Volume 3, Number 4
Studies of Demyelination following Hepatitis B Vaccination |
(Atlanta) A 15-year-old controversy between the nation's immunization community and vaccination protest groups escalated in January when ABC Television broadcast "Who's Calling the Shots," a segment on its newsmagazine, 20/20. The 12-minute piece raised questions about the safety of hepatitis B vaccine and the wisdom of the current U.S. policy of universal childhood vaccination. It was seen by an estimated 16 million people.
Controversy over the safety of hepatitis B vaccine is nothing new. Critics attacked the serum-derived hepatitis B vaccine soon after it was licensed in 1981, saying it might cause a variety of serious illnesses. No association was ever found.
The safety issue has continued to simmer in the era of recombinant vaccines. But now, immunization officials at CDC and state health departments are worried that the recent media attention may signal new strength in the vaccination protest movement. In a worst-case scenario, they fear, the movement could threaten the national goal of eliminating hepatitis B transmission by 2010, a goal that can only be reached by the universal vaccination of children.
Investigating a vaccine, TV style
The 20/20 program covered, in the words of an ABC advertisement, "serious new questions about a vaccine most schoolchildren are forced to get, one given every year to millions of babies," and asked, "Is it smart preventative medicine, or an unnecessary risk?" The show focused on the stories of nine patients who suffered illnesses allegedly caused by hepatitis B vaccination. The range of illnesses was broad, including "a rare and life-threatening form of arthritis," loss of vision, joint pains, muscle pains, fatigue, loss of motor function, seizures, and congestive heart failure. The piece also described the tragic sudden death of a five-week-old infant, Lyla Belkin, in her crib 16 hours after her second hepatitis B injection.
In the reporting style of TV newsmagazines, the patients'stories were told vividly, with dramatic "before and after" videos and photographs. One series of pictures showed a four-year-old boy with arthritis and swelling allegedly caused by hepatitis B vaccination. Other footage showed vaccine recipients in wheelchairs or seated near walkers.
The program cited Bonnie Dunbar, Ph.D., a cellular biologist at the Baylor College of Medicine, as believing that "in certain people, a genetic component [of the vaccine] sets off an explosive chain of events."
"The only thing that happened is that they took this vaccine, and within a month, most of these people have had completely debilitating lifestyle changes," Dunbar said. She has been a prominent skeptic of hepatitis B vaccine safety since her brother, Bohn, experienced a series of symptoms after vaccination. Her worries about the safety of the vaccine are based mainly on theories of vaccine-induced autoimmune disease caused by molecular mimicry. They are often cited by vaccination protest groups (www.909shot.com/profcellbio.htm).
Debate on cause and effect
At the regular meeting of ACIP in Atlanta three weeks later, the 20/20 show was a major topic of discussion. During public comment sessions at the meeting, vaccination protesters upbraided the Committee, saying that CDC staffers were "lying" about the true incidence of adverse events following hepatitis B vaccination. In an emotional statement, Michael Belkin (father of Lyla, mentioned above) told the Committee that there is a "real-world risk of a newborn infant dying or being injured by the hepatitis B vaccine." Describing his own study of FDA's Vaccine Adverse Event Reporting System (VAERS), Belkin said he found 1,209 serious illnesses and 73 deaths between 1990 and October 1998 in children under age 14 who received only hepatitis B vaccine. He and many other protesters are convinced that these events were caused by the vaccine.
But few epidemiologists believe that analyses like Belkins'can be used to establish a causal relationship. "We really do have to rely on epidemiologic study" to investigate possible causal links, said Dr. Robert T. Chen, director of the Vaccine Safety and Development Activity at the CDC's National Immunization Program in a presentation.
Chen, who has been working on vaccine safety since the late 1980s, reminded the Committee that the job of searching for vaccine-induced illnesses consists of comparing the rate of an illness in a vaccinated group against the rate in a similar unvaccinated group ‹ essentially, putting data into two-by-two tables. To do this, epidemiologists need a clinical syndrome that can be rigorously defined (by a particular lab result, for example) and a population for which the number of persons exposed and not exposed to a vaccine are known. These numbers are often difficult to find.
