With clinical trials now underway, it is natural to expect that a safe and effective vaccine against HIV will soon spell the end of AIDS in this country. But consider a more likely scenario:
Immediately after the Food and Drug Administration licenses the vaccine, the Centers for Disease Control and Prevention (CDC) recommend the immunization of all high-risk gay men, prostitutes, and intravenous drug users. Congress and state legislatures, however, do not rush to approve the funds needed to reach these groups. Years pass, and HIV infection rates barely budge.
Stymied, the CDC teams with the American Academy of Pediatrics to endorse vaccinating all newborn babies against HIV, which should eventually protect the entire population. This strategy Congress funds. But when scattered reports of possible vaccine complications mount, suburbanites start asking why their children are being vaccinated against a disease they're unlikely to contract. Politicians launch investigations. Some parents refuse to allow the shots. The infant vaccine strategy is threatened, and there's still scant funding for high-risk adults. And HIV marches on.
Not possible, you say? Think again. This scenario is precisely what is happening right now with a safe and effective vaccine against a different national killer. Nearly 20 years after licensure of a vaccine against the hepatitis B virus, that severe and potentially fatal liver pathogen still infects an estimated 300,000 Americans each year, killing about 5,000 annually. The story of the hepatitis B vaccine is a lesson in what not to do next time.
The typical patient with hepatitis B in the United States is a young adult unfortunate enough to have had sex (or shared needles) with someone who is infected. Estimated to be 50 to 100 times more contagious than HIV, the hepatitis B virus (HBV) finds its way to the bloodstream and gradually takes over the liver. About two to six months after infection, the patient typically suffers severe abdominal pain, vomiting, and jaundice. While this acute hepatitis phase is occasionally fatal, it is much more likely that the patient recovers completely. In about 5 percent of adult cases, however, the virus neither kills nor dies. Instead, it renders the afflicted forever contagious and places him or her at high risk of chronic liver failure and liver cancer.
The development of a vaccine--shown to be safe and effective by studies conducted in the 1970s--finally offered the hope that hepatitis B could be eliminated as a major cause of suffering and death. In 1982 the CDC recommended vaccination for those "persons at substantial risk of HBV infection"--including "illicit injectable drug users" and "homosexually active males." In 1985 the agency added to the list "persons who present for treatment of sexually transmitted diseases and who have histories of sexual activity with multiple partners." These three risk groups represented about half of all new cases.
Other than advise physicians on whom to vaccinate, however, public health officials in the Reagan era did little to bring the hepatitis B vaccine to those most likely to contract the disease. Over half the individuals actually immunized were persons at risk from occupational exposure to the virus (such as doctors and nurses), a group representing just 4 percent of new infections. As a CDC vaccine expert bluntly reported in Geneva at the 1989 International Conference on Prospects for Eradication of Hepatitis B Virus, "The U.S. has not put resources into vaccination of persons whose life-style puts them at risk, and that is unfortunate, but it is a fact."
As President Bush took office, CDC officials responsible for hepatitis B had little to show for their efforts. In a report meant only for internal discussion, the agency considered several new measures to jump-start the fight. One was to make the vaccine available to thousands of high-risk men and women in jails. Another was to regularly offer vaccination at clinics for sexually transmitted diseases (STDs). The CDC report assumed that Congress would fund only relatively small projects and that many of the people reached would fail to get the full regimen of three shots; nonetheless, the report estimated that such initiatives would prevent 49,350 acute infections and 3,950 chronic infections by the year 2000.
The report also considered expanding the popular system of universal childhood vaccination to include the hepatitis B vaccine. The political advantages of this approach were obvious: Rather than pleading with Congress for money to locate and vaccinate drug users (or even worse, jailed drug users), health agencies could call for funds to protect the nation's babies. But the public health advantages of this strategy would be a long time coming. Eventually universal infant vaccination would ensure sustainable protection for the entire population. But the CDC report estimated that--even assuming excellent outreach and compliance--exclusively vaccinating babies would decrease the incidence of hepatitis B by only 2 percent in the first 10 years of the strategy; the nation would have to wait "twenty or more years" to control the raging epidemic.
Recognizing the limitations of a babies-only approach, the CDC report favored a balance between targeted efforts to reach those at high risk and a more popular effort to universally vaccinate low-risk babies. But no comprehensive policy proposal or funding request went to Congress. It was not the CDC, but Dr. Sanford Kuvin from the private National Foundation for Infectious Diseases, who testified before the Senate in 1990 that
[o]ur public health service objectives for the year 2000 include a significant reduction in hepatitis B in all targeted groups... . Are these objectives attainable? Certainly, yes, but they will most certainly not be reached with the current level of national apathy, ignorance at the public level, lack of professional education, lack of public programs and public funding, and, in addition, the cost of the vaccine.
