the number of immunizations a baby can safely have at once. The Institute of Medicine concluded in 2002 that giving babies 20 shots against 11 diseases before age 2 did not raise the risk of juvenile diabetes (thought to be a result of an immune system in overdrive). But the IOM decided there wasn't enough evidence to prove or disprove an increased risk of allergies and asthma. Efforts are underway in Congress to fund a well-designed study comparing vaccinated kids against those who remain unvaccinated to see if there are differences in autism rates.

Avoiding immunizations altogether certainly isn't a good solution for families, because meningococcal, pertussis, and other infections could sharply rise if vaccination rates drop low enough­putting any unvaccinated child at risk. Measles cases rose recently in counties with the lowest vaccination rates. So, parents who choose not to vaccinate better hope that other parents aren't following their lead. Certain approaches, though, can help minimize risks without leaving children unprotected.

While researchers seek answers, some families are left wondering if their tragedies are vaccine-caused. Philip Tetlock, an organizational behavior professor at University of California­Berkeley's Haas School of Business, is desperately trying to determine if his 14-year-old daughter Jenny's juvenile amyotrophic lateral sclerosis (aka Lou Gehrig's disease) is a result of her Gardasil vaccination. Another young woman, Whitney Baird, 22, died in August from this disease, just 13 months after receiving Gardasil. Both were healthy before getting the shot, and the condition is extraordinarily rare, affecting just 1 in every 2 million people. The cases have been reviewed by CDC researchers who, says Iskander, "didn't feel that vaccines were the likely trigger." Yet Barbara Shapiro, an associate professor of neurology at Case Western Reserve University School of Medicine who has also pored over Jenny's and Whitney's medical records, believes the cases raise red flags.

Often, parents' only recourse is to try to collect damages in the Vaccine Court, which is expected to rule on a series of autism cases any day. Tawny Buck had to fight hard to convince the court that her infant daughter Quincy's seizures, which left the now-13-year-old with severe brain damage, were caused by a reaction to the live pertussis vaccine. Currently serving in a government vaccine-safety working group, Buck, of Wasilla, Alaska, hopes her experience can help make a difference when it comes to setting research priorities for the CDC. "Vaccines are important for keeping our communities safe, but they have problems," she says. "What happened to my daughter can't be forgotten."