Syndromes often attributed to vaccines, like fatigue and muscle pains, defy case definition and are very common in the general population. Furthermore, because the rate of serious adverse events reported after vaccination is extremely low, the studies must be very large, often involving many thousands of subjects, Chen said.
VAERS can not be used to rule in or rule out associations between vaccination and illnesses, Chen said. The system was designed only to accept reports of health effects that follow vaccination, regardless of cause. Many events reported to VAERS are duplicates. Other events may never be reported. More importantly, VAERS does not provide the denominators needed for rate calculations. "VAERS serves mainly as a way to generate hypotheses," Chen told the Committee.
Chen mentioned one such hypothesis-generating review of VAERS, which showed no unexpected events in infants who received an estimated 12 million doses of hepatitis B vaccine during 1991 to 1994 (Niu MT, Davis CM, Ellenberg SS. Recombinant hepatitis B vaccination of neonates and infants: emerging safety data from VAERS. Pediatr Infect Dis J 1996;15:771-76).
Because no unique post-hepatitis B vaccination syndrome has yet been identified, Chen said, separate epidemiologic studies must be done for each type of suspected adverse event‹neurological, musculoskeletal, neonatal deaths, etc. Each study is expensive and time-consuming and CDC resources are badly strained, he said.
Chen discussed four recent studies of demyelination and hepatitis B vaccination, none of which found a statistically significant association (see table). Two of these studies were used by the French government to justify discontinuing school-based hepatitis B vaccination in adolescents (for a review of the French actions, see Hepatitis Control Report, Summer 1998 issue). Three other studies of demyelination are now underway. A study of infant death after vaccination is also nearly completed.
Although no causal association has ever been established between hepatitis B vaccination and any serious adverse event, Chen said, "We must keep an open mind on the possibility of rare associations. The nation's experience with flu vaccine and Guillain-Barré syndrome teaches us that."
Sound and fury over federal vaccination policy
Vaccination protest groups have been working hard in several states to stop hepatitis B vaccination requirements for school entry or to enact philosophical exemptions. The groups have used safety arguments similar to Belkins', but have also argued that it is senseless to give vaccine to infants and young children who are not at risk for infection. To support their contention, they often cite CDC incidence data showing that the bulk of acute hepatitis B cases occurs in persons aged 20 to 39.
Barbara Loe Fisher, President of the National Vaccine Information Center (NVIC) in Vienna, Virginia, the nation's most prominent vaccination protest group (http://www.909shot.com/), told a hearing of the Illinois Board of Health last year that hepatitis B is not like smallpox, when just breathing the air next to an infected person could transmit the disease. With hepatitis B, as with HIV or AIDS, you have to directly exchange body fluids such as blood or semen with an infected person. Let's face it, there are not many fifth graders doing that in the state of Illinois. With 300 or even 1,000 cases of the disease, why not employ traditional public health measures such as educating children about drug use and high risk behaviors; and screening pregnant women in hospitals to make sure that the newborn babies of hepatitis B positive mothers get the vaccine; and targeting IV drug users and prostitutes for quarantine and vaccination. Why target two and a half million innocent newborns and children?
But CDC officials say the protesters misunderstand the rationale for mass immunization of children. "That's a tragedy," said Dr. Harold Margolis in an interview. Margolis is chief of CDC's hepatitis unit and a principal architect of the national vaccination strategy. "It's a disease where you have several periods of risk in your lifetime. There is perinatal risk, there is risk in the group under age five, and there is risk later on as adults. The recommendation to get newborns vaccinated and the state school entry requirements are part of a strategy to get kids protected during all those risk periods."
Margolis pointed out that four to five thousand people die each year from the sequelae of hepatitis B, of whom nearly all are chronically infected. Chronic infection is several times more likely to result from infection in children than from infection in adults. Thirty percent of chronic infections in the U.S. originate in children less than five years old. The majority of these are not acquired perinatally but later in life through household transmission. Their mothers are seronegative for hepatitis B surface antigen (HBsAg) and maternal screening programs will not prevent the infections. "Every year, there are about 20,000 children who are being infected this way, in the first five years of life," Margolis said.