Dr. Kuvin went on to refer to the CDC's estimates of the costs of reaching infants and high-risk adults and adolescents, and decried the lack of funding.
In response, Democratic Senator Jeff Bingaman of New Mexico angrily demanded to know why administration officials and the CDC had never sought this money. "Is our public system incapable of prioritizing and responding to the changing demands that we encounter?" he asked. "As a public health issue, where is the secretary of health? Why isn't he testifying to the Congress like you are?"
At the CDC, meanwhile, plans were slowly taking shape, but the political potency of babies was coming to overwhelm all other goals. In 1991 the CDC's policy-making committee on immunizations met to create new vaccine guidelines for clinicians. According to minutes from the committee's deliberations, experts said they didn't want to treat high-risk adults as "second-class citizens." Yet soon after approving a recommendation for universal infant vaccination, the committee squashed a recommendation that clinics provide the vaccine to all adolescents and adults upon diagnosis of the sexually transmitted disease gonorrhea. One reason for the decision was the notion that pressing to vaccinate both babies and high-risk adults, even though such a two-pronged approach was the best policy, would be impolitic. According to its minutes, the committee felt it "loses its credibility if it doesn't prioritize."
By 1992 the administration had requested funds to begin universal infant vaccinations, and Congress had provided them. But far away from the meeting rooms of the CDC, clinicians struggled to make sense of the new policy. As practitioners began to immunize hundreds of thousands of low-risk infants (many with the federally funded vaccine), they remained largely unable to address the elevated risks of the babies' mothers, fathers, sisters, and brothers. In Massachusetts, a January 1992 memo sent to physician offices statewide advised that the state health department (known as MDPH) "only has funding for enough vaccine to immunize infants. Use of MDPHsupplied hepatitis B vaccine for other individuals will result in a vaccine supply inadequate to ensure immunization of all infants. PLEASE RESTRICT USE OF MDPH-SUPPLIED HEPATITIS B VACCINE TO INFANTS ONLY."
In a 1993 research project (published later in the Journal of the National Medical Association), I found that only two of 178 high-risk adolescents and adults treated at a Boston community health center received any doses of the hepatitis B vaccine. Citywide, clinic directors cited the cost of the vaccine as the most significant barrier to administration and indicated that, were free vaccine made available to high-risk adolescents and adults, their clinics could reach over 400 additional high-risk patients each month.
Nationally, only 32 percent of pediatricians and 17 percent of family practitioners, in initial surveys, agreed with the strategy of universal infant vaccination, so the CDC launched a major public relations campaign. In professional journals, at medical society meetings, and on audiotapes mailed to physicians, the agency teamed with vaccine experts to spread the word: Because the risk-based strategy had "failed," universal infant vaccination was the best option left to fight hepatitis B.
The campaign did highlight some good reasons for vaccinating infants. Hepatitis B infection among children, for example, is much more likely than infection in adults to become severe and chronic. And the disorder can be transmitted with relatively casual contact--like blood exposure from a cut--so young children might become infected at camp or school. But when CDC officials and immunization experts argued that vaccination of high-risk adults had failed, they were misleading. The truth was that those efforts had never been adequately developed or funded. Pilot projects conducted in the 1980s at drug treatment centers, STD clinics, and school-based health clinics demonstrated that high-risk populations would accept vaccination if offered. Moreover, studies projected that such vaccination of high-risk individuals would save the health care system money.
Amidst all the rhetoric of failure, the chances of getting the federal government to launch any significant new initiatives aimed at high-risk adults grew slimmer and slimmer. Even the Clinton administration, which did expand access to the hepatitis B vaccine--funding vaccine for needy 11- and 12-year-olds in 1995 and older adolescents in 1997--has done little for high-risk adult groups.
Ironically, the basic public health facts, and the flaws in the infant-centered approach, were about to be exposed in a forum not known for frank discussions of high-risk behavior.
" Do the benefits of administering the vaccine to infants outweigh the risks?" On May 18, 1999, Republican Representative John L. Mica of Florida called to order a hearing of the House Subcommittee on Criminal Justice, Drug Policy and Human Resources entitled "The Hepatitis B Vaccine: Helping or Hurting Public Health?" Three months later, Republican Representative Dan Burton of Indiana convened "Vaccines: Finding the Balance between Public Safety and Personal Choice" in the Government Reform Committee. Spurred by Internet-savvy antivaccine groups, such as the National Vaccine Information Center, conservative lawmakers vowed to scrutinize routine childhood immunization against hepatitis B.
Their initial attacks focused on vaccine safety. Available evidence and years of experience around the world suggest that the hepatitis B vaccine is one of the safest vaccines ever made. Life-threatening immune reactions are extremely rare, and the possibility of an allergic response remote. Fewer than one in 10 children even experience the most common side effect, soreness at the site of injection. Yet antivaccine groups insisted that the hepatitis B vaccine is dangerous--causing sudden infant death syndrome, autism, diabetes, and multiple sclerosis. And they were not about to miss their day in Congress.
One after another, families came forward to testify about the severe medical complications their children had suffered after vaccination. While a few families did describe potentially real vaccine reactions, others blamed the vaccine for an assortment of dubiously related problems. For instance, an Indiana couple testified that their baby daughter suffered loose stools, low body temperature, and cyanosis in the first week of life. Her pediatrician told her she didn't need to come to the office. Another local pediatrician refused to see the patient because of her insurance--Medicaid. Soon afterward, the baby died. According to the parents, the coroner revealed that "the cause of death was the hepatitis B virus--which she could only have gotten from the vaccine." The congressional committee was sympathetic, but the story could not possibly have been true. The hepatitis B vaccine contains only a protein, not live virus, and so can never transmit active infection. Instead of blaming the hepatitis B vaccine, the family should have sued the pediatricians for denying care and questioned the competency of the coroner.
Responding to questions of vaccine safety, Dr. Susan Ellenberg, a senior official at the Food and Drug Administration, testified about extensive research demonstrating that the hepatitis B vaccine had "little in the way of verified serious risks." Congressional Republicans, however, questioned why children were being immunized at all, and to make their case, they exploited the very facts of the disease that the CDC had downplayed when it emphasized childhood immunization over high-risk immunization.
"Start off with hepatitis B cases," Representative Burton began in his cross-examination of Surgeon General David Satcher. "Can you tell us what percentage of hepatitis cases are not from sexual transmission or from blood or needle-exchange properties?" Satcher and his colleagues estimated about 25 to 30 percent. Later in the hearing, Republican Representative Dave Weldon of Florida contended that while "hepatitis B is a very serious illness and it costs a tremendous amount of money ... being that a major mode of transmission is sexual transmission, we have never proposed inoculating the whole population for a sexually transmitted disease. Am I correct?" Yes, a federal official conceded, he was.
These questions hit their mark. Unable to point to significant initiatives to reach those at highest risk of hepatitis B, the nation's public health leaders were left defending vaccination of infants for a disease that, by their own estimation before Congress, strikes children under nine in just 6 percent of new cases.
Vaccinate enough babies, of course, and you will eventually protect the entire country. But it would have been much better for the CDC to have also funded targeted high-risk vaccination all along and then responded, we are attacking hepatitis B at every turn, and we're turning the tide, but full victory will not be achieved until we act to protect all our children.
By failing to frame infant vaccination as part of a comprehensive attack on hepatitis B, the CDC's strategy has unwittingly fueled the antivaccine effort. So far, vaccine opponents have not convinced Congress to roll back funding for infant and adolescent immunization. But they can take heart from swelling legislative battles in several states over immunization requirements for school entry. In New Jersey, they recently won: Hepatitis B vaccination now is not required for children to start school. The American Academy of Pediatrics is worried about parents nationwide refusing the vaccine.
In January 1999, the CDC updated its hepatitis B recommendations to remind clinicians that "because most HBV infections in the United States occur among adults, vaccinating infants and adolescents aged 11-12 years alone will not substantially lower disease incidence for several years." The CDC suggested that practitioners "identify settings where adolescents and adults with high-risk drug and sexual practices can be routinely accessed and vaccinated (e.g., [STD] clinics, family planning clinics, drug treatment clinics, community-based [HIV] prevention sites, and correctional facilities)." Yet to this day, there's little federal funding to provide vaccine in these locations. The CDC spent $111 million in 1999 to purchase hepatitis B vaccines for children, but when CDC experts meet with prison officials to discuss the need to protect inmates from hepatitis B, the CDC side cannot offer funding for the vaccine.
It is high time for the CDC to propose to Congress large-scale efforts to reach high-risk individuals in jails, STD clinics, needle-exchange programs, and detoxification centers. Universal infant immunization should continue, but paired with a program of free vaccine for high-risk parents and other relatives. The message must be that protecting babies is just one part of a comprehensive solution to the hepatitis B epidemic.
If America's unfortunate experience with the hepatitis B virus yields any lesson, it is that we must confront public health challenges honestly in order to conquer them decisively. Nearly two decades after the hepatitis B vaccine was approved for use, CDC researchers recently concluded in the Journal of Infectious Disease that "from 1976 to 1994 ... the estimated incidence of infection did not change." It peaked in 1985, according to experts, and what gains have been made since then are largely due to improved health practices among high-risk groups rather than to vaccination. America's poor use of the hepatitis B vaccine will surely cast a shadow over efforts to prevent HIV, a disease with remarkably similar transmission patterns. To be successful, an HIV vaccine must not only be a safe and effective pharmaceutical. It must also reach the people who need it most. ¤