"We tried vaccinating just high risk groups in the 1980s and we were not successful in reducing the disease," Margolis recalled. By the late 1980s, CDC epidemiologists had learned that it is nearly impossible to vaccinate people after they have joined high-risk groups, such as sexually active adolescents and adults with multiple sexual partners or sexually transmitted diseases, men who have sex with men, and sexual and household contacts of infected persons.
"In those years, we did not appreciate how many chronically-infected people got their infections in childhood, under age five," Margolis said. When CDC staff realized this, through the national HANES serosurvey and other studies, they knew that, even if they could vaccinate all high-risk adults, they would still not prevent a high proportion of chronic infections. It became clear that universal vaccination was the only way to reduce chronic infection and its sequelae. That policy, adopted in 1991, has been well-accepted by pediatricians and family physicians, Margolis said.
"In the years since we began universal vaccination, we have seen a significant drop in incidence," Margolis said. "We are trying to eliminate hepatitis B transmission in all age groups in the U.S. by 2010. We can only do this by routinely vaccinating all children."
States are battleground for school entry mandates
School entry requirements are fast becoming a source of strife between state officials and vaccination protesters. Protesters reject the rationale for the requirements given by public health officials. "I don't think the government has a role to come in and mandate for children, that are clearly not at risk, that they need to receive the hepatitis B vaccine," said Sue Blevins on the 20/20 show. Blevins is President of the Institute for Health Freedom, an advocacy group in Washington, D.C (www.forhealthfreedom.org/).
Last year, NVIC's Fisher said in testimony before the Illinois State Board of Health: "How did we come to this point, where American citizens live in fear of state health officials, much the same way people under totalitarian rule live in fear of the secret police? This is not right. We are not living in the Gulag or in communist China or in some backward Third World dictatorship. This is America, where respect for individual human life and freedom and the right to obey our conscience says everything about who we are as a people and as a nation."
This year, Fisher's group is pushing the Illinois legislature to adopt a philosophical exemption to state vaccination requirements. State health officials, however, are not supporting the measure. "Our department is opposed to a philosophical exemption," said Karen McMahon, Acting Chief of the Immunization Section, Illinois Department of Public Health, in an interview. "The local chapter of NVIC is very vocal and very well organized," she said, "but a philosophical exemption is not the route we want to go." She cited the possibility of disruptions in delivery of vaccines and lowered coverage rates, especially in large cities like Chicago. Two years ago, a bill to create a philosophical exemption was defeated in the state.
In Indiana, the State Senate is considering a bill to repeal a hepatitis B vaccination requirement passed just last year. A February 11 editorial in the Indianapolis Star spoke well of the repeal, citing the case of Betty Fluck, a nurse who now uses leg braces to walk allegedly because of a reaction to hepatitis B vaccination. Fluck, now an activist against hepatitis B vaccination, was mentioned on the 20/20 program.
Vaccination protest groups have also been working in New Hampshire, New Jersey, North Dakota, and other states. Many groups maintain sites on the World Wide Web (for examples, see the sites listed above, plus the THINKTWICE Global Vaccine Institute at http://thinktwice.com/global.htm,and the Natural Immunity Information Network at (http://members.xoom.com/niin/).
Vaccine protests now part of the landscape
The recent escalation has taught CDC and state officials that concerns about hepatitis B vaccine safety are now a permanent part of the landscape. One CDC epidemiologist said recently, "We know now that this issue is not going to go away."
The immediate effect of the 20/20 broadcast on vaccination programs appears to be minimal. According to Beth Hibbs, RN, MPH, at the CDC National Immunization Program, the show did not cause a notable increase in calls to the agency's national hotline. State officials also noticed little effect beyond isolated reports of vaccine refusals by parents. One residential drug rehabilitation center in San Diego reported that parents are now refusing to allow their teenagers to be vaccinated against hepatitis B, citing the 20/20 program.
In the days since the 20/20 broadcast, the controversy has only increased in pitch. In a widely published February 2nd Washington Post story, NVIC's Fisher said, "This whole issue has become very, very polarized. Top authorities have committed themselves to a policy on the vaccine and insist there is no problem here. On the other side, people are suffering."
A spokesperson at CDC replied. "We take it very seriously when people use inappropriate information to undermine vaccine programs," said Barbara Reynolds. "There is a real chance they can push us back to a pre-vaccine, developing-country level of health care in the U.S.